The origin and early evolution of life on earth

NASA Technical Reports Server (NTRS)

Oro, J.; Miller, Stanley L.; Lazcano, Antonio

1990-01-01

Results of the studies that have provided insights into the cosmic and primitive earth environments are reviewed with emphasis on those environments in which life is thought to have originated. The evidence bearing on the antiquity of life on the earth and the prebiotic significance of organic compounds found in interstellar clouds and in primitive solar-system bodies such as comets, dark asteroids, and carbonaceous chondrites are assessed. The environmental models of the Hadean and early Archean earth are discussed, as well as the prebiotic formation of organic monomers and polymers essential to life. The processes that may have led to the appearance in the Archean of the first cells are considered, and possible effects of these processes on the early steps of biological evolution are analyzed. The significance of these results to the study of the distribution of life in the universe is evaluated.

Fission yeast Ags1 confers the essential septum strength needed for safe gradual cell abscission

PubMed Central

Sato, Mamiko; Muñoz, Javier; Moreno, M. Belén; Clemente-Ramos, Jose Angel; Ramos, Mariona; Okada, Hitoshi; Osumi, Masako; Durán, Angel; Ribas, Juan Carlos

2012-01-01

Fungal cytokinesis requires the assembly of a dividing septum wall. In yeast, the septum has to be selectively digested during the critical cell separation process. Fission yeast cell wall α(1-3)glucan is essential, but nothing is known about its localization and function in the cell wall or about cooperation between the α- and β(1-3)glucan synthases Ags1 and Bgs for cell wall and septum assembly. Here, we generate a physiological Ags1-GFP variant and demonstrate a tight colocalization with Bgs1, suggesting a cooperation in the important early steps of septum construction. Moreover, we define the essential functions of α(1-3)glucan in septation and cell separation. We show that α(1-3)glucan is essential for both secondary septum formation and the primary septum structural strength needed to support the physical forces of the cell turgor pressure during cell separation. Consequently, the absence of Ags1 and therefore α(1-3)glucan generates a special and unique side-explosive cell separation due to an instantaneous primary septum tearing caused by the turgor pressure. PMID:22891259

Resonantly driven CNOT gate for electron spins

NASA Astrophysics Data System (ADS)

Zajac, D. M.; Sigillito, A. J.; Russ, M.; Borjans, F.; Taylor, J. M.; Burkard, G.; Petta, J. R.

2018-01-01

To build a universal quantum computer—the kind that can handle any computational task you throw at it—an essential early step is to demonstrate the so-called CNOT gate, which acts on two qubits. Zajac et al. built an efficient CNOT gate by using electron spin qubits in silicon quantum dots, an implementation that is especially appealing because of its compatibility with existing semiconductor-based electronics (see the Perspective by Schreiber and Bluhm). To showcase the potential, the authors used the gate to create an entangled quantum state called the Bell state.

Homeostatic Agent for General Environment

NASA Astrophysics Data System (ADS)

Yoshida, Naoto

2018-03-01

One of the essential aspect in biological agents is dynamic stability. This aspect, called homeostasis, is widely discussed in ethology, neuroscience and during the early stages of artificial intelligence. Ashby's homeostats are general-purpose learning machines for stabilizing essential variables of the agent in the face of general environments. However, despite their generality, the original homeostats couldn't be scaled because they searched their parameters randomly. In this paper, first we re-define the objective of homeostats as the maximization of a multi-step survival probability from the view point of sequential decision theory and probabilistic theory. Then we show that this optimization problem can be treated by using reinforcement learning algorithms with special agent architectures and theoretically-derived intrinsic reward functions. Finally we empirically demonstrate that agents with our architecture automatically learn to survive in a given environment, including environments with visual stimuli. Our survival agents can learn to eat food, avoid poison and stabilize essential variables through theoretically-derived single intrinsic reward formulations.

Text-based Analytics for Biosurveillance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Charles, Lauren E.; Smith, William P.; Rounds, Jeremiah

The ability to prevent, mitigate, or control a biological threat depends on how quickly the threat is identified and characterized. Ensuring the timely delivery of data and analytics is an essential aspect of providing adequate situational awareness in the face of a disease outbreak. This chapter outlines an analytic pipeline for supporting an advanced early warning system that can integrate multiple data sources and provide situational awareness of potential and occurring disease situations. The pipeline, includes real-time automated data analysis founded on natural language processing (NLP), semantic concept matching, and machine learning techniques, to enrich content with metadata related tomore » biosurveillance. Online news articles are presented as an example use case for the pipeline, but the processes can be generalized to any textual data. In this chapter, the mechanics of a streaming pipeline are briefly discussed as well as the major steps required to provide targeted situational awareness. The text-based analytic pipeline includes various processing steps as well as identifying article relevance to biosurveillance (e.g., relevance algorithm) and article feature extraction (who, what, where, why, how, and when). The ability to prevent, mitigate, or control a biological threat depends on how quickly the threat is identified and characterized. Ensuring the timely delivery of data and analytics is an essential aspect of providing adequate situational awareness in the face of a disease outbreak. This chapter outlines an analytic pipeline for supporting an advanced early warning system that can integrate multiple data sources and provide situational awareness of potential and occurring disease situations. The pipeline, includes real-time automated data analysis founded on natural language processing (NLP), semantic concept matching, and machine learning techniques, to enrich content with metadata related to biosurveillance. Online news articles are presented as an example use case for the pipeline, but the processes can be generalized to any textual data. In this chapter, the mechanics of a streaming pipeline are briefly discussed as well as the major steps required to provide targeted situational awareness. The text-based analytic pipeline includes various processing steps as well as identifying article relevance to biosurveillance (e.g., relevance algorithm) and article feature extraction (who, what, where, why, how, and when).« less

Building regional early flood warning systems by AI techniques

NASA Astrophysics Data System (ADS)

Chang, F. J.; Chang, L. C.; Amin, M. Z. B. M.

2017-12-01

Building early flood warning system is essential for the protection of the residents against flood hazards and make actions to mitigate the losses. This study implements AI technology for forecasting multi-step-ahead regional flood inundation maps during storm events. The methodology includes three major schemes: (1) configuring the self-organizing map (SOM) to categorize a large number of regional inundation maps into a meaningful topology; (2) building dynamic neural networks to forecast multi-step-ahead average inundated depths (AID); and (3) adjusting the weights of the selected neuron in the constructed SOM based on the forecasted AID to obtain real-time regional inundation maps. The proposed models are trained, and tested based on a large number of inundation data sets collected in regions with the most frequent and serious flooding in the river basin. The results appear that the SOM topological relationships between individual neurons and their neighbouring neurons are visible and clearly distinguishable, and the hybrid model can continuously provide multistep-ahead visible regional inundation maps with high resolution during storm events, which have relatively small RMSE values and high R2 as compared with numerical simulation data sets. The computing time is only few seconds, and thereby leads to real-time regional flood inundation forecasting and make early flood inundation warning system. We demonstrate that the proposed hybrid ANN-based model has a robust and reliable predictive ability and can be used for early warning to mitigate flood disasters.

Malaria parasites target the hepatocyte receptor EphA2 for successful host infection.

PubMed

Kaushansky, Alexis; Douglass, Alyse N; Arang, Nadia; Vigdorovich, Vladimir; Dambrauskas, Nicholas; Kain, Heather S; Austin, Laura S; Sather, D Noah; Kappe, Stefan H I

2015-11-27

The invasion of a suitable host hepatocyte by mosquito-transmitted Plasmodium sporozoites is an essential early step in successful malaria parasite infection. Yet precisely how sporozoites target their host cell and facilitate productive infection remains largely unknown. We found that the hepatocyte EphA2 receptor was critical for establishing a permissive intracellular replication compartment, the parasitophorous vacuole. Sporozoites productively infected hepatocytes with high EphA2 expression, and the deletion of EphA2 protected mice from liver infection. Lack of host EphA2 phenocopied the lack of the sporozoite proteins P52 and P36. Our data suggest that P36 engages EphA2, which is likely to be a key step in establishing the permissive replication compartment. Copyright © 2015, American Association for the Advancement of Science.

Essentials of Career Interest Assessment. Essentials of Psychological Assessment Series.

ERIC Educational Resources Information Center

Prince, Jeffrey P.; Heiser, Lisa J.

This book is a quick reference source to guide the career professional through the essentials of using the most popular career interest tools. It summarizes important technical aspects of each inventory, and offers step-by-step guidance in the interpretation and use of the various inventories. The chapters are: (1) "Overview"; (2)…

Animal cloning by somatic cell nuclear transfer.

PubMed

Smith, Lawrence C; Yoo, Jae-Gyu

2009-01-01

Animal cloning is becoming increasingly useful for its applications in biological inquiry and for its potential use in pharmaceutical, medical, and agricultural fields. Due to the complexity of the numerous steps required in reconstructing oocytes by nuclear transfer, detailed protocols are required to minimize the developmental damages inflicted during these manipulations and to standardize procedures across laboratories. Moreover, because oogenesis and early embryogenesis differ widely among mammalian species, it is essential that protocols be adapted according to each species concerned. Our objective here is to detail the protocols that have been most successful in producing laboratory and domestic animal clones.

Accelerated Life Testing and Service Lifetime Prediction for PV Technologies in the Twenty-First Century

DOE Office of Scientific and Technical Information (OSTI.GOV)

Czanderna, A. W.; Jorgensen, G. J.

The purposes of this paper are to (1) discuss the necessity for conducting accelerated life testing (ALT) in the early stages of developing new photovoltaic (PV) technologies, (2) elucidate the crucial importance for combining ALT with real-time testing (RTT) in terrestrial environments for promising PV technologies for the 21st century, and (3) outline the essential steps for making a service lifetime prediction (SLP) for any PV technology. The specific objectives are to (a) illustrate the essential need for ALT of complete, encapsulated multilayer PV devices, (b) indicate the typical causes of degradation in PV stacks, (c) elucidate the complexity associatedmore » with quantifying the durability of the devices, (d) explain the major elements that constitute a generic SLP methodology, (e) show how the introduction of the SLP methodology in the early stages of new device development can reduce the cost of technology development, and (f) outline the procedure for combining the results of ALT and RTT, establishing degradation mechanisms, using sufficient numbers of samples, and applying the SLP methodology to produce a SLP for existing or new PV technologies.« less

The placenta: the forgotten essential organ of iron transport

PubMed Central

Cao, Chang

2016-01-01

Optimal iron nutrition in utero is essential for development of the fetus and helps establish birth iron stores adequate to sustain growth in early infancy. In species with hemochorial placentas, such as humans and rodents, iron in the maternal circulation is transferred to the fetus by directly contacting placental syncytiotrophoblasts. Early kinetic studies provided valuable data on the initial uptake of maternal transferrin, an iron-binding protein, by the placenta. However, the remaining steps of iron trafficking across syncytiotrophoblasts and through the fetal endothelium into the fetal blood remain poorly characterized. Over the last 20 years, identification of transmembrane iron transporters and the iron regulatory hormone hepcidin has greatly expanded the knowledge of cellular iron transport and its regulation by systemic iron status. In addition, emerging human and animal data demonstrating comprised fetal iron stores in severe maternal iron deficiency challenge the classic dogma of exclusive fetal control over the transfer process and indicate that maternal and local signals may play a role in regulating this process. This review compiles current data on the kinetic, molecular, and regulatory aspects of placental iron transport and considers new questions and knowledge gaps raised by these advances. PMID:27261274

Aging effect on step adjustments and stability control in visually perturbed gait initiation.

PubMed

Sun, Ruopeng; Cui, Chuyi; Shea, John B

2017-10-01

Gait adaptability is essential for fall avoidance during locomotion. It requires the ability to rapidly inhibit original motor planning, select and execute alternative motor commands, while also maintaining the stability of locomotion. This study investigated the aging effect on gait adaptability and dynamic stability control during a visually perturbed gait initiation task. A novel approach was used such that the anticipatory postural adjustment (APA) during gait initiation were used to trigger the unpredictable relocation of a foot-size stepping target. Participants (10 young adults and 10 older adults) completed visually perturbed gait initiation in three adjustment timing conditions (early, intermediate, late; all extracted from the stereotypical APA pattern) and two adjustment direction conditions (medial, lateral). Stepping accuracy, foot rotation at landing, and Margin of Dynamic Stability (MDS) were analyzed and compared across test conditions and groups using a linear mixed model. Stepping accuracy decreased as a function of adjustment timing as well as stepping direction, with older subjects exhibited a significantly greater undershoot in foot placement to late lateral stepping. Late adjustment also elicited a reaching-like movement (i.e. foot rotation prior to landing in order to step on the target), regardless of stepping direction. MDS measures in the medial-lateral and anterior-posterior direction revealed both young and older adults exhibited reduced stability in the adjustment step and subsequent steps. However, young adults returned to stable gait faster than older adults. These findings could be useful for future study of screening deficits in gait adaptability and preventing falls. Copyright © 2017 Elsevier B.V. All rights reserved.

Early Reconstructions of Complex Lower Extremity Battlefield Soft Tissue Wounds

PubMed Central

Ebrahimi, Ali; Nejadsarvari, Nasrin; Ebrahimi, Azin; Rasouli, Hamid Reza

2017-01-01

BACKGROUND Severe lower extremity trauma as a devastating combat related injury is on the rise and this presents reconstructive surgeons with significant challenges to reach optimal cosmetic and functional outcomes. This study assessed early reconstructions of complex lower extremity battlefield soft tissue wounds. METHODS This was a prospective case series study of battled field injured patients which was done in the Department of Plastic Surgery, Baqiyatallah University of Medical Sciences hospitals, Tehran, Iran between 2013-2015. In this survey, 73 patients were operated for reconstruction of lower extremity soft tissue defects due to battlefield injuries RESULTS Seventy-three patients (65 men, 8 womens) ranging from 21-48 years old (mean: 35 years) were enrolled. Our study showed that early debridement and bone stabilization and later coverage of complex battlefields soft tissue wounds with suitable flaps and grafts of lower extremity were effective method for difficult wounds managements with less amputation and infections. CONCLUSION Serial debridement and bone stabilization before early soft tissue reconstruction according to reconstructive ladder were shown to be essential steps. PMID:29218283

Early experiences in evolving an enterprise-wide information model for laboratory and clinical observations.

PubMed

Chen, Elizabeth S; Zhou, Li; Kashyap, Vipul; Schaeffer, Molly; Dykes, Patricia C; Goldberg, Howard S

2008-11-06

As Electronic Healthcare Records become more prevalent, there is an increasing need to ensure unambiguous data capture, interpretation, and exchange within and across heterogeneous applications. To address this need, a common, uniform, and comprehensive approach for representing clinical information is essential. At Partners HealthCare System, we are investigating the development and implementation of enterprise-wide information models to specify the representation of clinical information to support semantic interoperability. This paper summarizes our early experiences in: (1) defining a process for information model development, (2) reviewing and comparing existing healthcare information models, (3) identifying requirements for representation of laboratory and clinical observations, and (4) exploring linkages to existing terminology and data standards. These initial findings provide insight to the various challenges ahead and guidance on next steps for adoption of information models at our organization.

Early recycling compartment trafficking of CD1a is essential for its intersection and presentation of lipid antigens.

PubMed

Cernadas, Manuela; Cavallari, Marco; Watts, Gerald; Mori, Lucia; De Libero, Gennaro; Brenner, Michael B

2010-02-01

A major step in understanding differences in the nature of Ag presentation was the realization that MHC class I samples peptides transported to the endoplasmic reticulum from the cytosol, whereas MHC class II samples peptides from lysosomes. In contrast to MHC class I and II molecules that present protein Ags, CD1 molecules present lipid Ags for recognition by specific T cells. Each of the five members of the CD1 family (CD1a-e) localizes to a distinct subcompartment of endosomes. Accordingly, it has been widely assumed that the distinct trafficking of CD1 isoforms must also have evolved to enable them to sample lipid Ags that traffic via different routes. Among the CD1 isoforms, CD1a is unusual because it does not have a tyrosine-based cytoplasmic sorting motif and uniquely localizes to the early endocytic recycling compartment. This led us to predict that CD1a might have evolved to focus on lipids that localize to early endocytic/recycling compartments. Strikingly, we found that the glycolipid Ag sulfatide also localized almost exclusively to early endocytic and recycling compartments. Consistent with colocalization of CD1a and sulfatide, wild-type CD1a molecules efficiently presented sulfatide to CD1a-restricted, sulfatide-specific T cells. In contrast, CD1a:CD1b tail chimeras, that retain the same Ag-binding capacity as CD1a but traffic based on the cytoplasmic tail of CD1b to lysosomes, failed to present sulfatide efficiently. Thus, the intracellular trafficking route of CD1a is essential for efficient presentation of lipid Ags that traffic through the early endocytic and recycling pathways.

[Ethic rounds in intensive care. Possible instrument for a clinical-ethical assessment in intensive care units].

PubMed

Scheffold, N; Paoli, A; Gross, J; Riemann, U; Hennersdorf, M

2012-10-01

Ethical problems, such as medical end-of-life decisions or withdrawing life-sustaining treatment are viewed as an essential task in intensive care units. This article presents the ethics rounds as an instrument for evaluation of ethical problems in intensive care medicine units. The benchmarks of ethical reflection during the ethics rounds are considerations of ethical theory of principle-oriented medical ethics. Besides organizational aspects and the institutional framework, the role of the ethicist is described. The essential evaluation steps, as a basis of the ethics rounds are presented. In contrast to the clinical ethics consultation, the ethicist in the ethics rounds model is integrated as a member of the ward round team. Therefore ethical problems may be identified and analyzed very early before the conflict escalates. This preventive strategy makes the ethics rounds a helpful instrument in intensive care units.

Interactions of Aspergillus fumigatus Conidia with Airway Epithelial Cells: A Critical Review

PubMed Central

Croft, Carys A.; Culibrk, Luka; Moore, Margo M.; Tebbutt, Scott J.

2016-01-01

Aspergillus fumigatus is an environmental filamentous fungus that also acts as an opportunistic pathogen able to cause a variety of symptoms, from an allergic response to a life-threatening disseminated fungal infection. The infectious agents are inhaled conidia whose first point of contact is most likely to be an airway epithelial cell (AEC). The interaction between epithelial cells and conidia is multifaceted and complex, and has implications for later steps in pathogenesis. Increasing evidence has demonstrated a key role for the airway epithelium in the response to respiratory pathogens, particularly at early stages of infection; therefore, elucidating the early stages of interaction of conidia with AECs is essential to understand the establishment of infection in cohorts of at-risk patients. Here, we present a comprehensive review of the early interactions between A. fumigatus and AECs, including bronchial and alveolar epithelial cells. We describe mechanisms of adhesion, internalization of conidia by AECs, the immune response of AECs, as well as the role of fungal virulence factors, and patterns of fungal gene expression characteristic of early infection. A clear understanding of the mechanisms involved in the early establishment of infection by A. fumigatus could point to novel targets for therapy and prophylaxis. PMID:27092126

A Novel Pheromone Quorum-Sensing System Controls the Development of Natural Competence in Streptococcus thermophilus and Streptococcus salivarius▿ †

PubMed Central

Fontaine, Laetitia; Boutry, Céline; de Frahan, Marie Henry; Delplace, Brigitte; Fremaux, Christophe; Horvath, Philippe; Boyaval, Patrick; Hols, Pascal

2010-01-01

In streptococcal species, the key step of competence development is the transcriptional induction of comX, which encodes the alternative sigma factor σX, which positively regulates genes necessary for DNA transformation. In Streptococcus species belonging to the mitis and mutans groups, induction of comX relies on the activation of a three-component system consisting of a secreted pheromone, a histidine kinase, and a response regulator. In Streptococcus thermophilus, a species belonging to the salivarius group, the oligopeptide transporter Ami is essential for comX expression under competence-inducing conditions. This suggests a different regulation pathway of competence based on the production and reimportation of a signal peptide. The objective of our work was to identify the main actors involved in the early steps of comX induction in S. thermophilus LMD-9. Using a transcriptomic approach, four highly induced early competence operons were identified. Among them, we found a Rgg-like regulator (Ster_0316) associated with a nonannotated gene encoding a 24-amino-acid hydrophobic peptide (Shp0316). Through genetic deletions, we showed that these two genes are essential for comX induction. Moreover, addition to the medium of synthetic peptides derived from the C-terminal part of Shp0316 restored comX induction and transformation of a Shp0316-deficient strain. These peptides also induced competence in S. thermophilus and Streptococcus salivarius strains that are poorly transformable or not transformable. Altogether, our results show that Ster_0316 and Shp0316, renamed ComRS, are the two members of a novel quorum-sensing system responsible for comX induction in species from the salivarius group, which differs from the classical phosphorelay three-component system identified previously in streptococci. PMID:20023010

The roles of SSU processome components and surveillance factors in the initial processing of human ribosomal RNA

PubMed Central

Sloan, Katherine E.; Bohnsack, Markus T.; Schneider, Claudia; Watkins, Nicholas J.

2014-01-01

During eukaryotic ribosome biogenesis, three of the mature ribosomal (r)RNAs are released from a single precursor transcript (pre-rRNA) by an ordered series of endonucleolytic cleavages and exonucleolytic processing steps. Production of the 18S rRNA requires the removal of the 5′ external transcribed spacer (5′ETS) by endonucleolytic cleavages at sites A0 and A1/site 1. In metazoans, an additional cleavage in the 5′ETS, at site A′, upstream of A0, has also been reported. Here, we have investigated how A′ processing is coordinated with assembly of the early preribosomal complex. We find that only the tUTP (UTP-A) complex is critical for A′ cleavage, while components of the bUTP (UTP-B) and U3 snoRNP are important, but not essential, for efficient processing at this site. All other factors involved in the early stages of 18S rRNA processing that were tested here function downstream from this processing step. Interestingly, we show that the RNA surveillance factors XRN2 and MTR4 are also involved in A′ cleavage in humans. A′ cleavage is largely bypassed when XRN2 is depleted, and we also discover that A′ cleavage is not always the initial processing event in all cell types. Together, our data suggest that A′ cleavage is not a prerequisite for downstream pre-rRNA processing steps and may, in fact, represent a quality control step for initial pre-rRNA transcripts. Furthermore, we show that components of the RNA surveillance machinery, including the exosome and TRAMP complexes, also play key roles in the recycling of excised spacer fragments and degradation of aberrant pre-rRNAs in human cells. PMID:24550520

Quality assurance and stability reference (QUASAR) monitoring concept for calibration/validation

NASA Astrophysics Data System (ADS)

Teillet, Philippe M.; Horler, D. N.; O'Neill, Norman T.

1997-12-01

The paper introduces the concept that calibration/validation (cal/val) can play an essential role in bringing remote sensing to mainstream consumers in an information-based society, provided that cal/val is an integral part of a quality-assurance strategy. A market model for remote sensing is introduced and used to demonstrate that quality assurance is the key to bridging the gap between early adopters of technology and mainstream markets. The paper goes on to propose the semi-continuous monitoring of quality assurance and stability reference (QUASAR) sites as an important first step towards a cal/val infrastructure beneficial to mainstream users. Prospective QUASAR test sites are described.

Formylpeptide receptors are critical for rapid neutrophil mobilization in host defense against Listeria monocytogenes

PubMed Central

Liu, Mingyong; Chen, Keqiang; Yoshimura, Teizo; Liu, Ying; Gong, Wanghua; Wang, Aimin; Gao, Ji-Liang; Murphy, Philip M.; Wang, Ji Ming

2012-01-01

Listeria monocytogenes (Listeria) causes opportunistic infection in immunocompromised hosts with high mortality. Resistance to Listeria depends on immune responses and recruitment of neutrophils of the immune system into infected sites is an early and critical step. Mouse neutrophils express two G protein-coupled formylpeptide receptor subtypes Fpr1 and Fpr2 that recognize bacterial and host-derived chemotactic molecules including Listeria peptides for cell migration and activation. Here we report deficiency in Fprs exacerbated the severity of the infection and increased the mortality of infected mice. The mechanism involved impaired early neutrophil recruitment to the liver with Fpr1 and Fpr2 being sole receptors for neutrophils to sense Listeria chemoattractant signals and for production of bactericidal superoxide. Thus, Fprs are essential sentinels to guide the first wave of neutrophil infiltration in the liver of Listeria-infected mice for effective elimination of the invading pathogen. PMID:23139859

Mouse Embryo Compaction.

PubMed

White, M D; Bissiere, S; Alvarez, Y D; Plachta, N

2016-01-01

Compaction is a critical first morphological event in the preimplantation development of the mammalian embryo. Characterized by the transformation of the embryo from a loose cluster of spherical cells into a tightly packed mass, compaction is a key step in the establishment of the first tissue-like structures of the embryo. Although early investigation of the mechanisms driving compaction implicated changes in cell-cell adhesion, recent work has identified essential roles for cortical tension and a compaction-specific class of filopodia. During the transition from 8 to 16 cells, as the embryo is compacting, it must also make fundamental decisions regarding cell position, polarity, and fate. Understanding how these and other processes are integrated with compaction requires further investigation. Emerging imaging-based techniques that enable quantitative analysis from the level of cell-cell interactions down to the level of individual regulatory molecules will provide a greater understanding of how compaction shapes the early mammalian embryo. © 2016 Elsevier Inc. All rights reserved.

Rapid Statistical Learning Supporting Word Extraction From Continuous Speech.

PubMed

Batterink, Laura J

2017-07-01

The identification of words in continuous speech, known as speech segmentation, is a critical early step in language acquisition. This process is partially supported by statistical learning, the ability to extract patterns from the environment. Given that speech segmentation represents a potential bottleneck for language acquisition, patterns in speech may be extracted very rapidly, without extensive exposure. This hypothesis was examined by exposing participants to continuous speech streams composed of novel repeating nonsense words. Learning was measured on-line using a reaction time task. After merely one exposure to an embedded novel word, learners demonstrated significant learning effects, as revealed by faster responses to predictable than to unpredictable syllables. These results demonstrate that learners gained sensitivity to the statistical structure of unfamiliar speech on a very rapid timescale. This ability may play an essential role in early stages of language acquisition, allowing learners to rapidly identify word candidates and "break in" to an unfamiliar language.

GGA1 regulates signal-dependent sorting of BACE1 to recycling endosomes, which moderates Aβ production

PubMed Central

Toh, Wei Hong; Chia, Pei Zhi Cheryl; Hossain, Mohammed Iqbal; Gleeson, Paul A.

2018-01-01

The diversion of the membrane-bound β-site amyloid precursor protein–(APP) cleaving enzyme (BACE1) from the endolysosomal pathway to recycling endosomes represents an important transport step in the regulation of amyloid beta (Aβ) production. However, the mechanisms that regulate endosome sorting of BACE1 are poorly understood. Here we assessed the transport of BACE1 from early to recycling endosomes and have identified essential roles for the sorting nexin 4 (SNX4)-mediated, signal-independent pathway and for a novel signal-mediated pathway. The signal-mediated pathway is regulated by the phosphorylation of the DXXLL-motif sequence DISLL in the cytoplasmic tail of BACE1. The phosphomimetic S498D BACE1 mutant was trafficked to recycling endosomes at a faster rate compared with wild-type BACE1 or the nonphosphorylatable S498A mutant. The rapid transit of BACE1 S498D from early endosomes was coupled with reduced levels of amyloid precursor protein processing and Aβ production, compared with the S498A mutant. We show that the adaptor, GGA1, and retromer are essential to mediate rapid trafficking of phosphorylated BACE1 to recycling endosomes. In addition, the BACE1 DISLL motif is phosphorylated and regulates endosomal trafficking, in primary neurons. Therefore, post-translational phosphorylation of DISLL enhances the exit of BACE1 from early endosomes, a pathway mediated by GGA1 and retromer, which is important in regulating Aβ production. PMID:29142073

Don't ask don't tell: substance abuse and addiction among nurses.

PubMed

Monroe, Todd; Kenaga, Heidi

2011-02-01

The purpose of this manuscript is to illustrate the challenges faced by nurses who abuse substances and to promote international dialogue about what practitioners, administrators, health care providers and students can do when they suspect someone in the profession is abusing substances, or they may themselves be suffering from addiction. Addiction among nurses has been recognised by professionals in the field for over 100 years, and current estimates place rates of substance misuse, abuse and addiction rates as high as 20% among practicing nurses. Unfortunately, fear of punishment and discipline may keep nurses or students from asking for help for themselves or from reporting a colleague or friend who is in need of help. Discursive paper. This paper synthesises the results of three previous papers conducted on substance abuse policies in the nursing profession. In the first paper, the authors reviewed the history of addiction in nursing and compared disciplinary and alternative-to-discipline policies. The second focused on the development of an alternative-to-dismissal policy for substance abuse in a school of nursing and using telephone and email interviews, and the final paper reported findings of what types of policies seem to be working to retain and rehabilitate nurses who suffer from addiction in the USA. Lastly, this paper introduces international policy for nurses with addictions. Poor or ineffective policies that mandate punitive action endanger the public by making it difficult for impaired students or professionals to ask for help. Providing early intervention and assistance is essential in helping colleagues and students recover from an addictive disorder and providing a non-punitive atmosphere of support may well be a life-saving first step for nurses and those in their care. Many territories and countries throughout the world now offer confidential, non-punitive, assistance for nurses suffering from addictions. Recognition of a colleague's need of treatment is the important first step in the rehabilitation process. Early intervention and assistance are essential for helping colleagues and students to recover from an addictive disorder and providing a confidential, non-punitive atmosphere of support may well be a life-saving first step for nurses and those in their care. © 2010 Blackwell Publishing Ltd.

Essentials of Millon Inventories Assessment. Essentials of Psychological Assessment Series.

ERIC Educational Resources Information Center

Strack, Stephen

This step-by-step reference guide to the five key Millon personality inventories includes vital information about each of the tests, including information on psychometric characteristics, special populations, assets-limitations, reliability-validity, and interpretation. The tests are: the Millon Clinical Multiaxial Inventory III (MCMI-III); the…

Sex-specific early survival drives adult sex ratio bias in snowy plovers and impacts mating system and population growth

PubMed Central

Küpper, Clemens; Miller, Tom E. X.; Cruz-López, Medardo; Maher, Kathryn H.; dos Remedios, Natalie; Stoffel, Martin A.; Hoffman, Joseph I.; Krüger, Oliver; Székely, Tamás

2017-01-01

Adult sex ratio (ASR) is a central concept in population biology and a key factor in sexual selection, but why do most demographic models ignore sex biases? Vital rates often vary between the sexes and across life history, but their relative contributions to ASR variation remain poorly understood—an essential step to evaluate sex ratio theories in the wild and inform conservation. Here, we combine structured two-sex population models with individual-based mark–recapture data from an intensively monitored polygamous population of snowy plovers. We show that a strongly male-biased ASR (0.63) is primarily driven by sex-specific survival of juveniles rather than adults or dependent offspring. This finding provides empirical support for theories of unbiased sex allocation when sex differences in survival arise after the period of parental investment. Importantly, a conventional model ignoring sex biases significantly overestimated population viability. We suggest that sex-specific population models are essential to understand the population dynamics of sexual organisms: reproduction and population growth are most sensitive to perturbations in survival of the limiting sex. Overall, our study suggests that sex-biased early survival may contribute toward mating system evolution and population persistence, with implications for both sexual selection theory and biodiversity conservation. PMID:28634289

Essential medicines for breast cancer in low and middle income countries.

PubMed

Bazargani, Y T; de Boer, A; Schellens, J H M; Leufkens, H G M; Mantel-Teeuwisse, Aukje K

2015-08-18

Breast cancer is the most common type of cancer among women worldwide. In low and middle-income countries (LMICs), appropriate selection of medicines on national essential medicines lists (NEMLs) is a first step towards adequate access to treatment. We studied selection of systemic treatments for breast cancer on NEMLs and assessed its alignment with treatment guidelines for different types of early and advanced breast cancer. Furthermore, influence of country characteristics on the selection was investigated. NEMLs from 75 LMICs were studied for inclusion of all components of therapy in each stage of breast cancer according to international consensus guidelines. The results were then grouped by income level, WHO region and the NEMLs' release date. Non parametric tests were used for statistical analysis. Unlike HER2-targeted therapies (<10%), aromatase inhibitors (12%) and taxanes (28%); tamoxifen and first generation chemotherapeutic regimens (e.g., anthracycline-based regimens) were frequently found in the NEMLs (71-78%). Consequently, all components of treatment for "Luminal A" early breast cancer and non HER2 overexpressed advanced breast cancer were found on the NEMLs of over 70% of countries. However, 40% of the low income countries did not have all the components of therapy for any type of early breast cancer in their NEMLs, and adequate treatment of HER2 overexpressed breast cancer was hardly possible with the current selections. Recent NEMLs were more aligned with the guidelines (p < 0.05). Eastern Mediterranean and African regions less frequently incorporated all components of breast cancer treatment in their NEMLs. Alignment of selection with guidelines' recommendations was inconsistent for different types of early and advanced breast cancer in NEMLs. Regular updates and more attention to clinical guidelines is therefore recommended.

APWPs: Critical Building Steps and Potential for Future Geodynamical Studies.

NASA Astrophysics Data System (ADS)

Besse, J.

2004-12-01

Among other items, the Apparent Polar Wander Paths (APWP) of individual tectonic blocks contain information on geodynamical events from both shallower lithospheric sources (e.g. continental breakups and collisions) and deeper mantle sources affected by convection. Recent advances in the Earth Sciences, such as provided by global tomography or climate modeling, have emphasized the essential need for accurate reconstructions of the Earth's surface (blocks, plates and their boundaries and topographies), in order for instance to compare the initial positions of downgoing slabs or emerging hot spots with deeper mantle features, or to understand why and how time-varying climates and biomes may be related. A half century after its initial pionneering contributions to the formulation of continental drift and plate tectonics, paleomagnetism remains an invaluable tool which will allow us to solve a very large range of problems concerning both internal and external geodynamics (solid, fluid and bio-spheres). The accurate determination of the APWPs of crustal and lithospheric blocks remains one of the main goals that must be pursued by the paleomagnetic community. Based on two examples, one extending from Permian to Present, the other in the Late Proterozoic to Early Paleozoic, I will discuss various aspects of the construction of APWPs and reconstruction of past plate positions. Critical steps involve: 1) how are original paleomagnetic data selected? 2) how are the kinematic models used to transfer data from one plate to the other determined ? 3) how can poles coming from deformed (e.g. rotated) regions be used ? and 4) how good is the geocentric axial dipole (GAD) assumption, which is fundamental for reliable plate reconstructions ? Particular emphasis will be given to this last topic, since the GAD hypothesis has recently been challenged, with suggestions that significant long-term octupolar contributions might have existed from the Precambrian throughout to the early Tertiary. These might account for the low inclinations observed in central Asia in the Cretaceous and early Tertiary, or for the misfits of Pangea (Pangea A or B?). GAD hypothesis appears to be essentially correct and APWPs still have a bright future.

Essentials of Myers-Briggs Type Indicator[R] Assessment. Essentials of Psychological Assessment Series.

ERIC Educational Resources Information Center

Quenk, Naomi L.

This book provides step-by-step guidance on the administration, scoring, and interpretation of the Myers-Briggs Type Indicator[R] (MBTI). The book also contains assessment of the test's strengths and weaknesses, advice on its clinical applications, and several case reports. The chapters are: (1) "Overview"; (2) "How To Administer…

A Taxonomy of Instructional Strategies in Early Childhood Education; Toward a Developmental Theory of Instructional Design.

ERIC Educational Resources Information Center

Vance, Barbara

This paper suggests two steps in instructional deisgn for early childhood that can be derived from a recent major paper on instructional strategy taxonomy. These steps, together with the instructional design variables involved in each step, are reviewed relative to current research in child development and early education. The variables reviewed…

The origin and early evolution of life on Earth.

PubMed

Oró, J; Miller, S L; Lazcano, A

1990-01-01

We do not have a detailed knowledge of the processes that led to the appearance of life on Earth. In this review we bring together some of the most important results that have provided insights into the cosmic and primitive Earth environments, particularly those environments in which life is thought to have originated. To do so, we first discuss the evidence bearing on the antiquity of life on our planet and the prebiotic significance of organic compounds found in interstellar clouds and in primitive solar system bodies such as comets, dark asteroids, and carbonaceous chondrites. This is followed by a discussion on the environmental models of the Hadean and early Archean Earth, as well as on the prebiotic formation of organic monomers and polymers essential to life. We then consider the processes that may have led to the appearance in the Archean of the first cells, and how these processes may have affected the early steps of biological evolution. Finally, the significance of these results to the study of the distribution of life in the Universe is discussed.

The wall traction induced by flowing red blood cells in model microvessels and its potential mechanotransduction

NASA Astrophysics Data System (ADS)

Freund, Jonathan; Vermot, Julien

2013-11-01

There is evidence in early embryonic development, even well before advective oxygen transport is important, that the presence of red bloods cells per se trigger essential steps of normal vascular development. For example, showed that sequestration of blood cells early in the development of a mouse, such that the hematocrit is reduced, suppresses normal vascular network development. Vascular development also provides a model for remodeling and angiogenesis. We consider the transient stresses associated with blood cells flowing in model microvessels of comparable diameter to those at early stages of development (6 μm to 12 μm). A detailed simulation tool is used to show that passing blood cells present a significant fluctuating traction signature on the vessel wall, well above the mean stresses. This is particularly pronounced for slow flows (<= 50 μm/s) or small diameters (<= 7 μm), for which root-mean-square wall traction fluctuations can exceed their mean. These events potentially present mechanotranduction triggers that direct development or remodeling. Attenuation of such fluctuating tractions by a viscoelastic endothelial glycocalyx layer is also considered. NSF supported.

Assessment of Cultivation Factors that Affect Biomass and Geraniol Production in Transgenic Tobacco Cell Suspension Cultures

PubMed Central

Vasilev, Nikolay; Schmitz, Christian; Grömping, Ulrike; Fischer, Rainer; Schillberg, Stefan

2014-01-01

A large-scale statistical experimental design was used to determine essential cultivation parameters that affect biomass accumulation and geraniol production in transgenic tobacco (Nicotiana tabacum cv. Samsun NN) cell suspension cultures. The carbohydrate source played a major role in determining the geraniol yield and factors such as filling volume, inoculum size and light were less important. Sucrose, filling volume and inoculum size had a positive effect on geraniol yield by boosting growth of plant cell cultures whereas illumination of the cultures stimulated the geraniol biosynthesis. We also found that the carbohydrates sucrose and mannitol showed polarizing effects on biomass and geraniol accumulation. Factors such as shaking frequency, the presence of conditioned medium and solubilizers had minor influence on both plant cell growth and geraniol content. When cells were cultivated under the screened conditions for all the investigated factors, the cultures produced ∼5.2 mg/l geraniol after 12 days of cultivation in shaking flasks which is comparable to the yield obtained in microbial expression systems. Our data suggest that industrial experimental designs based on orthogonal arrays are suitable for the selection of initial cultivation parameters prior to the essential medium optimization steps. Such designs are particularly beneficial in the early optimization steps when many factors must be screened, increasing the statistical power of the experiments without increasing the demand on time and resources. PMID:25117009

Assessment of cultivation factors that affect biomass and geraniol production in transgenic tobacco cell suspension cultures.

PubMed

Vasilev, Nikolay; Schmitz, Christian; Grömping, Ulrike; Fischer, Rainer; Schillberg, Stefan

2014-01-01

A large-scale statistical experimental design was used to determine essential cultivation parameters that affect biomass accumulation and geraniol production in transgenic tobacco (Nicotiana tabacum cv. Samsun NN) cell suspension cultures. The carbohydrate source played a major role in determining the geraniol yield and factors such as filling volume, inoculum size and light were less important. Sucrose, filling volume and inoculum size had a positive effect on geraniol yield by boosting growth of plant cell cultures whereas illumination of the cultures stimulated the geraniol biosynthesis. We also found that the carbohydrates sucrose and mannitol showed polarizing effects on biomass and geraniol accumulation. Factors such as shaking frequency, the presence of conditioned medium and solubilizers had minor influence on both plant cell growth and geraniol content. When cells were cultivated under the screened conditions for all the investigated factors, the cultures produced ∼ 5.2 mg/l geraniol after 12 days of cultivation in shaking flasks which is comparable to the yield obtained in microbial expression systems. Our data suggest that industrial experimental designs based on orthogonal arrays are suitable for the selection of initial cultivation parameters prior to the essential medium optimization steps. Such designs are particularly beneficial in the early optimization steps when many factors must be screened, increasing the statistical power of the experiments without increasing the demand on time and resources.

Consumer-Based Physical Activity Monitor as a Practical Way to Measure Walking Intensity During Inpatient Stroke Rehabilitation.

PubMed

Klassen, Tara D; Semrau, Jennifer A; Dukelow, Sean P; Bayley, Mark T; Hill, Michael D; Eng, Janice J

2017-09-01

Identifying practical ways to accurately measure exercise intensity and dose in clinical environments is essential to advancing stroke rehabilitation. This is especially relevant in monitoring walking activity during inpatient rehabilitation where recovery is greatest. This study evaluated the accuracy of a readily available consumer-based physical activity monitor during daily inpatient stroke rehabilitation physical therapy sessions. Twenty-one individuals admitted to inpatient rehabilitation were monitored for a total of 471 one-hour physical therapy sessions which consisted of walking and nonwalking therapeutic activities. Participants wore a consumer-based physical activity monitor (Fitbit One) and the gold standard for assessing step count (StepWatch Activity Monitor) during physical therapy sessions. Linear mixed modeling was used to assess the relationship of the step count of the Fitbit to the StepWatch Activity Monitor. Device accuracy is reported as the percent error of the Fitbit compared with the StepWatch Activity Monitor. A strong relationship (slope=0.99; 95% confidence interval, 0.97-1.01) was found between the number of steps captured by the Fitbit One and the StepWatch Activity Monitor. The Fitbit One had a mean error of 10.9% (5.3) for participants with walking velocities <0.4 m/s, 6.8% (3.0) for walking velocities between 0.4 and 0.8 m/s, and 4.4% (2.8) for walking velocities >0.8 m/s. This study provides preliminary evidence that the Fitbit One, when positioned on the nonparetic ankle, can accurately measure walking steps early after stroke during inpatient rehabilitation physical therapy sessions. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01915368. © 2017 American Heart Association, Inc.

In vitro comparison of three common essential oils mosquito repellents as inhibitors of the Ross River virus

PubMed Central

Ralambondrainy, Miora; Belarbi, Essia; Viranaicken, Wildriss; Baranauskienė, Renata; Venskutonis, Petras Rimantas; Desprès, Philippe; El Kalamouni, Chaker; Sélambarom, Jimmy

2018-01-01

Background The essential oils of Cymbopogon citratus (CC), Pelargonium graveolens (PG) and Vetiveria zizanioides (VZ) are commonly used topically to prevent mosquito bites and thus the risk of infection by their vectored pathogens such as arboviruses. However, since mosquito bites are not fully prevented, the effect of these products on the level of viral infection remains unknown. Objectives To evaluate in vitro the essentials oils from Reunion Island against one archetypal arbovirus, the Ross River virus (RRV), and investigate the viral cycle step that was impaired by these oils. Methods The essential oils were extracted by hydrodistillation and analyzed by a combination of GC-FID and GC×GC-TOF MS techniques. In vitro studies were performed on HEK293T cells to determine their cytotoxicity, their cytoprotective and virucidal capacities on RRV-T48 strain, and the level of their inhibitory effect on the viral replication and residual infectivity prior, during or following viral adsorption using the reporter virus RRV-renLuc. Results Each essential oil was characterized by an accurate quantification of their terpenoid content. PG yielded the least-toxic extract (CC50 > 1000 μg.mL-1). For the RRV-T48 strain, the monoterpene-rich CC and PG essential oils reduced the cytopathic effect but did not display virucidal activity. The time-of-addition assay using the gene reporter RRV-renLuc showed that the CC and PG essential oils significantly reduced viral replication and infectivity when applied prior, during and early after viral adsorption. Overall, no significant effect was observed for the low monoterpene-containing VZ essential oil. Conclusion The inhibitory profiles of the three essential oils suggest the high value of the monoterpene-rich essential oils from CC and PG against RRV infection. Combined with their repellent activity, the antiviral activity of the essential oils of CC and PG may provide a new option to control arboviral infection. PMID:29771946

Complete method to obtain, culture, and transfer mouse blastocysts nonsurgically to study implantation and development.

PubMed

Moreno-Moya, Juan Manuel; Ramírez, Leslie; Vilella, Felipe; Martínez, Sebastián; Quiñonero, Alicia; Noguera, Inmaculada; Pellicer, Antonio; Simón, Carlos

2014-03-01

To illustrate an efficient, complete, step-by-step protocol for studying implantation in mice. Video presentation of an animal model for research in reproductive biology. Mouse (Mus musculus). A nonsurgical embryo transfer system very similar to that used for human embryo transfer. The protocols with recipient and donor mice are performed in parallel in the same week. For the donor mice: the first step is ovarian stimulation, followed by ovulation induction and mating; finally, the mice are sacrificed, and the embryos are collected and cultured. For recipient mice: first estrous synchrony is induced, followed by mating with a vasectomized male, visualization of the vaginal plug, and nonsurgical transfer of the embryos. Finally (optionally), the implantation sites can be visualized on day 7.5 of development. (All animal experiments were performed with the approval of the institutional review board.) Implantation is an essential step in human reproduction although, because of technical and ethics considerations, still relatively little is known about human implantation and early development. Conversely, mouse models are well established and can be used for preliminary experiments. However, there are various bottlenecks in the procedure for obtaining and transferring murine embryos, which makes experimentation with this model more difficult. These difficulties include pseudopregnancy, ovarian hyperstimulation, and embryo collection, culture, and transfer. We have proposed a complete, efficient method for obtaining, culturing, and transferring mouse blastocysts that can be easily applied in research. Potential applications include testing new media components that do not affect preimplantation but do affect implantation and early development. The embryo transfer method proposed here has been demonstrated to achieve embryo implantation easier and faster than, and in approximately similar rates as other traditional surgery methods. This workflow is the first set of complete step-by-step instructions available that incorporate advances such as nonsurgical mouse embryo transfer. This will facilitate research into different reproduction events such as embryo development, embryo implantation, or contraception. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Novel therapeutic strategies targeting innate immune responses and early inflammation after stroke.

PubMed

Shichita, Takashi; Ago, Tetsuro; Kamouchi, Masahiro; Kitazono, Takanari; Yoshimura, Akihiko; Ooboshi, Hiroaki

2012-11-01

Post-ischemic inflammation is an essential step in the progression of ischemic stroke. This review focuses on the function of infiltrating immune cells, macrophages, and T cells, in ischemic brain injury. The brain is a sterile organ; however, the activation of Toll-like receptor (TLR) 2 and TLR4 is pivotal in the beginning of post-ischemic inflammation. Some endogenous TLR ligands are released from injured brain cells, including high mobility group box 1 and peroxiredoxin family proteins, and activate the infiltrating macrophages and induce the expression of inflammatory cytokines. Following this step, T cells also infiltrate into the ischemic brain and mediate post-ischemic inflammation in the delayed phase. Various cytokines from helper T cells and γδT cells function as neurotoxic (IL-23/IL-17, IFN-γ) or neuroprotective (IL-10, IL-4) mediators. Novel neuroprotective strategies should therefore be developed through more detailed understanding of this process and the regulation of post-ischemic inflammation. © 2012 The Authors Journal of Neurochemistry © International Society for Neurochemistry.

High-resolution gene expression data from blastoderm embryos of the scuttle fly Megaselia abdita

PubMed Central

Wotton, Karl R; Jiménez-Guri, Eva; Crombach, Anton; Cicin-Sain, Damjan; Jaeger, Johannes

2015-01-01

Gap genes are involved in segment determination during early development in dipteran insects (flies, midges, and mosquitoes). We carried out a systematic quantitative comparative analysis of the gap gene network across different dipteran species. Our work provides mechanistic insights into the evolution of this pattern-forming network. As a central component of our project, we created a high-resolution quantitative spatio-temporal data set of gap and maternal co-ordinate gene expression in the blastoderm embryo of the non-drosophilid scuttle fly, Megaselia abdita. Our data include expression patterns in both wild-type and RNAi-treated embryos. The data—covering 10 genes, 10 time points, and over 1,000 individual embryos—consist of original embryo images, quantified expression profiles, extracted positions of expression boundaries, and integrated expression patterns, plus metadata and intermediate processing steps. These data provide a valuable resource for researchers interested in the comparative study of gene regulatory networks and pattern formation, an essential step towards a more quantitative and mechanistic understanding of developmental evolution. PMID:25977812

Temporal dynamics and developmental memory of 3D chromatin architecture at Hox gene loci

PubMed Central

Noordermeer, Daan; Leleu, Marion; Schorderet, Patrick; Joye, Elisabeth; Chabaud, Fabienne; Duboule, Denis

2014-01-01

Hox genes are essential regulators of embryonic development. Their step-wise transcriptional activation follows their genomic topology and the various states of activation are subsequently memorized into domains of progressively overlapping gene products. We have analyzed the 3D chromatin organization of Hox clusters during their early activation in vivo, using high-resolution circular chromosome conformation capture. Initially, Hox clusters are organized as single chromatin compartments containing all genes and bivalent chromatin marks. Transcriptional activation is associated with a dynamic bi-modal 3D organization, whereby the genes switch autonomously from an inactive to an active compartment. These local 3D dynamics occur within a framework of constitutive interactions within the surrounding Topological Associated Domains, indicating that this regulation process is mostly cluster intrinsic. The step-wise progression in time is fixed at various body levels and thus can account for the chromatin architectures previously described at a later stage for different anterior to posterior levels. DOI: http://dx.doi.org/10.7554/eLife.02557.001 PMID:24843030

Triggers of key calcium signals during erythrocyte invasion by Plasmodium falciparum

PubMed Central

Gao, Xiaohong; Gunalan, Karthigayan; Yap, Sally Shu Lin; Preiser, Peter R.

2013-01-01

Invasion of erythrocytes by Plasmodium falciparum merozoites is a complex multi-step process mediated by specific interactions between host receptors and parasite ligands. Reticulocyte-binding protein homologues (RHs) and erythrocyte-binding-like (EBL) proteins are discharged from specialized organelles and used in early steps of invasion. Here we show that monoclonal antibodies against PfRH1 (an RH) block merozoite invasion by specifically inhibiting calcium signalling in the parasite, whereas invasion-inhibiting monoclonal antibodies targeting EBA175 (an EBL protein) have no effect on signalling. We further show that inhibition of this calcium signalling prevents EBA175 discharge and thereby formation of the junction between parasite and host cell. Our results indicate that PfRH1 has an initial sensing as well as signal transduction role that leads to the subsequent release of EBA175. They also provide new insights on how RH–host cell interactions lead to essential downstream signalling events in the parasite, suggesting new targets for malaria intervention. PMID:24280897

Detection and localization of damage using empirical mode decomposition and multilevel support vector machine

NASA Astrophysics Data System (ADS)

Dushyanth, N. D.; Suma, M. N.; Latte, Mrityanjaya V.

2016-03-01

Damage in the structure may raise a significant amount of maintenance cost and serious safety problems. Hence detection of the damage at its early stage is of prime importance. The main contribution pursued in this investigation is to propose a generic optimal methodology to improve the accuracy of positioning of the flaw in a structure. This novel approach involves a two-step process. The first step essentially aims at extracting the damage-sensitive features from the received signal, and these extracted features are often termed the damage index or damage indices, serving as an indicator to know whether the damage is present or not. In particular, a multilevel SVM (support vector machine) plays a vital role in the distinction of faulty and healthy structures. Formerly, when a structure is unveiled as a damaged structure, in the subsequent step, the position of the damage is identified using Hilbert-Huang transform. The proposed algorithm has been evaluated in both simulation and experimental tests on a 6061 aluminum plate with dimensions 300 mm × 300 mm × 5 mm which accordingly yield considerable improvement in the accuracy of estimating the position of the flaw.

Different dynamin blockers interfere with distinct phases of synaptic endocytosis during stimulation in motoneurones

PubMed Central

Linares-Clemente, Pedro; Rozas, José L; Mircheski, Josif; García-Junco-Clemente, Pablo; Martínez-López, José A; Nieto-González, José L; Vázquez, M Eugenio; Pintado, C Oscar; Fernández-Chacón, Rafael

2015-01-01

Key points Neurotransmitter release requires a tight coupling between synaptic vesicle exocytosis and endocytosis with dynamin being a key protein in that process. We used imaging techniques to examine the time course of endocytosis at mouse motor nerve terminals expressing synaptopHluorin, a genetically encoded reporter of the synaptic vesicle cycle. We separated two sequential phases of endocytosis taking place during the stimulation train: early and late endocytosis. Freshly released synaptic vesicle proteins are preferentially retrieved during the early phase, which is very sensitive to dynasore, an inhibitor of dynamin GTPase activity. Synaptic vesicle proteins pre-existing at the plasma membrane before the stimulation are preferentially retrieved during the late phase, which is very sensitive to myristyl trimethyl ammonium bromide (MitMAB), an inhibitor of the dynamin–phospholipid interaction. Abstract Synaptic endocytosis is essential at nerve terminals to maintain neurotransmitter release by exocytosis. Here, at the neuromuscular junction of synaptopHluorin (spH) transgenic mice, we have used imaging to study exo- and endocytosis occurring simultaneously during nerve stimulation. We observed two endocytosis components, which occur sequentially during stimulation. The early component of endocytosis apparently internalizes spH molecules freshly exocytosed. This component was sensitive to dynasore, a blocker of dynamin 1 GTPase activity. In contrast, this early component was resistant to myristyl trimethyl ammonium bromide (MiTMAB), a competitive agent that blocks dynamin binding to phospholipid membranes. The late component of endocytosis is likely to internalize spH molecules that pre-exist at the plasma membrane before stimulation starts. This component was blocked by MiTMAB, perhaps by impairing the binding of dynamin or other key endocytic proteins to phospholipid membranes. Our study suggests the co-existence of two sequential synaptic endocytosis steps taking place during stimulation that are susceptible to pharmacological dissection: an initial step, preferentially sensitive to dynasore, that internalizes vesicular components immediately after they are released, and a MiTMAB-sensitive step that internalizes vesicular components pre-existing at the plasma membrane surface. In addition, we report that post-stimulus endocytosis also has several components with different sensitivities to dynasore and MiTMAB. PMID:25981717

Different dynamin blockers interfere with distinct phases of synaptic endocytosis during stimulation in motoneurones.

PubMed

Linares-Clemente, Pedro; Rozas, José L; Mircheski, Josif; García-Junco-Clemente, Pablo; Martínez-López, José A; Nieto-González, José L; Vázquez, M Eugenio; Pintado, C Oscar; Fernández-Chacón, Rafael

2015-07-01

Neurotransmitter release requires a tight coupling between synaptic vesicle exocytosis and endocytosis with dynamin being a key protein in that process. We used imaging techniques to examine the time course of endocytosis at mouse motor nerve terminals expressing synaptopHluorin, a genetically encoded reporter of the synaptic vesicle cycle. We separated two sequential phases of endocytosis taking place during the stimulation train: early and late endocytosis. Freshly released synaptic vesicle proteins are preferentially retrieved during the early phase, which is very sensitive to dynasore, an inhibitor of dynamin GTPase activity. Synaptic vesicle proteins pre-existing at the plasma membrane before the stimulation are preferentially retrieved during the late phase, which is very sensitive to myristyl trimethyl ammonium bromide (MitMAB), an inhibitor of the dynamin-phospholipid interaction. Synaptic endocytosis is essential at nerve terminals to maintain neurotransmitter release by exocytosis. Here, at the neuromuscular junction of synaptopHluorin (spH) transgenic mice, we have used imaging to study exo- and endocytosis occurring simultaneously during nerve stimulation. We observed two endocytosis components, which occur sequentially during stimulation. The early component of endocytosis apparently internalizes spH molecules freshly exocytosed. This component was sensitive to dynasore, a blocker of dynamin 1 GTPase activity. In contrast, this early component was resistant to myristyl trimethyl ammonium bromide (MiTMAB), a competitive agent that blocks dynamin binding to phospholipid membranes. The late component of endocytosis is likely to internalize spH molecules that pre-exist at the plasma membrane before stimulation starts. This component was blocked by MiTMAB, perhaps by impairing the binding of dynamin or other key endocytic proteins to phospholipid membranes. Our study suggests the co-existence of two sequential synaptic endocytosis steps taking place during stimulation that are susceptible to pharmacological dissection: an initial step, preferentially sensitive to dynasore, that internalizes vesicular components immediately after they are released, and a MiTMAB-sensitive step that internalizes vesicular components pre-existing at the plasma membrane surface. In addition, we report that post-stimulus endocytosis also has several components with different sensitivities to dynasore and MiTMAB. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

Rho is Required for the Initiation of Calcium Signaling and Phagocytosis by Fcγ Receptors in Macrophages

PubMed Central

Hackam, David J.; Rotstein, Ori D.; Schreiber, Alan; Zhang, Wei-jian; Grinstein, Sergio

1997-01-01

Phagocytosis of bacteria by macrophages and neutrophils is an essential component of host defense against infection. The mechanism whereby the interaction of opsonized particles with Fcγ receptors triggers the engulfment of opsonized particles remains incompletely understood, although activation of tyrosine kinases has been recognized as an early step. Recent studies in other systems have demonstrated that tyrosine kinases can in turn signal the activation of small GTPases of the ras superfamily. We therefore investigated the possible role of Rho in Fc receptor–mediated phagocytosis. To this end we microinjected J774 macrophages with C3 exotoxin from Clostridium botulinum, which ADP-ribosylates and inactivates Rho. C3 exotoxin induced the retraction of filopodia, the disappearance of focal complexes, and a global decrease in the F-actin content of J774 cells. In addition, these cells exhibited increased spreading and the formation of vacuolar structures. Importantly, inactivation of Rho resulted in the complete abrogation of phagocytosis. Inhibition of Fcγ receptor–mediated phagocytosis by C3 exotoxin was confirmed in COS cells, which become phagocytic upon transfection of the FcγRIIA receptor. Rho was found to be essential for the accumulation of phosphotyrosine and of F-actin around phagocytic cups and for Fcγ receptor–mediated Ca2+ signaling. The clustering of receptors in response to opsonin, an essential step in Fcγ-induced signaling, was the earliest event shown to be inhibited by C3 exotoxin. The effect of the toxin was specific, since clustering and internalization of transferrin receptors were unaffected by microinjection of C3. These data identify a role for small GTPases in Fcγ receptor–mediated phagocytosis by leukocytes. PMID:9294149

ß-Cyanoalanine Synthase Action in Root Hair Elongation is Exerted at Early Steps of the Root Hair Elongation Pathway and is Independent of Direct Cyanide Inactivation of NADPH Oxidase.

PubMed

Arenas-Alfonseca, Lucía; Gotor, Cecilia; Romero, Luis C; García, Irene

2018-05-01

In Arabidopsis thaliana, cyanide is produced concomitantly with ethylene biosynthesis and is mainly detoxified by the ß-cyanoalanine synthase CAS-C1. In roots, CAS-C1 activity is essential to maintain a low level of cyanide for proper root hair development. Root hair elongation relies on polarized cell expansion at the growing tip, and we have observed that CAS-C1 locates in mitochondria and accumulates in root hair tips during root hair elongation, as shown by observing the fluorescence in plants transformed with the translational construct ProC1:CASC1-GFP, containing the complete CAS-C1 gene fused to green fluorescent protein (GFP). Mutants in the SUPERCENTIPEDE (SCN1) gene, that regulate the NADPH oxidase gene ROOT HAIR DEFECTIVE 2 (RHD2)/AtrbohC, are affected at the very early steps of the development of root hair that do not elongate and do not show a preferential localization of the GFP accumulation in the tips of the root hair primordia. Root hairs of mutants in CAS-C1 or RHD2/AtrbohC, whose protein product catalyzes the generation of ROS and the Ca2+ gradient, start to grow out correctly, but they do not elongate. Genetic crosses between the cas-c1 mutant and scn1 or rhd2 mutants were performed, and the detailed phenotypic and molecular characterization of the double mutants demonstrates that scn1 mutation is epistatic to cas-c1 and cas-c1 is epistatic to rhd2 mutation, indicating that CAS-C1 acts in early steps of the root hair development process. Moreover, our results show that the role of CAS-C1 in root hair elongation is independent of H2O2 production and of a direct NADPH oxidase inhibition by cyanide.

Perinatal Depression Algorithm: A Home Visitor Step-by-Step Guide for Advanced Management of Perinatal Depressive Symptoms

ERIC Educational Resources Information Center

Laszewski, Audrey; Wichman, Christina L.; Doering, Jennifer J.; Maletta, Kristyn; Hammel, Jennifer

2016-01-01

Early childhood professionals do many things to support young families. This is true now more than ever, as researchers continue to discover the long-term benefits of early, healthy, nurturing relationships. This article provides an overview of the development of an advanced practice perinatal depression algorithm created as a step-by-step guide…

Proposal for the development of biologics in pediatric rheumatology.

PubMed

Mori, Masaaki; Nakagawa, Masao; Tsuchida, Nao; Kawada, Kou; Sato, Junko; Sakiyama, Michiyo; Hirano, Shinya; Sato, Katsuaki; Nakamura, Hidefumi

2018-02-01

In order to assess the development, approval and early introduction into clinical practice of biologics in the pediatric field, we herein describe the current status of the development to approval of biologics as anti-rheumatic agents for children in Japan, discuss the present problems and provide a proposal for the future. It has become apparent that the duration of the review period required for the preparation of clinical trials and Pharmaceuticals and Medical Devices Agency approval is clearly reduced compared with the past. Thus, it was speculated that a rate-limiting step in the process from development to approval was the duration of clinical trials from start to end. Hence, we focused on the following key words with regard to promotion of the development of biologics and their early practical use: "registry", "centralization", and "global cooperation", all of which are related to the reduction of duration of a clinical trial. In conclusion, to reduce the duration of a clinical trial, it is essential to complete a world-scale registry system by developing the registry system established by the Pediatric Rheumatology Association of Japan. The next step is then to carefully plan to participate in the international network using the world-scale registry system, and develop global cooperative trials in which we can ensure a sufficient number of entries from Japan. © 2017 Japan Pediatric Society.

Experimental evolution of an alternating uni- and multicellular life cycle in Chlamydomonas reinhardtii

PubMed Central

Ratcliff, William C.; Herron, Matthew D.; Howell, Kathryn; Pentz, Jennifer T.; Rosenzweig, Frank; Travisano, Michael

2013-01-01

The transition to multicellularity enabled the evolution of large, complex organisms, but early steps in this transition remain poorly understood. Here we show that multicellular complexity, including development from a single cell, can evolve rapidly in a unicellular organism that has never had a multicellular ancestor. We subject the alga Chlamydomonas reinhardtii to conditions that favour multicellularity, resulting in the evolution of a multicellular life cycle in which clusters reproduce via motile unicellular propagules. While a single-cell genetic bottleneck during ontogeny is widely regarded as an adaptation to limit among-cell conflict, its appearance very early in this transition suggests that it did not evolve for this purpose. Instead, we find that unicellular propagules are adaptive even in the absence of intercellular conflict, maximizing cluster-level fecundity. These results demonstrate that the unicellular bottleneck, a trait essential for evolving multicellular complexity, can arise rapidly via co-option of the ancestral unicellular form. PMID:24193369

Rodent Zic Genes in Neural Network Wiring.

PubMed

Herrera, Eloísa

2018-01-01

The formation of the nervous system is a multistep process that yields a mature brain. Failure in any of the steps of this process may cause brain malfunction. In the early stages of embryonic development, neural progenitors quickly proliferate and then, at a specific moment, differentiate into neurons or glia. Once they become postmitotic neurons, they migrate to their final destinations and begin to extend their axons to connect with other neurons, sometimes located in quite distant regions, to establish different neural circuits. During the last decade, it has become evident that Zic genes, in addition to playing important roles in early development (e.g., gastrulation and neural tube closure), are involved in different processes of late brain development, such as neuronal migration, axon guidance, and refinement of axon terminals. ZIC proteins are therefore essential for the proper wiring and connectivity of the brain. In this chapter, we review our current knowledge of the role of Zic genes in the late stages of neural circuit formation.

Affordable Exploration of Mars: Recommendations from a Community Workshop

NASA Technical Reports Server (NTRS)

Thronson, Harley A.; Carberry, Chris; Cassady, R. Joseph; Cooke, Doug; Kirkpatrick, Jim; Perino, Maria Antonietta; Raftery, Michael; Westenberg, Artemis; Zucker, Richard

2014-01-01

There is a growing opinion that within two decades initial human missions to Mars are affordable under plausible budget scenarios, with sustained international participation, and --- especially --- without requiring those first missions to achieve a burdensome number of goals. In response to this view, a group of experts from the Mars exploration stakeholder communities attended the "Affording Mars" workshop at George Washington University in December 2013. Participants reviewed scenarios for proposed affordable and sustainable human and robotic exploration of Mars, the role of the International Space Station as the essential early step toward humans to Mars, possible "bridge" or "transition" missions in the 2020s, key capabilities required for affordable initial missions, international partnerships, and usable definitions of affordability and sustainability. We report here the findings, observations, and recommendations that were agreed to at that workshop. In the context of affordable early missions to Mars, we also discuss the recent report of the National Research Council on human space flight and a pair of recent scenarios that appear to promise reduced costs.

Functional and Radiographic Outcomes Following Growth-Sparing Management of Early-Onset Scoliosis.

PubMed

Johnston, Charles E; Tran, Dong-Phuong; McClung, Anna

2017-06-21

In this study, we sought to evaluate radiographic, functional, and quality-of-life outcomes of patients who have completed growth-sparing management of early-onset scoliosis. This prospective study involved patients with early-onset scoliosis who underwent growth-sparing treatment and either "final" fusion or observation for ≥2 years since the last lengthening procedure. Demographics, radiographic parameters, pulmonary function test (PFT) values, and scores of patient-reported assessments (Early-Onset Scoliosis Questionnaire [EOSQ] and Scoliosis Research Society [SRS]-30) were obtained. At the most recent follow-up, patients performed 2 additional functional outcome tests: step-activity monitoring and a treadmill exercise-tolerance test. Twelve patients were evaluated as "graduates" of growth-sparing management of early-onset scoliosis (mean of 37 months since the most recent surgery). The major scoliosis curve measurement averaged 88° before treatment and 47° at the most recent follow-up. T1-S1 height increased from a mean of 22.3 cm to 34.7 cm and T1-T12 height, from 13.3 to 22.3 cm. At the most recent follow-up, the mean forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) as a percentage of the predicted volume were 52.1% and 55.3%, respectively, and were essentially unchanged from the earliest PFT that patients could perform (FEV1 = 53.8% of predicted and FVC = 53.5% of predicted). There was no difference between graduates and controls with respect to activity time or total steps in step-activity monitoring, and in the exercise-tolerance test, graduates walked at the same speed but at a higher heart rate and at a significantly higher (p <0.001) VO2 cost (rate of oxygen consumed per distance traveled). The EOSQ mean score was 102.2 of a possible 120 points, and the SRS mean score was 4.1 of a possible 5 points. A realistic long-term goal for the management of early-onset scoliosis appears to be spine elongation and maintenance of pulmonary function at a level that is no less than the percentage of normal at initial presentation. Functional testing and patient-reported outcomes at a mean of 3 years from the last surgery suggest that activity levels were generally equal to those of controls but required greater physiologic demand. General health and physical function outcomes revealed continued impairment in these domains. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Idaho's Blueprint for Early Learning: "The Essential Elements."

ERIC Educational Resources Information Center

Wheeler, Myrl, Ed.

Designed to provide information related to quality early care and education services for providers, policy makers, and clients in Idaho, This "blueprint" outlines the nine essential elements for best practices in early care and education settings. The document is presented in three parts. Part 1 delineates standards and indicators in…

REFLECTION IN HOME VISITING: THE WHAT, WHY, AND A BEGINNING STEP TOWARD HOW.

PubMed

Tomlin, Angela M; Hines, Elesia; Sturm, Lynne

2016-11-01

The work of home visitors in early childhood fields may include addressing many challenges to achieving curricular outcomes, including issues such as maintaining boundaries and managing one's own reactions to children, parents, and overall family situations. Increasingly, reflective supervision and consultation are recognized as a way for workers in home-visiting early intervention and early care fields to address these personal and professional challenges and build competence (Watson, Gatti, Cox, Harrison, & Hennes, ). The features of home visiting that make reflective supervision/consultation essential are discussed. Next, results of a pilot project in which a sample of Part C early intervention providers respond to a vignette portraying a challenging parent-child interaction are briefly presented and discussed. Despite often stating the importance of relationships, participants did not identify concrete methods of supporting relationship or demonstrate recognition of parallel process. In addition, providers seldom endorsed the use of reflective skills such as observing, listening, wondering, or reflecting (Weatherston, ), and no providers discussed a need for reflective supervision/consultation. We suggest that these findings illustrate some of the areas in which early intervention home visitors could benefit from participation in reflective supervision/consultation to move from identifying reflective skills as important to actually being able to use such skills in their work with families. © 2016 Michigan Association for Infant Mental Health.

pH-Controlled Two-Step Uncoating of Influenza Virus

PubMed Central

Li, Sai; Sieben, Christian; Ludwig, Kai; Höfer, Chris T.; Chiantia, Salvatore; Herrmann, Andreas; Eghiaian, Frederic; Schaap, Iwan A.T.

2014-01-01

Upon endocytosis in its cellular host, influenza A virus transits via early to late endosomes. To efficiently release its genome, the composite viral shell must undergo significant structural rearrangement, but the exact sequence of events leading to viral uncoating remains largely speculative. In addition, no change in viral structure has ever been identified at the level of early endosomes, raising a question about their role. We performed AFM indentation on single viruses in conjunction with cellular assays under conditions that mimicked gradual acidification from early to late endosomes. We found that the release of the influenza genome requires sequential exposure to the pH of both early and late endosomes, with each step corresponding to changes in the virus mechanical response. Step 1 (pH 7.5–6) involves a modification of both hemagglutinin and the viral lumen and is reversible, whereas Step 2 (pH <6.0) involves M1 dissociation and major hemagglutinin conformational changes and is irreversible. Bypassing the early-endosomal pH step or blocking the envelope proton channel M2 precludes proper genome release and efficient infection, illustrating the importance of viral lumen acidification during the early endosomal residence for influenza virus infection. PMID:24703306

Guiding Principles for the New Early Childhood Professional: Building on Strength and Competence. Early Childhood Education Series

ERIC Educational Resources Information Center

Washington, Valora; Gadson, Brenda

2017-01-01

With growing evidence about the critical period of birth to age 5 for child development and learning, the imperative to professionalize the early childhood education workforce has never been greater. In this follow-up to "The New Early Childhood Professional: A Step-By-Step Guide to Overcoming Goliath", the authors share lessons learned…

TRIM25 in the Regulation of the Antiviral Innate Immunity.

PubMed

Martín-Vicente, María; Medrano, Luz M; Resino, Salvador; García-Sastre, Adolfo; Martínez, Isidoro

2017-01-01

TRIM25 is an E3 ubiquitin ligase enzyme that is involved in various cellular processes, including regulation of the innate immune response against viruses. TRIM25-mediated ubiquitination of the cytosolic pattern recognition receptor RIG-I is an essential step for initiation of the intracellular antiviral response and has been thoroughly documented. In recent years, however, additional roles of TRIM25 in early innate immunity are emerging, including negative regulation of RIG-I, activation of the melanoma differentiation-associated protein 5-mitochondrial antiviral signaling protein-TRAF6 antiviral axis and modulation of p53 levels and activity. In addition, the ability of TRIM25 to bind RNA may uncover new mechanisms by which this molecule regulates intracellular signaling and/or RNA virus replication.

The Need for a Privacy Standard for Medical Devices That Transmit Protected Health Information Used in the Precision Medicine Initiative for Diabetes and Other Diseases.

PubMed

Klonoff, David C; Price, W Nicholson

2017-03-01

Privacy is an important concern for the Precision Medicine Initiative (PMI) because success of this initiative will require the public to be willing to participate by contributing large amounts of genetic/genomic information and sensor data. This sensitive personal information is intended to be used only for specified research purposes. Public willingness to participate will depend on the public's level of trust that their information will be protected and kept private. Medical devices may constantly provide information. Therefore, assuring privacy for device-generated information may be essential for broad participation in the PMI. Privacy standards for devices should be an important early step in the development of the PMI.

Early Childhood Physical Education. The Essential Elements.

ERIC Educational Resources Information Center

Gabbard, Carl

1988-01-01

Details are presented regarding the essential elements of an effective early childhood physical education curriculum. Components include movement awareness, fundamental locomotor skills, fundamental nonlocomotor skills, fundamental manipulative skills, and health-related fitness. (CB)

FOXO1 opposition of CD8+ T cell effector programming confers early memory properties and phenotypic diversity.

PubMed

Delpoux, Arnaud; Lai, Chen-Yen; Hedrick, Stephen M; Doedens, Andrew L

2017-10-17

The factors and steps controlling postinfection CD8 + T cell terminal effector versus memory differentiation are incompletely understood. Whereas we found that naive TCF7 (alias "Tcf-1") expression is FOXO1 independent, early postinfection we report bimodal, FOXO1-dependent expression of the memory-essential transcription factor TCF7 in pathogen-specific CD8 + T cells. We determined the early postinfection TCF7 high population is marked by low TIM3 expression and bears memory signature hallmarks before the appearance of established memory precursor marker CD127 (IL-7R). These cells exhibit diminished TBET, GZMB, mTOR signaling, and cell cycle progression. Day 5 postinfection, TCF7 high cells express higher memory-associated BCL2 and EOMES, as well as increased accumulation potential and capacity to differentiate into memory phenotype cells. TCF7 retroviral transduction opposes GZMB expression and the formation of KLRG1 pos phenotype cells, demonstrating an active role for TCF7 in extinguishing the effector program and forestalling terminal differentiation. Past the peak of the cellular immune response, we report a gradient of FOXO1 and TCF7 expression, which functions to oppose TBET and orchestrate a continuum of effector-to-memory phenotypes.

Asteroidal Differentiation Processes Deduced from Ultramafic Achondrite Ureilite Meteorites

NASA Technical Reports Server (NTRS)

Downes, Hilary; Mittlefehldt, David W.; Hudson, Pierre; Romanek, Christopher S.; Franchi, Ian

2006-01-01

Ureilites are the second largest achondrite group. They are ultramafic achondrites that have experienced igneous processing whilst retaining some degree of nebula-derived chemical heterogeneity. They differ from other achondrites in that they contain abundant carbon and their oxygen isotope compositions are very heterogeneous and similar to those of the carbonaceous chondrite anhydrous mineral line. Their carbonaceous nature and some compositional characteristics indicative of nebular origin suggest that they are primitive materials that form a link between nebular processes and early periods of planetesimal accretion. However, despite numerous studies, the exact origin of ureilites remains unclear. Current opinion is that they represent the residual mantle of an asteroid that underwent silicate and Fe-Ni-S partial melting and melt removal. Recent studies of short-lived chronometers indicate that the parent asteroid of the ureilites differentiated very early in the history of the Solar System. Therefore, they contain important information about processes that formed small rocky planetesimals in the early Solar System. In effect, they form a bridge between nebula processes and differentiation in small planetesimals prior to accretion into larger planets and so a correct interpretation of ureilite petrogenesis is essential for understanding this critical step.

Physiological optics, cognition and emotion: a novel look at the early work of Wilhelm Wundt.

PubMed

Wassmann, Claudia

2009-04-01

The German physiologist Wilhelm Wundt, who later founded experimental psychology, arguably developed the first modern scientific conception of emotion. In the first edition of Vorlesungen über die Menschen- und Thierseele (Lectures on human and animal psychology), which was published in 1863, Wundt tried to establish that emotions were essential parts of rational thought. In fact, he considered them unconscious steps of decision-making that were implied in all processes of conscious thought. His early work deserves attention not only because it is the attempt to conceptualize cognition and emotion strictly from a neural point of view but also because it represents the very foundation of the debate about the nature of emotion that revolved around William James' theory of emotion during the 1890s. However, this aspect of his work is little known because scholars who have analyzed Wundt's work focused on his late career. Furthermore, historical analysis interpreted Wundt's work within a philosophical framework, rather than placing it in the context of German medical and physiological research in which it belongs. In addition, Wundt's early works are hardly available to an English speaking audience because they were never translated.

Biomechanical and neuromuscular adaptations during the landing phase of a stepping-down task in patients with early or established knee osteoarthritis.

PubMed

Sanchez-Ramirez, Diana C; Malfait, Bart; Baert, Isabel; van der Leeden, Marike; van Dieën, Jaap; Lems, Willem F; Dekker, Joost; Luyten, Frank P; Verschueren, Sabine

2016-06-01

To compare the knee joint kinematics, kinetics and EMG activity patterns during a stepping-down task in patients with knee osteoarthritis (OA) with control subjects. 33 women with knee OA (early OA, n=14; established OA n=19) and 14 female control subjects performed a stepping-down task from a 20cm step. Knee joint kinematics, kinetics and EMG activity were recorded on the stepping-down leg during the loading phase. During the stepping-down task patients with established knee OA showed greater normalized medial hamstrings activity (p=0.034) and greater vastus lateralis-medial hamstrings co-contraction (p=0.012) than controls. Greater vastus medialis-medial hamstrings co-contraction was found in patients with established OA compared to control subjects (p=0.040) and to patients with early OA (p=0.023). Self-reported knee instability was reported in 7% and 32% of the patients with early and established OA, respectively. The greater EMG co-activity found in established OA might suggest a less efficient use of knee muscles or an attempt to compensate for greater knee laxity usually present in patients with established OA. In the early stage of the disease, the biomechanical and neuromuscular control of stepping-down is not altered compared to healthy controls. Copyright © 2016 Elsevier B.V. All rights reserved.

pH-Controlled two-step uncoating of influenza virus.

PubMed

Li, Sai; Sieben, Christian; Ludwig, Kai; Höfer, Chris T; Chiantia, Salvatore; Herrmann, Andreas; Eghiaian, Frederic; Schaap, Iwan A T

2014-04-01

Upon endocytosis in its cellular host, influenza A virus transits via early to late endosomes. To efficiently release its genome, the composite viral shell must undergo significant structural rearrangement, but the exact sequence of events leading to viral uncoating remains largely speculative. In addition, no change in viral structure has ever been identified at the level of early endosomes, raising a question about their role. We performed AFM indentation on single viruses in conjunction with cellular assays under conditions that mimicked gradual acidification from early to late endosomes. We found that the release of the influenza genome requires sequential exposure to the pH of both early and late endosomes, with each step corresponding to changes in the virus mechanical response. Step 1 (pH 7.5-6) involves a modification of both hemagglutinin and the viral lumen and is reversible, whereas Step 2 (pH <6.0) involves M1 dissociation and major hemagglutinin conformational changes and is irreversible. Bypassing the early-endosomal pH step or blocking the envelope proton channel M2 precludes proper genome release and efficient infection, illustrating the importance of viral lumen acidification during the early endosomal residence for influenza virus infection. Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Quick and Easy Adaptations and Accommodations for Early Childhood Students

ERIC Educational Resources Information Center

Breitfelder, Leisa M.

2008-01-01

Research-based information is used to support the idea of the use of adaptations and accommodations for early childhood students who have varying disabilities. Multiple adaptations and accommodations are outlined. A step-by-step plan is provided on how to make specific adaptations and accommodations to fit the specific needs of early childhood…

Using the Teaching and Guidance Policy Essentials Checklist to Build and Support Effective Early Childhood Systems

ERIC Educational Resources Information Center

Garrity, Sarah M.; Longstreth, Sascha L.; Salcedo-Potter, Nina S.; Staub, April

2016-01-01

The prevalence of preschool expulsion, coupled with racial disparities in expulsion rates and the potential long term negative effects of challenging behaviors in the early years, has created an urgent need to build early childhood systems to address these issues. The teaching and guidance policy essentials checklist (TAG-PEC) has been developed…

Why is Leu55→Pro55 transthyretin variant the most amyloidogenic: Insights from molecular dynamics simulations of transthyretin monomers

PubMed Central

Yang, Mingfeng; Lei, Ming; Huo, Shuanghong

2003-01-01

Transthyretin (TTR) is one of the known human amyloidogenic proteins. Its native state is a homotetramer with each monomer having a β-sandwich structure. Strong experimental evidence suggests that TTR dissociates into monomeric intermediates and that the monomers subsequently self-assemble to form amyloid deposits and insoluble fibrils. However, details on the early steps along the pathway of TTR amyloid formation are unclear, although various experimental approaches with resolutions at the molecular or residue level have provided some clues. It is highly likely that the stability and flexibility of monomeric TTR play crucial roles in the early steps of amyloid formation; thereby, it is essential to characterize initial conformational changes of TTR monomers. In this article we probe the possibility that the differences in the monomeric forms of wild-type (WT) TTR and its variants are responsible for differential amyloidogenesis. We begin with the simulations of WT, Val30→Met (V30M), and Leu55→Pro (L55P) TTR monomers. Nanosecond time scale molecular dynamics simulations at 300 K were performed using AMBER. The results indicate that the L55P-TTR monomer undergoes substantial structural changes relative to fluctuations observed in the WT and V30M TTR monomers. The observation supports earlier speculation that the L55P mutation may lead to disruption of the β-sheet structure through the disorder of the “edge strands” that might facilitate amyloidogenesis. PMID:12761393

Storybridging: Four Steps for Constructing Effective Health Narratives

ERIC Educational Resources Information Center

Boeijinga, Anniek; Hoeken, Hans; Sanders, José

2017-01-01

Objective: To develop a practical step-by-step approach to constructing narrative health interventions in response to the mixed results and wide diversity of narratives used in health-related narrative persuasion research. Method: Development work was guided by essential narrative characteristics as well as principles enshrined in the Health…

Deployment and Validation of a Smart System for Screening of Language Disorders in Primary Care

PubMed Central

Martín-Ruiz, María Luisa; Duboy, Miguel Ángel Valero; de la Cruz, Iván Pau

2013-01-01

Neuro-evolutive development from birth until the age of six years is a decisive factor in a child's quality of life. Early detection of development disorders in early childhood can facilitate necessary diagnosis and/or treatment. Primary-care pediatricians play a key role in its detection as they can undertake the preventive and therapeutic actions requested to promote a child's optimal development. However, the lack of time and little specific knowledge at primary-care avoid to applying continuous early-detection anomalies procedures. This research paper focuses on the deployment and evaluation of a smart system that enhances the screening of language disorders in primary care. Pediatricians get support to proceed with early referral of language disorders. The proposed model provides them with a decision-support tool for referral actions to trigger essential diagnostic and/or therapeutic actions for a comprehensive individual development. The research was conducted by starting from a sample of 60 cases of children with language disorders. Validation was carried out through two complementary steps: first, by including a team of seven experts from the fields of neonatology, pediatrics, neurology and language therapy, and, second, through the evaluation of 21 more previously diagnosed cases. The results obtained show that therapist positively accepted the system proposal in 18 cases (86%) and suggested system redesign for single referral to a speech therapist in three remaining cases. PMID:23752564

Deployment and validation of a smart system for screening of language disorders in primary care.

PubMed

Martín-Ruiz, María Luisa; Duboy, Miguel Ángel Valero; de la Cruz, Iván Pau

2013-06-10

Neuro-evolutive development from birth until the age of six years is a decisive factor in a child's quality of life. Early detection of development disorders in early childhood can facilitate necessary diagnosis and/or treatment. Primary-care pediatricians play a key role in its detection as they can undertake the preventive and therapeutic actions requested to promote a child's optimal development. However, the lack of time and little specific knowledge at primary-care avoid to applying continuous early-detection anomalies procedures. This research paper focuses on the deployment and evaluation of a smart system that enhances the screening of language disorders in primary care. Pediatricians get support to proceed with early referral of language disorders. The proposed model provides them with a decision-support tool for referral actions to trigger essential diagnostic and/or therapeutic actions for a comprehensive individual development. The research was conducted by starting from a sample of 60 cases of children with language disorders. Validation was carried out through two complementary steps: first, by including a team of seven experts from the fields of neonatology, pediatrics, neurology and language therapy, and, second, through the evaluation of 21 more previously diagnosed cases. The results obtained show that therapist positively accepted the system proposal in 18 cases (86%) and suggested system redesign for single referral to a speech therapist in three remaining cases.

TRIM25 in the Regulation of the Antiviral Innate Immunity

PubMed Central

Martín-Vicente, María; Medrano, Luz M.; Resino, Salvador; García-Sastre, Adolfo; Martínez, Isidoro

2017-01-01

TRIM25 is an E3 ubiquitin ligase enzyme that is involved in various cellular processes, including regulation of the innate immune response against viruses. TRIM25-mediated ubiquitination of the cytosolic pattern recognition receptor RIG-I is an essential step for initiation of the intracellular antiviral response and has been thoroughly documented. In recent years, however, additional roles of TRIM25 in early innate immunity are emerging, including negative regulation of RIG-I, activation of the melanoma differentiation-associated protein 5–mitochondrial antiviral signaling protein–TRAF6 antiviral axis and modulation of p53 levels and activity. In addition, the ability of TRIM25 to bind RNA may uncover new mechanisms by which this molecule regulates intracellular signaling and/or RNA virus replication. PMID:29018447

Affordable Exploration of Mars: Recommendations from a Community Workshop on Sustainable Initial Human Missions

NASA Technical Reports Server (NTRS)

Thronson, Harley; Carberry, Chris; Cassady, R. J.; Cooke, Doug; Hopkins, Joshua; Perino, Maria A.; Kirkpatrick, Jim; Raftery, Michael; Westenberg, Artemis; Zucker, Richard

2013-01-01

There is a growing consensus that within two decades initial human missions to Mars are affordable under plausible budget assumptions and with sustained international participation. In response to this idea, a distinguished group of experts from the Mars exploration stakeholder communities attended the "Affording Mars" workshop at George Washington University in December, 2013. Participants reviewed and discussed scenarios for affordable and sustainable human and robotic exploration of Mars, the role of the International Space Station over the coming decade as the essential early step toward humans to Mars, possible "bridge" missions in the 2020s, key capabilities required for affordable initial missions, international partnerships, and a usable definition of affordability and sustainability. We report here the findings, observations, and recommendations that were agreed to at that workshop.

The Need for a Privacy Standard for Medical Devices That Transmit Protected Health Information Used in the Precision Medicine Initiative for Diabetes and Other Diseases

PubMed Central

Klonoff, David C.; Price, W. Nicholson

2017-01-01

Privacy is an important concern for the Precision Medicine Initiative (PMI) because success of this initiative will require the public to be willing to participate by contributing large amounts of genetic/genomic information and sensor data. This sensitive personal information is intended to be used only for specified research purposes. Public willingness to participate will depend on the public’s level of trust that their information will be protected and kept private. Medical devices may constantly provide information. Therefore, assuring privacy for device-generated information may be essential for broad participation in the PMI. Privacy standards for devices should be an important early step in the development of the PMI. PMID:27920271

Acute Pancreatitis Etiology Investigation: A Workup Algorithm Proposal

PubMed Central

da Silva, Sílvia; Rocha, Mónica; Pinto-de-Sousa, João

2017-01-01

Background Acute pancreatitis represents a significant number of hospital admissions. Most of the patients are admitted in an acute setting. Early identification of its etiology is an essential step toward the rational approach, both for its implications in the immediate therapy and the prevention of recurrence. Although often obvious, the etiological workup of acute pancreatitis can be challenging. Conclusion There are several studies emphasizing the multiple etiologies underlying acute pancreatitis but lacking structured diagnostic workups to allow a rational and organized study. The main goal of this work is to develop an algorithm proposal, which aims to serve as a guide for the investigation of the etiology of acute pancreatitis based on a review of already published literature, adjusted to the reality of our hospital and the available resources. PMID:28848797

Small endometrial carcinoma 10 mm or less in diameter: clinicopathologic and histogenetic study of 131 cases for early detection and treatment

PubMed Central

Hasumi, Katsuhiko; Sugiyama, Yuko; Sakamoto, Kimihiko; Akiyama, Futoshi

2013-01-01

Natural history and clinicopathologic features of early endometrial carcinoma are not evident. Its knowledge is essential to make up strategies for prevention, early detection, and treatment of endometrial carcinoma. Especially it is important to know pathways of endometrial carcinogenesis and frequency of endometrial carcinomas arising from endometrial hyperplasia. Clinicopathologically 131 patients with endometrial carcinoma measuring ≤10 mm in diameter (“small endometrial carcinoma”) were studied to get useful information for early diagnosis, treatment, and histogenesis. The entire endometrium of surgically removed uterus was step-cut and examined. The patients were, on average, 5 years younger than the controls whose carcinomas measure >10 mm (P < 0.0001). Of the 131 patients, 20% were asymptomatic although only 5% of the controls were asymptomatic (P < 0.0001). Seventy-six percent had the carcinomas located in the upper third section of the uterine corpus. Macroscopically 44% of the tumors were flat and 56% were elevated. Incidence of nodal and ovarian metastases were <1%. Forty percent of “small endometrial carcinomas” were associated with endometrial hyperplasia and 60% were not. It is logical to believe that there are two pathways of endometrial carcinogenesis: carcinomas occurring from hyperplasia (40%) and carcinomas occurring from normal endometrium (60%). As hyperplasia-carcinoma sequence is not a main route, we cannot probably prevent carcinomas only by treatment of hyperplasia. Effort must be focused on detecting early de novo carcinomas. As most “small endometrial carcinomas” arise in the upper third of the corpus, careful endometrial sampling there is important for early detection. PMID:24403260

Benign Essential Blepharospasm

MedlinePlus

... Supplements Peer Review Process Review Committees Application Support Library Clinical Research Next Steps Pre-Funding: After Review Terms of ... Supplements Peer Review Process Review Committees Application Support Library Clinical Research Next Steps Pre-Funding: After Review Terms of ...

Technical Steps to Support Nuclear Arsenal Downsizing: A Report by the APS Panel on Public Affairs

DTIC Science & Technology

2010-02-01

play a critical role in advancing the US plan to balance deter- rence with downsizing the US nuclear arsenal. In particular, S&T are essential to enable...nuclear-armed nations must be assured that they will continue to be able to meet those critical security needs. While individual nuclear-armed...steps are essential to progress towards the eventual elimination of nuclear arsenals. Science and technology (S&T) will play a critical role in

Responder Status Criterion for Stepped Care Trauma-Focused Cognitive Behavioral Therapy for Young Children

PubMed Central

Salloum, Alison; Scheeringa, Michael S.; Cohen, Judith A.; Storch, Eric A.

2014-01-01

Background In order to develop Stepped Care Trauma-Focused Cognitive Behavioral Therapy (TF-CBT), a definition of early response/non-response is needed to guide decisions about the need for subsequent treatment. Objective The purpose of this article is to (1) establish criterion for defining an early indicator of response/nonresponse to the first step within Stepped Care TF-CBT, and (2) to explore the preliminary clinical utility of the early response/non-response criterion. Method Data from two studies were used: (1) treatment outcome data from a clinical trial in which 17 young children (ages 3 to 6 years) received therapist-directed CBT for children with PTSS were examined to empirically establish the number of posttraumatic stress symptoms to define early treatment response/non-response; and (2) three case examples with young children in Stepped Care TF-CBT were used to explore the utility of the treatment response criterion. Results For defining the responder status criterion, an algorithm of either 3 or fewer PTSS on a clinician-rated measure or being below the clinical cutoff score on a parent-rated measure of childhood PTSS, and being rated as improved, much improved or free of symptoms functioned well for determining whether or not to step up to more intensive treatment. Case examples demonstrated how the criterion were used to guide subsequent treatment, and that responder status criterion after Step One may or may not be aligned with parent preference. Conclusion Although further investigation is needed, the responder status criterion for young children used after Step One of Stepped Care TF-CBT appears promising. PMID:25663796

The S/T-Rich Motif in the DNAJB6 Chaperone Delays Polyglutamine Aggregation and the Onset of Disease in a Mouse Model.

PubMed

Kakkar, Vaishali; Månsson, Cecilia; de Mattos, Eduardo P; Bergink, Steven; van der Zwaag, Marianne; van Waarde, Maria A W H; Kloosterhuis, Niels J; Melki, Ronald; van Cruchten, Remco T P; Al-Karadaghi, Salam; Arosio, Paolo; Dobson, Christopher M; Knowles, Tuomas P J; Bates, Gillian P; van Deursen, Jan M; Linse, Sara; van de Sluis, Bart; Emanuelsson, Cecilia; Kampinga, Harm H

2016-04-21

Expanded CAG repeats lead to debilitating neurodegenerative disorders characterized by aggregation of proteins with expanded polyglutamine (polyQ) tracts. The mechanism of aggregation involves primary and secondary nucleation steps. We show how a noncanonical member of the DNAJ-chaperone family, DNAJB6, inhibits the conversion of soluble polyQ peptides into amyloid fibrils, in particular by suppressing primary nucleation. This inhibition is mediated by a serine/threonine-rich region that provides an array of surface-exposed hydroxyl groups that bind to polyQ peptides and may disrupt the formation of the H bonds essential for the stability of amyloid fibrils. Early prevention of polyQ aggregation by DNAJB6 occurs also in cells and leads to delayed neurite retraction even before aggregates are visible. In a mouse model, brain-specific coexpression of DNAJB6 delays polyQ aggregation, relieves symptoms, and prolongs lifespan, pointing to DNAJB6 as a potential target for disease therapy and tool for unraveling early events in the onset of polyQ diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

Coronary involvement in Churg-Strauss syndrome.

PubMed

Dendramis, Gregory; Paleologo, Claudia; Piraino, Davide; Arrotti, Salvatore; Assennato, Pasquale

2015-01-01

Systemic autoimmune diseases are themselves a relevant and independent risk factor for atherosclerosis and coronary ectasia. We describe a case of a 58-year-old Caucasian man who was admitted to our department for unstable angina. History of asthma, paranasal sinus abnormality, and peripheral eosinophilia given a high suspicion of Churg-Strauss syndrome (CSS). Diagnosis was performed with 5 of the 6 American College of Rheumatology criteria. The knowledge that CSS is often associated with significant coronary artery involvement and the persistence of chest pain led us to performing immediately a coronary angiography. Coronary angiography showed diffuse ectasic lesions, chronic occlusion of left anterior descending artery with homocoronary collateral circulation from left circumflex artery and subocclusive stenosis in the proximal tract of posterior descending artery. The early recognition of CSS, an aggressive invasive diagnostic approach, and an early appropriate therapy are important to prevent the progressive and permanent cardiac damage in these patients. In the setting of a multidisciplinary approach, careful cardiac assessment is an essential step in CSS, even in mildly symptomatic patients. Copyright © 2015 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

A horizontal gene transfer at the origin of phenylpropanoid metabolism: a key adaptation of plants to land.

PubMed

Emiliani, Giovanni; Fondi, Marco; Fani, Renato; Gribaldo, Simonetta

2009-02-16

The pioneering ancestor of land plants that conquered terrestrial habitats around 500 million years ago had to face dramatic stresses including UV radiation, desiccation, and microbial attack. This drove a number of adaptations, among which the emergence of the phenylpropanoid pathway was crucial, leading to essential compounds such as flavonoids and lignin. However, the origin of this specific land plant secondary metabolism has not been clarified. We have performed an extensive analysis of the taxonomic distribution and phylogeny of Phenylalanine Ammonia Lyase (PAL), which catalyses the first and essential step of the general phenylpropanoid pathway, leading from phenylalanine to p-Coumaric acid and p-Coumaroyl-CoA, the entry points of the flavonoids and lignin routes. We obtained robust evidence that the ancestor of land plants acquired a PAL via horizontal gene transfer (HGT) during symbioses with soil bacteria and fungi that are known to have established very early during the first steps of land colonization. This horizontally acquired PAL represented then the basis for further development of the phenylpropanoid pathway and plant radiation on terrestrial environments. Our results highlight a possible crucial role of HGT from soil bacteria in the path leading to land colonization by plants and their subsequent evolution. The few functional characterizations of sediment/soil bacterial PAL (production of secondary metabolites with powerful antimicrobial activity or production of pigments) suggest that the initial advantage of this horizontally acquired PAL in the ancestor of land plants might have been either defense against an already developed microbial community and/or protection against UV.

Rab4b controls an early endosome sorting event by interacting with the γ-subunit of the clathrin adaptor complex 1.

PubMed

Perrin, Laura; Laura, Perrin; Lacas-Gervais, Sandra; Sandra, Lacas-Gervais; Gilleron, Jérôme; Jérôme, Gilleron; Ceppo, Franck; Franck, Ceppo; Prodon, François; François, Prodon; Benmerah, Alexandre; Alexandre, Benmerah; Tanti, Jean-François; Jean-François, Tanti; Cormont, Mireille; Mireille, Cormont

2013-11-01

The endocytic pathway is essential for cell homeostasis and numerous small Rab GTPases are involved in its control. The endocytic trafficking step controlled by Rab4b has not been elucidated, although recent data suggested it could be important for glucose homeostasis, synaptic homeostasis or adaptive immunity. Here, we show that Rab4b is required for early endosome sorting of transferrin receptors (TfRs) to the recycling endosomes, and we identified the AP1γ subunit of the clathrin adaptor AP-1 as a Rab4b effector and key component of the machinery of early endosome sorting. We show that internalised transferrin (Tf) does not reach Vamp3/Rab11 recycling endosomes in the absence of Rab4b, whereas it is rapidly recycled back to the plasma membrane. By contrast, overexpression of Rab4b leads to the accumulation of internalised Tf within AP-1- and clathrin-coated vesicles. These vesicles are poor in early and recycling endocytic markers except for TfR and require AP1γ for their formation. Furthermore, the targeted overexpression of the Rab4b-binding domain of AP1γ to early endosome upon its fusion with FYVE domains inhibited the interaction between Rab4b and endogenous AP1γ, and perturbed Tf traffic. We thus proposed that the interaction between early endocytic Rab4b and AP1γ could allow the budding of clathrin-coated vesicles for subsequent traffic to recycling endosomes. The data also uncover a novel type of endosomes, characterised by low abundance of either early or recycling endocytic markers, which could potentially be generated in cell types that naturally express high level of Rab4b.

Pediatricians Transitioning Practices, Youth With Special Health Care Needs in New York State.

PubMed

Davidson, Lynn F; Chhabra, Rosy; Cohen, Hillel W; Lechuga, Claudia; Diaz, Patricia; Racine, Andrew

2015-10-01

To assess current practices of New York State pediatricians as they transition youth with special health care needs to adult-oriented medical care. A survey of New York State pediatricians included 6 critical steps from 2002 consensus statement, 11 essential steps adapted from recent literature, and questions targeting age of starting transition and availability of transition policy. Of 181 respondents, only 11% have a transition policy. Most assist patients in transition process; identify an adult provider (92%); and create portable medical summary (57%). Only 3% start planning process at recommended age. No respondents are compliant with all 6 critical steps; subspecialists were more likely to report compliance to more than 4 steps. Participating pediatricians are making gains, yet effort is needed, to incorporate the essential steps into practice for transitioning youth with special health care needs. Recognition of barriers, use of electronic tools, and clarifying subspecialist's approach, may improve compliance with transition recommendations. © The Author(s) 2015.

Functional Synergy between Rab5 Effector Rabaptin-5 and Exchange Factor Rabex-5 When Physically Associated in a Complex

PubMed Central

Lippé, Roger; Miaczynska, Marta; Rybin, Vladimir; Runge, Anja; Zerial, Marino

2001-01-01

Rab GTPases are central elements of the vesicular transport machinery. An emerging view is that downstream effectors of these GTPases are multiprotein complexes that include nucleotide exchange factors to ensure coupling between GTPase activation and effector function. We have previously shown that Rab5, which regulates various steps of transport along the early endocytic pathway, is activated by a complex consisting of Rabex-5, a Rab5 nucleotide exchange factor, and the effector Rabaptin-5. We postulated that the physical association of these two proteins is necessary for their activity in Rab5-dependent endocytic membrane transport. To evaluate the functional implications of such complex formation, we have reconstituted it with the use of recombinant proteins and characterized its properties. First, we show that Rabaptin-5 increases the exchange activity of Rabex-5 on Rab5. Second, Rab5-dependent recruitment of Rabaptin-5 to early endosomes is completely dependent on its physical association with Rabex-5. Third, complex formation between Rabaptin-5 and Rabex-5 is essential for early endosome homotypic fusion. These results reveal a functional synergy between Rabaptin-5 and Rabex-5 in the complex and have implications for the function of analogous complexes for Rab and Rho GTPases. PMID:11452015

Separating the influences of prereading skills on early word and nonword reading.

PubMed

Shapiro, Laura R; Carroll, Julia M; Solity, Jonathan E

2013-10-01

The essential first step for a beginning reader is to learn to match printed forms to phonological representations. For a new word, this is an effortful process where each grapheme must be translated individually (serial decoding). The role of phonological awareness in developing a decoding strategy is well known. We examined whether beginning readers recruit different skills depending on the nature of the words being read (familiar words vs. nonwords). Print knowledge, phoneme and rhyme awareness, rapid automatized naming (RAN), phonological short-term memory (STM), nonverbal reasoning, vocabulary, auditory skills, and visual attention were measured in 392 prereaders 4 and 5 years of age. Word and nonword reading were measured 9 months later. We used structural equation modeling to examine the skills-reading relationship and modeled correlations between our two reading outcomes and among all prereading skills. We found that a broad range of skills were associated with reading outcomes: early print knowledge, phonological STM, phoneme awareness and RAN. Whereas all of these skills were directly predictive of nonword reading, early print knowledge was the only direct predictor of word reading. Our findings suggest that beginning readers draw most heavily on their existing print knowledge to read familiar words. Copyright © 2013 Elsevier Inc. All rights reserved.

A Randomized Controlled Trial of the First Step to Success Early Intervention: Demonstration of Program Efficacy Outcomes in a Diverse, Urban School District

ERIC Educational Resources Information Center

Walker, Hill M.; Seeley, John R.; Small, Jason; Severson, Herbert H.; Graham, Bethany A.; Feil, Edward G.; Serna, Loretta; Golly, Annemieke M.; Forness, Steven R.

2009-01-01

This article reports on a randomized controlled trial of the First Step to Success early intervention that was conducted over a 4-year period in Albuquerque Public Schools. First Step is a selected intervention for students in Grades 1 through 3 with externalizing behavior problems, and it addresses secondary prevention goals and objectives. It…

In Vitro Stretch Injury Induces Time- and Severity-Dependent Alterations of STEP Phosphorylation and Proteolysis in Neurons

PubMed Central

Mesfin, Mahlet N.; von Reyn, Catherine R.; Mott, Rosalind E.; Putt, Mary E.

2012-01-01

Abstract Striatal-enriched tyrosine phosphatase (STEP) has been identified as a component of physiological and pathophysiological signaling pathways mediated by N-methyl-d-aspartate (NMDA) receptor/calcineurin/calpain activation. Activation of these pathways produces a subsequent change in STEP isoform expression or activation via dephosphorylation. In this study, we evaluated changes in STEP phosphorylation and proteolysis in dissociated cortical neurons after sublethal and lethal mechanical injury using an in vitro stretch injury device. Sublethal stretch injury produces minimal changes in STEP phosphorylation at early time points, and increased STEP phosphorylation at 24 h that is blocked by the NMDA-receptor antagonist APV, the calcineurin-inhibitor FK506, and the sodium channel blocker tetrodotoxin. Lethal stretch injury produces rapid STEP dephosphorylation via NR2B-containing NMDA receptors, but not calcineurin, and a subsequent biphasic phosphorylation pattern. STEP61 expression progressively increases after sublethal stretch with no change in calpain-mediated STEP33 formation, while lethal stretch injury results in STEP33 formation via a NR2B-containing NMDA receptor pathway within 1 h of injury. Blocking calpain activation in the initial 30 min after stretch injury increases the ratio of active STEP in cells and blocks STEP33 formation, suggesting that STEP is an early substrate of calpain after mechanical injury. There is a strong correlation between the amount of STEP33 formed and the degree of cell death observed after lethal stretch injury. In summary, these data demonstrate that previously characterized pathways of STEP regulation via the NMDA receptor are generally conserved in mechanical injury, and suggest that calpain-mediated cleavage of STEP33 should be further examined as an early marker of neuronal fate after stretch injury. PMID:22435660

N-terminus of Cardiac Myosin Essential Light Chain Modulates Myosin Step-Size

PubMed Central

Wang, Yihua; Ajtai, Katalin; Kazmierczak, Katarzyna; Szczesna-Cordary, Danuta; Burghardt, Thomas P.

2016-01-01

Muscle myosin cyclically hydrolyzes ATP to translate actin. Ventricular cardiac myosin (βmys) moves actin with three distinct unitary step-sizes resulting from its lever-arm rotation and with step-frequencies that are modulated in a myosin regulation mechanism. The lever-arm associated essential light chain (vELC) binds actin by its 43 residue N-terminal extension. Unitary steps were proposed to involve the vELC N-terminal extension with the 8 nm step engaging the vELC/actin bond facilitating an extra ~19 degrees of lever-arm rotation while the predominant 5 nm step forgoes vELC/actin binding. A minor 3 nm step is the unlikely conversion of the completed 5 to the 8 nm step. This hypothesis was tested using a 17 residue N-terminal truncated vELC in porcine βmys (Δ17βmys) and a 43 residue N-terminal truncated human vELC expressed in transgenic mouse heart (Δ43αmys). Step-size and step-frequency were measured using the Qdot motility assay. Both Δ17βmys and Δ43αmys had significantly increased 5 nm step-frequency and coincident loss in the 8 nm step-frequency compared to native proteins suggesting the vELC/actin interaction drives step-size preference. Step-size and step-frequency probability densities depend on the relative fraction of truncated vELC and relate linearly to pure myosin species concentrations in a mixture containing native vELC homodimer, two truncated vELCs in the modified homodimer, and one native and one truncated vELC in the heterodimer. Step-size and step-frequency, measured for native homodimer and at two or more known relative fractions of truncated vELC, are surmised for each pure species by using a new analytical method. PMID:26671638

Measuring and Improving Quality in Early Childhood Environments

ERIC Educational Resources Information Center

Bernard van Leer Foundation, 2015

2015-01-01

The International Consultation, convened in Leiden (the Netherlands) in September 2014, brought together early childhood experts and stakeholders--supported by the International Step by Step Association (ISSA), the United Nations Children's Fund (UNICEF), the United Nations Educational, Scientific, and Cultural Organization (UNESCO) and the…

Lessons learned in stepped chute research

USDA-ARS?s Scientific Manuscript database

Early research on stepped chutes focused on steep gravity style stepped chutes. Today, the research trend has shifted to stepped chutes applied to more moderate slopes like those for aging embankment dams. Research contributions have been made on hydraulic properties of stepped chutes including ai...

Regulation of Epithelial Sodium Transport via Epithelial Na+ Channel

PubMed Central

Marunaka, Yoshinori; Niisato, Naomi; Taruno, Akiyuki; Ohta, Mariko; Miyazaki, Hiroaki; Hosogi, Shigekuni; Nakajima, Ken-ichi; Kusuzaki, Katsuyuki; Ashihara, Eishi; Nishio, Kyosuke; Iwasaki, Yoshinobu; Nakahari, Takashi; Kubota, Takahiro

2011-01-01

Renal epithelial Na+ transport plays an important role in homeostasis of our body fluid content and blood pressure. Further, the Na+ transport in alveolar epithelial cells essentially controls the amount of alveolar fluid that should be kept at an appropriate level for normal gas exchange. The epithelial Na+ transport is generally mediated through two steps: (1) the entry step of Na+ via epithelial Na+ channel (ENaC) at the apical membrane and (2) the extrusion step of Na+ via the Na+, K+-ATPase at the basolateral membrane. In general, the Na+ entry via ENaC is the rate-limiting step. Therefore, the regulation of ENaC plays an essential role in control of blood pressure and normal gas exchange. In this paper, we discuss two major factors in ENaC regulation: (1) activity of individual ENaC and (2) number of ENaC located at the apical membrane. PMID:22028593

Standardizing bimanual vaginal examination using cognitive task analysis.

PubMed

Plumptre, Isabella; Mulki, Omar; Granados, Alejandro; Gayle, Claudine; Ahmed, Shahla; Low-Beer, Naomi; Higham, Jenny; Bello, Fernando

2017-10-01

To create a standardized universal list of procedural steps for bimanual vaginal examination (BVE) for teaching, assessment, and simulator development. This observational study, conducted from June-July 2012 and July-December 2014, collected video data of 10 expert clinicians performing BVE in a nonclinical environment. Video data were analyzed to produce a cognitive task analysis (CTA) of the examination steps performed. The CTA was further refined through structured interviews to make it suitable for teaching or assessment. It was validated through its use as a procedural examination checklist to rate expert clinician performance. BVE was deconstructed into 88 detailed steps outlining the complete examination process. These initial 88 steps were reduced to 35 by focusing on the unseen internal examination, then further refined through interviews with five experts into 30 essential procedural steps, five of which are additional steps if pathology is suspected. Using the CTA as a procedural checklist, the mean number of steps performed and/or verbalized was 21.6 ± 3.12 (72% ± 10.4%; range, 15.9-27.9, 53%-93%). This approach identified 30 essential steps for performing BVE, producing a new technique and standardized tool for teaching, assessment, and simulator development. © 2017 International Federation of Gynecology and Obstetrics.

Stepwise Organization of the β-Structure Identifies Key Regions Essential for the Propagation and Cytotoxicity of Insulin Amyloid Fibrils*

PubMed Central

Chatani, Eri; Imamura, Hiroshi; Yamamoto, Naoki; Kato, Minoru

2014-01-01

Amyloid fibrils are supramolecular assemblies, the deposition of which is associated with many serious diseases including Alzheimer, prion, and Huntington diseases. Several smaller aggregates such as oligomers and protofibrils have been proposed to play a role in early stages of the fibrillation process; however, little is known about how these species contribute to the formation of mature amyloid fibrils with a rigid cross-β structure. Here, we identified a new pathway for the formation of insulin amyloid fibrils at a high concentration of salt in which mature fibrils were formed in a stepwise manner via a prefibrillar intermediate: minute prefibrillar species initially accumulated, followed by the subsequent formation of thicker amyloid fibrils. Fourier transform infrared spectra suggested the sequential formation of two types of β-sheets with different strength hydrogen bonds, one of which was developed concomitantly with the mutual assembly of the prefibrillar intermediate to form mature fibrils. Interestingly, fibril propagation and cellular toxicity appeared only after the later step of structural organization, and a comparison of β-sheet regions between the prefibrillar intermediate and mature fibrils using proteolysis led to the proposal of specific regions essential for manifestation of these properties. PMID:24569992

An essential role of a FoxD gene in notochord induction in Ciona embryos.

PubMed

Imai, Kaoru S; Satoh, Nori; Satou, Yutaka

2002-07-01

A key issue for understanding the early development of the chordate body plan is how the endoderm induces notochord formation. In the ascidian Ciona, nuclear accumulation of beta-catenin is the first step in the process of endoderm specification. We show that nuclear accumulation of beta-catenin directly activates the gene (Cs-FoxD) for a winged helix/forkhead transcription factor and that this gene is expressed transiently at the 16- and 32-cell stages in endodermal cells. The function of Cs-FoxD, however, is not associated with differentiation of the endoderm itself but is essential for notochord differentiation or induction. In addition, it is likely that the inductive signal that appears to act downstream of Cs-FoxD does not act over a long range. It has been suggested that FGF or Notch signal transduction pathway mediates ascidian notochord induction. Our previous study suggests that Cs-FGF4/6/9 is partially involved in the notochord induction. The present experimental results suggest that the expression and function of Cs-FGF4/6/9 and Cs-FoxD are not interdependent, and that the Notch pathway is involved in B-line notochord induction downstream of Cs-FoxD.

Using the Fine Arts to Teach Early Childhood Essential Elements.

ERIC Educational Resources Information Center

Education Service Center Region 11, Ft. Worth, TX.

This extensive curriculum guide provides teachers of young children ages three to six with some specific lesson plans using the fine arts--music, drama, creative movement, and visual arts--to teach the "essential elements" in early childhood education. In addition, systematic, thorough evaluations of a variety of materials, kits, resource and…

Challenges in Implementation of Early Childhood Education in Nigeria: The Way Forward

ERIC Educational Resources Information Center

Akinrotimi, Adenike A.; Olowe, Peter K.

2016-01-01

Early Childhood Education (ECE) comprises essential programmes and activities which are critical to holistic development, academic success and future achievements of children. ECE is recognised by the federal government of Nigeria as a foundational and essential programme that Nigerian children must experience. This is why the government has given…

Smoke regions extraction based on two steps segmentation and motion detection in early fire

NASA Astrophysics Data System (ADS)

Jian, Wenlin; Wu, Kaizhi; Yu, Zirong; Chen, Lijuan

2018-03-01

Aiming at the early problems of video-based smoke detection in fire video, this paper proposes a method to extract smoke suspected regions by combining two steps segmentation and motion characteristics. Early smoldering smoke can be seen as gray or gray-white regions. In the first stage, regions of interests (ROIs) with smoke are obtained by using two step segmentation methods. Then, suspected smoke regions are detected by combining the two step segmentation and motion detection. Finally, morphological processing is used for smoke regions extracting. The Otsu algorithm is used as segmentation method and the ViBe algorithm is used to detect the motion of smoke. The proposed method was tested on 6 test videos with smoke. The experimental results show the effectiveness of our proposed method over visual observation.

Improvements in newborn care and newborn resuscitation following a quality improvement program at scale: results from a before and after study in Tanzania.

PubMed

Makene, Christina Lulu; Plotkin, Marya; Currie, Sheena; Bishanga, Dunstan; Ugwi, Patience; Louis, Henry; Winani, Kiholeth; Nelson, Brett D

2014-11-19

Every year, more than a million of the world's newborns die on their first day of life; as many as two-thirds of these deaths could be saved with essential care at birth and the early newborn period. Simple interventions to improve the quality of essential newborn care in health facilities - for example, improving steps to help newborns breathe at birth - have demonstrated up to 47% reduction in newborn mortality in health facilities in Tanzania. We conducted an evaluation of the effects of a large-scale maternal-newborn quality improvement intervention in Tanzania that assessed the quality of provision of essential newborn care and newborn resuscitation. Cross-sectional health facility surveys were conducted pre-intervention (2010) and post intervention (2012) in 52 health facilities in the program implementation area. Essential newborn care provided by health care providers immediately following birth was observed for 489 newborns in 2010 and 560 in 2012; actual management of newborns with trouble breathing were observed in 2010 (n = 18) and 2012 (n = 40). Assessments of health worker knowledge were conducted with case studies (2010, n = 206; 2012, n = 217) and a simulated resuscitation using a newborn mannequin (2010, n = 299; 2012, n = 213). Facility audits assessed facility readiness for essential newborn care. Index scores for quality of observed essential newborn care showed significant overall improvement following the quality-of-care intervention, from 39% to 73% (p <0.0001). Health worker knowledge using a case study significantly improved as well, from 23% to 41% (p <0.0001) but skills in resuscitation using a newborn mannequin were persistently low. Availability of essential newborn care supplies, which was high at baseline in the regional hospitals, improved at the lower-level health facilities. Within two years, the quality improvement program was successful in raising the quality of essential newborn care services in the program facilities. Some gaps in newborn care were persistent, notably practical skills in newborn resuscitation. Continued investment in life-saving improvements to newborn care through the health services is a priority for reduction of newborn mortality in Tanzania.

Viral evasion of DNA-stimulated innate immune responses

PubMed Central

Christensen, Maria H; Paludan, Søren R

2017-01-01

Cellular sensing of virus-derived nucleic acids is essential for early defenses against virus infections. In recent years, the discovery of DNA sensing proteins, including cyclic GMP–AMP synthase (cGAS) and gamma-interferon-inducible protein (IFI16), has led to understanding of how cells evoke strong innate immune responses against incoming pathogens carrying DNA genomes. The signaling stimulated by DNA sensors depends on the adaptor protein STING (stimulator of interferon genes), to enable expression of antiviral proteins, including type I interferon. To facilitate efficient infections, viruses have evolved a wide range of evasion strategies, targeting host DNA sensors, adaptor proteins and transcription factors. In this review, the current literature on virus-induced activation of the STING pathway is presented and we discuss recently identified viral evasion mechanisms targeting different steps in this antiviral pathway. PMID:26972769

Discrimination of dynamical system models for biological and chemical processes.

PubMed

Lorenz, Sönke; Diederichs, Elmar; Telgmann, Regina; Schütte, Christof

2007-06-01

In technical chemistry, systems biology and biotechnology, the construction of predictive models has become an essential step in process design and product optimization. Accurate modelling of the reactions requires detailed knowledge about the processes involved. However, when concerned with the development of new products and production techniques for example, this knowledge often is not available due to the lack of experimental data. Thus, when one has to work with a selection of proposed models, the main tasks of early development is to discriminate these models. In this article, a new statistical approach to model discrimination is described that ranks models wrt. the probability with which they reproduce the given data. The article introduces the new approach, discusses its statistical background, presents numerical techniques for its implementation and illustrates the application to examples from biokinetics.

Contribution of radiation hybrids to genome mapping in domestic animals.

PubMed

Faraut, T; de Givry, S; Hitte, C; Lahbib-Mansais, Y; Morisson, M; Milan, D; Schiex, T; Servin, B; Vignal, A; Galibert, F; Yerle, M

2009-01-01

Radiation hybrid mapping has emerged in the end of the 1990 s as a successful and complementary approach to map genomes, essentially because of its ability to bridge the gaps between genetic and clone-based physical maps, but also using comparative mapping approaches, between 'gene-rich' and 'gene-poor' maps. Since its early development in human, radiation hybrid mapping played a pivotal role in the process of mapping animal genomes, especially mammalian ones. We review here all the different steps involved in radiation hybrid mapping from the constitution of panels to the construction of maps. A description of its contribution to whole genome maps with a special emphasis on domestic animals will also be presented. Finally, current applications of radiation hybrid mapping in the context of whole genome assemblies will be described. (c) 2009 S. Karger AG, Basel.

Drug shortages in Israel: regulatory perspectives, challenges and solutions.

PubMed

Schwartzberg, Eyal; Ainbinder, Denize; Vishkauzan, Alla; Gamzu, Ronni

2017-01-01

Pharmaceutical drug shortages (DSs) are a global problem which presents challenges to countries around the world. Shortages of pharmaceutical products may have a direct detrimental impact on public health and patients' wellbeing by causing delayed, or even lack of, treatment. Moreover, DSs may force both patients and caregivers to use unfamiliar drugs, which could lead to medication errors. The objective of our study was to analyze DSs in Israel during the years 2013-2015, assessing their etiology and exploring the steps taken for their mitigation and prevention. The database of the Israeli Ministry of Health (MoH) on drug shortages contains all the DSs recorded in Israel since 2013, detailing the cause of the DS, its duration, steps taken in its' management and the availability of generic or therapeutic alternatives. Selected examples of DSs from the database are described in this paper in order to identify the causes of DSs, the scope of the problem and possible solutions. Additionally, we have reviewed the recent activities performed by European Medicine Agency (EMA) and the American Food and Drug Administration (FDA) in their efforts to minimize this problem. Several factors contributing towards DSs in Israel were identified, including quality problems in both the final drug product and in the raw materials, upgrades and improvements of the manufacturing process required by the MoH, manufacturing by a sole supplier, dramatic price decrease in off-patent medications causing the manufacturer to discontinue the distribution of the product in Israel, just-in-time inventory control, and others. One of the most important steps in managing drug shortages was identified to be early notification of the shortage by the Marketing Authorization Holder (MAH) to the MoH. In 2013, the Israeli MoH updated the regulation on drug shortages instructing MAHs on their obligation of early notification to the MoH. Furthermore, various steps dealing with marketing withdrawal of drugs and temporary drug shortages are being implemented in Israel, such as suspending any further reductions in drug prices below 17 new Israeli shekels, instructing all MAHs to maintain no less than 1 month supply of all registered and non-registered drugs in Israel and allowing an expedited registration pathway for well-established use/grandfather drugs. Drug shortages pose significant public health hazards worldwide. Early notification to the MoH and open dialog with MAHs are essential for managing DSs and mitigating their impact. Despite the efforts carried out by health regulatory authorities worldwide, DSs still pose a significant threat to public health.

Sequential protein association with nascent 60S ribosomal particles.

PubMed

Saveanu, Cosmin; Namane, Abdelkader; Gleizes, Pierre-Emmanuel; Lebreton, Alice; Rousselle, Jean-Claude; Noaillac-Depeyre, Jacqueline; Gas, Nicole; Jacquier, Alain; Fromont-Racine, Micheline

2003-07-01

Ribosome biogenesis in eukaryotes depends on the coordinated action of ribosomal and nonribosomal proteins that guide the assembly of preribosomal particles. These intermediate particles follow a maturation pathway in which important changes in their protein composition occur. The mechanisms involved in the coordinated assembly of the ribosomal particles are poorly understood. We show here that the association of preribosomal factors with pre-60S complexes depends on the presence of earlier factors, a phenomenon essential for ribosome biogenesis. The analysis of the composition of purified preribosomal complexes blocked in maturation at specific steps allowed us to propose a model of sequential protein association with, and dissociation from, early pre-60S complexes for several preribosomal factors such as Mak11, Ssf1, Rlp24, Nog1, and Nog2. The presence of either Ssf1 or Nog2 in complexes that contain the 27SB pre-rRNA defines novel, distinct pre-60S particles that contain the same pre-rRNA intermediates and that differ only by the presence or absence of specific proteins. Physical and functional interactions between Rlp24 and Nog1 revealed that the assembly steps are, at least in part, mediated by direct protein-protein interactions.

Targeting RNA Splicing for Disease Therapy

PubMed Central

Havens, Mallory A.; Duelli, Dominik M.

2013-01-01

Splicing of pre-messenger RNA into mature messenger RNA is an essential step for expression of most genes in higher eukaryotes. Defects in this process typically affect cellular function and can have pathological consequences. Many human genetic diseases are caused by mutations that cause splicing defects. Furthermore, a number of diseases are associated with splicing defects that are not attributed to overt mutations. Targeting splicing directly to correct disease-associated aberrant splicing is a logical approach to therapy. Splicing is a favorable intervention point for disease therapeutics, because it is an early step in gene expression and does not alter the genome. Significant advances have been made in the development of approaches to manipulate splicing for therapy. Splicing can be manipulated with a number of tools including antisense oligonucleotides, modified small nuclear RNAs (snRNAs), trans-splicing, and small molecule compounds, all of which have been used to increase specific alternatively spliced isoforms or to correct aberrant gene expression resulting from gene mutations that alter splicing. Here we describe clinically relevant splicing defects in disease states, the current tools used to target and alter splicing, specific mutations and diseases that are being targeted using splice-modulating approaches, and emerging therapeutics. PMID:23512601

Targeting RNA splicing for disease therapy.

PubMed

Havens, Mallory A; Duelli, Dominik M; Hastings, Michelle L

2013-01-01

Splicing of pre-messenger RNA into mature messenger RNA is an essential step for the expression of most genes in higher eukaryotes. Defects in this process typically affect cellular function and can have pathological consequences. Many human genetic diseases are caused by mutations that cause splicing defects. Furthermore, a number of diseases are associated with splicing defects that are not attributed to overt mutations. Targeting splicing directly to correct disease-associated aberrant splicing is a logical approach to therapy. Splicing is a favorable intervention point for disease therapeutics, because it is an early step in gene expression and does not alter the genome. Significant advances have been made in the development of approaches to manipulate splicing for therapy. Splicing can be manipulated with a number of tools including antisense oligonucleotides, modified small nuclear RNAs (snRNAs), trans-splicing, and small molecule compounds, all of which have been used to increase specific alternatively spliced isoforms or to correct aberrant gene expression resulting from gene mutations that alter splicing. Here we describe clinically relevant splicing defects in disease states, the current tools used to target and alter splicing, specific mutations and diseases that are being targeted using splice-modulating approaches, and emerging therapeutics. Copyright © 2013 John Wiley & Sons, Ltd.

Stress history and fracture pattern in fault-related folds based on limit analysis: application to the Sub-Andean thrust belt of Bolivia

NASA Astrophysics Data System (ADS)

Barbe, Charlotte; Leroy, Yves; Ben Miloud, Camille

2017-04-01

A methodology is proposed to construct the stress history of a complex fault-related fold in which the deformation mechanisms are essentially frictional. To illustrate the approach, fours steps of the deformation of an initially horizontally layered sand/silicone laboratory experiment (Driehaus et al., J. of Struc. Geol., 65, 2014) are analysed with the kinematic approach of limit analysis (LA). The stress, conjugate to the virtual velocity gradient in the sense of mechanicam power, is a proxy for the true statically admmissible stress field which prevailed over the structure. The material properties, friction angles and cohesion, including their time evolution are selected such that the deformation pattern predicted by the LA is consistent with the two main thrusting events, the first forward and the second backward once the layers have sufficiently rotated. The fractures associated to the stress field determined at each step are convected on today configuration to define the complete pattern which should be observed. The end results are presented along virtual vertical wells and could be used within the oil industry at an early phase of exploration to prepare drealing operations.

Terminological aspects of data elements

DOE Office of Scientific and Technical Information (OSTI.GOV)

Strehlow, R.A.; Kenworthey, W.H. Jr.; Schuldt, R.E.

1991-01-01

The creation and display of data comprise a process that involves a sequence of steps requiring both semantic and systems analysis. An essential early step in this process is the choice, definition, and naming of data element concepts and is followed by the specification of other needed data element concept attributes. The attributes and the values of data element concept remain associated with them from their birth as a concept to a generic data element that serves as a template for final application. Terminology is, therefore, centrally important to the entire data creation process. Smooth mapping from natural language tomore » a database is a critical aspect of database, and consequently, it requires terminology standardization from the outset of database work. In this paper the semantic aspects of data elements are analyzed and discussed. Seven kinds of data element concept information are considered and those that require terminological development and standardization are identified. The four terminological components of a data element are the hierarchical type of a concept, functional dependencies, schematas showing conceptual structures, and definition statements. These constitute the conventional role of terminology in database design. 12 refs., 8 figs., 1 tab.« less

Classic Nuclear Localization Signals and a Novel Nuclear Localization Motif Are Required for Nuclear Transport of Porcine Parvovirus Capsid Proteins

PubMed Central

Boisvert, Maude; Bouchard-Lévesque, Véronique; Fernandes, Sandra

2014-01-01

ABSTRACT Nuclear targeting of capsid proteins (VPs) is important for genome delivery and precedes assembly in the replication cycle of porcine parvovirus (PPV). Clusters of basic amino acids, corresponding to potential nuclear localization signals (NLS), were found only in the unique region of VP1 (VP1up, for VP1 unique part). Of the five identified basic regions (BR), three were important for nuclear localization of VP1up: BR1 was a classic Pat7 NLS, and the combination of BR4 and BR5 was a classic bipartite NLS. These NLS were essential for viral replication. VP2, the major capsid protein, lacked these NLS and contained no region with more than two basic amino acids in proximity. However, three regions of basic clusters were identified in the folded protein, assembled into a trimeric structure. Mutagenesis experiments showed that only one of these three regions was involved in VP2 transport to the nucleus. This structural NLS, termed the nuclear localization motif (NLM), is located inside the assembled capsid and thus can be used to transport trimers to the nucleus in late steps of infection but not for virions in initial infection steps. The two NLS of VP1up are located in the N-terminal part of the protein, externalized from the capsid during endosomal transit, exposing them for nuclear targeting during early steps of infection. Globally, the determinants of nuclear transport of structural proteins of PPV were different from those of closely related parvoviruses. IMPORTANCE Most DNA viruses use the nucleus for their replication cycle. Thus, structural proteins need to be targeted to this cellular compartment at two distinct steps of the infection: in early steps to deliver viral genomes to the nucleus and in late steps to assemble new viruses. Nuclear targeting of proteins depends on the recognition of a stretch of basic amino acids by cellular transport proteins. This study reports the identification of two classic nuclear localization signals in the minor capsid protein (VP1) of porcine parvovirus. The major protein (VP2) nuclear localization was shown to depend on a complex structural motif. This motif can be used as a strategy by the virus to avoid transport of incorrectly folded proteins and to selectively import assembled trimers into the nucleus. Structural nuclear localization motifs can also be important for nuclear proteins without a classic basic amino acid stretch, including multimeric cellular proteins. PMID:25078698

Small endometrial carcinoma 10 mm or less in diameter: clinicopathologic and histogenetic study of 131 cases for early detection and treatment.

PubMed

Hasumi, Katsuhiko; Sugiyama, Yuko; Sakamoto, Kimihiko; Akiyama, Futoshi

2013-12-01

Natural history and clinicopathologic features of early endometrial carcinoma are not evident. Its knowledge is essential to make up strategies for prevention, early detection, and treatment of endometrial carcinoma. Especially it is important to know pathways of endometrial carcinogenesis and frequency of endometrial carcinomas arising from endometrial hyperplasia. Clinicopathologically 131 patients with endometrial carcinoma measuring ≤10 mm in diameter ("small endometrial carcinoma") were studied to get useful information for early diagnosis, treatment, and histogenesis. The entire endometrium of surgically removed uterus was step-cut and examined. The patients were, on average, 5 years younger than the controls whose carcinomas measure >10 mm (P < 0.0001). Of the 131 patients, 20% were asymptomatic although only 5% of the controls were asymptomatic (P < 0.0001). Seventy-six percent had the carcinomas located in the upper third section of the uterine corpus. Macroscopically 44% of the tumors were flat and 56% were elevated. Incidence of nodal and ovarian metastases were <1%. Forty percent of "small endometrial carcinomas" were associated with endometrial hyperplasia and 60% were not. It is logical to believe that there are two pathways of endometrial carcinogenesis: carcinomas occurring from hyperplasia (40%) and carcinomas occurring from normal endometrium (60%). As hyperplasia-carcinoma sequence is not a main route, we cannot probably prevent carcinomas only by treatment of hyperplasia. Effort must be focused on detecting early de novo carcinomas. As most "small endometrial carcinomas" arise in the upper third of the corpus, careful endometrial sampling there is important for early detection. © 2013 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Structure-guided Mutational Analysis of the Nucleotidyltransferase Domain of Escherichia coli DNA Ligase (LigA).

PubMed

Wang, Li Kai; Zhu, Hui; Shuman, Stewart

2009-03-27

NAD(+)-dependent DNA ligases (LigA) are ubiquitous in bacteria, where they are essential for growth and present attractive targets for antimicrobial drug discovery. LigA has a distinctive modular structure in which a nucleotidyltransferase catalytic domain is flanked by an upstream NMN-binding module and by downstream OB-fold, zinc finger, helix-hairpin-helix, and BRCT domains. Here we conducted a structure-function analysis of the nucleotidyltransferase domain of Escherichia coli LigA, guided by the crystal structure of the LigA-DNA-adenylate intermediate. We tested the effects of 29 alanine and conservative mutations at 15 amino acids on ligase activity in vitro and in vivo. We thereby identified essential functional groups that coordinate the reactive phosphates (Arg(136)), contact the AMP adenine (Lys(290)), engage the phosphodiester backbone flanking the nick (Arg(218), Arg(308), Arg(97) plus Arg(101)), or stabilize the active domain fold (Arg(171)). Finer analysis of the mutational effects revealed step-specific functions for Arg(136), which is essential for the reaction of LigA with NAD(+) to form the covalent ligase-AMP intermediate (step 1) and for the transfer of AMP to the nick 5'-PO(4) to form the DNA-adenylate intermediate (step 2) but is dispensable for phosphodiester formation at a preadenylylated nick (step 3).

Expression of phosphatidylcholine biosynthetic enzymes during early embryogenesis in the amphibian Bufo arenarum.

PubMed

Fernández-Bussy, Rodrigo; Mouguelar, Valeria; Banchio, Claudia; Coux, Gabriela

2015-04-01

In the principal route of phosphatidylcholine (PC) synthesis the regulatory steps are catalysed by CTP:phosphocholine cytidylyltransferase (CCT) and choline kinase (CK). Knock-out mice in Pcyt1a (CCT gene) and Chka1 (CK gene) resulted in preimplantation embryonic lethality, demonstrating the essential role of this pathway. However, there is still a lack of detailed CCT and CK expression analysis during development. The aim of the current work was to study the expression during early development of both enzymes in the external-fertilization vertebrate Bufo arenarum. Reverse transcription polymerase chain reaction (RT-PCR) and western blot confirmed their presence in unfertilized eggs. Analysis performed in total extracts from staged embryos showed constant protein levels of both enzymes until the 32-cell stage: then they decreased, reaching a minimum in the gastrula before starting to recover. CTP:phosphocholine cytidylyltransferase is an amphitropic enzyme that inter-converts between cytosolic inactive and membrane-bound active forms. Immunoblot analysis demonstrated that the cytosolic:total CCT protein ratio does not change throughout embryogenesis, suggesting a progressive decline of CCT activity in early development. However, PC (and phosphatidylethanolamine) content per egg/embryo remained constant throughout the stages analysed. In conclusion, the current data for B. arenarum suggest that net synthesis of PC mediated by CCT and CK is not required in early development and that supplies for membrane biosynthesis are fulfilled by lipids already present in the egg/embryo reservoirs.

Three steps to writing adaptive study protocols in the early phase clinical development of new medicines

PubMed Central

2014-01-01

This article attempts to define terminology and to describe a process for writing adaptive, early phase study protocols which are transparent, self-intuitive and uniform. It provides a step by step guide, giving templates from projects which received regulatory authorisation and were successfully performed in the UK. During adaptive studies evolving data is used to modify the trial design and conduct within the protocol-defined remit. Adaptations within that remit are documented using non-substantial protocol amendments which do not require regulatory or ethical review. This concept is efficient in gathering relevant data in exploratory early phase studies, ethical and time- and cost-effective. PMID:24980283

Humic First Theory: A New Theory on the Origin of Life

NASA Astrophysics Data System (ADS)

Daei, Mohammad Ali; Daei, Manijeh; Daei, Bijan

2017-04-01

In 1953, Miller & Urey through a brilliant experiment demonstrated that the building blocks of life could evolve in primitive earth conditions [1]. During the recent years scientists revealed that organic matters are not very rare compounds in comets, asteroids, and meteorites which have bombarded the ancient earth repeatedly [2]. So simple organic molecules on early earth could be quite enough to start chemical evolution and steadily, proceeded to the very simple form of life. Many theories have tried to explain how life emerged from non life, but failed, largely due to the lack of a distinct methodology. There is a huge gap between the simple building blocks, like amino acid, sugar, and lipid molecules, to a living cell with a very sophisticated structure and organization. It is unacceptable to fill this great distance, only by accidental reactions in a passive media (primitive soap) even, over a very long time. Obviously, manufacturing of a primitive cell required a natural factory with rather firm and resistant basement, plenty of organic and inorganic raw materials and qualified production line, plus some sources of energy. There were plenty of solar energy and water in the early Earth, but what about the other factors? Availability of essential minerals was not guaranteed at all, in primitive earth which covered with bare, dead rocks. While we are not able today, to multiply any microorganisms in ideal conditions of modern laboratory in the absence of only one of essential nutrients or elements, how can we expect primitive cells appear on early earth conditions without the support of soluble minerals and organic matters? Ideal production line must be active and protective, have catalyzing ability, could provide numerous opportunities for interaction between basic bio molecules (mainly RNA and proteins) and above all, have capability to react with different sources of energy. There are strong evidences that show only some form of stable, rich and active organic matter like modern "humic substances" could perform this great and complicated duty. A mass of warm, wet clay mixed with enough humic substances (HS) in suitable PH, could provide all above requirements, and promote biochemical evolution step by step toward a functional primitive cell. HS are fluorescent compounds and could transform UV radiation to usable light. In addition these protective materials could provide chemical energy plus balanced minerals and organic molecules. While everything in non living world is reducing energy, HS can collect more and more material and energy like a living organism. Fortunately, there are reliable evidences that HS could be accessible on ancient Earth. In fact Ziechman et al [7], in 1994 by finding humic material in Miller's experimental vessels proved that humic substances could be generated on early Earth conditions by polymerizing simple organic molecules. Our investigations show elemental selection and also chairal selection for life are proportionately tailored to Humic materials. For example nearly all heavy metals make insoluble compounds with HS, hence omitted from life processes. In contrast all essential elements have appropriate affinity and workability with HS. There is reliable evidence that shows HS prefer left amino acids and right sugars. As you see many signs and symptoms are referring to "humic substances" as the mother of life, at least on this planet.

Molecular mechanisms involved in the early steps of flavivirus cell entry.

PubMed

Kaufmann, Bärbel; Rossmann, Michael G

2011-01-01

Flaviviruses enter their host cells by receptor-mediated endocytosis, a well-orchestrated process of receptor recognition, penetration and uncoating. Recent findings on these early steps in the life cycle of flaviviruses are the focus of this review. Copyright © 2010 Institut Pasteur. Published by Elsevier SAS. All rights reserved.

Gossip-Free Zones: Problem Solving to Prevent Power Struggles

ERIC Educational Resources Information Center

Bruno, Holly

2007-01-01

Gossiping staff in early childhood programs models destructive behavior and harms families' trust in the professionalism of the program. Bruno identifies some of the causes and motives for gossip and examines its occurrence in early care and education settings. She offers step-by-step strategies to help supervisors set and enact policies that…

Efficacy Trial of the Second Step Early Learning (SSEL) Curriculum: Preliminary Outcomes

ERIC Educational Resources Information Center

Upshur, Carole C.; Heyman, Miriam; Wenz-Gross, Melodie

2017-01-01

A classroom randomized trial (n = 31 classrooms) was conducted using the Second Step Early Learning (SSEL) curriculum compared to usual curricula. Head Start and community preschool classrooms enrolling low income children were randomly assigned to deliver SSEL (n = 16) or usual curricula (n = 15). Data are reported for four year olds…

First Steps to School Readiness: South Carolina's Response to At-Risk Early Childhood Population.

ERIC Educational Resources Information Center

Buford, Rhonda; Stegelin, Dolores A.

2003-01-01

Describes South Carolina's new state early childhood program, First Steps to School Readiness. Includes a profile of the state's at-risk child population, noting poverty and education risk indicators, and describing key program components. The article discusses program oversight, local program partnerships, program funding mechanisms, and local…

Feasibility of Focused Stepping Practice During Inpatient Rehabilitation Poststroke and Potential Contributions to Mobility Outcomes.

PubMed

Hornby, T George; Holleran, Carey L; Leddy, Abigail L; Hennessy, Patrick; Leech, Kristan A; Connolly, Mark; Moore, Jennifer L; Straube, Donald; Lovell, Linda; Roth, Elliot

2015-01-01

Optimal physical therapy strategies to maximize locomotor function in patients early poststroke are not well established. Emerging data indicate that substantial amounts of task-specific stepping practice may improve locomotor function, although stepping practice provided during inpatient rehabilitation is limited (<300 steps/session). The purpose of this investigation was to determine the feasibility of providing focused stepping training to patients early poststroke and its potential association with walking and other mobility outcomes. Daily stepping was recorded on 201 patients <6 months poststroke (80% < 1 month) during inpatient rehabilitation following implementation of a focused training program to maximize stepping practice during clinical physical therapy sessions. Primary outcomes included distance and physical assistance required during a 6-minute walk test (6MWT) and balance using the Berg Balance Scale (BBS). Retrospective data analysis included multiple regression techniques to evaluate the contributions of demographics, training activities, and baseline motor function to primary outcomes at discharge. Median stepping activity recorded from patients was 1516 steps/d, which is 5 to 6 times greater than that typically observed. The number of steps per day was positively correlated with both discharge 6MWT and BBS and improvements from baseline (changes; r = 0.40-0.87), independently contributing 10% to 31% of the total variance. Stepping activity also predicted level of assistance at discharge and discharge location (home vs other facility). Providing focused, repeated stepping training was feasible early poststroke during inpatient rehabilitation and was related to mobility outcomes. Further research is required to evaluate the effectiveness of these training strategies on short- or long-term mobility outcomes as compared with conventional interventions. © The Author(s) 2015.

Impaired Endothelial Repair Capacity of Early Endothelial Progenitor Cells in Hypertensive Patients With Primary Hyperaldosteronemia: Role of 5,6,7,8-Tetrahydrobiopterin Oxidation and Endothelial Nitric Oxide Synthase Uncoupling.

PubMed

Chen, Long; Ding, Mei-Lin; Wu, Fang; He, Wen; Li, Jin; Zhang, Xiao-Yu; Xie, Wen-Li; Duan, Sheng-Zhong; Xia, Wen-Hao; Tao, Jun

2016-02-01

Although hyperaldosteronemia exerts detrimental impacts on vascular endothelium in addition to elevating blood pressure, the effects and molecular mechanisms of hyperaldosteronemia on early endothelial progenitor cell (EPC)-mediated endothelial repair after arterial damage are yet to be determined. The aim of this study was to investigate the endothelial repair capacity of early EPCs from hypertensive patients with primary hyperaldosteronemia (PHA). In vivo endothelial repair capacity of early EPCs from PHAs (n=20), age- and blood pressure-matched essential hypertension patients (n=20), and age-matched healthy subjects (n=20) was evaluated by transplantation into a nude mouse carotid endothelial denudation model. Endothelial function was evaluated by flow-mediated dilation of brachial artery in human subjects. In vivo endothelial repair capacity of early EPCs and flow-mediated dilation were impaired both in PHAs and in essential hypertension patients when compared with age-matched healthy subjects; however, the early EPC in vivo endothelial repair capacity and flow-mediated dilation of PHAs were impaired more severely than essential hypertension patients. Oral spironolactone improved early EPC in vivo endothelial repair capacity and flow-mediated dilation of PHAs. Increased oxidative stress, oxidative 5,6,7,8-tetrahydrobiopterin degradation, endothelial nitric oxide synthase uncoupling and decreased nitric oxide production were found in early EPCs from PHAs. Nicotinamide adenine dinucleotide phosphate oxidase subunit p47(phox) knockdown or 5,6,7,8-tetrahydrobiopterin supplementation attenuated endothelial nitric oxide synthase uncoupling and enhanced in vivo endothelial repair capacity of early EPCs from PHAs. In conclusion, PHAs exhibited more impaired endothelial repair capacity of early EPCs than did essential hypertension patients independent of blood pressure, which was associated with mineralocorticoid receptor-dependent oxidative stress and subsequently 5,6,7,8-tetrahydrobiopterin degradation and endothelial nitric oxide synthase uncoupling. © 2015 American Heart Association, Inc.

Important Late-Stage Symbiotic Role of the Sinorhizobium meliloti Exopolysaccharide Succinoglycan.

PubMed

Arnold, Markus F F; Penterman, Jon; Shabab, Mohammed; Chen, Esther J; Walker, Graham C

2018-07-01

Sinorhizobium meliloti enters into beneficial symbiotic interactions with Medicago species of legumes. Bacterial exopolysaccharides play critical signaling roles in infection thread initiation and growth during the early stages of root nodule formation. After endocytosis of S. meliloti by plant cells in the developing nodule, plant-derived nodule-specific cysteine-rich (NCR) peptides mediate terminal differentiation of the bacteria into nitrogen-fixing bacteroids. Previous transcriptional studies showed that the intensively studied cationic peptide NCR247 induces expression of the exo genes that encode the proteins required for succinoglycan biosynthesis. In addition, genetic studies have shown that some exo mutants exhibit increased sensitivity to the antimicrobial action of NCR247. Therefore, we investigated whether the symbiotically active S. meliloti exopolysaccharide succinoglycan can protect S. meliloti against the antimicrobial activity of NCR247. We discovered that high-molecular-weight forms of succinoglycan have the ability to protect S. meliloti from the antimicrobial action of the NCR247 peptide but low-molecular-weight forms of wild-type succinoglycan do not. The protective function of high-molecular-weight succinoglycan occurs via direct molecular interactions between anionic succinoglycan and the cationic NCR247 peptide, but this interaction is not chiral. Taken together, our observations suggest that S. meliloti exopolysaccharides not only may be critical during early stages of nodule invasion but also are upregulated at a late stage of symbiosis to protect bacteria against the bactericidal action of cationic NCR peptides. Our findings represent an important step forward in fully understanding the complete set of exopolysaccharide functions during legume symbiosis. IMPORTANCE Symbiotic interactions between rhizobia and legumes are economically important for global food production. The legume symbiosis also is a major part of the global nitrogen cycle and is an ideal model system to study host-microbe interactions. Signaling between legumes and rhizobia is essential to establish symbiosis, and understanding these signals is a major goal in the field. Exopolysaccharides are important in the symbiotic context because they are essential signaling molecules during early-stage symbiosis. In this study, we provide evidence suggesting that the Sinorhizobium meliloti exopolysaccharide succinoglycan also protects the bacteria against the antimicrobial action of essential late-stage symbiosis plant peptides. Copyright © 2018 American Society for Microbiology.

DDX41 Recognizes RNA/DNA Retroviral Reverse Transcripts and Is Critical for In Vivo Control of Murine Leukemia Virus Infection.

PubMed

Stavrou, Spyridon; Aguilera, Alexya N; Blouch, Kristin; Ross, Susan R

2018-06-05

Host recognition of viral nucleic acids generated during infection leads to the activation of innate immune responses essential for early control of virus. Retrovirus reverse transcription creates numerous potential ligands for cytosolic host sensors that recognize foreign nucleic acids, including single-stranded RNA (ssRNA), RNA/DNA hybrids, and double-stranded DNA (dsDNA). We and others recently showed that the sensors cyclic GMP-AMP synthase (cGAS), DEAD-box helicase 41 (DDX41), and members of the Aim2-like receptor (ALR) family participate in the recognition of retroviral reverse transcripts. However, why multiple sensors might be required and their relative importance in in vivo control of retroviral infection are not known. Here, we show that DDX41 primarily senses the DNA/RNA hybrid generated at the first step of reverse transcription, while cGAS recognizes dsDNA generated at the next step. We also show that both DDX41 and cGAS are needed for the antiretroviral innate immune response to murine leukemia virus (MLV) and HIV in primary mouse macrophages and dendritic cells (DCs). Using mice with cell type-specific knockout of the Ddx41 gene, we show that DDX41 sensing in DCs but not macrophages was critical for controlling in vivo MLV infection. This suggests that DCs are essential in vivo targets for infection, as well as for initiating the antiviral response. Our work demonstrates that the innate immune response to retrovirus infection depends on multiple host nucleic acid sensors that recognize different reverse transcription intermediates. IMPORTANCE Viruses are detected by many different host sensors of nucleic acid, which in turn trigger innate immune responses, such as type I interferon (IFN) production, required to control infection. We show here that at least two sensors are needed to initiate a highly effective innate immune response to retroviruses-DDX41, which preferentially senses the RNA/DNA hybrid generated at the first step of retrovirus replication, and cGAS, which recognizes double-stranded DNA generated at the second step. Importantly, we demonstrate using mice lacking DDX41 or cGAS that both sensors are needed for the full antiviral response needed to control in vivo MLV infection. These findings underscore the need for multiple host factors to counteract retroviral infection. Copyright © 2018 Stavrou et al.

Review These Essential Steps before Starting a Foundation.

ERIC Educational Resources Information Center

Executive Educator, 1983

1983-01-01

Outlines the legal status of nonprofit foundations as fund-raising entities for public schools (including information on tax deductions), offers four steps for planning such foundations, presents possible objections to foundation funding, and gives the addresses of three organizations to write for further information. (JBM)

Tools for Transition in Early Childhood: A Step-by-Step Guide for Agencies, Teachers, and Families

ERIC Educational Resources Information Center

Rous, Beth S., Ed.D; Hallam, Rena A.

2006-01-01

For young children with and without disabilities, positive outcomes depend on smooth, effective transitions between and within early intervention programs, preschool programs, and public school programs. Now there is a how-to guide that helps professionals across programs work together to make these transitions happen. Coauthored by top expert…

Cellular uptake mediated by epidermal growth factor receptor facilitates the intracellular activity of phosphorothioate-modified antisense oligonucleotides

PubMed Central

Wang, Shiyu; Allen, Nickolas; Vickers, Timothy A; Revenko, Alexey S; Sun, Hong; Liang, Xue-hai; Crooke, Stanley T

2018-01-01

Abstract Chemically modified antisense oligonucleotides (ASOs) with phosphorothioate (PS) linkages have been extensively studied as research and therapeutic agents. PS-ASOs can enter the cell and trigger cleavage of complementary RNA by RNase H1 even in the absence of transfection reagent. A number of cell surface proteins have been identified that bind PS-ASOs and mediate their cellular uptake; however, the mechanisms that lead to productive internalization of PS-ASOs are not well understood. Here, we characterized the interaction between PS-ASOs and epidermal growth factor receptor (EGFR). We found that PS-ASOs trafficked together with EGF and EGFR into clathrin-coated pit structures. Their co-localization was also observed at early endosomes and inside enlarged late endosomes. Reduction of EGFR decreased PS-ASO activity without affecting EGF-mediated signaling pathways and overexpression of EGFR increased PS-ASO activity in cells. Furthermore, reduction of EGFR delays PS-ASO trafficking from early to late endosomes. Thus, EGFR binds to PS-ASOs at the cell surface and mediates essential steps for active (productive) cellular uptake of PS-ASOs through its cargo-dependent trafficking processes which migrate PS-ASOs from early to late endosomes. This EGFR-mediated process can also serve as an additional model to better understand the mechanism of intracellular uptake and endosomal release of PS-ASOs. PMID:29514240

Dealing with the sulfur part of cysteine: four enzymatic steps degrade l-cysteine to pyruvate and thiosulfate in Arabidopsis mitochondria.

PubMed

Höfler, Saskia; Lorenz, Christin; Busch, Tjorven; Brinkkötter, Mascha; Tohge, Takayuki; Fernie, Alisdair R; Braun, Hans-Peter; Hildebrandt, Tatjana M

2016-07-01

Amino acid catabolism is essential for adjusting pool sizes of free amino acids and takes part in energy production as well as nutrient remobilization. The carbon skeletons are generally converted to precursors or intermediates of the tricarboxylic acid cycle. In the case of cysteine, the reduced sulfur derived from the thiol group also has to be oxidized in order to prevent accumulation to toxic concentrations. Here we present a mitochondrial sulfur catabolic pathway catalyzing the complete oxidation of l-cysteine to pyruvate and thiosulfate. After transamination to 3-mercaptopyruvate, the sulfhydryl group from l-cysteine is transferred to glutathione by sulfurtransferase 1 and oxidized to sulfite by the sulfur dioxygenase ETHE1. Sulfite is then converted to thiosulfate by addition of a second persulfide group by sulfurtransferase 1. This pathway is most relevant during early embryo development and for vegetative growth under light-limiting conditions. Characterization of a double mutant produced from Arabidopsis thaliana T-DNA insertion lines for ETHE1 and sulfurtransferase 1 revealed that an intermediate of the ETHE1 dependent pathway, most likely a persulfide, interferes with amino acid catabolism and induces early senescence. © 2016 Scandinavian Plant Physiology Society.

Endoplasmic Reticulum Stress and Unfolded Protein Response in Cartilage Pathophysiology; Contributing Factors to Apoptosis and Osteoarthritis.

PubMed

Hughes, Alexandria; Oxford, Alexandra E; Tawara, Ken; Jorcyk, Cheryl L; Oxford, Julia Thom

2017-03-20

Chondrocytes of the growth plate undergo apoptosis during the process of endochondral ossification, as well as during the progression of osteoarthritis. Although the regulation of this process is not completely understood, alterations in the precisely orchestrated programmed cell death during development can have catastrophic results, as exemplified by several chondrodystrophies which are frequently accompanied by early onset osteoarthritis. Understanding the mechanisms that underlie chondrocyte apoptosis during endochondral ossification in the growth plate has the potential to impact the development of therapeutic applications for chondrodystrophies and associated early onset osteoarthritis. In recent years, several chondrodysplasias and collagenopathies have been recognized as protein-folding diseases that lead to endoplasmic reticulum stress, endoplasmic reticulum associated degradation, and the unfolded protein response. Under conditions of prolonged endoplasmic reticulum stress in which the protein folding load outweighs the folding capacity of the endoplasmic reticulum, cellular dysfunction and death often occur. However, unfolded protein response (UPR) signaling is also required for the normal maturation of chondrocytes and osteoblasts. Understanding how UPR signaling may contribute to cartilage pathophysiology is an essential step toward therapeutic modulation of skeletal disorders that lead to osteoarthritis.

Comparison of the Gene Expression Profiles from Normal and Fgfrl1 Deficient Mouse Kidneys Reveals Downstream Targets of Fgfrl1 Signaling

PubMed Central

Gerber, Simon D.; Amann, Ruth; Wyder, Stefan; Trueb, Beat

2012-01-01

Fgfrl1 (fibroblast growth factor receptor-like 1) is a transmembrane receptor that is essential for the development of the metanephric kidney. It is expressed in all nascent nephrogenic structures and in the ureteric bud. Fgfrl1 null mice fail to develop the metanephric kidneys. Mutant kidney rudiments show a dramatic reduction of ureteric branching and a lack of mesenchymal-to-epithelial transition. Here, we compared the expression profiles of wildtype and Fgfrl1 mutant kidneys to identify genes that act downstream of Fgfrl1 signaling during the early steps of nephron formation. We detected 56 differentially expressed transcripts with 2-fold or greater reduction, among them many genes involved in Fgf, Wnt, Bmp, Notch, and Six/Eya/Dach signaling. We validated the microarray data by qPCR and whole-mount in situ hybridization and showed the expression pattern of candidate genes in normal kidneys. Some of these genes might play an important role during early nephron formation. Our study should help to define the minimal set of genes that is required to form a functional nephron. PMID:22432025

Steps to consider in the approach and management of critically ill patient with spontaneous intracerebral hemorrhage

PubMed Central

Godoy, Daniel Agustin; Piñero, Gustavo Rene; Koller, Patricia; Masotti, Luca; Di Napoli, Mario

2015-01-01

Spontaneous intracerebral hemorrhage is a type of stroke associated with poor outcomes. Mortality is elevated, especially in the acute phase. From a pathophysiological point of view the bleeding must traverse different stages dominated by the possibility of re-bleeding, edema, intracranial hypertension, inflammation and neurotoxicity due to blood degradation products, mainly hemoglobin and thrombin. Neurological deterioration and death are common in early hours, so it is a true neurological-neurosurgical emergency. Time is brain so that action should be taken fast and accurately. The most significant prognostic factors are level of consciousness, location, volume and ventricular extension of the bleeding. Nihilism and early withdrawal of active therapy undoubtedly influence the final result. Although there are no proven therapeutic measures, treatment should be individualized and guided preferably by pathophysiology. The multidisciplinary teamwork is essential. Results of recently completed studies have birth to promising new strategies. For correct management it’s important to establish an orderly and systematic strategy based on clinical stabilization, evaluation and establishment of prognosis, avoiding secondary insults and adoption of specific individualized therapies, including hemostatic therapy and intensive control of elevated blood pressure. Uncertainty continues regarding the role of surgery. PMID:26261773

Early stages of zeolite growth

NASA Astrophysics Data System (ADS)

Kumar, Sandeep

Zeolites are crystalline nonporous aluminosilicates with important applications in separation, purification, and adsorption of liquid and gaseous molecules. However, an ability to tailor the zeolite microstructure, such as particle size/shape and pore-size, to make it benign for specific application requires control over nucleation and particle growth processes. But, the nucleation and crystallization mechanisms of zeolites are not fully understood. In this context, the synthesis of an all-silica zeolite with MFI-type framework has been studied extensively as a model system. Throughout chapters 2, 4 and 5, MFI growth process has been investigated by small-angle x-ray scattering (SAXS) and transmission electron microscopy (TEM). Of fundamental importance is the role of nanoparticles (~5 nm), which are present in the precursor sol, in MFI nucleation and crystallization. Formation of amorphous aggregates and their internal restructuring are concluded as essential steps in MFI nucleation. Early stage zeolite particles have disordered and less crystalline regions within, which indicates the role of structurally distributed population of nanoparticles in growth. Faceting occurs after the depletion of nanoparticles. The chapter 6 presents growth studies in silica sols prepared by using a dimer of tertaprpylammonium (TPA) and reports that MFI nucleation and crystallization are delayed with a more pronounced delay in crystal growth.

Anterior clinoidectomy using an extradural and intradural 2-step hybrid technique.

PubMed

Tayebi Meybodi, Ali; Lawton, Michael T; Yousef, Sonia; Guo, Xiaoming; González Sánchez, Jose Juan; Tabani, Halima; García, Sergio; Burkhardt, Jan-Karl; Benet, Arnau

2018-02-23

Anterior clinoidectomy is a difficult yet essential technique in skull base surgery. Two main techniques (extradural and intradural) with multiple modifications have been proposed to increase efficiency and avoid complications. In this study, the authors sought to develop a hybrid technique based on localization of the optic strut (OS) to combine the advantages and avoid the disadvantages of both techniques. Ten cadaveric specimens were prepared for surgical simulation. After a standard pterional craniotomy, the anterior clinoid process (ACP) was resected in 2 steps. The segment anterior to the OS was resected extradurally, while the segment posterior to the OS was resected intradurally. The proposed technique was performed in 6 clinical cases to evaluate its safety and efficiency. Anterior clinoidectomy was successfully performed in all cadaveric specimens and all 6 patients by using the proposed technique. The extradural phase enabled early decompression of the optic nerve while avoiding the adjacent internal carotid artery. The OS was drilled intradurally under direct visualization of the adjacent neurovascular structures. The described landmarks were easily identifiable and applicable in the surgically treated patients. No operative complication was encountered. A proposed 2-step hybrid technique combines the advantages of the extradural and intradural techniques while avoiding their disadvantages. This technique allows reduced intradural drilling and subarachnoid bone dust deposition. Moreover, the most critical part of the clinoidectomy-that is, drilling of the OS and removal of the body of the ACP-is left for the intradural phase, when critical neurovascular structures can be directly viewed.

Medial knee loading is altered in subjects with early osteoarthritis during gait but not during step-up-and-over task

PubMed Central

Wesseling, Mariska; Smith, Colin R.; Thelen, Darryl G.; Verschueren, Sabine; Jonkers, Ilse

2017-01-01

This study evaluates knee joint loading during gait and step-up-and-over tasks in control subjects, subjects with early knee OA and those with established knee OA. Thirty-seven subjects with varying degrees of medial compartment knee OA severity (eighteen with early OA and sixteen with established OA), and nineteen healthy controls performed gait and step-up-and-over tasks. Knee joint moments, contact forces (KCF), the magnitude of contact pressures and center of pressure (CoP) location were analyzed for the three groups for both activities using a multi-body knee model with articular cartilage contact, 14 ligaments, and six degrees of freedom tibiofemoral and patellofemoral joints. During gait, the first peak of the medial KCF was significantly higher for patients with early knee OA (p = 0.048) and established knee OA (p = 0.001) compared to control subjects. Furthermore, the medial contact pressure magnitudes and CoP location were significantly different in both groups of patients compared to controls. Knee rotation moments (KRMs) and external rotation angles were significantly higher during early stance in both patient groups (p < 0.0001) compared to controls. During step-up-and-over, there was a high variability between the participants and no significant differences in KCF were observed between the groups. Knee joint loading and kinematics were found to be altered in patients with early knee OA only during gait. This is an indication that an excessive medial KCF and altered loading location, observed in these patients, is a contributor to early progression of knee OA. PMID:29117248

Preparative separation of bioactive compounds from essential oil of Flaveria bidentis (L.) Kuntze using steam distillation extraction and one step high-speed counter-current chromatography.

PubMed

Wei, Yun; Du, Jilin; Lu, Yuanyuan

2012-10-01

In order to utilize and control the invasive weed, bioactive compounds from essential oil of Flaveria bidentis (L.) Kuntze were studied. Steam distillation extraction and one step high-speed counter-current chromatography were applied to separate and purify the caryophyllene oxide, 7,11-dimethyl-3-methylene-1,6,10-dodecatriene, and caryophyllene from essential oil of Flaveria bidentis (L.) Kuntze. The two-phase solvent system containing n-hexane/acetonitrile/ethanol (5:4:3, v/v/v) was selected for the one step separation mode according to the partition coefficient values (K) of the target compounds and the separation factor (α). The purity of each isolated fraction after a single high-speed counter-current chromatography run was determined by high performance liquid chromatography. A 3.2 mg of caryophyllene oxide at a purity of 92.6%, 10.4 mg of 7,11-dimethyl-3-methylene-1,6,10-dodecatriene at a purity of 99.1% and 5.7 mg of caryophyllene at a purity of 98.8% were obtained from 200 mg essential oil of Flaveria bidentis (L.) Kuntze. The chemical structures of these components were identified by GC-MS, (1) H-NMR, and (13) C-NMR. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Nurse-led clinics: 10 essential steps to setting up a service.

PubMed

Hatchett, Richard

This article outlines 10 key steps for practitioners to consider when setting up and running a nurse-led clinic. It lays emphasis on careful planning, professional development and the need to audit and evaluate the service to ensure the clinic is measurably effective.

Tobacco control efforts in the Gulf Cooperation Council countries: achievements and challenges.

PubMed

Hassounah, S; Rawaf, D; Khoja, T; Rawaf, S; Hussein, M S; Qidwai, W; Majeed, A

2014-08-19

This paper reports a review into the current state of tobacco use, governance and national commitment for control, and current intervention frameworks in place to reduce the use of tobacco among the populations of the Gulf Cooperation Council (GCC) member states and Yemen. It further reviews structured policy-oriented interventions (in line with the MPOWER package of 6 evidence-based tobacco control measures) that represent government actions to strengthen, implement and manage tobacco control programmes and to address the growing epidemic of tobacco use. Our findings show that tobacco control in the GCC countries has witnessed real progress over the past decades. These are still early days but they indicate steps in the right direction. Future investment in implementation and enforcement of the Framework Convention on Tobacco Control, production of robust tobacco control legislation and the establishment of universally available tobacco cessation services are essential to sustain and strengthen tobacco control in the GCC region.

A Framework for Modeling Emerging Diseases to Inform Management

PubMed Central

Katz, Rachel A.; Richgels, Katherine L.D.; Walsh, Daniel P.; Grant, Evan H.C.

2017-01-01

The rapid emergence and reemergence of zoonotic diseases requires the ability to rapidly evaluate and implement optimal management decisions. Actions to control or mitigate the effects of emerging pathogens are commonly delayed because of uncertainty in the estimates and the predicted outcomes of the control tactics. The development of models that describe the best-known information regarding the disease system at the early stages of disease emergence is an essential step for optimal decision-making. Models can predict the potential effects of the pathogen, provide guidance for assessing the likelihood of success of different proposed management actions, quantify the uncertainty surrounding the choice of the optimal decision, and highlight critical areas for immediate research. We demonstrate how to develop models that can be used as a part of a decision-making framework to determine the likelihood of success of different management actions given current knowledge. PMID:27983501

Activation of formylmethanofuran synthesis in cell extracts of Methanobacterium thermoautotrophicum.

PubMed Central

Bobik, T A; Wolfe, R S

1989-01-01

In cell extracts of Methanobacterium thermoautotrophicum, formylmethanofuran (formyl-MFR) synthesis (an essential CO2 fixation reaction that is an early step in CO2 reduction to methane) is subject to a complex activation that involves a heterodisulfide of coenzyme M and N-(7-mercaptoheptanoyl)threonine O3-phosphate (CoM-S-S-HTP). In this paper we report that titanium(III) citrate, a low-potential reducing agent, stimulated CO2 reduction to methane and activated formyl-MFR synthesis in cell extracts. Titanium(III) citrate functioned as the sole source of electrons for formyl-MFR synthesis and enabled this reaction to occur independently of CoM-S-S-HTP. In addition, CoM-S-S-HTP was found to activate an unknown electron carrier that reduced metronidazole. The activation of formyl-MFR synthesis by CoM-S-S-HTP may involve the activation of a low-potential electron carrier. PMID:2921239

Omics on bioleaching: current and future impacts.

PubMed

Martinez, Patricio; Vera, Mario; Bobadilla-Fazzini, Roberto A

2015-10-01

Bioleaching corresponds to the microbial-catalyzed process of conversion of insoluble metals into soluble forms. As an applied biotechnology globally used, it represents an extremely interesting field of research where omics techniques can be applied in terms of knowledge development, but moreover in terms of process design, control, and optimization. In this mini-review, the current state of genomics, proteomics, and metabolomics of bioleaching and the major impacts of these analytical methods at industrial scale are highlighted. In summary, genomics has been essential in the determination of the biodiversity of leaching processes and for development of conceptual and functional metabolic models. Proteomic impacts are mostly related to microbe-mineral interaction analysis, including copper resistance and biofilm formation. Early steps of metabolomics in the field of bioleaching have shown a significant potential for the use of metabolites as industrial biomarkers. Development directions are given in order to enhance the future impacts of the omics in biohydrometallurgy.

The parvoviral capsid controls an intracellular phase of infection essential for efficient killing of stepwise-transformed human fibroblasts

PubMed Central

Paglino, Justin; Tattersall, Peter

2011-01-01

Members of the rodent subgroup of the genus Parvovirus exhibit lytic replication and spread in many human tumor cells and are therefore attractive candidates for oncolytic virotherapy. However, the significant variation in tumor tropism observed for these viruses remains largely unexplained. We report here that LuIII kills BJ-ELR ‘stepwise-transformed’ human fibroblasts efficiently, while MVM does not. Using viral chimeras, we mapped this property to the LuIII capsid gene, VP2, which is necessary and sufficient to confer the killer phenotype on MVM. LuIII VP2 facilitates a post-entry, pre-DNA-amplification step early in the life cycle, suggesting the existence of an intracellular moiety whose efficient interaction with the incoming capsid shell is critical to infection. Thus targeting of human cancers of different tissue-type origins will require use of parvoviruses with capsids that effectively make this critical interaction. PMID:21600623

Preventive strategies for mental health.

PubMed

Arango, Celso; Díaz-Caneja, Covadonga M; McGorry, Patrick D; Rapoport, Judith; Sommer, Iris E; Vorstman, Jacob A; McDaid, David; Marín, Oscar; Serrano-Drozdowskyj, Elena; Freedman, Robert; Carpenter, William

2018-05-14

Available treatment methods have shown little effect on the burden associated with mental health disorders. We review promising universal, selective, and indicated preventive mental health strategies that might reduce the incidence of mental health disorders, or shift expected trajectories to less debilitating outcomes. Some of these interventions also seem to be cost-effective. In the transition to mental illness, the cumulative lifetime effect of multiple small effect size risk factors progressively increases vulnerability to mental health disorders. This process might inform different levels and stages of tailored interventions to lessen risk, or increase protective factors and resilience, especially during sensitive developmental periods. Gaps between knowledge, policy, and practice need to be bridged. Future steps should emphasise mental health promotion, and improvement of early detection and interventions in clinical settings, schools, and the community, with essential support from society and policy makers. Copyright © 2018 Elsevier Ltd. All rights reserved.

A Framework for Modeling Emerging Diseases to Inform Management.

PubMed

Russell, Robin E; Katz, Rachel A; Richgels, Katherine L D; Walsh, Daniel P; Grant, Evan H C

2017-01-01

The rapid emergence and reemergence of zoonotic diseases requires the ability to rapidly evaluate and implement optimal management decisions. Actions to control or mitigate the effects of emerging pathogens are commonly delayed because of uncertainty in the estimates and the predicted outcomes of the control tactics. The development of models that describe the best-known information regarding the disease system at the early stages of disease emergence is an essential step for optimal decision-making. Models can predict the potential effects of the pathogen, provide guidance for assessing the likelihood of success of different proposed management actions, quantify the uncertainty surrounding the choice of the optimal decision, and highlight critical areas for immediate research. We demonstrate how to develop models that can be used as a part of a decision-making framework to determine the likelihood of success of different management actions given current knowledge.

Convergence and Extrusion Are Required for Normal Fusion of the Mammalian Secondary Palate

PubMed Central

Kim, Seungil; Lewis, Ace E.; Singh, Vivek; Ma, Xuefei; Adelstein, Robert; Bush, Jeffrey O.

2015-01-01

The fusion of two distinct prominences into one continuous structure is common during development and typically requires integration of two epithelia and subsequent removal of that intervening epithelium. Using confocal live imaging, we directly observed the cellular processes underlying tissue fusion, using the secondary palatal shelves as a model. We find that convergence of a multi-layered epithelium into a single-layer epithelium is an essential early step, driven by cell intercalation, and is concurrent to orthogonal cell displacement and epithelial cell extrusion. Functional studies in mice indicate that this process requires an actomyosin contractility pathway involving Rho kinase (ROCK) and myosin light chain kinase (MLCK), culminating in the activation of non-muscle myosin IIA (NMIIA). Together, these data indicate that actomyosin contractility drives cell intercalation and cell extrusion during palate fusion and suggest a general mechanism for tissue fusion in development. PMID:25848986

Impact of proteolytic enzymes in colorectal cancer development and progression.

PubMed

Herszényi, László; Barabás, Loránd; Hritz, István; István, Gábor; Tulassay, Zsolt

2014-10-07

Tumor invasion and metastasis is a highly complicated, multi-step phenomenon. In the complex event of tumor progression, tumor cells interact with basement membrane and extracellular matrix components. Proteolytic enzymes (proteinases) are involved in the degradation of extracellular matrix, but also in cancer invasion and metastasis. The four categories of proteinases (cysteine-, serine-, aspartic-, and metalloproteinases) are named and classified according to the essential catalytic component in their active site. We and others have shown that proteolytic enzymes play a major role not only in colorectal cancer (CRC) invasion and metastasis, but also in malignant transformation of precancerous lesions into cancer. Tissue and serum-plasma antigen concentrations of proteinases might be of great value in identifying patients with poor prognosis in CRC. Our results, in concordance with others indicate the potential tumor marker impact of proteinases for the early diagnosis of CRC. In addition, proteinases may also serve as potential target molecules for therapeutic agents.

A framework for modeling emerging diseases to inform management

USGS Publications Warehouse

Russell, Robin E.; Katz, Rachel A.; Richgels, Katherine L. D.; Walsh, Daniel P.; Grant, Evan H. Campbell

2017-01-01

The rapid emergence and reemergence of zoonotic diseases requires the ability to rapidly evaluate and implement optimal management decisions. Actions to control or mitigate the effects of emerging pathogens are commonly delayed because of uncertainty in the estimates and the predicted outcomes of the control tactics. The development of models that describe the best-known information regarding the disease system at the early stages of disease emergence is an essential step for optimal decision-making. Models can predict the potential effects of the pathogen, provide guidance for assessing the likelihood of success of different proposed management actions, quantify the uncertainty surrounding the choice of the optimal decision, and highlight critical areas for immediate research. We demonstrate how to develop models that can be used as a part of a decision-making framework to determine the likelihood of success of different management actions given current knowledge.

A step-by-step guide to systematically identify all relevant animal studies.

PubMed

Leenaars, Marlies; Hooijmans, Carlijn R; van Veggel, Nieky; ter Riet, Gerben; Leeflang, Mariska; Hooft, Lotty; van der Wilt, Gert Jan; Tillema, Alice; Ritskes-Hoitinga, Merel

2012-01-01

Before starting a new animal experiment, thorough analysis of previously performed experiments is essential from a scientific as well as from an ethical point of view. The method that is most suitable to carry out such a thorough analysis of the literature is a systematic review (SR). An essential first step in an SR is to search and find all potentially relevant studies. It is important to include all available evidence in an SR to minimize bias and reduce hampered interpretation of experimental outcomes. Despite the recent development of search filters to find animal studies in PubMed and EMBASE, searching for all available animal studies remains a challenge. Available guidelines from the clinical field cannot be copied directly to the situation within animal research, and although there are plenty of books and courses on searching the literature, there is no compact guide available to search and find relevant animal studies. Therefore, in order to facilitate a structured, thorough and transparent search for animal studies (in both preclinical and fundamental science), an easy-to-use, step-by-step guide was prepared and optimized using feedback from scientists in the field of animal experimentation. The step-by-step guide will assist scientists in performing a comprehensive literature search and, consequently, improve the scientific quality of the resulting review and prevent unnecessary animal use in the future.

A step-by-step guide to systematically identify all relevant animal studies

PubMed Central

Leenaars, Marlies; Hooijmans, Carlijn R; van Veggel, Nieky; ter Riet, Gerben; Leeflang, Mariska; Hooft, Lotty; van der Wilt, Gert Jan; Tillema, Alice; Ritskes-Hoitinga, Merel

2012-01-01

Before starting a new animal experiment, thorough analysis of previously performed experiments is essential from a scientific as well as from an ethical point of view. The method that is most suitable to carry out such a thorough analysis of the literature is a systematic review (SR). An essential first step in an SR is to search and find all potentially relevant studies. It is important to include all available evidence in an SR to minimize bias and reduce hampered interpretation of experimental outcomes. Despite the recent development of search filters to find animal studies in PubMed and EMBASE, searching for all available animal studies remains a challenge. Available guidelines from the clinical field cannot be copied directly to the situation within animal research, and although there are plenty of books and courses on searching the literature, there is no compact guide available to search and find relevant animal studies. Therefore, in order to facilitate a structured, thorough and transparent search for animal studies (in both preclinical and fundamental science), an easy-to-use, step-by-step guide was prepared and optimized using feedback from scientists in the field of animal experimentation. The step-by-step guide will assist scientists in performing a comprehensive literature search and, consequently, improve the scientific quality of the resulting review and prevent unnecessary animal use in the future. PMID:22037056

Some Suggestions for Conducting Film Competitions and Film Festivals.

ERIC Educational Resources Information Center

Eastman Kodak Co., Rochester, NY.

Four essentials in staging film festivals and competitions are: facilities, films, equipment, and an audience. Basic steps in getting these essentials together are outlined. Surveying available facilities first helps you gauge the scale of the festival, estimate the likely costs and receipts, and plan for the projection equipment necessary.…

Early Intervention for Preschoolers at Risk for Attention-Deficit/Hyperactivity Disorder: Preschool First Step to Success

ERIC Educational Resources Information Center

Feil, Edward G.; Small, Jason W.; Seeley, John R.; Walker, Hill M.; Golly, Annemieke; Frey, Andy; Forness, Steven R.

2016-01-01

This study evaluated the efficacy of the Preschool First Step (PFS) to Success early intervention for children at risk for attention deficit hyperactivity disorder (ADHD). PFS is a targeted intervention for children 3-5 years old with externalizing behavior problems and addresses secondary prevention goals and objectives. As part of a larger…

Starting Strong V: Transitions from Early Childhood Education and Care to Primary Education

ERIC Educational Resources Information Center

OECD Publishing, 2017

2017-01-01

The transition from early childhood education to primary school is a big step for all children, and a step which more and more children are having to take. Quality transitions should be well-prepared and child-centred, managed by trained staff collaborating with one another, and guided by an appropriate and aligned curriculum. Transitions like…

Responder Status Criterion for Stepped Care Trauma-Focused Cognitive Behavioral Therapy for Young Children

ERIC Educational Resources Information Center

Salloum, Alison; Scheeringa, Michael S.; Cohen, Judith A.; Storch, Eric A.

2015-01-01

Background: In order to develop Stepped Care trauma-focused cognitive behavioral therapy (TF-CBT), a definition of early response/non-response is needed to guide decisions about the need for subsequent treatment. Objective: The purpose of this article is to (1) establish criterion for defining an early indicator of response/non-response to the…

Biomedical Information Extraction: Mining Disease Associated Genes from Literature

ERIC Educational Resources Information Center

Huang, Zhong

2014-01-01

Disease associated gene discovery is a critical step to realize the future of personalized medicine. However empirical and clinical validation of disease associated genes are time consuming and expensive. In silico discovery of disease associated genes from literature is therefore becoming the first essential step for biomarker discovery to…

Histone variant H3.3-mediated chromatin remodeling is essential for paternal genome activation in mouse preimplantation embryos.

PubMed

Kong, Qingran; Banaszynski, Laura A; Geng, Fuqiang; Zhang, Xiaolei; Zhang, Jiaming; Zhang, Heng; O'Neill, Claire L; Yan, Peidong; Liu, Zhonghua; Shido, Koji; Palermo, Gianpiero D; Allis, C David; Rafii, Shahin; Rosenwaks, Zev; Wen, Duancheng

2018-03-09

Derepression of chromatin-mediated transcriptional repression of paternal and maternal genomes is considered the first major step that initiates zygotic gene expression after fertilization. The histone variant H3.3 is present in both male and female gametes and is thought to be important for remodeling the paternal and maternal genomes for activation during both fertilization and embryogenesis. However, the underlying mechanisms remain poorly understood. Using our H3.3B-HA-tagged mouse model, engineered to report H3.3 expression in live animals and to distinguish different sources of H3.3 protein in embryos, we show here that sperm-derived H3.3 (sH3.3) protein is removed from the sperm genome shortly after fertilization and extruded from the zygotes via the second polar bodies (PBII) during embryogenesis. We also found that the maternal H3.3 (mH3.3) protein is incorporated into the paternal genome as early as 2 h postfertilization and is detectable in the paternal genome until the morula stage. Knockdown of maternal H3.3 resulted in compromised embryonic development both of fertilized embryos and of androgenetic haploid embryos. Furthermore, we report that mH3.3 depletion in oocytes impairs both activation of the Oct4 pluripotency marker gene and global de novo transcription from the paternal genome important for early embryonic development. Our results suggest that H3.3-mediated paternal chromatin remodeling is essential for the development of preimplantation embryos and the activation of the paternal genome during embryogenesis. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Factors controlling sperm migration through the oviduct revealed by gene-modified mouse models

PubMed Central

Fujihara, Yoshitaka; Miyata, Haruhiko; Ikawa, Masahito

2018-01-01

Mammalian fertilization is comprised of many steps including sperm survival in the uterus, sperm migration in the female reproductive tract, physiological and morphological changes to the spermatozoa, and sperm-egg interaction in the oviduct. In vitro studies have revealed essential factors for these fertilization steps for over half a century. However, the molecular mechanism of fertilization has recently been revised by the emergence of genetically modified animals. Here, we focus on essential factors for sperm fertilizing ability and describe recent advances in our knowledge of the mechanisms of mammalian fertilization, especially of sperm migration from the uterus into the oviduct. PMID:29353867

Kinetic modeling of plant metabolism and its predictive power: peppermint essential oil biosynthesis as an example.

PubMed

Lange, Bernd Markus; Rios-Estepa, Rigoberto

2014-01-01

The integration of mathematical modeling with analytical experimentation in an iterative fashion is a powerful approach to advance our understanding of the architecture and regulation of metabolic networks. Ultimately, such knowledge is highly valuable to support efforts aimed at modulating flux through target pathways by molecular breeding and/or metabolic engineering. In this article we describe a kinetic mathematical model of peppermint essential oil biosynthesis, a pathway that has been studied extensively for more than two decades. Modeling assumptions and approximations are described in detail. We provide step-by-step instructions on how to run simulations of dynamic changes in pathway metabolites concentrations.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Singh, Mahavir; Wang, Zhonghua; Cascio, Duilio

Shq1 is an essential protein involved in the early steps of biogenesis and assembly of H/ACA ribonucleoprotein particles (RNPs). Shq1 binds to dyskerin (Cbf5 in yeast) at an early step of H/ACA RNP assembly and is subsequently displaced by the H/ACA RNA. Shq1 contains an N-terminal CS and a C-terminal Shq1-specific domain (SSD). Dyskerin harbors many mutations associated with dyskeratosis congenita. Structures of yeast Shq1 SSD bound to Cbf5 revealed that only a subset of these mutations is in the SSD binding site, implicating another subset in the putative CS binding site. Here in this paper, we present the crystalmore » structure of human Shq1 CS (hCS) and the nuclear magnetic resonance (NMR) and crystal structures of hCS containing a serine substitution for proline 22 that is associated with some prostate cancers. The structure of hCS is similar to yeast Shq1 CS domain (yCS) and consists of two β-sheets that form an immunoglobulin-like β-sandwich fold. The N-terminal affinity tag sequence AHHHHHH associates with a neighboring protein in the crystal lattice to form an extra β-strand. Deletion of this tag was required to get spectra suitable for NMR structure determination, while the tag was required for crystallization. NMR chemical shift perturbation (CSP) experiments with peptides derived from putative CS binding sites on dyskerin and Cbf5 revealed a conserved surface on CS important for Cbf5/dyskerin binding. A HADDOCK (high-ambiguity-driven protein-protein docking) model of a Shq1-Cbf5 complex that defines the position of CS domain in the pre-H/ACA RNP was calculated using the CSP data.« less

Structure and Interactions of the CS Domain of Human H/ACA RNP Assembly Protein Shq1

DOE PAGES

Singh, Mahavir; Wang, Zhonghua; Cascio, Duilio; ...

2014-12-29

Shq1 is an essential protein involved in the early steps of biogenesis and assembly of H/ACA ribonucleoprotein particles (RNPs). Shq1 binds to dyskerin (Cbf5 in yeast) at an early step of H/ACA RNP assembly and is subsequently displaced by the H/ACA RNA. Shq1 contains an N-terminal CS and a C-terminal Shq1-specific domain (SSD). Dyskerin harbors many mutations associated with dyskeratosis congenita. Structures of yeast Shq1 SSD bound to Cbf5 revealed that only a subset of these mutations is in the SSD binding site, implicating another subset in the putative CS binding site. Here in this paper, we present the crystalmore » structure of human Shq1 CS (hCS) and the nuclear magnetic resonance (NMR) and crystal structures of hCS containing a serine substitution for proline 22 that is associated with some prostate cancers. The structure of hCS is similar to yeast Shq1 CS domain (yCS) and consists of two β-sheets that form an immunoglobulin-like β-sandwich fold. The N-terminal affinity tag sequence AHHHHHH associates with a neighboring protein in the crystal lattice to form an extra β-strand. Deletion of this tag was required to get spectra suitable for NMR structure determination, while the tag was required for crystallization. NMR chemical shift perturbation (CSP) experiments with peptides derived from putative CS binding sites on dyskerin and Cbf5 revealed a conserved surface on CS important for Cbf5/dyskerin binding. A HADDOCK (high-ambiguity-driven protein-protein docking) model of a Shq1-Cbf5 complex that defines the position of CS domain in the pre-H/ACA RNP was calculated using the CSP data.« less

Drosophila tubulin-binding cofactor B is required for microtubule network formation and for cell polarity

PubMed Central

Baffet, Alexandre D.; Benoit, Béatrice; Januschke, Jens; Audo, Jennifer; Gourhand, Vanessa; Roth, Siegfried; Guichet, Antoine

2012-01-01

Microtubules (MTs) are essential for cell division, shape, intracellular transport, and polarity. MT stability is regulated by many factors, including MT-associated proteins and proteins controlling the amount of free tubulin heterodimers available for polymerization. Tubulin-binding cofactors are potential key regulators of free tubulin concentration, since they are required for α-β–tubulin dimerization in vitro. In this paper, we show that mutation of the Drosophila tubulin-binding cofactor B (dTBCB) affects the levels of both α- and β-tubulins and dramatically destabilizes the MT network in different fly tissues. However, we find that dTBCB is dispensable for the early MT-dependent steps of oogenesis, including cell division, and that dTBCB is not required for mitosis in several tissues. In striking contrast, the absence of dTBCB during later stages of oogenesis causes major defects in cell polarity. We show that dTBCB is required for the polarized localization of the axis-determining mRNAs within the oocyte and for the apico-basal polarity of the surrounding follicle cells. These results establish a developmental function for the dTBCB gene that is essential for viability and MT-dependent cell polarity, but not cell division. PMID:22855530

Sexual Orientation and Gender Identity Data Collection Update: U.S. Government Takes Steps to Promote Sexual Orientation and Gender Identity Data Collection Through Meaningful Use Guidelines.

PubMed

Cahill, Sean; Makadon, Harvey J

2014-09-01

Collecting data on sexual orientation and gender identity (SO/GI) in healthcare settings and in electronic health records (EHRs) is essential to understanding, addressing, and reducing LGBT health disparities. The federal government took two key steps in early 2014 in support of asking SO/GI questions in clinical settings as part of the meaningful use of EHRs. First, the Office of the National Coordinator for Health Information Technology issued proposed 2015 Edition Certified EHR Technology (CEHRT) Criteria, which suggest Systematized Nomenclature of Medicine (SNOMED) code sets for SO/GI data collection in 2017. To facilitate the effective and accurate collection of SO/GI data, 153 LGBT and HIV groups recommended that the national coordinator request that the National Library of Medicine develop new codes to reflect SO/GI data. Second, the Health Information Technology Policy Committee submitted recommendations to the national coordinator, including the recommendation that "CEHRT [certified EHR technology] provides the functionality to capture … sexual orientation, gender identity." If the national coordinator accepts this recommendation, it will be put up for public comment in fall 2014 along with other Stage 3 proposed rules. Also, the 2017 Edition CEHRT Notice of Proposed Rule Making Criteria will be up for comment in fall 2014. Final Stage 3 Meaningful Use Guidelines will be published in summer 2015, and other key steps will take place into 2017. A critical parallel step is the training of clinical staff on LGBT health disparities and how to use SO/GI data and manage them in ways that meet the clinical needs of LGBT patients and protect confidentiality and privacy. We must also educate LGBT community members about why offering this information is important for their health and how collecting SO/GI data in EHRs is an important step to understanding LGBT health, reducing disparities, and improving outcomes.

Challenges of Early Detection of Oral Cancer: Raising Awareness as a First Step to Successful Campaigning

ERIC Educational Resources Information Center

Baumann, Eva; Koller, Michael; Wiltfang, Jörg; Wenz, Hans-Jürgen; Möller, Björn; Hertrampf, Katrin

2016-01-01

In Germany, ~13 000 people are found to have oral and pharyngeal cancer every year. Awareness and knowledge about this cancer remain insufficient, particularly amongst elderly people. A campaign for early detection was launched in Northern Germany in April 2012. The first step of the campaign was to increase awareness about oral cancer. Prior to a…

Guidelines for producing training films and videos.

PubMed

Harper, P B

1991-01-01

Drawing from experience in producing a film on the surgical procedure of female sterilization, 4 guidelines to technical film production for training purposes are presented and discussed in this paper. In order of presentation in the text, the paper 1st encourages identifying and securing a technical expert, then clearly identifying steps of the technical procedure, involving trainees and trainers in the production process, and working with experienced producers, scriptwriters, and crew members. Returning to the 1st guideline, the technical advisor will have a central presence during all photography and editing, and ideally should not have any personal investment in the procedure being shown. Prior to script finalization and sorting, research is urged to ensure concrete procedural steps. Printed materials, slides, interviews of experienced clinicians, procedure observation, and test videotape shooting may be called upon and employed as parts of the research phase. Trainees should participate during preliminary research, script development, and pretesting of early film versions, their suggestions for change incorporated where appropriate in the final version. On the final point of securing experienced workers, country nationals sensitive to relevant cultural and background dynamics should be included in the team. The special concerns of airport security regulation and customs requirements knowledge are essential, as well as their attention to assuring adequate on-site electricity for camera equipment.

Structure of the human transcobalamin beta domain in four distinct states

PubMed Central

Bloch, Joël S.; Ruetz, Markus; Kräutler, Bernhard

2017-01-01

Vitamin B12 (cyanocobalamin, CNCbl) is an essential cofactor-precursor for two biochemical reactions in humans. When ingested, cobalamins (Cbl) are transported via a multistep transport system into the bloodstream, where the soluble protein transcobalamin (TC) binds Cbl and the complex is taken up into the cells via receptor mediated endocytosis. Crystal structures of TC in complex with CNCbl have been solved previously. However, the initial steps of holo-TC assembly have remained elusive. Here, we present four crystal structures of the beta domain of human TC (TC-beta) in different substrate-bound states. These include the apo and CNCbl-bound states, providing insight into the early steps of holo-TC assembly. We found that in vitro assembly of TC-alpha and TC-beta to a complex was Cbl-dependent. We also determined the structure of TC-beta in complex with cobinamide (Cbi), an alternative substrate, shedding light on the specificity of TC. We finally determined the structure of TC-beta in complex with an inhibitory antivitamin B12 (anti-B12). We used this structure to model the binding of anti-B12 into full-length holo-TC and could rule out that the inhibitory function of anti-B12 was based on an inability to form a functional complex with TC. PMID:28910388

Full-Mouth Intraoral Radiographic Survey in Rabbits.

PubMed

Regalado, Adriana; Legendre, Loïc

2017-09-01

Dental pathologies are highly prevalent in pet rabbit populations, making oral radiography an essential tool in the evaluation of lagomorph dentitions. The unique anatomy of the rabbit's mouth limits the examination of the conscious animal to the rostral portion of it's mouth. In addition, the oral examination of an aradicular hypsodont tooth is restricted to the short coronal fraction of its crown. Erstwhile images obtained by the extraoral technique were once considered the most practical and informative tool in rabbit dentistry; however, limited visualization of the key structures of individual teeth became the major drawback of this technique. As new imaging technologies are becoming widely available and affordable for veterinarians, intraoral radiography offers the ability to prevent, diagnose, and treat oral pathologies in lagomorphs. This article describes a step-by-step procedure to obtain a full-mouth radiographic survey in rabbits. For this technique, a standard dental X-ray generator and intraoral storage phosphor plates are used while applying the bisecting angle technique. Among the advantages of this technique are detailed visualization of internal and external dental structures, identification of early lesions, and detection of occult pathologies. Furthermore, intraoral images offer superior resolution and higher diagnostic quality with minimal radiation exposure, making this method safer for the veterinarian, staff members, and their patients.

Ten Steps to Conducting a Large, Multi-Site, Longitudinal Investigation of Language and Reading in Young Children

PubMed Central

Farquharson, Kelly; Murphy, Kimberly A.

2016-01-01

Purpose: This paper describes methodological procedures involving execution of a large-scale, multi-site longitudinal study of language and reading comprehension in young children. Researchers in the Language and Reading Research Consortium (LARRC) developed and implemented these procedures to ensure data integrity across multiple sites, schools, and grades. Specifically, major features of our approach, as well as lessons learned, are summarized in 10 steps essential for successful completion of a large-scale longitudinal investigation in early grades. Method: Over 5 years, children in preschool through third grade were administered a battery of 35 higher- and lower-level language, listening, and reading comprehension measures (RCM). Data were collected from children, their teachers, and their parents/guardians at four sites across the United States. Substantial and rigorous effort was aimed toward maintaining consistency in processes and data management across sites for children, assessors, and staff. Conclusion: With appropriate planning, flexibility, and communication strategies in place, LARRC developed and executed a successful multi-site longitudinal research study that will meet its goal of investigating the contribution and role of language skills in the development of children's listening and reading comprehension. Through dissemination of our design strategies and lessons learned, research teams embarking on similar endeavors can be better equipped to anticipate the challenges. PMID:27064308

Facilities Planning for Small Colleges.

ERIC Educational Resources Information Center

O'Neill, Joseph P.; And Others

This second publication in a three-part series called "Alternative Futures" is essentially a workbook that, followed step by step, allows a college to see how its use of space has changed over time. Especially designed for small colleges, the kit makes use of the information that is routinely collected, such as annual financial statements and…

Evaluation of an early step-down strategy from intravenous anidulafungin to oral azole therapy for the treatment of candidemia and other forms of invasive candidiasis: results from an open-label trial.

PubMed

Vazquez, Jose; Reboli, Annette C; Pappas, Peter G; Patterson, Thomas F; Reinhardt, John; Chin-Hong, Peter; Tobin, Ellis; Kett, Daniel H; Biswas, Pinaki; Swanson, Robert

2014-02-21

Hospitalized patients are at increased risk for candidemia and invasive candidiasis (C/IC). Improved therapeutic regimens with enhanced clinical and pharmacoeconomic outcomes utilizing existing antifungal agents are still needed. An open-label, non-comparative study evaluated an intravenous (i.v.) to oral step-down strategy. Patients with C/IC were treated with i.v. anidulafungin and after 5 days of i.v. therapy had the option to step-down to oral azole therapy (fluconazole or voriconazole) if they met prespecified criteria. The primary endpoint was the global response rate (clinical + microbiological) at end of treatment (EOT) in the modified intent-to-treat (MITT) population (at least one dose of anidulafungin plus positive Candida within 96 hours of study entry). Secondary endpoints included efficacy at other time points and in predefined patient subpopulations. Patients who stepped down early (≤ 7 days' anidulafungin) were identified as the "early switch" subpopulation. In total, 282 patients were enrolled, of whom 250 were included in the MITT population. The MITT global response rate at EOT was 83.7% (95% confidence interval, 78.7-88.8). Global response rates at all time points were generally similar in the early switch subpopulation compared with the MITT population. Global response rates were also similar across multiple Candida species, including C. albicans, C. glabrata, and C. parapsilosis. The most common treatment-related adverse events were nausea and vomiting (four patients each). A short course of i.v. anidulafungin, followed by early step-down to oral azole therapy, is an effective and well-tolerated approach for the treatment of C/IC. ClinicalTrials.gov: NCT00496197.

Evaluation of an early step-down strategy from intravenous anidulafungin to oral azole therapy for the treatment of candidemia and other forms of invasive candidiasis: results from an open-label trial

PubMed Central

2014-01-01

Background Hospitalized patients are at increased risk for candidemia and invasive candidiasis (C/IC). Improved therapeutic regimens with enhanced clinical and pharmacoeconomic outcomes utilizing existing antifungal agents are still needed. Methods An open-label, non-comparative study evaluated an intravenous (IV) to oral step-down strategy. Patients with C/IC were treated with IV anidulafungin and after 5 days of IV therapy had the option to step-down to oral azole therapy (fluconazole or voriconazole) if they met prespecified criteria. The primary endpoint was the global response rate (clinical + microbiological) at end of treatment (EOT) in the modified intent-to-treat (MITT) population (at least one dose of anidulafungin plus positive Candida within 96 hours of study entry). Secondary endpoints included efficacy at other time points and in predefined patient subpopulations. Patients who stepped down early (≤ 7 days’ anidulafungin) were identified as the "early switch" subpopulation. Results In total, 282 patients were enrolled, of whom 250 were included in the MITT population. The MITT global response rate at EOT was 83.7% (95% confidence interval, 78.7–88.8). Global response rates at all time points were generally similar in the early switch subpopulation compared with the MITT population. Global response rates were also similar across multiple Candida species, including C. albicans, C. glabrata, and C. parapsilosis. The most common treatment-related adverse events were nausea and vomiting (four patients each). Conclusions A short course of IV anidulafungin, followed by early step-down to oral azole therapy, is an effective and well-tolerated approach for the treatment of C/IC. Trial registration ClinicalTrials.gov: NCT00496197 PMID:24559321

Expanding the Range of the First Step to Success Intervention: Tertiary-Level Support for Children, Teachers, and Families

ERIC Educational Resources Information Center

Frey, Andy J.; Small, Jason W.; Lee, Jon; Walker, Hill M.; Seeley, John R.; Feil, Edward G.; Golly, Annemeike

2015-01-01

This study presents the findings of a quasi-experimental feasibility study examining the Tertiary First Step intervention, an enhanced version of the First Step to Success early intervention program. Tertiary FirstStep was developed to engage families more effectively and influence and improve parenting practices for children having challenging…

Expanding the Range of the First Step to Success Intervention: Tertiary-Level Support for Children, Teachers, and Families

ERIC Educational Resources Information Center

Frey, Andy J.; Small, Jason W.; Lee, Jon; Walker, Hill M.; Seeley, John R.; Feil, Edward G.; Golly, Annemeike

2015-01-01

This study presents the findings of a quasi-experimental feasibility study examining the Tertiary First Step intervention, an enhanced version of the First Step to Success early intervention program. Tertiary First Step was developed to engage families more effectively and influence and improve parenting practices for children having challenging…

Views of Teachers, Parents, and Counselors toward the Preschool Version of First Step to Success Early Intervention Program (FSS-PSV) in Preventing Antisocial Behaviors

ERIC Educational Resources Information Center

Çolak, Aysun; Tomris, Gözde; Diken, Ibrahim H.; Arikan, Arzu; Aksoy, Funda; Çelik, Seçil

2015-01-01

This study aims to describe the views of teachers, parents, and FSS-PSV counselors on the Preschool Version of First Step to Success Early Intervention Program (FSS-PSV) in preventing antisocial behaviors; in addition, the implementation process and contributions from the program will also be outlined. The study was conducted in six different…

Update on the biologic role of the vitamin D endocrine system.

PubMed

Dusso, Adriana S

2014-03-01

The integrity of the vitamin D endocrine system is essential for human health. Nutritional vitamin D deficiency in otherwise healthy individuals, associates with a higher risk of mortality for all causes, despite normal serum calcitriol. These deadly causes extend beyond the recognized adverse impact of vitamin D deficiency on calcium and phosphate homeostasis predisposing to secondary hyperparathyroidism, bone loss and vascular calcification. Vitamin D deficiency also associates with an early onset of disorders of aging, including hypertension, proteinuria, insulin resistance, immune abnormalities that enhance the propensity for viral and bacterial infections, autoimmune disorders, cancer, and multiple organ damage due to excessive systemic inflammation causing atherosclerosis, vascular stiffness, renal lesions, and impaired DNA-damage responses. The frequency and severity of all of these disorders markedly increase in chronic kidney disease (CKD) because the kidney is essential to maintain serum levels of calcitriol, the most potent endogenous endocrine activator of the vitamin D receptor (VDR), and also of 25-hydroxyvitamin D, for local rather than systemic VDR activation. The goal of this review is to update the current understanding of the pathophysiology behind the classical and non-classical actions of VDR activation that help prevent the onset and/or attenuate the progression of renal and cardiovascular damage in CKD. This knowledge is essential to identify non-invasive, sensitive and accurate biomarkers of the severity of these disorders, a first step to generate evidence-based recommendations for a safe correction of vitamin D and/or calcitriol deficiency in the course of CKD that effectively improves outcomes.

ANTICIPATORY POSTURAL ADJUSTMENTS PRIOR TO STEP INITIATION ARE HYPOMETRIC IN UNTREATED PARKINSON'S DISEASE: AN ACCELEROMETER-BASED APPROACH

PubMed Central

Mancini, Martina; Zampieri, Cris; Carlson-Kuhta, Patricia; Chiari, Lorenzo; Horak, Fay B.

2010-01-01

Background and purpose Anticipatory postural adjustments (APAs), prior to step initiation, are bradykinetic in advanced Parkinson's disease (PD) and may be one of the factors associated with ‘start hesitation’. However, little is known about APAs in the early stage of PD. In this study, we determined whether body-worn accelerometers could be used to characterize step initiation deficits in subjects with early-to-moderate, untreated PD. Methods Eleven PD and 12 healthy control subjects were asked to take two steps. Postural adjustments were compared from center of pressure (COP) and from acceleration of the trunk at the center of mass level (L5). Results Our findings show that APAs measured from the peak COP displacement towards the swing leg and the peak trunk acceleration towards the stance leg were smaller in untreated PD compared to control subjects. The magnitude of APAs measured from peak COP displacements and accelerations were correlated. Conclusion These results suggest that quantitative analysis of step initiation from one accelerometer on the trunk could provide useful information for the characterization of patients in early stages of PD, when clinical evidence of start hesitation may not be detectable. Ambulatory monitoring of step initiation is also promising for monitoring patient progression in the home environment, and eventually providing feedback for preventing freezing of gait episodes. PMID:19473350

Methanation of gas streams containing carbon monoxide and hydrogen

DOEpatents

Frost, Albert C.

1983-01-01

Carbon monoxide-containing gas streams having a relatively high concentration of hydrogen are pretreated so as to remove the hydrogen in a recoverable form for use in the second step of a cyclic, essentially two-step process for the production of methane. The thus-treated streams are then passed over a catalyst to deposit a surface layer of active surface carbon thereon essentially without the formation of inactive coke. This active carbon is reacted with said hydrogen removed from the feed gas stream to form methane. The utilization of the CO in the feed gas stream is appreciably increased, enhancing the overall process for the production of relatively pure, low-cost methane from CO-containing waste gas streams.

How Important Is Where You Start? Early Mathematics Knowledge and Later School Success

ERIC Educational Resources Information Center

Claessens, Amy; Engel, Mimi

2013-01-01

Background: Children's early skills are essential for their later success in school. Recent evidence highlights the importance of early mathematics, relative to reading and socioemotional skills, for elementary school achievement. Key advocacy groups for both early childhood and mathematics education have issued position statements on the…

A multidisciplinary network for the care of abnormal fatigue and chronic fatigue syndrome in the provinces of East and West Flanders in Belgium.

PubMed

Tobback, E; Mariman, A; Heytens, S; Declercq, T; Bouwen, A; Spooren, D; Snoeck, P; Van Dessel, K; D'Hooghe, S; Rimbaut, S; Vogelaers, D

2014-10-01

The organization of care for patients with the chronic fatigue syndrome (CFS) in tertiary care referral centres from 2002 onwards, was negatively evaluated by the Belgian Health Care Knowledge Centre on the endpoint of socio-professional reintegration. Subsequently, the federal health authorities asked for the elaboration of a new and innovative model of stepped care, aiming at improved integration of diagnosis and treatment into primary care and between levels of health care for patients with CFS. The reference centre of the University Hospital Ghent took the initiative of recruiting partners in the Belgian provinces of East and West Flanders to guarantee the care for patients with medically unexplained symptoms, in particular abnormal fatigue and CFS. A new and innovative care model, in which general practitioners play a central role, emphasizes the importance of early recognition of the patient 'at risk', correct diagnosis and timely referral. Early detection and intervention is essential in order to avoid or minimize illness progression towards chronicity, to safeguard opportunities for significant health improvement as well as to enhance successful socio-professional reintegration. This approach covers both the large sample of patients developing somatic complaints without obvious disease in an early phase as well as the more limited group of patients with chronic illness, including CFS. Cognitive behavioural therapy and graded exposure/exercise therapy are the evidence based main components of therapy in the latter. A biopsychosocial model underlies the proposed path of care.

Toll-like receptor 4 orchestrates neutrophil recruitment into airways during the first hours of Bordetella pertussis infection.

PubMed

Moreno, Griselda; Errea, Agustina; Van Maele, Laurye; Roberts, Roy; Léger, Hélène; Sirard, Jean Claude; Benecke, Arndt; Rumbo, Martin; Hozbor, Daniela

2013-01-01

Most of the knowledge on the impact of Bordetella pertussis lipo-oligosaccharide (LOS) on the infectious process was obtained when the bacteria was established within the host. The aim of the present work was to determine the role of TLR4 at a very early step of the infectious process. To this end we used a transcriptomic approach on B. pertussis intranasal infection model in C3H/HeN, a TLR4-competent mouse strain, and C3H/HeJ, a TLR4-deficient mouse strain. The expression of approximately 140 genes was significantly changed 2 h post-infection in the C3H/HeN animals compared to the C3H/HeJ animals, which were essentially non-responders at this early time point. Pathways specific for immunity and defense, chemokine- and cytokine-mediated functions and TLR signaling, were activated upon infection in the TLR4 competent mice either at 2 h or 24 h. Furthermore, we observed that TLR4 signaling is absolutely required to promote the rapid recruitment of neutrophils into the airways. Interestingly, the depletion of those neutrophils impacted on B. pertussis lung counts in the first three days, thereby exacerbating the lung infection. In summary, we determined that TLR4 is a central player in initial neutrophil recruitment and orchestration of the very early innate defense against B. pertussis. Copyright © 2013 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Intestinal Ostomy.

PubMed

Ambe, Peter C; Kurz, Nadja Rebecca; Nitschke, Claudia; Odeh, Siad F; Möslein, Gabriela; Zirngibl, Hubert

2018-03-16

About 100 000 ostomy carriers are estimated to live in Germany today. The creation of an ostomy represents a major life event that can be associated with impaired quality of life. Optimal ostomy creation and proper ostomy care are crucially important determinants of the success of treatment and of the patients' quality of life. This article is based on pertinent publications retrieved by a selective search in PubMed, GoogleScholar, and Scopus, and on the authors' experience. Intestinal stomata can be created using either the small or the large bowel. More than 75% of all stomata are placed as part of the treatment of colorectal cancer. The incidence of stoma-related complications is reported to be 10-70%. Skin irritation, erosion, and ulceration are the most common early complications, with a combined incidence of 25-34%, while stoma prolapse is the most common late complication, with an incidence of 8-75%. Most early complications can be managed conservatively, while most late complications require surgical revision. In 19% of cases, an ostomy that was initially planned to be temporary becomes permanent. Inappropriate stoma location and inadequate ostomy care are the most common causes of early complications. Both surgical and patient-related factors influence late complications. Every step from the planning of a stoma to its postoperative care should be discussed with the patient in detail. Preoperative marking is essential for an optimal stoma site. Optimal patient management with the involvement of an ostomy nurse increases ostomy acceptance, reduces ostomy-related complications, and improves the quality of life of ostomy carriers.

[Sea urchin embryo, DNA-damaged cell cycle checkpoint and the mechanisms initiating cancer development].

PubMed

Bellé, Robert; Le Bouffant, Ronan; Morales, Julia; Cosson, Bertrand; Cormier, Patrick; Mulner-Lorillon, Odile

2007-01-01

Cell division is an essential process for heredity, maintenance and evolution of the whole living kingdom. Sea urchin early development represents an excellent experimental model for the analysis of cell cycle checkpoint mechanisms since embryonic cells contain a functional DNA-damage checkpoint and since the whole sea urchin genome is sequenced. The DNA-damaged checkpoint is responsible for an arrest in the cell cycle when DNA is damaged or incorrectly replicated, for activation of the DNA repair mechanism, and for commitment to cell death by apoptosis in the case of failure to repair. New insights in cancer biology lead to two fundamental concepts about the very first origin of cancerogenesis. Cancers result from dysfunction of DNA-damaged checkpoints and cancers appear as a result of normal stem cell (NCS) transformation into a cancer stem cell (CSC). The second aspect suggests a new definition of "cancer", since CSC can be detected well before any clinical evidence. Since early development starts from the zygote, which is a primary stem cell, sea urchin early development allows analysis of the early steps of the cancerization process. Although sea urchins do not develop cancers, the model is alternative and complementary to stem cells which are not easy to isolate, do not divide in a short time and do not divide synchronously. In the field of toxicology and incidence on human health, the sea urchin experimental model allows assessment of cancer risk from single or combined molecules long before any epidemiologic evidence is available. Sea urchin embryos were used to test the worldwide used pesticide Roundup that contains glyphosate as the active herbicide agent; it was shown to activate the DNA-damage checkpoint of the first cell cycle of development. The model therefore allows considerable increase in risk evaluation of new products in the field of cancer and offers a tool for the discovery of molecular markers for early diagnostic in cancer biology. Prevention and early diagnosis are two decisive elements of human cancer therapy.

Feedback Consequences and Steps Toward Implementation: A Guide to Educational Outcome Measurements and Their Uses. Seminar No. 6.

ERIC Educational Resources Information Center

Mushkin, Selma J.; Billings, Bradley B.

This guide is essentially designed as a teaching aid for those who would inform planners, officials of educational ministries, school administrators, principals, and teachers about educational outcome measurements. In outline and graphic form, the guide presents topics for discussion in a seminar dealing with feedback consequences and steps toward…

Changing the School Climate Is the First Step to Reform in Many Schools with Federal Improvement Grants

ERIC Educational Resources Information Center

McMurrer, Jennifer

2012-01-01

School Improvement Grants (SIGs) financed through the economic stimulus package are intended to spur dramatic change in persistently low-performing schools. Many state and local officials charged with implementing SIGs view the creation of a safe, orderly, collegial, and productive school climate as an essential step in raising student…

Designing and Implementing Two-Way Bilingual Programs: A Step-by-Step Guide for Administrators, Teachers, and Parents.

ERIC Educational Resources Information Center

Calderon, Margarita Espino; Minaya-Rowe, Liliana

This book provides school administrators, teachers, and parents with the basic knowledge necessary for planning and implementing effective two-way bilingual programs. It offers essential elements to help students gain literacy in two languages, increase cross-cultural understanding, and meet high levels of achievement in all core academic areas.…

Fundraising Strategies for Community Colleges: The Definitive Guide for Advancement

ERIC Educational Resources Information Center

Klingaman, Steve

2012-01-01

"Fundraising Strategies for Community Colleges" is a hands-on, step-by-step guide to building a million-dollar-a-year development office. Community colleges educate nearly half the undergraduates in America yet receive as little as two percent of all gifts to higher education. Private philanthropy is now essential to the mission of community…

Communication for the Workplace: An Integrated Language Approach. Second Edition. Job Skills. Net Effect Series.

ERIC Educational Resources Information Center

Ettinger, Blanche; Perfetto, Edda

Using a developmental, hands-on approach, this text/workbook helps students master the basic English skills that are essential to write effective business correspondence, to recognize language errors, and to develop decision-making and problem-solving skills. Its step-by-step focus and industry-specific format encourages students to review,…

Motivational Interviewing for Effective Classroom Management: The Classroom Check-Up. Practical Intervention in the Schools Series

ERIC Educational Resources Information Center

Reinke, Wendy M.; Herman, Keith C.; Sprick, Randy

2011-01-01

Highly accessible and user-friendly, this book focuses on helping K-12 teachers increase their use of classroom management strategies that work. It addresses motivational aspects of teacher consultation that are essential, yet often overlooked. The Classroom Check-Up is a step-by-step model for assessing teachers' organizational, instructional,…

Suicide Prevention in the Schools: Guidelines for Middle and High School Settings. Second Edition

ERIC Educational Resources Information Center

Capuzzi, David

2009-01-01

In this book, David Capuzzi, a renowned expert on suicide, encourages suicide prevention in schools through the use of a clear and effective crisis management plan designed to identify and serve at-risk youth. His concise, step-by-step framework provides essential information for school counselors, administrators, and faculty on suicide…

Starting with Worldviews: A Five-Step Preparatory Approach to Integrative Interdisciplinary Learning

ERIC Educational Resources Information Center

Augsburg, Tanya; Chitewere, Tendai

2013-01-01

In this article we propose a five-step sequenced approach to integrative interdisciplinary learning in undergraduate gateway courses. Drawing from the literature of interdisciplinarity, transformative learning theory, and theories of reflective learning, we utilize a sequence of five steps early in our respective undergraduate gateway courses to…

A Selection Method That Succeeds!

ERIC Educational Resources Information Center

Weitman, Catheryn J.

Provided a structural selection method is carried out, it is possible to find quality early childhood personnel. The hiring process involves five definite steps, each of which establishes a base for the next. A needs assessment formulating basic minimal qualifications is the first step. The second step involves review of current job descriptions…

Group sequential designs for stepped-wedge cluster randomised trials

PubMed Central

Grayling, Michael J; Wason, James MS; Mander, Adrian P

2017-01-01

Background/Aims: The stepped-wedge cluster randomised trial design has received substantial attention in recent years. Although various extensions to the original design have been proposed, no guidance is available on the design of stepped-wedge cluster randomised trials with interim analyses. In an individually randomised trial setting, group sequential methods can provide notable efficiency gains and ethical benefits. We address this by discussing how established group sequential methodology can be adapted for stepped-wedge designs. Methods: Utilising the error spending approach to group sequential trial design, we detail the assumptions required for the determination of stepped-wedge cluster randomised trials with interim analyses. We consider early stopping for efficacy, futility, or efficacy and futility. We describe first how this can be done for any specified linear mixed model for data analysis. We then focus on one particular commonly utilised model and, using a recently completed stepped-wedge cluster randomised trial, compare the performance of several designs with interim analyses to the classical stepped-wedge design. Finally, the performance of a quantile substitution procedure for dealing with the case of unknown variance is explored. Results: We demonstrate that the incorporation of early stopping in stepped-wedge cluster randomised trial designs could reduce the expected sample size under the null and alternative hypotheses by up to 31% and 22%, respectively, with no cost to the trial’s type-I and type-II error rates. The use of restricted error maximum likelihood estimation was found to be more important than quantile substitution for controlling the type-I error rate. Conclusion: The addition of interim analyses into stepped-wedge cluster randomised trials could help guard against time-consuming trials conducted on poor performing treatments and also help expedite the implementation of efficacious treatments. In future, trialists should consider incorporating early stopping of some kind into stepped-wedge cluster randomised trials according to the needs of the particular trial. PMID:28653550

Group sequential designs for stepped-wedge cluster randomised trials.

PubMed

Grayling, Michael J; Wason, James Ms; Mander, Adrian P

2017-10-01

The stepped-wedge cluster randomised trial design has received substantial attention in recent years. Although various extensions to the original design have been proposed, no guidance is available on the design of stepped-wedge cluster randomised trials with interim analyses. In an individually randomised trial setting, group sequential methods can provide notable efficiency gains and ethical benefits. We address this by discussing how established group sequential methodology can be adapted for stepped-wedge designs. Utilising the error spending approach to group sequential trial design, we detail the assumptions required for the determination of stepped-wedge cluster randomised trials with interim analyses. We consider early stopping for efficacy, futility, or efficacy and futility. We describe first how this can be done for any specified linear mixed model for data analysis. We then focus on one particular commonly utilised model and, using a recently completed stepped-wedge cluster randomised trial, compare the performance of several designs with interim analyses to the classical stepped-wedge design. Finally, the performance of a quantile substitution procedure for dealing with the case of unknown variance is explored. We demonstrate that the incorporation of early stopping in stepped-wedge cluster randomised trial designs could reduce the expected sample size under the null and alternative hypotheses by up to 31% and 22%, respectively, with no cost to the trial's type-I and type-II error rates. The use of restricted error maximum likelihood estimation was found to be more important than quantile substitution for controlling the type-I error rate. The addition of interim analyses into stepped-wedge cluster randomised trials could help guard against time-consuming trials conducted on poor performing treatments and also help expedite the implementation of efficacious treatments. In future, trialists should consider incorporating early stopping of some kind into stepped-wedge cluster randomised trials according to the needs of the particular trial.

Tackling cancer control in the Gulf Cooperation Council Countries.

PubMed

Al-Othman, Saleh; Haoudi, Abdelali; Alhomoud, Samar; Alkhenizan, Abdullah; Khoja, Tawfik; Al-Zahrani, Ali

2015-05-01

Cancer is a major health problem in both high income and middle-to-low income countries, and is the second leading cause of death in the world. Although more than a third of cancer could be prevented and another third could be cured if diagnosed early, it remains a huge challenge to health-care systems worldwide. Despite substantial improvements in health services some of the countries in the Gulf region, the burden of non-communicable diseases is a major threat, primarily due to the rapid socioeconomic shifts that have led to unfavourable changes in lifestyle such as increased tobacco use, decreased physical activity, and consumption of unhealthy food. In the Gulf Cooperation Council states (United Arab Emirates, Bahrain, Saudi Arabia, Oman, Qatar, and Kuwait), advanced breast cancer, colorectal cancer, leukaemia, thyroid cancer, and non-Hodgkin lymphomas are the most common cancers affecting younger populations compared with other countries. By contrast with cancer prevalence in developed countries, prostate, lung, and cervical cancers are not among the most common cancers in the Gulf region. In view of the increased cost of cancer management worldwide, integrated approaches between primary, secondary, and tertiary health-care systems with special focus on prevention and early detection is an essential step in the countries' efforts in the fight against cancer. Copyright © 2015 Elsevier Ltd. All rights reserved.

Earth's early atmosphere as seen from carbon and nitrogen isotopic analysis of Archean sediments

NASA Technical Reports Server (NTRS)

Gibson, E. K., Jr.; Carr, L. P.; Gilmour, I.; Pillinger, C. T.

1986-01-01

The origin and evolution of the Earth's early atmosphere has long been a topic of great interest but determination of actual compositions over geologic time is a difficult problem. However, recent systematic studies of stromatolite deposits (Precambrian Paleobiology Research Group) has extended our knowledge of Archean ecosystems. It has been shown that many stromatolite deposits have undergone negligible alteration since their time of formation. The discovery of primary fluid inclusions within unaltered 3.5 b.y. old Archiean sediments and the observation that the 3.3 b.y. old Barberton cherts have remained closed to argon loss and have not been subjected to thermal metamorphism suggests that an opportunity exists for the direct measurement of the volatile constituents present at their time of formation. Of primary interest to this study was the possibility that the stromatolites and other Archean sediments might retain a vestige of the atmosphere and thus afford an indication of the variations in carbon dioxide and nitrogen isotopic compositions with time. A suite of essentially unaltered Archean stromatolites and the cherts of different ages and geologic sites have been analyzed for their trapped carbon dioxide and nitrogen compositions by the stepped combustion extraction tech nique utilizing static mass spectrometers for the isotope measurements.

Convergence of nanotechnology and cancer prevention: are we there yet?

PubMed

Menter, David G; Patterson, Sherri L; Logsdon, Craig D; Kopetz, Scott; Sood, Anil K; Hawk, Ernest T

2014-10-01

Nanotechnology is emerging as a promising modality for cancer treatment; however, in the realm of cancer prevention, its full utility has yet to be determined. Here, we discuss the potential of integrating nanotechnology in cancer prevention to augment early diagnosis, precision targeting, and controlled release of chemopreventive agents, reduced toxicity, risk/response assessment, and personalized point-of-care monitoring. Cancer is a multistep, progressive disease; the functional and acquired characteristics of the early precancer phenotype are intrinsically different from those of a more advanced anaplastic or invasive malignancy. Therefore, applying nanotechnology to precancers is likely to be far more challenging than applying it to established disease. Frank cancers are more readily identifiable through imaging and biomarker and histopathologic assessment than their precancerous precursors. In addition, prevention subjects routinely have more rigorous intervention criteria than therapy subjects. Any nanopreventive agent developed to prevent sporadic cancers found in the general population must exhibit a very low risk of serious side effects. In contrast, a greater risk of side effects might be more acceptable in subjects at high risk for cancer. Using nanotechnology to prevent cancer is an aspirational goal, but clearly identifying the intermediate objectives and potential barriers is an essential first step in this exciting journey. ©2014 American Association for Cancer Research.

Convergence of Nanotechnology and Cancer Prevention: Are We There Yet?

PubMed Central

Menter, David G.; Patterson, Sherri L.; Logsdon, Craig D.; Kopetz, Scott; Sood, Anil K.; Hawk, Ernest T.

2014-01-01

Nanotechnology is emerging as a promising modality for cancer treatment; however, in the realm of cancer prevention, its full utility has yet to be determined. Here, we discuss the potential of integrating nanotechnology in cancer prevention to augment early diagnosis, precision targeting and controlled release of chemopreventive agents, reduced toxicity, risk/response assessment, and personalized point-of-care monitoring. Cancer is a multistep, progressive disease; the functional and acquired characteristics of the early precancer phenotype are intrinsically different from those of a more advanced anaplastic or invasive malignancy. Therefore, applying nanotechnology to precancers is likely to be far more challenging than applying it to established disease. Frank cancers are more readily identifiable through imaging and biomarker and histopathologic assessment than their precancerous precursors. In addition, prevention subjects routinely have more rigorous intervention criteria than therapy subjects. Any nanopreventive agent developed to prevent sporadic cancers found in the general population must exhibit a very low risk of serious side effects. In contrast, a greater risk of side effects might be more acceptable in subjects at high risk for cancer. Using nanotechnology to prevent cancer is an aspirational goal, but clearly identifying the intermediate objectives and potential barriers is an essential first step in this exciting journey. PMID:25060262

Moving Triadic Gaze Intervention Into Practice: Measuring Clinician Attitude and Implementation Fidelity

PubMed Central

Olswang, Lesley B.; Greenslade, Kathryn; Pinder, Gay Lloyd; Dowden, Patricia; Madden, Jodi

2017-01-01

Purpose This research investigated a first step in implementing the dynamic assessment (DA) component of Triadic Gaze Intervention (Olswang, Feuerstein, Pinder, & Dowden, 2013; Olswang et al., 2014), an evidence-based protocol for teaching early signals of communication to young children with physical disabilities. Clinician attitudes about adopting external evidence into practice and implementation fidelity in DA protocol delivery were examined following training. Method Seven early intervention clinicians from multiple disciplines were trained to deliver the four essential elements of the DA protocol: (a) provide communication opportunity, (b) recognize child's potentially communicative signal, (c) shape child's signal toward triadic gaze, and (d) reinforce with play. Clinician attitude regarding adopting evidence into practice was measured at baseline and follow-up, with the Evidence-Based Practice Attitude Scale (Aarons, 2004). Implementation fidelity in delivering the protocol was measured for adherence (accuracy) and competence (quality) during trial implementation. Results Clinicians' attitudes about trying new evidence that at first was perceived as incongruent with their practice improved over the course of the research. Clinicians demonstrated strong adherence to the DA protocol; however, competence varied across clinicians and appeared related to child performance. Conclusions The results provided insight into moving Triadic Gaze Intervention into practice and yielded valuable information regarding the implementation process, with implications for future research. PMID:28525577

Assessing Teacher Beliefs about Early Literacy Curriculum Implementation

ERIC Educational Resources Information Center

McKenney, Susan; Bradley, Barbara

2016-01-01

Against the backdrop of growing international concern for a narrowing view of early literacy, this study was initiated to determine how teachers of four-year-olds view their task of fostering early literacy. This paper reports on the first steps to design and validate an instrument which captures teachers' perceptions of early literacy content…

Red-breasted nuthatches detect early increases in spruce budworm populations

Treesearch

Hewlette S. Crawford; Daniel T. Jennings; Timothy L. Stone

1990-01-01

Early suppression .of increasing spruce budworm populations is essential to prevent epidemics; however, early changes in budworm numbers are difficult to detect. An effective and inexpensive method to detect early increases is needed. Red-breasted nuthatches eat more spruce budworm larvae and pupae as the insect increases in number. We estimated the number of large...

Essential Role of Chromatin Remodeling Protein Bptf in Early Mouse Embryos and Embryonic Stem Cells

PubMed Central

Landry, Joseph; Sharov, Alexei A.; Piao, Yulan; Sharova, Lioudmila V.; Xiao, Hua; Southon, Eileen; Matta, Jennifer; Tessarollo, Lino; Zhang, Ying E.; Ko, Minoru S. H.; Kuehn, Michael R.; Yamaguchi, Terry P.; Wu, Carl

2008-01-01

We have characterized the biological functions of the chromatin remodeling protein Bptf (Bromodomain PHD-finger Transcription Factor), the largest subunit of NURF (Nucleosome Remodeling Factor) in a mammal. Bptf mutants manifest growth defects at the post-implantation stage and are reabsorbed by E8.5. Histological analyses of lineage markers show that Bptf−/− embryos implant but fail to establish a functional distal visceral endoderm. Microarray analysis at early stages of differentiation has identified Bptf-dependent gene targets including homeobox transcriptions factors and genes essential for the development of ectoderm, mesoderm, and both definitive and visceral endoderm. Differentiation of Bptf−/− embryonic stem cell lines into embryoid bodies revealed its requirement for development of mesoderm, endoderm, and ectoderm tissue lineages, and uncovered many genes whose activation or repression are Bptf-dependent. We also provide functional and physical links between the Bptf-containing NURF complex and the Smad transcription factors. These results suggest that Bptf may co-regulate some gene targets of this pathway, which is essential for establishment of the visceral endoderm. We conclude that Bptf likely regulates genes and signaling pathways essential for the development of key tissues of the early mouse embryo. PMID:18974875

δ opioid receptor antagonist, ICI 174,864, is suitable for the early treatment of uncontrolled hemorrhagic shock in rats.

PubMed

Liu, Liangming; Tian, Kunlun; Zhu, Yu; Ding, Xiaoli; Li, Tao

2013-08-01

Fluid resuscitation is the essential step for early treatment of traumatic hemorrhagic shock. However, its implementation is greatly limited before hospital or during evacuation. The authors investigated whether δ opioid receptor antagonist ICI 174,864 was suitable for the early treatment of traumatic hemorrhagic shock. With uncontrolled hemorrhagic-shock rats, the antishock effects of six dosages of ICI 174,864 (0.1, 0.3, 0.5, 1, 3, and 5 mg/kg) infused with or without a small volume of lactated Ringer's solution (LR) before bleeding controlled or bleeding cessation at different times were observed. ICI 174,864 (0.1-3 mg/kg) with or without 1/4 volume of LR infusion showed dose-dependent increase in the mean arterial blood pressure, and significantly prolonged the survival time and 8-h survival rate, as compared with ICI 174,864 plus 1/2 volume of LR infusion. The best effect was shown with 3 mg/kg of ICI 174,864. Bleeding cessation at 1, 2, or 3 h during infusion of ICI 174,864 (3 mg/kg) plus 1/4 volume of LR improved subsequent treatment (70% 24-h survival rate vs. 50 and 10% 24-h survival rate in hypotensive resuscitation and LR group, respectively). There was significant improvement in hemodynamic parameters, oxygen delivery, and tissue perfusion of hemorrhagic-shock rats with 3 mg/kg of ICI 174,864 plus 1/4 volume of LR infusion. δ Opioid receptor antagonist ICI 174,864 alone or with small volume of fluid infusion has good beneficial effect on uncontrolled hemorrhagic shock. Its early application can "buy" time for subsequent treatment of traumatic shock.

Defects in cholesterol synthesis genes in mouse and in humans: lessons for drug development and safer treatments.

PubMed

Horvat, Simon; McWhir, Jim; Rozman, Damjana

2011-02-01

This review describes the mouse knockout models of cholesterol synthesis, together with human malformations and drugs that target cholesterogenic enzymes. Generally, the sooner a gene acts in cholesterol synthesis, the earlier the phenotype occurs. Humans with loss of function of early cholesterogenic enzymes have not yet been described, and in the mouse, loss of Hmgcr is preimplantation lethal. Together, these results indicate that the widely prescribed cholesterol-lowering statins are potentially teratogenic. The Mvk knockout is early embryonic lethal in the mouse, the absence of Fdft1 is lethal at E9.5-12.5 dpc, while the Cyp51 knockouts die at 15.0 dpc. Fungal CYP51 inhibitor azoles are teratogenic in humans, potentially leading to symptoms of Antley-Bixler syndrome. The X-linked mutations in Nsdhl and Ebp are embryonic lethal in male mice, while heterozygous females are also affected. Consequently, the anticancer drugs, tamoxifen and toremifene, inhibiting human EBP, may be harmful in early pregnancy. The Dhcr7 and Dhcr24 knockout mice die shortly after birth, while humans survive with Smith-Lemli-Opitz syndrome or desmosterolosis. Since cholesterol is essential for hedgehog signaling, disturbance of this pathway by antipsychotics and -depressants explains some drug side effects. In conclusion, defects in cholesterol synthesis are generally lethal in mice, while humans with impaired later steps of the pathway can survive with severe malformations. Evidence shows that drugs targeting or, by coincidence, inhibiting human cholesterol synthesis are better avoided in early pregnancy. Since some drugs with teratogenic potential still stay on the market, this should be avoided in new cholesterol-related drug development.

New models of hemostasis.

PubMed

McMichael, Maureen

2012-05-01

Hemostasis is an essential protective mechanism that depends on a delicate balance of procoagulant and anticoagulant processes. The waterfall/cascade models of coagulation are useful for understanding several essential steps of coagulation in vitro. These have resulted in the creation of the plasma-based tests used commonly and the ability to identify deficiencies in the extrinsic, intrinsic, and common pathways of coagulation. The model was also essential in elucidating the role of several of the inhibitors of coagulation and is currently used to demonstrate coagulation as it occurs in plasma in a static environment that is devoid of endothelial interactions. The intrinsic pathway originally described by these models does not appear to be essential for in vivo hemostasis but may play a role in pathologic thrombosis. The waterfall/cascade models' lack of cellular elements sets the stage for the cell-based model of coagulation. The cell-based model of blood coagulation, which includes the varied, complicated network of factors necessary for appropriate in vivo coagulation to occur, was the next step in the evolution of our understanding of coagulation. Recently, researchers have focused on real-time, in vivo models of hemostasis and this research reveals unexpected phenomena. Copyright © 2012 Elsevier Inc. All rights reserved.

The optimization of essential oils supercritical CO2 extraction from Lavandula hybrida through static-dynamic steps procedure and semi-continuous technique using response surface method

PubMed Central

Kamali, Hossein; Aminimoghadamfarouj, Noushin; Golmakani, Ebrahim; Nematollahi, Alireza

2015-01-01

Aim: The aim of this study was to examine and evaluate crucial variables in essential oils extraction process from Lavandula hybrida through static-dynamic and semi-continuous techniques using response surface method. Materials and Methods: Essential oil components were extracted from Lavandula hybrida (Lavandin) flowers using supercritical carbon dioxide via static-dynamic steps (SDS) procedure, and semi-continuous (SC) technique. Results: Using response surface method the optimum extraction yield (4.768%) was obtained via SDS at 108.7 bar, 48.5°C, 120 min (static: 8×15), 24 min (dynamic: 8×3 min) in contrast to the 4.620% extraction yield for the SC at 111.6 bar, 49.2°C, 14 min (static), 121.1 min (dynamic). Conclusion: The results indicated that a substantial reduction (81.56%) solvent usage (kg CO2/g oil) is observed in the SDS method versus the conventional SC method. PMID:25598636

The transcriptome landscape of early maize meiosis

USDA-ARS?s Scientific Manuscript database

Meiosis, particularly meiotic recombination, is a major factor affecting yield and breeding of plants. To gain insight into the transcriptome landscape during early initiation steps of meiotic recombination, we profiled early prophase I meiocytes from maize using RNA-seq. Our analyses of genes prefe...

Early Infantile Autism and Autistic Psychopathy

ERIC Educational Resources Information Center

Van Krevelen, D. Arn

1971-01-01

The paper tries to assign to autistic psychopathy a definite place in psychiatric nosology and to delineate sharply the differences between the essential characteristics of it and of early infantile autism. (Author)

Subsurface oxide plays a critical role in CO2 activation by Cu(111) surfaces to form chemisorbed CO2, the first step in reduction of CO2.

PubMed

Favaro, Marco; Xiao, Hai; Cheng, Tao; Goddard, William A; Yano, Junko; Crumlin, Ethan J

2017-06-27

A national priority is to convert CO 2 into high-value chemical products such as liquid fuels. Because current electrocatalysts are not adequate, we aim to discover new catalysts by obtaining a detailed understanding of the initial steps of CO 2 electroreduction on copper surfaces, the best current catalysts. Using ambient pressure X-ray photoelectron spectroscopy interpreted with quantum mechanical prediction of the structures and free energies, we show that the presence of a thin suboxide structure below the copper surface is essential to bind the CO 2 in the physisorbed configuration at 298 K, and we show that this suboxide is essential for converting to the chemisorbed CO 2 in the presence of water as the first step toward CO 2 reduction products such as formate and CO. This optimum suboxide leads to both neutral and charged Cu surface sites, providing fresh insights into how to design improved carbon dioxide reduction catalysts.

Subsurface oxide plays a critical role in CO2 activation by Cu(111) surfaces to form chemisorbed CO2, the first step in reduction of CO2

PubMed Central

Favaro, Marco; Yano, Junko; Crumlin, Ethan J.

2017-01-01

A national priority is to convert CO2 into high-value chemical products such as liquid fuels. Because current electrocatalysts are not adequate, we aim to discover new catalysts by obtaining a detailed understanding of the initial steps of CO2 electroreduction on copper surfaces, the best current catalysts. Using ambient pressure X-ray photoelectron spectroscopy interpreted with quantum mechanical prediction of the structures and free energies, we show that the presence of a thin suboxide structure below the copper surface is essential to bind the CO2 in the physisorbed configuration at 298 K, and we show that this suboxide is essential for converting to the chemisorbed CO2 in the presence of water as the first step toward CO2 reduction products such as formate and CO. This optimum suboxide leads to both neutral and charged Cu surface sites, providing fresh insights into how to design improved carbon dioxide reduction catalysts. PMID:28607092

Titanium diboride-chromium diboride-yttrium titanium oxide ceramic composition and a process for making the same

DOEpatents

Holcombe, Cressie E.; Dykes, Norman L.

1991-01-01

A ceramic composition is described. The ceramic composition consists essentially of from about 84 to 96 w/o titanium diboride, from about 1 to 9 w/o chromium diboride, and from about 3 to about 15 w/o yttrium-titanium-oxide. A method of making the ceramic composition is also described. The method of making the ceramic composition comprises the following steps: Step 1--A consolidated body containing stoichiometric quantities of titanium diboride and chromium diboride is provided. Step 2--The consolidated body is enclosed in and in contact with a thermally insulated package of yttria granules having a thickness of at least 0.5 inches. Step 3--The consolidated body enclosed in the thermally insulated package of yttria granules is heated in a microwave oven with microwave energy to a temperature equal to or greater than 1,900 degrees centigrade to sinter and uniformly disperse yttria particles having a size range from about 1 to about 12 microns throughout the consolidated body forming a densified body consisting essentially of titanium diboride, chromium diboride, and yttrium-titanium-oxide. The resulting densified body has enhanced fracture toughness and hardness.

Process for making a titanium diboride-chromium diboride-yttrium titanium oxide ceramic composition

DOEpatents

Holcombe, Cressie E.; Dykes, Norman L.

1992-01-01

A ceramic composition composition is described. The ceramic composition consists essentially of from about 84 to 96 w/o titanium diboride, from about 1 to 9 w/o chromium diboride, and from about 3 to aobut 15 w/o yttrium-titanium-oxide. A method of making the ceramic composition is also described. The method of making the ceramic composition comprises the following steps: Step 1--A consolidated body containing stoichiometric quantities of titanium diboride and chromium diboride is provided. Step 2--The consolidated body is enclosed in and in contact with a thermally insulated package of yttria granules having a thickness of at least 0.5 inches. Step 3--The consolidated body enclosed in the thermally insulated package of yttria granules is heated in a microwave oven with microwave energy to a temperature equal to or greater than 1,900 degrees centigrade to sinter and uniformly disperse yttria particles having a size range from about 1 to about 12 microns throughout the consolidated body forming a densified body consisting essentially of titanium diboride, chromium diboride, and yttrium-titanium-oxide. The resulting densified body has enhanced fracture toughness and hardness.

Process for making a titanium diboride-chromium diboride-yttrium titanium oxide ceramic composition

DOEpatents

Holcombe, C.E.; Dykes, N.L.

1992-04-28

A ceramic composition is described. The ceramic composition consists essentially of from about 84 to 96 w/o titanium diboride, from about 1 to 9 w/o chromium diboride, and from about 3 to about 15 w/o yttrium-titanium-oxide. A method of making the ceramic composition is also described. The method of making the ceramic composition comprises the following steps: Step 1--A consolidated body containing stoichiometric quantities of titanium diboride and chromium diboride is provided. Step 2--The consolidated body is enclosed in and in contact with a thermally insulated package of yttria granules having a thickness of at least 0.5 inches. Step 3--The consolidated body enclosed in the thermally insulated package of yttria granules is heated in a microwave oven with microwave energy to a temperature equal to or greater than 1,900 degrees centigrade to sinter and uniformly disperse yttria particles having a size range from about 1 to about 12 microns throughout the consolidated body forming a densified body consisting essentially of titanium diboride, chromium diboride, and yttrium-titanium-oxide. The resulting densified body has enhanced fracture toughness and hardness. No Drawings

Health Security Preparedness and Industry Trends

PubMed Central

2015-01-01

Given the number and diversity of risks in today's complex society, it is essential to focus on global risks that can be reduced through affordable, feasible approaches. Thus, the risks that should command the greatest focus are emergent infectious diseases. Fortunately, preparing responses to such threats can be entirely agnostic as to source or intent of the threat. This article considers the emergent infectious clinical threats, characterizes the steps that are essential to take to prepare for such threats, and discusses the roles that the biomedical industry should play in both the preparation for and response to such threats. The author assesses the readiness of the industry to play its role and suggests steps to consider to enable a more robust response. PMID:25813972

Health security preparedness and industry trends.

PubMed

Crooke, Stanley T

2015-01-01

Given the number and diversity of risks in today's complex society, it is essential to focus on global risks that can be reduced through affordable, feasible approaches. Thus, the risks that should command the greatest focus are emergent infectious diseases. Fortunately, preparing responses to such threats can be entirely agnostic as to source or intent of the threat. This article considers the emergent infectious clinical threats, characterizes the steps that are essential to take to prepare for such threats, and discusses the roles that the biomedical industry should play in both the preparation for and response to such threats. The author assesses the readiness of the industry to play its role and suggests steps to consider to enable a more robust response.

Supporting Early Learning Act

THOMAS, 113th Congress

Rep. Himes, James A. [D-CT-4

2014-02-03

House - 06/13/2014 Referred to the Subcommittee on Early Childhood, Elementary, and Secondary Education. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

Early Learning Innovation Act

THOMAS, 111th Congress

Rep. Himes, James A. [D-CT-4

2009-10-29

House - 12/08/2009 Referred to the Subcommittee on Early Childhood, Elementary, and Secondary Education. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

Early Learning Alignment Act

THOMAS, 111th Congress

Rep. Altmire, Jason [D-PA-4

2010-09-29

House - 11/18/2010 Referred to the Subcommittee on Early Childhood, Elementary, and Secondary Education. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

Early Head Start Relationships: Association with Program Outcomes

ERIC Educational Resources Information Center

Elicker, James; Wen, Xiaoli; Kwon, Kyong-Ah; Sprague, Jill B.

2013-01-01

Research Findings: Interpersonal relationships among staff caregivers, parents, and children have been recommended as essential aspects of early childhood intervention. This study explored the associations of these relationships with program outcomes for children and parents in 3 Early Head Start programs. A total of 71 children (8-35 months,…

Identifying At-Risk Students for Early Reading Intervention: Challenges and Possible Solutions

ERIC Educational Resources Information Center

McAlenney, Athena Lentini; Coyne, Michael D.

2011-01-01

Accurate identification of at-risk kindergarten and 1st-grade students through early reading screening is an essential element of responsiveness to intervention models of reading instruction. The authors consider predictive validity and classification accuracy of early reading screening assessments with attention to sensitivity and specificity.…

Starting Strong: Evidence-­Based Early Literacy Practices

ERIC Educational Resources Information Center

Blamey, Katrin; Beauchat, Katherine

2016-01-01

Four evidence-based instructional approaches create an essential resource for any early literacy teacher or coach. Improve your teaching practices in all areas of early literacy. Use four proven instructional approaches--standards based, evidenced based, assessment based, and student based--to improve their teaching practice in all areas of early…

Effort and Potential Efficiencies for Aquatic Non-native Species Early Detection

EPA Science Inventory

This manuscript is based on the early aquatic non-native species detection research in the Duluth-Superior harbor. The problem of early detection is essentially that of a "needle in a haystack" - to detect a newly arrived and presumably rare non-native species with a high probabi...

Writing Research Articles for Publication in Early Childhood Education

ERIC Educational Resources Information Center

Saracho, Olivia N.

2013-01-01

Published research results in early childhood education contribute to the field's knowledge, theory, and practice. They also guide future early childhood education research studies. The publication of research articles is an essential requirement for academics. For some researchers, however, writing may be a difficult activity, particularly the…

The influence of EDDS on the uptake of heavy metals in hydroponically grown sunflowers.

PubMed

Tandy, Susan; Schulin, Rainer; Nowack, Bernd

2006-03-01

Phytoextraction is an environmentally friendly in situ technique for cleaning up metal contaminated land. Unfortunately, efficient metal uptake by remediation plants is often limited by low phytoavailability of the targeted metals. Chelant assisted phytoextraction has been proposed to improve the efficiency of phytoextraction. Phytoremediation involves several subsequent steps: transfer of metals from the bulk soil to the root surfaces, uptake into the roots and translocation to the shoots. Nutrient solution experiments address the latter two steps. In this context we investigated the influence of the biodegradable chelating agent SS-EDDS on uptake of essential (Cu and Zn) and non-essential (Pb) metals by sunflowers from nutrient solution. EDDS was detected in shoots and xylem sap for the first time, proving that it is taken up into the above ground biomass of plants. The essential metals Cu and Zn were decreased in shoots in the presence of EDDS whereas uptake of the non-essential Pb was enhanced. We suggest that in the presence of EDDS all three metals were taken up by the non-selective apoplastic pathway as the EDDS complexes, whereas in the absence of EDDS essential metal uptake was primarily selective along the symplastic pathway. This shows that synthetic chelating agents do not necessarily increase uptake of heavy metals, when soluble concentrations are equal in the presence and absence of chelates.

Rural Early Education Access Act

THOMAS, 111th Congress

Rep. Hare, Phil [D-IL-17

2009-03-26

House - 05/14/2009 Referred to the Subcommittee on Early Childhood, Elementary, and Secondary Education. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

Starting Early Starting Right Act

THOMAS, 111th Congress

Rep. Baldwin, Tammy [D-WI-2

2009-12-16

House - 02/23/2010 Referred to the Subcommittee on Early Childhood, Elementary, and Secondary Education. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

Does Attendance in Early Education Predict Attendance in Elementary School? An Analysis of DCPS's Early Education Program. Research Report

ERIC Educational Resources Information Center

Dubay, Lisa; Holla, Nikhil

2016-01-01

Enrollment in early childhood education programs can be an important stepping stone to higher educational achievement, particularly for low-income children. However, children cannot succeed in these programs unless they are present. The Early Childhood Education Division (ECED) in the District of Columbia Public Schools (DCPS) has identified…

Vietnamese Textual Methodologies: A Comparison of Australian with Swedish and New Zealand Early Childhood Visual Literacy Contexts

ERIC Educational Resources Information Center

Gilmore, Gwen; Truong, Thi My Dung; Reilly, Michelle

2016-01-01

For preservice teachers in early childhood education, having a rich exposure to multiple forms of literacy in diverse communities is an essential dimension of their teacher education. In this study, 10 Australian preservice early childhood education students, in the first year of their course, visit two early childhood settings in a large city in…

Defining Quality in Visual Art Education for Young Children: Building on the Position Statement of the Early Childhood Art Educators

ERIC Educational Resources Information Center

McClure, Marissa; Tarr, Patricia; Thompson, Christine Marmé; Eckhoff, Angela

2017-01-01

This article reflects the collective voices of four early childhood visual arts educators, each of whom is a member of the Early Childhood Art Educators (ECAE) Issues Group of the National Arts Educators Association. The authors frame the article around the ECAE position statement, "Art: Essential for Early Learning" (2016), which…

Reliability and Structural Validity of The Teacher Rating Scales of Early Academic Competence

ERIC Educational Resources Information Center

Reid, Erin E.; Diperna, James C.; Missall, Kristen; Volpe, Robert J.

2014-01-01

Currently, there are few strengths-based preschool rating scales that sample a wide array of behaviors believed to be essential for early academic success. The purpose of this study was to assess the factor structure of a new measure of early academic competence for at-risk preschool populations. The Teacher Rating Scales of Early Academic…

Entry Mode–Dependent Function of an Indole Glucosinolate Pathway in Arabidopsis for Nonhost Resistance against Anthracnose Pathogens[W

PubMed Central

Hiruma, Kei; Onozawa-Komori, Mariko; Takahashi, Fumika; Asakura, Makoto; Bednarek, Paweł; Okuno, Tetsuro; Schulze-Lefert, Paul; Takano, Yoshitaka

2010-01-01

When faced with nonadapted fungal pathogens, Arabidopsis thaliana mounts nonhost resistance responses, which typically result in the termination of early pathogenesis steps. We report that nonadapted anthracnose fungi engage two alternative entry modes during pathogenesis on leaves: turgor-mediated invasion beneath melanized appressoria, and a previously undiscovered hyphal tip–based entry (HTE) that is independent of appressorium formation. The frequency of HTE is positively regulated by carbohydrate nutrients and appears to be subject to constitutive inhibition by the fungal mitogen-activated protein kinase (MAPK) cascade of MAPK ESSENTIAL FOR APPRESSORIUM FORMATION1. The same MAPK cascade is essential for appressorium formation. Unexpectedly, the Arabidopsis indole glucosinolate pathway restricts entry of the nonadapted anthracnose fungi only when these pathogens employ HTE. Arabidopsis mutants defective in indole glucosinolate biosynthesis or metabolism support the initiation of postinvasion growth of nonadapted Colletotrichum gloeosporioides and Colletotrichum orbiculare. However, genetic disruption of Colletotrichum appressorium formation does not permit HTE on host plants. Thus, Colletotrichum appressoria play a critical role in the suppression of preinvasion plant defenses, in addition to their previously described role in turgor-mediated plant cell invasion. We also show that HTE is the predominant morphogenetic response of Colletotrichum at wound sites. This implies the existence of a fungal sensing system to trigger appropriate morphogenetic responses during pathogenesis at wound sites and on intact leaf tissue. PMID:20605856

Strain Mediated Adaptation Is Key for Myosin Mechanochemistry: Discovering General Rules for Motor Activity.

PubMed

Jana, Biman; Onuchic, José N

2016-08-01

A structure-based model of myosin motor is built in the same spirit of our early work for kinesin-1 and Ncd towards physical understanding of its mechanochemical cycle. We find a structural adaptation of the motor head domain in post-powerstroke state that signals faster ADP release from it compared to the same from the motor head in the pre-powerstroke state. For dimeric myosin, an additional forward strain on the trailing head, originating from the postponed powerstroke state of the leading head in the waiting state of myosin, further increases the rate of ADP release. This coordination between the two heads is the essence of the processivity of the cycle. Our model provides a structural description of the powerstroke step of the cycle as an allosteric transition of the converter domain in response to the Pi release. Additionally, the variation in structural elements peripheral to catalytic motor domain is the deciding factor behind diverse directionalities of myosin motors (myosin V & VI). Finally, we observe that there are general rules for functional molecular motors across the different families. Allosteric structural adaptation of the catalytic motor head in different nucleotide states is crucial for mechanochemistry. Strain-mediated coordination between motor heads is essential for processivity and the variation of peripheral structural elements is essential for their diverse functionalities.

Strain Mediated Adaptation Is Key for Myosin Mechanochemistry: Discovering General Rules for Motor Activity

PubMed Central

Jana, Biman; Onuchic, José N.

2016-01-01

A structure-based model of myosin motor is built in the same spirit of our early work for kinesin-1 and Ncd towards physical understanding of its mechanochemical cycle. We find a structural adaptation of the motor head domain in post-powerstroke state that signals faster ADP release from it compared to the same from the motor head in the pre-powerstroke state. For dimeric myosin, an additional forward strain on the trailing head, originating from the postponed powerstroke state of the leading head in the waiting state of myosin, further increases the rate of ADP release. This coordination between the two heads is the essence of the processivity of the cycle. Our model provides a structural description of the powerstroke step of the cycle as an allosteric transition of the converter domain in response to the Pi release. Additionally, the variation in structural elements peripheral to catalytic motor domain is the deciding factor behind diverse directionalities of myosin motors (myosin V & VI). Finally, we observe that there are general rules for functional molecular motors across the different families. Allosteric structural adaptation of the catalytic motor head in different nucleotide states is crucial for mechanochemistry. Strain-mediated coordination between motor heads is essential for processivity and the variation of peripheral structural elements is essential for their diverse functionalities. PMID:27494025

Antiviral Type I and Type III Interferon Responses in the Central Nervous System

PubMed Central

Sorgeloos, Frédéric; Kreit, Marguerite; Hermant, Pascale; Lardinois, Cécile; Michiels, Thomas

2013-01-01

The central nervous system (CNS) harbors highly differentiated cells, such as neurons that are essential to coordinate the functions of complex organisms. This organ is partly protected by the blood-brain barrier (BBB) from toxic substances and pathogens carried in the bloodstream. Yet, neurotropic viruses can reach the CNS either by crossing the BBB after viremia, or by exploiting motile infected cells as Trojan horses, or by using axonal transport. Type I and type III interferons (IFNs) are cytokines that are critical to control early steps of viral infections. Deficiencies in the IFN pathway have been associated with fatal viral encephalitis both in humans and mice. Therefore, the IFN system provides an essential protection of the CNS against viral infections. Yet, basal activity of the IFN system appears to be low within the CNS, likely owing to the toxicity of IFN to this organ. Moreover, after viral infection, neurons and oligodendrocytes were reported to be relatively poor IFN producers and appear to keep some susceptibility to neurotropic viruses, even in the presence of IFN. This review addresses some trends and recent developments concerning the role of type I and type III IFNs in: i) preventing neuroinvasion and infection of CNS cells; ii) the identity of IFN-producing cells in the CNS; iii) the antiviral activity of ISGs; and iv) the activity of viral proteins of neurotropic viruses that target the IFN pathway. PMID:23503326

Antiviral type I and type III interferon responses in the central nervous system.

PubMed

Sorgeloos, Frédéric; Kreit, Marguerite; Hermant, Pascale; Lardinois, Cécile; Michiels, Thomas

2013-03-15

The central nervous system (CNS) harbors highly differentiated cells, such as neurons that are essential to coordinate the functions of complex organisms. This organ is partly protected by the blood-brain barrier (BBB) from toxic substances and pathogens carried in the bloodstream. Yet, neurotropic viruses can reach the CNS either by crossing the BBB after viremia, or by exploiting motile infected cells as Trojan horses, or by using axonal transport. Type I and type III interferons (IFNs) are cytokines that are critical to control early steps of viral infections. Deficiencies in the IFN pathway have been associated with fatal viral encephalitis both in humans and mice. Therefore, the IFN system provides an essential protection of the CNS against viral infections. Yet, basal activity of the IFN system appears to be low within the CNS, likely owing to the toxicity of IFN to this organ. Moreover, after viral infection, neurons and oligodendrocytes were reported to be relatively poor IFN producers and appear to keep some susceptibility to neurotropic viruses, even in the presence of IFN. This review addresses some trends and recent developments concerning the role of type I and type III IFNs in: i) preventing neuroinvasion and infection of CNS cells; ii) the identity of IFN-producing cells in the CNS; iii) the antiviral activity of ISGs; and iv) the activity of viral proteins of neurotropic viruses that target the IFN pathway.

Control of the proportion of inner cells by asymmetric divisions and the ensuing resilience of cloned rabbit embryos

PubMed Central

Duranthon, Véronique

2018-01-01

ABSTRACT Mammalian embryo cloning by nuclear transfer has a low success rate. This is hypothesized to correlate with a high variability of early developmental steps that segregate outer cells, which are fated to extra-embryonic tissues, from inner cells, which give rise to the embryo proper. Exploring the cell lineage of wild-type embryos and clones, imaged in toto until hatching, highlights the respective contributions of cell proliferation, death and asymmetric divisions to phenotypic variability. Preferential cell death of inner cells in clones, probably pertaining to the epigenetic plasticity of the transferred nucleus, is identified as a major difference with effects on the proportion of inner cell. In wild type and clones, similar patterns of outer cell asymmetric divisions are shown to be essential to the robust proportion of inner cells observed in wild type. Asymmetric inner cell division, which is not described in mice, is identified as a regulator of the proportion of inner cells and likely gives rise to resilient clones. PMID:29567671

Birth order dependent growth cone segregation determines synaptic layer identity in the Drosophila visual system.

PubMed

Kulkarni, Abhishek; Ertekin, Deniz; Lee, Chi-Hon; Hummel, Thomas

2016-03-17

The precise recognition of appropriate synaptic partner neurons is a critical step during neural circuit assembly. However, little is known about the developmental context in which recognition specificity is important to establish synaptic contacts. We show that in the Drosophila visual system, sequential segregation of photoreceptor afferents, reflecting their birth order, lead to differential positioning of their growth cones in the early target region. By combining loss- and gain-of-function analyses we demonstrate that relative differences in the expression of the transcription factor Sequoia regulate R cell growth cone segregation. This initial growth cone positioning is consolidated via cell-adhesion molecule Capricious in R8 axons. Further, we show that the initial growth cone positioning determines synaptic layer selection through proximity-based axon-target interactions. Taken together, we demonstrate that birth order dependent pre-patterning of afferent growth cones is an essential pre-requisite for the identification of synaptic partner neurons during visual map formation in Drosophila.

ESA multibody simulator for spacecrafts' ascent and landing in a microgravity environment

NASA Astrophysics Data System (ADS)

Toso, Mario; Pennestrì, Ettore; Rossi, Valerio

2015-09-01

The investigation of planets, moons and small bodies, including comets and asteroids can contribute substantially to our understanding of the formation and history of the solar system. In situ observations by landers play an important role in this field: for example, the Rosetta Lander Philae has been the first spacecraft to accomplish a soft touchdown on a comet. Since the last decade, the urgency to anticipate hardware performance and correlate testing results with mathematical models is generating the trend for more extensively applying multibody approach in supporting the design and verification of complex aerospace systems, from the early phases of the project. Some of the essential multibody technologies assisting the analysis of this class of problems consist of a reliable attitude control algorithm, a variable-step and variable-order numerical integrator and a consistent contact-friction formulation. This paper illustrates the particular implementation of these crucial features in the European Space Agency's multibody software DCAP and shows a direct application to a feasibility case study.

Optimal causal filtering for 1 /fα-type noise in single-electrode EEG signals.

PubMed

Paris, Alan; Atia, George; Vosoughi, Azadeh; Berman, Stephen A

2016-08-01

Understanding the mode of generation and the statistical structure of neurological noise is one of the central problems of biomedical signal processing. We have developed a broad class of abstract biological noise sources we call hidden simplicial tissues. In the simplest cases, such tissue emits what we have named generalized van der Ziel-McWhorter (GVZM) noise which has a roughly 1/fα spectral roll-off. Our previous work focused on the statistical structure of GVZM frequency spectra. However, causality of processing operations (i.e., dependence only on the past) is an essential requirement for real-time applications to seizure detection and brain-computer interfacing. In this paper we outline the theoretical background for optimal causal time-domain filtering of deterministic signals embedded in GVZM noise. We present some of our early findings concerning the optimal filtering of EEG signals for the detection of steady-state visual evoked potential (SSVEP) responses and indicate the next steps in our ongoing research.

Models of protocellular structures, functions and evolution

NASA Technical Reports Server (NTRS)

Pohorille, Andrew; New, Michael H.; DeVincenzi, Donald L. (Technical Monitor)

2000-01-01

The central step in the origin of life was the emergence of organized structures from organic molecules available on the early earth. These predecessors to modern cells, called 'proto-cells,' were simple, membrane bounded structures able to maintain themselves, grow, divide, and evolve. Since there is no fossil record of these earliest of life forms, it is a scientific challenge to discover plausible mechanisms for how these entities formed and functioned. To meet this challenge, it is essential to create laboratory models of protocells that capture the main attributes associated with living systems, while remaining consistent with known, or inferred, protobiological conditions. This report provides an overview of a project which has focused on protocellular metabolism and the coupling of metabolism to energy transduction. We have assumed that the emergence of systems endowed with genomes and capable of Darwinian evolution was preceded by a pre-genomic phase, in which protocells functioned and evolved using mostly proteins, without self-replicating nucleic acids such as RNA.

Monitoring biological diversity: strategies, tools, limitations, and challenges

USGS Publications Warehouse

Beever, E.A.

2006-01-01

Monitoring is an assessment of the spatial and temporal variability in one or more ecosystem properties, and is an essential component of adaptive management. Monitoring can help determine whether mandated environmental standards are being met and can provide an early-warning system of ecological change. Development of a strategy for monitoring biological diversity will likely be most successful when based upon clearly articulated goals and objectives and may be enhanced by including several key steps in the process. Ideally, monitoring of biological diversity will measure not only composition, but also structure and function at the spatial and temporal scales of interest. Although biodiversity monitoring has several key limitations as well as numerous theoretical and practical challenges, many tools and strategies are available to address or overcome such challenges; I summarize several of these. Due to the diversity of spatio-temporal scales and comprehensiveness encompassed by existing definitions of biological diversity, an effective monitoring design will reflect the desired sampling domain of interest and its key stressors, available funding, legal requirements, and organizational goals.

Tau and spectraplakins promote synapse formation and maintenance through Jun kinase and neuronal trafficking

PubMed Central

Voelzmann, Andre; Okenve-Ramos, Pilar; Qu, Yue; Chojnowska-Monga, Monika; del Caño-Espinel, Manuela; Prokop, Andreas; Sanchez-Soriano, Natalia

2016-01-01

The mechanisms regulating synapse numbers during development and ageing are essential for normal brain function and closely linked to brain disorders including dementias. Using Drosophila, we demonstrate roles of the microtubule-associated protein Tau in regulating synapse numbers, thus unravelling an important cellular requirement of normal Tau. In this context, we find that Tau displays a strong functional overlap with microtubule-binding spectraplakins, establishing new links between two different neurodegenerative factors. Tau and the spectraplakin Short Stop act upstream of a three-step regulatory cascade ensuring adequate delivery of synaptic proteins. This cascade involves microtubule stability as the initial trigger, JNK signalling as the central mediator, and kinesin-3 mediated axonal transport as the key effector. This cascade acts during development (synapse formation) and ageing (synapse maintenance) alike. Therefore, our findings suggest novel explanations for intellectual disability in Tau deficient individuals, as well as early synapse loss in dementias including Alzheimer’s disease. DOI: http://dx.doi.org/10.7554/eLife.14694.001 PMID:27501441

Evaluation of common elbow pathologies: a focus on physical examination.

PubMed

Laratta, Joseph; Caldwell, Jon-Michael; Lombardi, Joseph; Levine, William; Ahmad, Christopher

2017-05-01

Elbow tendinopathy accounts for the majority of elbow pathology in patients presenting to upper extremity and sports medicine surgeons. With increased participation in overhead sports in an aging population, the incidence of elbow injuries has risen. A comprehensive knowledge of elbow anatomy and biomechanical function of the elbow complex is prerequisite in the assessment of patients with elbow injuries; however, a thorough understanding of alternative and confounding pathologies is essential for accurate diagnosis. Because tendinopathy, tendonitis, and tendon tears have an anatomic basis for their pathology, a targeted history and meticulous physical examination often yields an accurate clinical diagnosis. The importance of physical examination and provocative examination maneuvers must be stressed in a technologically advanced era where clinical diagnosis is too commonly attained solely by advanced imaging modalities. A revived dedication to the physical examination may enhance our ability to correctly diagnose various pathologies about the elbow. Early and accurate clinical diagnosis is the first step in the proper initiation of treatment modalities and improvement in overall patient outcome.

The Arabidopsis mutant cev1 has constitutively active jasmonate and ethylene signal pathways and enhanced resistance to pathogens.

PubMed

Ellis, C; Turner, J G

2001-05-01

Jasmonates (JAs) inhibit plant growth and induce plant defense responses. To define genes in the Arabidopsis JA signal pathway, we screened for mutants with constitutive expression of a luciferase reporter for the JA-responsive promoter from the vegetative storage protein gene VSP1. One mutant, named constitutive expression of VSP1 (cev1), produced plants that were smaller than wild type, had stunted roots with long root hairs, accumulated anthocyanin, had constitutive expression of the defense-related genes VSP1, VSP2, Thi2.1, PDF1.2, and CHI-B, and had enhanced resistance to powdery mildew diseases. Genetic evidence indicated that the cev1 phenotype required both COI1, an essential component of the JA signal pathway, and ETR1, which encodes the ethylene receptor. We conclude that cev1 stimulates both the JA and the ethylene signal pathways and that CEV1 regulates an early step in an Arabidopsis defense pathway.

The Arabidopsis Mutant cev1 Has Constitutively Active Jasmonate and Ethylene Signal Pathways and Enhanced Resistance to Pathogens

PubMed Central

Ellis, Christine; Turner, John G.

2001-01-01

Jasmonates (JAs) inhibit plant growth and induce plant defense responses. To define genes in the Arabidopsis JA signal pathway, we screened for mutants with constitutive expression of a luciferase reporter for the JA-responsive promoter from the vegetative storage protein gene VSP1. One mutant, named constitutive expression of VSP1 (cev1), produced plants that were smaller than wild type, had stunted roots with long root hairs, accumulated anthocyanin, had constitutive expression of the defense-related genes VSP1, VSP2, Thi2.1, PDF1.2, and CHI-B, and had enhanced resistance to powdery mildew diseases. Genetic evidence indicated that the cev1 phenotype required both COI1, an essential component of the JA signal pathway, and ETR1, which encodes the ethylene receptor. We conclude that cev1 stimulates both the JA and the ethylene signal pathways and that CEV1 regulates an early step in an Arabidopsis defense pathway. PMID:11340179

Elucidating steroid alkaloid biosynthesis in Veratrum californicum: production of verazine in Sf9 cells

PubMed Central

Augustin, Megan M.; Ruzicka, Dan R.; Shukla, Ashutosh K.; Augustin, Jörg M.; Starks, Courtney M.; O’Neil-Johnson, Mark; McKain, Michael R.; Evans, Bradley S.; Barrett, Matt D.; Smithson, Ann; Wong, Gane Ka-Shu; Deyholos, Michael K.; Edger, Patrick P.; Pires, J. Chris; Leebens-Mack, James H.; Mann, David A.; Kutchan, Toni M.

2015-01-01

Summary Steroid alkaloids have been shown to elicit a wide range of pharmacological effects that include anticancer and antifungal activities. Understanding the biosynthesis of these molecules is essential to bioengineering for sustainable production. Herein, we investigate the biosynthetic pathway to cyclopamine, a steroid alkaloid that shows promising antineoplastic activities. Supply of cyclopamine is limited, as the current source is solely derived from wild collection of the plant Veratrum californicum. To elucidate the early stages of the pathway to cyclopamine, we interrogated a V. californicum RNA-seq dataset using the cyclopamine accumulation profile as a predefined model for gene expression with the pattern-matching algorithm Haystack. Refactoring candidate genes in Sf9 insect cells led to discovery of four enzymes that catalyze the first six steps in steroid alkaloid biosynthesis to produce verazine, a predicted precursor to cyclopamine. Three of the enzymes are cytochromes P450 while the fourth is a γ-aminobutyrate transaminase; together they produce verazine from cholesterol. PMID:25939370

The diagnosis of plant pathogenic bacteria: a state of art.

PubMed

Scala, Valeria; Pucci, Nicoletta; Loreti, Stefania

2018-03-01

Plant protection plays an important role in agriculture for the food quality and quantity. The diagnosis of plant diseases and the identification of the pathogens are essential prerequisites for their understanding and control. Among the plant pests, the bacterial pathogens have devastating effects on plant productivity and yield. Different techniques (microscopy, serology, biochemical, physiological, molecular tools and culture propagation) are currently used to detect and identify bacterial pathogens. Detection and identification are critical steps for the appropriate application of phytosanitary measures. The "harmonization of phytosanitary regulations and all other areas of official plant protection action" mean the good practices for plant protection and plant material certification. The prevention of diseases progression and spread by early detection are a valuable strategy for proper pest management and disease control. For this purpose, innovative methods aim achieving results within a shorter time and higher performance, to provide rapidly, accurately and reliably diagnosis. In this review, we focus on the techniques for plant bacterial diagnosis and on the regulations for harmonizing plant protection issue.

Exhaled molecular profiles in the assessment of cystic fibrosis and primary ciliary dyskinesia.

PubMed

Paff, T; van der Schee, M P; Daniels, J M A; Pals, G; Postmus, P E; Sterk, P J; Haarman, E G

2013-09-01

Early diagnosis and monitoring of disease activity are essential in cystic fibrosis (CF) and primary ciliary dyskinesia (PCD). We aimed to establish exhaled molecular profiles as the first step in assessing the potential of breath analysis. Exhaled breath was analyzed by electronic nose in 25 children with CF, 25 with PCD and 23 controls. Principle component reduction and canonical discriminant analysis were used to construct internally cross-validated ROC curves. CF and PCD patients had significantly different breath profiles when compared to healthy controls (CF: sensitivity 84%, specificity 65%; PCD: sensitivity 88%, specificity 52%) and from each other (sensitivity 84%, specificity 60%). Patients with and without exacerbations had significantly different breath profiles (CF: sensitivity 89%, specificity 56%; PCD: sensitivity 100%, specificity 90%). Exhaled molecular profiles significantly differ between patients with CF, PCD and controls. The eNose may have potential in disease monitoring based on the influence of exacerbations on the VOC-profile. Copyright © 2012 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

African swine fever virus infects macrophages, the natural host cells, via clathrin- and cholesterol-dependent endocytosis.

PubMed

Galindo, Inmaculada; Cuesta-Geijo, Miguel Angel; Hlavova, Karolina; Muñoz-Moreno, Raquel; Barrado-Gil, Lucía; Dominguez, Javier; Alonso, Covadonga

2015-03-16

The main cellular target for African swine fever virus (ASFV) is the porcine macrophage. However, existing data about the early phases of infection were previously characterized in non-leukocyte cells such as Vero cells. Here, we report that ASFV enters the natural host cell using dynamin-dependent and clathrin-mediated endocytosis. This pathway is strongly pH-dependent during the first steps of infection in porcine macrophages. We investigated the effect of drugs inhibiting several endocytic pathways in macrophages and compared ASFV with vaccinia virus (VV), which apparently involves different entry pathways. The presence of cholesterol in cellular membranes was found to be essential for a productive ASFV infection while actin-dependent endocytosis and the participation of phosphoinositide-3-kinase (PI3K) activity were other cellular factors required in the process of viral entry. These findings improved our understanding of the ASFV interactions with macrophages that allow for successful viral replication. Copyright © 2015 Elsevier B.V. All rights reserved.

More than just sugar: allocation of nectar amino acids and fatty acids in a Lepidopteran.

PubMed

Levin, Eran; McCue, Marshall D; Davidowitz, Goggy

2017-02-08

The ability to allocate resources, even when limited, is essential for survival and fitness. We examine how nutrients that occur in minute amounts are allocated among reproductive, somatic, and metabolic demands. In addition to sugar, flower nectars contain two macronutrients-amino acids and fatty acids. We created artificial nectars spiked with 13 C-labelled amino acids and fatty acids and fed these to adult moths (Manduca sexta: Sphingidae) to understand how they allocate these nutrients among competing sinks (reproduction, somatic tissue, and metabolic fuel). We found that both essential and non-essential amino acids were allocated to eggs and flight muscles and were still detectable in early-instar larvae. Parental-derived essential amino acids were more conserved in the early-instars than non-essential amino acids. All amino acids were used as metabolic fuel, but the non-essential amino acids were oxidized at higher rates than essential amino acids. Surprisingly, the nectar fatty acids were not vertically transferred to offspring, but were readily used as a metabolic fuel by the moth, minimizing losses of endogenous nutrient stores. We conclude that the non-carbohydrate components of nectar may play important roles in both reproductive success and survival of these nectar-feeding animals. © 2017 The Author(s).

More than just sugar: allocation of nectar amino acids and fatty acids in a Lepidopteran

PubMed Central

McCue, Marshall D.; Davidowitz, Goggy

2017-01-01

The ability to allocate resources, even when limited, is essential for survival and fitness. We examine how nutrients that occur in minute amounts are allocated among reproductive, somatic, and metabolic demands. In addition to sugar, flower nectars contain two macronutrients—amino acids and fatty acids. We created artificial nectars spiked with 13C-labelled amino acids and fatty acids and fed these to adult moths (Manduca sexta: Sphingidae) to understand how they allocate these nutrients among competing sinks (reproduction, somatic tissue, and metabolic fuel). We found that both essential and non-essential amino acids were allocated to eggs and flight muscles and were still detectable in early-instar larvae. Parental-derived essential amino acids were more conserved in the early-instars than non-essential amino acids. All amino acids were used as metabolic fuel, but the non-essential amino acids were oxidized at higher rates than essential amino acids. Surprisingly, the nectar fatty acids were not vertically transferred to offspring, but were readily used as a metabolic fuel by the moth, minimizing losses of endogenous nutrient stores. We conclude that the non-carbohydrate components of nectar may play important roles in both reproductive success and survival of these nectar-feeding animals. PMID:28148746

Cross-sectional observational assessment of quality of newborn care immediately after birth in health facilities across six sub-Saharan African countries

PubMed Central

de Graft-Johnson, Joseph; Vesel, Linda; Rosen, Heather E; Rawlins, Barbara; Abwao, Stella; Mazia, Goldy; Bozsa, Robert; Mwebesa, Winifrede; Khadka, Neena; Kamunya, Rosemary; Getachew, Ashebir; Tibaijuka, Gaudiosa; Rakotovao, Jean Pierre; Tekleberhan, Alemnesh

2017-01-01

Objective To present information on the quality of newborn care services and health facility readiness to provide newborn care in 6 African countries, and to advocate for the improvement of providers' essential newborn care knowledge and skills. Design Cross-sectional observational health facility assessment. Setting Ethiopia, Kenya, Madagascar, Mozambique, Rwanda and Tanzania. Participants Health workers in 643 facilities. 1016 health workers were interviewed, and 2377 babies were observed in the facilities surveyed. Main outcome measures Indicators of quality of newborn care included (1) provision of immediate essential newborn care: thermal care, hygienic cord care, and early and exclusive initiation of breast feeding; (2) actual and simulated resuscitation of asphyxiated newborn infants; and (3) knowledge of health workers on essential newborn care, including resuscitation. Results Sterile or clean cord cutting instruments, suction devices, and tables or firm surfaces for resuscitation were commonly available. 80% of newborns were immediately dried after birth and received clean cord care in most of the studied facilities. In all countries assessed, major deficiencies exist for essential newborn care supplies and equipment, as well as for health worker knowledge and performance of key routine newborn care practices, particularly for immediate skin-to-skin contact and breastfeeding initiation. Of newborns who did not cry at birth, 89% either recovered on their own or through active steps taken by the provider through resuscitation with initial stimulation and/or ventilation. 11% of newborns died. Assessment of simulated resuscitation using a NeoNatalie anatomic model showed that less than a third of providers were able to demonstrate ventilation skills correctly. Conclusions The findings shared in this paper call attention to the critical need to improve health facility readiness to provide quality newborn care services and to ensure that service providers have the necessary equipment, supplies, knowledge and skills that are critical to save newborn lives. PMID:28348194

Development and comparative evaluation of SYBR Green I-based one-step real-time RT-PCR assay for detection and quantification of West Nile virus in human patients.

PubMed

Kumar, Jyoti S; Saxena, Divyasha; Parida, Manmohan

2014-01-01

The recent outbreaks of West Nile Virus (WNV) in the Northeastern American continents and other regions of the world have made it essential to develop an efficient protocol for surveillance of WN virus. Nucleic acid based techniques like, RT-PCR have the advantage of sensitivity, specificity and rapidity. A one step single tube Env gene specific real-time RT-PCR was developed for early and reliable clinical diagnosis of WNV infection in clinical samples. The applicability of this assay for clinical diagnosis was validated with 105 suspected acute-phase serum and plasma samples from the recent epidemic of mysterious fever in Tamil Nadu, India in 2009-10. The comparative evaluation revealed the higher sensitivity of real-time RT-PCR assay by picking up 4 additional samples with low copy number of template in comparison to conventional RT-PCR. All the real-time positive samples further confirmed by CDC reported TaqMan real-time RT-PCR and quantitative real-time RT-PCR assays for the simultaneous detection of WNV lineage 1 and 2 strains. The quantitation of the viral load samples was done using a standard curve. These findings demonstrated that the assay has the potential usefulness for clinical diagnosis due to detection and quantification of WNV in acute-phase patient serum samples. Copyright © 2014 Elsevier Ltd. All rights reserved.

The World Database for Pediatric and Congenital Heart Surgery: The Dawn of a New Era of Global Communication and Quality Improvement in Congenital Heart Disease.

PubMed

St Louis, James D; Kurosawa, Hiromi; Jonas, Richard A; Sandoval, Nestor; Cervantes, Jorge; Tchervenkov, Christo I; Jacobs, Jeffery P; Sakamoto, Kisaburo; Stellin, Giovanni; Kirklin, James K

2017-09-01

The World Society for Pediatric and Congenital Heart Surgery was founded with the mission to "promote the highest quality comprehensive cardiac care to all patients with congenital heart disease, from the fetus to the adult, regardless of the patient's economic means, with an emphasis on excellence in teaching, research, and community service." Early on, the Society's members realized that a crucial step in meeting this goal was to establish a global database that would collect vital information, allowing cardiac surgical centers worldwide to benchmark their outcomes and improve the quality of congenital heart disease care. With tireless efforts from all corners of the globe and utilizing the vast experience and invaluable input of multiple international experts, such a platform of global information exchange was created: The World Database for Pediatric and Congenital Heart Disease went live on January 1, 2017. This database has been thoughtfully designed to produce meaningful performance and quality analyses of surgical outcomes extending beyond immediate hospital survival, allowing capture of important morbidities and mortalities for up to 1 year postoperatively. In order to advance the societal mission, this quality improvement program is available free of charge to WSPCHS members. In establishing the World Database, the Society has taken an essential step to further the process of global improvement in care for children with congenital heart disease.

Intravital multiphoton imaging reveals multicellular streaming as a crucial component of in vivo cell migration in human breast tumors

PubMed Central

Patsialou, Antonia; Bravo-Cordero, Jose Javier; Wang, Yarong; Entenberg, David; Liu, Huiping; Clarke, Michael; Condeelis, John S.

2014-01-01

Metastasis is the main cause of death in breast cancer patients. Cell migration is an essential component of almost every step of the metastatic cascade, especially the early step of invasion inside the primary tumor. In this report, we have used intravital multiphoton microscopy to visualize the different migration patterns of human breast tumor cells in live primary tumors. We used xenograft tumors of MDA-MB-231 cells as well as a low passage xenograft tumor from orthotopically injected patient-derived breast tumor cells. Direct visualization of human tumor cells in vivo shows two patterns of high-speed migration inside primary tumors: a. single cells and b. multicellular streams (i.e., cells following each other in a single file but without cohesive cell junctions). Critically, we found that only streaming and not random migration of single cells was significantly correlated with proximity to vessels, with intravasation and with numbers of elevated circulating tumor cells in the bloodstream. Finally, although the two human tumors were derived from diverse genetic backgrounds, we found that their migratory tumor cells exhibited coordinated gene expression changes that led to the same end-phenotype of enhanced migration involving activating actin polymerization and myosin contraction. Our data are the first direct visualization and assessment of in vivo migration within a live patient-derived breast xenograft tumor. PMID:25013744

Effects of 12-week brisk walking training on exercise blood pressure in elderly patients with essential hypertension: a pilot study.

PubMed

He, L I; Wei, Wang Ren; Can, Zhao

2018-01-24

Essential hypertension (EP) is characterized by blood pressure (BP) elevations, which often lead to target organ damage and cardiovascular illness. The following study investigates whether aerobic exercise programs with different intensities could reduce the magnitude of BP rise. Patients with essential hypertension were recruited from the Baoshan Community Health Service Center. A total of 46 patients were finally selected and randomly assigned into two groups: control group (CON) included patients who did not participate in exercise intervention training; treatment group (TRG) included patients who participated in 12-week brisk walking training (60-min of brisk walking, three times a week for a total of 12 weeks). 3-minute step tests of low and high intensity were conducted pre- and post-intervention. To compare the effects of exercise intervention, 23 subjects with normal blood pressure (NBP) who did not participate in 12-week brisk walking training, were recruited. After 12 weeks of brisk walking, SBP of TRG during resting, low and high-intensity exercise was significantly reduced by 8.3mmHg, 15.6mmHg, and 22.6mmHg, respectively; while HR of TRG's during resting, low and high intensity was significantly reduced by 3.6beats/minute, 8.7beats/minute and 11.3beats/minute, respectively. Meanwhile, after 12 weeks of brisk walking, TRG's steps per day, [Formula: see text]o 2max , moderate physical activity time and physical activity energy expenditure significantly increased by 6000 steps, 2.4 ml/kg/m, 40 minutes and 113 kcal, respectively. At the same time, TRG's body fat rate and sedentary time significantly reduced by 2% and 60 minutes per day. Brisk walking can reduce the magnitude of BP rise during exercise of different intensities and may be reduced the risk of acute cardiovascular incidents in elderly patients with essential hypertension. EP: Essential hypertension; BP: blood pressure; CON: control group; TRG: treatment group; NBP: normal blood pressure; PA: physical activity.

Effective myotube formation in human adipose tissue-derived stem cells expressing dystrophin and myosin heavy chain by cellular fusion with mouse C2C12 myoblasts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eom, Young Woo; Biomedical Research Institute, Lifeliver Co., Ltd., Suwon; Lee, Jong Eun

2011-04-29

Highlights: {yields} hASCs were differentiated into skeletal muscle cells by treatment with 5-azacytidine, FGF-2, and the supernatant of cultured hASCs. {yields} Dystrophin and MyHC were expressed in late differentiation step by treatment with the supernatant of cultured hASCs. {yields} hASCs expressing dystrophin and MyHC contributed to myotube formation during co-culture with mouse myoblast C2C12 cells. -- Abstract: Stem cell therapy for muscular dystrophies requires stem cells that are able to participate in the formation of new muscle fibers. However, the differentiation steps that are the most critical for this process are not clear. We investigated the myogenic phases of humanmore » adipose tissue-derived stem cells (hASCs) step by step and the capability of myotube formation according to the differentiation phase by cellular fusion with mouse myoblast C2C12 cells. In hASCs treated with 5-azacytidine and fibroblast growth factor-2 (FGF-2) for 1 day, the early differentiation step to express MyoD and myogenin was induced by FGF-2 treatment for 6 days. Dystrophin and myosin heavy chain (MyHC) expression was induced by hASC conditioned medium in the late differentiation step. Myotubes were observed only in hASCs undergoing the late differentiation step by cellular fusion with C2C12 cells. In contrast, hASCs that were normal or in the early stage were not involved in myotube formation. Our results indicate that stem cells expressing dystrophin and MyHC are more suitable for myotube formation by co-culture with myoblasts than normal or early differentiated stem cells expressing MyoD and myogenin.« less

Outward Bound to the Galaxies--One Step at a Time

ERIC Educational Resources Information Center

Ward, R. Bruce; Miller-Friedmann, Jaimie; Sienkiewicz, Frank; Antonucci, Paul

2012-01-01

Less than a century ago, astronomers began to unlock the cosmic distances within and beyond the Milky Way. Understanding the size and scale of the universe is a continuing, step-by-step process that began with the remarkably accurate measurement of the distance to the Moon made by early Greeks. In part, the authors have ITEAMS (Innovative…

Integrating Behavioral Health Support into a Pediatric Setting: What Happens in the Exam Room?

ERIC Educational Resources Information Center

Cuno, Kate; Krug, Laura M.; Umylny, Polina

2015-01-01

This article presents an overview of the Healthy Steps for Young Children (Healthy Steps) program at Montefiore Medical Center, in the Bronx, NY. The authors review the theoretical underpinnings of this national program for the promotion of early childhood mental health. The Healthy Steps program at Montefiore is integrated into outpatient…

Chapter 9: Planting hardwood tree seedlings on reclaimed mine land in the Appalachian region

Treesearch

V. Davis; J. Franklin; C. Zipper; P. Angel

2017-01-01

The Forestry Reclamation Approach (FRA) is a method of reclaiming surface coal mines to forested postmining land use (Chapter 2, this volume). "Use proper tree planting techniques" is Step 5 of the FRA; when used with the other FRA steps, proper tree planting can help to ensure successful reforestation. Proper care and planting of tree seedlings is essential...

Bridging the Gap between Structures and Properties: An Investigation and Evaluation of Students' Representational Competence

ERIC Educational Resources Information Center

Underwood, Sonia Miller

2011-01-01

The heart of learning chemistry is the ability to connect a compound's structure to its function; Lewis structures provide an essential link in this process. In many cases, their construction is taught using an algorithmic approach, containing a set of step-by-step rules. We believe that this approach is in direct conflict with the precepts of…

Raising Children Who Soar: A Guide to Healthy Risk-Taking in an Uncertain World

ERIC Educational Resources Information Center

Davis, Susan; Eppler-Wolff, Nancy

2009-01-01

How can we keep children safe in an uncertain world, but also raise them to be confident in taking the healthy, emotional risks necessary to succeed in life? The authors of this unique book--two clinical psychologists, who are also mothers--provide essential guidance for parents and teachers. They explain, step-by-step, how to help children become…

Status of Implementation of Strategic Recommendations for Advancing Ohio's Innovation Economy. Sixth Report on the Condition of Higher Education in Ohio

ERIC Educational Resources Information Center

Ohio Board of Regents, 2013

2013-01-01

This Sixth Condition Report represents a snapshot of a moment in time. It focuses on critical enabling conditions and initial implementation steps for a strategically chosen subset of the action steps embedded in the Task Force's full slate of recommendations. As such, this report serves four essential purposes: (1) It identifies a selective set…

Research and Teaching: The Impact of a Four-Step Laboratory Pedagogical Framework on Biology Students' Perceptions of Laboratory Skills, Knowledge, and Interest in Research

ERIC Educational Resources Information Center

McLaughlin, Jacqueline Shea; Favre, David E.; Weinstein, Suzanne E.; Goedhart, Christine M.

2017-01-01

Authentic undergraduate research laboratory experiences are essential to aid in the implementation of science education reform mandates and to effectively train a new generation of biology students. Here we present assessment data on a unique four-step laboratory pedagogical framework that allows students to develop scientific thinking and…

Supporting State Systems of Early Learning Act

THOMAS, 112th Congress

Rep. Himes, James A. [D-CT-4

2011-11-02

House - 11/18/2011 Referred to the Subcommittee on Early Childhood, Elementary, and Secondary Education. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

78 FR 13868 - New England Fishery Management Council; Public Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-01

.... It is an important early step in what will be a multi-step process to develop the policy. The agenda... opportunity for communications between participants about management and science issues that relate to the ABC...

Biochemistry and Cell Wall Changes Associated with Noni (Morinda citrifolia L.) Fruit Ripening.

PubMed

Cárdenas-Coronel, Wendy G; Carrillo-López, Armando; Vélez de la Rocha, Rosabel; Labavitch, John M; Báez-Sañudo, Manuel A; Heredia, José B; Zazueta-Morales, José J; Vega-García, Misael O; Sañudo-Barajas, J Adriana

2016-01-13

Quality and compositional changes were determined in noni fruit harvested at five ripening stages, from dark-green to thaslucent-grayish. Fruit ripening was accompanied by acidity and soluble solids accumulation but pH diminution, whereas the softening profile presented three differential steps named early (no significant softening), intermediate (significant softening), and final (dramatic softening). At early step the extensive depolymerization of hydrosoluble pectins and the significantly increment of pectinase activities did not correlate with the slight reduction in firmness. The intermediate step showed an increment of pectinases and hemicellulases activities. The final step was accompanied by the most significant reduction in the yield of alcohol-insoluble solids as well as in the composition of uronic acids and neutral sugars; pectinases increased their activity and depolymerization of hemicellulosic fractions occurred. Noni ripening is a process conducted by the coordinated action of pectinases and hemicellulases that promote the differential dissasembly of cell wall polymers.

Novel, In-House, SYBR Green Based One-Step rRT-PCR: Rapid and Accurate Diagnosis of Crimean-Congo Hemorrhagic Fever Virus in Suspected Patients From Iran.

PubMed

Zahraei, Bentolhoda; Hashemzadeh, Mohammad Sadegh; Najarasl, Mohammad; Zahiriyeganeh, Samaneh; Tat, Mahdi; Metanat, Maliheh; Sepehri Rad, Nahid; Khansari-Nejad, Behzad; Zafari, Ehsan; Sharti, Mojtaba; Dorostkar, Ruhollah

2016-01-01

The Crimean-Congo hemorrhagic fever (CCHF) virus causes severe disease in humans, with a high mortality rate. Since, there is no approved vaccine or specific treatment for CCHF, an early and accurate diagnosis, as well as reliable surveillance, is essential for case management and patient improvement. For this research, our aim was to evaluate the application of a novel SYBR Green based one-step real-time reverse-transcriptase polymerase chain reaction (rRT-PCR) assay for the in-house diagnosis of the CCHF virus. In this experimental study, the highly conserved S-region sequence of the CCHF viral genome was first adapted from GenBank, and the specific primers targeting this region were designed. Then, the viral RNA was extracted from 75 serum samples from different patients in eastern Iran. The sensitivity and specificity of the primers were also evaluated in positive serum samples previously confirmed to have the CCHF virus, by this one-step rRT-PCR assay, as well as a DNA sequencing analysis. From a total of 75 suspected serum samples, 42 were confirmed to be positive for CCHF virus, with no false-positives detected by the sequencing results. After 40 amplification cycles, the melting curve analysis revealed a mean melting temperature (Tm) of 86.5 ± 0.6°C (quite different from those of the primer-dimers), and the positive samples showed only a small variation in the parameters. In all of the positive samples, the predicted length of 420 bp was confirmed by electrophoresis. Moreover, the sensitivity test showed that this assay can detect less than 20 copies of viral RNA per reaction. This study showed that this novel one-step rRT-PCR assay is a rapid, reliable, repeatable, specific, sensitive, and simple tool for the detection of the CCHF virus.

Asb2α-Filamin A Axis Is Essential for Actin Cytoskeleton Remodeling During Heart Development.

PubMed

Métais, Arnaud; Lamsoul, Isabelle; Melet, Armelle; Uttenweiler-Joseph, Sandrine; Poincloux, Renaud; Stefanovic, Sonia; Valière, Amélie; Gonzalez de Peredo, Anne; Stella, Alexandre; Burlet-Schiltz, Odile; Zaffran, Stéphane; Lutz, Pierre G; Moog-Lutz, Christel

2018-03-16

Heart development involves differentiation of cardiac progenitors and assembly of the contractile sarcomere apparatus of cardiomyocytes. However, little is known about the mechanisms that regulate actin cytoskeleton remodeling during cardiac cell differentiation. The Asb2α (Ankyrin repeat-containing protein with a suppressor of cytokine signaling box 2) CRL5 (cullin 5 RING E3 ubiquitin ligase) triggers polyubiquitylation and subsequent degradation by the proteasome of FLNs (filamins). Here, we investigate the role of Asb2α in heart development and its mechanisms of action. Using Asb2 knockout embryos, we show that Asb2 is an essential gene, critical to heart morphogenesis and function, although its loss does not interfere with the overall patterning of the embryonic heart tube. We show that the Asb2α E3 ubiquitin ligase controls Flna stability in immature cardiomyocytes. Importantly, Asb2α-mediated degradation of the actin-binding protein Flna marks a previously unrecognized intermediate step in cardiac cell differentiation characterized by cell shape changes and actin cytoskeleton remodeling. We further establish that in the absence of Asb2α, myofibrils are disorganized and that heartbeats are inefficient, leading to embryonic lethality in mice. These findings identify Asb2α as an unsuspected key regulator of cardiac cell differentiation and shed light on the molecular and cellular mechanisms determining the onset of myocardial cell architecture and its link with early cardiac function. Although Flna is known to play roles in cytoskeleton organization and to be required for heart function, this study now reveals that its degradation mediated by Asb2α ensures essential functions in differentiating cardiac progenitors. © 2018 American Heart Association, Inc.

Utilizing Electronic Medical Records to Discover Changing Trends of Medical Behaviors Over Time.

PubMed

Yin, Liangying; Huang, Zhengxing; Dong, Wei; He, Chunhua; Duan, Huilong

2017-05-05

Medical behaviors are playing significant roles in the delivery of high quality and cost-effective health services. Timely discovery of changing frequencies of medical behaviors is beneficial for the improvement of health services. The main objective of this work is to discover the changing trends of medical behaviors over time. This study proposes a two-steps approach to detect essential changing patterns of medical behaviors from Electronic Medical Records (EMRs). In detail, a probabilistic topic model, i.e., Latent Dirichlet allocation (LDA), is firstly applied to disclose yearly treatment patterns in regard to the risk stratification of patients from a large volume of EMRs. After that, the changing trends by comparing essential/critical medical behaviors in a specific time period are detected and analyzed, including changes of significant patient features with their values, and changes of critical treatment interventions with their occurring time stamps. We verify the effectiveness of the proposed approach on a clinical dataset containing 12,152 patient cases with a time range of 10 years. Totally, 135 patients features and 234 treatment interventions in three treatment patterns were selected to detect their changing trends. In particular, evolving trends of yearly occurring probabilities of the selected medical behaviors were categorized into six content changing patterns (i.e, 112 growing, 123 declining, 43 up-down, 16 down-up, 35 steady, and 40 jumping), using the proposed approach. Besides, changing trends of execution time of treatment interventions were classified into three occurring time changing patterns (i.e., 175 early-implemented, 50 steady-implemented and 9 delay-implemented). Experimental results show that our approach has an ability to utilize EMRs to discover essential evolving trends of medical behaviors, and thus provide significant potential to be further explored for health services redesign and improvement.

A Coordinated Interdependent Protein Circuitry Stabilizes the Kinetochore Ensemble to Protect CENP-A in the Human Pathogenic Yeast Candida albicans

PubMed Central

Thakur, Jitendra; Sanyal, Kaustuv

2012-01-01

Unlike most eukaryotes, a kinetochore is fully assembled early in the cell cycle in budding yeasts Saccharomyces cerevisiae and Candida albicans. These kinetochores are clustered together throughout the cell cycle. Kinetochore assembly on point centromeres of S. cerevisiae is considered to be a step-wise process that initiates with binding of inner kinetochore proteins on specific centromere DNA sequence motifs. In contrast, kinetochore formation in C. albicans, that carries regional centromeres of 3–5 kb long, has been shown to be a sequence independent but an epigenetically regulated event. In this study, we investigated the process of kinetochore assembly/disassembly in C. albicans. Localization dependence of various kinetochore proteins studied by confocal microscopy and chromatin immunoprecipitation (ChIP) assays revealed that assembly of a kinetochore is a highly coordinated and interdependent event. Partial depletion of an essential kinetochore protein affects integrity of the kinetochore cluster. Further protein depletion results in complete collapse of the kinetochore architecture. In addition, GFP-tagged kinetochore proteins confirmed similar time-dependent disintegration upon gradual depletion of an outer kinetochore protein (Dam1). The loss of integrity of a kinetochore formed on centromeric chromatin was demonstrated by reduced binding of CENP-A and CENP-C at the centromeres. Most strikingly, Western blot analysis revealed that gradual depletion of any of these essential kinetochore proteins results in concomitant reduction in cellular protein levels of CENP-A. We further demonstrated that centromere bound CENP-A is protected from the proteosomal mediated degradation. Based on these results, we propose that a coordinated interdependent circuitry of several evolutionarily conserved essential kinetochore proteins ensures integrity of a kinetochore formed on the foundation of CENP-A containing centromeric chromatin. PMID:22536162

Organization Spotlight: The Power of an Association in Early Childhood Education and Care: ISSA--An Engine for Advocacy, Capacity Building, and Creating a Growing Learning Community

ERIC Educational Resources Information Center

Ionescu, Mihaela

2015-01-01

The International Step by Step Association (ISSA) is an association that believes in learning from each other across cultures and borders, building on each other's strengths, and tapping into the power of a network. Building on the strong legacy of the Open Society Foundations' Step by Step program, ISSA has nurtured a culture of belonging to a…

First Steps: Stories on Inclusion in Early Childhood Education.

ERIC Educational Resources Information Center

United Nations Educational, Scientific, and Cultural Organization, Paris (France).

This publication presents papers from 13 nations that describe the integration of children with disabilities into early childhood education programs. The compilation of case studies will serve as a reference document for the International Consultation on Early Childhood Education and Special Educational Needs, organized by UNESCO in collaboration…

Correlates of Early Assessment of Neurodevelopmental Disorders in Lebanon

ERIC Educational Resources Information Center

Dirani, Leyla Akoury; Salamoun, Mariana

2014-01-01

Children with neurodevelopmental disorders who receive early therapeutic interventions present a better developmental pathway than children who do not. Early assessment of neurodevelopmental disorders is the first step in this process. This study aims at describing the variables that are in play in the first assessment of children with autism…

Discovery of Cellular Proteins Required for the Early Steps of HCV Infection Using Integrative Genomics

PubMed Central

Yang, Jae-Seong; Kwon, Oh Sung; Kim, Sanguk; Jang, Sung Key

2013-01-01

Successful viral infection requires intimate communication between virus and host cell, a process that absolutely requires various host proteins. However, current efforts to discover novel host proteins as therapeutic targets for viral infection are difficult. Here, we developed an integrative-genomics approach to predict human genes involved in the early steps of hepatitis C virus (HCV) infection. By integrating HCV and human protein associations, co-expression data, and tight junction-tetraspanin web specific networks, we identified host proteins required for the early steps in HCV infection. Moreover, we validated the roles of newly identified proteins in HCV infection by knocking down their expression using small interfering RNAs. Specifically, a novel host factor CD63 was shown to directly interact with HCV E2 protein. We further demonstrated that an antibody against CD63 blocked HCV infection, indicating that CD63 may serve as a new therapeutic target for HCV-related diseases. The candidate gene list provides a source for identification of new therapeutic targets. PMID:23593195

Universal Prekindergarten and Early Childhood Education Act of 2013

THOMAS, 113th Congress

Rep. Norton, Eleanor Holmes [D-DC-At Large

2013-02-27

House - 04/23/2013 Referred to the Subcommittee on Early Childhood, Elementary, and Secondary Education. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

Universal Prekindergarten and Early Childhood Education Act of 2011

THOMAS, 112th Congress

Rep. Norton, Eleanor Holmes [D-DC-At Large

2011-11-17

House - 03/29/2012 Referred to the Subcommittee on Early Childhood, Elementary, and Secondary Education. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

Early Detection of Dyslexia in Children Act of 2009

THOMAS, 111th Congress

Rep. Jackson-Lee, Sheila [D-TX-18

2009-01-06

House - 03/16/2009 Referred to the Subcommittee on Early Childhood, Elementary, and Secondary Education. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

Universal Prekindergarten and Early Childhood Education Act of 2009

THOMAS, 111th Congress

Rep. Norton, Eleanor Holmes [D-DC-At Large

2009-10-08

House - 11/16/2009 Referred to the Subcommittee on Early Childhood, Elementary, and Secondary Education. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

Early Childhood Education Professional Improvement Act of 2013

THOMAS, 113th Congress

Rep. Meng, Grace [D-NY-6

2013-10-28

House - 01/22/2014 Referred to the Subcommittee on Early Childhood, Elementary, and Secondary Education. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

Thyroidectomy: post-operative care and common complications.

PubMed

Furtado, L

Any surgical procedure involves risks. Thyroid surgery can cause potentially fatal complications during the early post-operative phase. It is essential that nurses have the knowledge and skills to detect early signs and symptoms of potential complications and take appropriate action. Early detection and rapid response are key to maintaining patient safety and minimising harm.

Early detection monitoring of Phytophthora ramorum in high-risk forests of California

Treesearch

Ross Meentemeyer; Elizabeth Lotz; David M. Rizzo; Kelly Buja; Walter Mark

2006-01-01

Early detection monitoring is essential for successful control of invasive organisms. Detection of invasions at an early stage of establishment when a population is small and isolated makes eradication more feasible and less costly. Sudden oak death, caused by the recently described pathogen Phytophthora ramorum, is an emerging forest disease that...

Making the Grade: Texas Early College High Schools Prepare Students for College. Executive Summary

ERIC Educational Resources Information Center

Jobs for the Future, 2011

2011-01-01

Early college high schools are improving student outcomes in Texas. This performance is being achieved by youth who are underrepresented in college, including Hispanic youth, economically disadvantaged students, and first-generation college goers. In improving readiness for college and careers, early college schools have become an essential part…

Striving for Quality in Early Childhood Inclusion

ERIC Educational Resources Information Center

Brancato, Kimberly

2013-01-01

An essential component of best practice in the field of early childhood special education is the inclusion of children with disabilities in typical early childhood settings. As the practice of inclusion has increased in recent years it has become imperative to ensure that children with disabilities attend quality programs. The main purpose of this…

The Funding of Early Care and Education Programmes in Sweden, 1845-1943

ERIC Educational Resources Information Center

Westberg, Johannes

2011-01-01

What significance did donations, bequests, tuition fees and fund-raising events have for early care and education programmes during the nineteenth and early twentieth century? Through an examination of 24 Swedish infant schools, day nurseries and free kindergartens, this article verifies that donations and bequests were essential for the economy…

Early Literacy Intervention for Preschoolers Who Need Tier 3 Support

ERIC Educational Resources Information Center

Kaminski, Ruth A.; Powell-Smith, Kelly A.

2017-01-01

Phonemic awareness has been consistently identified as an essential skill for as well as an important predictor of later reading achievement. Children who lack these early literacy skills at kindergarten entry are more likely to demonstrate both short- and long-term reading difficulties. Despite the importance of providing intervention early,…

Practice versus Politics in Danish Day-Care Centres: How to Bridge the Gap in Early Learning?

ERIC Educational Resources Information Center

Clasen, Line Engel; Jensen de López, Kristine

2016-01-01

It is essential that early educators in day-care services possess adequate pedagogical tools for supporting children's communicative development. Early literacy programmes (ELPs) are potential tools. However, studies investigating the effects of ELPs seldom address implementation processes or the programme users' perspectives. This study sheds…

Optimizing identification and management of COPD patients – reviewing the role of the community pharmacist

PubMed Central

van Boven, Job F. M.; Maguire, Terence; Goyal, Pankaj; Altman, Pablo

2016-01-01

The aim of this paper was to propose key steps for community pharmacist integration into a patient care pathway for chronic obstructive pulmonary disease (COPD) management. A literature search was conducted to identify publications focusing on the role of the community pharmacist in identification and management of COPD. The literature search highlighted evidence supporting an important role for pharmacists at each of the four key steps in the patient care pathway for COPD management. Step 1 (primary prevention): pharmacists are ideally placed to provide information on disease awareness and risk prevention campaigns, and to encourage lifestyle interventions, including smoking cessation. Step 2 (early detection/case finding): pharmacists are often the first point of contact between the patient and the healthcare system and can therefore play an important role in the early identification of patients with COPD. Step 3 (management and ongoing support): pharmacists can assist patients by providing advice and education on dosage, inhaler technique, treatment expectations and the importance of adherence, and by supporting self‐management, including recognition and treatment of COPD exacerbations. Step 4 (review and follow‐up): pharmacists can play an important role in monitoring adherence and ongoing inhaler technique in patients with COPD. In summary, pharmacists are ideally positioned to play a vital role in all key stages of an integrated COPD patient care pathway from early disease detection to the support of management plans, including advice and counselling regarding medications, inhaler technique and treatment adherence. Areas requiring additional consideration include pharmacist training, increasing awareness of the pharmacist role, administration and reimbursement, and increasing physician–pharmacist collaboration. PMID:27510273

Overexpression of the Coq8 Kinase in Saccharomyces cerevisiae coq Null Mutants Allows for Accumulation of Diagnostic Intermediates of the Coenzyme Q6 Biosynthetic Pathway*

PubMed Central

Xie, Letian X.; Ozeir, Mohammad; Tang, Jeniffer Y.; Chen, Jia Y.; Jaquinod, Sylvie-Kieffer; Fontecave, Marc; Clarke, Catherine F.; Pierrel, Fabien

2012-01-01

Most of the Coq proteins involved in coenzyme Q (ubiquinone or Q) biosynthesis are interdependent within a multiprotein complex in the yeast Saccharomyces cerevisiae. Lack of only one Coq polypeptide, as in Δcoq strains, results in the degradation of several Coq proteins. Consequently, Δcoq strains accumulate the same early intermediate of the Q6 biosynthetic pathway; this intermediate is therefore not informative about the deficient biosynthetic step in a particular Δcoq strain. In this work, we report that the overexpression of the protein Coq8 in Δcoq strains restores steady state levels of the unstable Coq proteins. Coq8 has been proposed to be a kinase, and we provide evidence that the kinase activity is essential for the stabilizing effect of Coq8 in the Δcoq strains. This stabilization results in the accumulation of several novel Q6 biosynthetic intermediates. These Q intermediates identify chemical steps impaired in cells lacking Coq4 and Coq9 polypeptides, for which no function has been established to date. Several of the new intermediates contain a C4-amine and provide information on the deamination reaction that takes place when para-aminobenzoic acid is used as a ring precursor of Q6. Finally, we used synthetic analogues of 4-hydroxybenzoic acid to bypass deficient biosynthetic steps, and we show here that 2,4-dihydroxybenzoic acid is able to restore Q6 biosynthesis and respiratory growth in a Δcoq7 strain overexpressing Coq8. The overexpression of Coq8 and the use of 4-hydroxybenzoic acid analogues represent innovative tools to elucidate the Q biosynthetic pathway. PMID:22593570

Overexpression of the Coq8 kinase in Saccharomyces cerevisiae coq null mutants allows for accumulation of diagnostic intermediates of the coenzyme Q6 biosynthetic pathway.

PubMed

Xie, Letian X; Ozeir, Mohammad; Tang, Jeniffer Y; Chen, Jia Y; Jaquinod, Sylvie-Kieffer; Fontecave, Marc; Clarke, Catherine F; Pierrel, Fabien

2012-07-06

Most of the Coq proteins involved in coenzyme Q (ubiquinone or Q) biosynthesis are interdependent within a multiprotein complex in the yeast Saccharomyces cerevisiae. Lack of only one Coq polypeptide, as in Δcoq strains, results in the degradation of several Coq proteins. Consequently, Δcoq strains accumulate the same early intermediate of the Q(6) biosynthetic pathway; this intermediate is therefore not informative about the deficient biosynthetic step in a particular Δcoq strain. In this work, we report that the overexpression of the protein Coq8 in Δcoq strains restores steady state levels of the unstable Coq proteins. Coq8 has been proposed to be a kinase, and we provide evidence that the kinase activity is essential for the stabilizing effect of Coq8 in the Δcoq strains. This stabilization results in the accumulation of several novel Q(6) biosynthetic intermediates. These Q intermediates identify chemical steps impaired in cells lacking Coq4 and Coq9 polypeptides, for which no function has been established to date. Several of the new intermediates contain a C4-amine and provide information on the deamination reaction that takes place when para-aminobenzoic acid is used as a ring precursor of Q(6). Finally, we used synthetic analogues of 4-hydroxybenzoic acid to bypass deficient biosynthetic steps, and we show here that 2,4-dihydroxybenzoic acid is able to restore Q(6) biosynthesis and respiratory growth in a Δcoq7 strain overexpressing Coq8. The overexpression of Coq8 and the use of 4-hydroxybenzoic acid analogues represent innovative tools to elucidate the Q biosynthetic pathway.

Assessing the performance of regional landslide early warning models: the EDuMaP method

NASA Astrophysics Data System (ADS)

Calvello, M.; Piciullo, L.

2015-10-01

The paper proposes the evaluation of the technical performance of a regional landslide early warning system by means of an original approach, called EDuMaP method, comprising three successive steps: identification and analysis of the Events (E), i.e. landslide events and warning events derived from available landslides and warnings databases; definition and computation of a Duration Matrix (DuMa), whose elements report the time associated with the occurrence of landslide events in relation to the occurrence of warning events, in their respective classes; evaluation of the early warning model Performance (P) by means of performance criteria and indicators applied to the duration matrix. During the first step, the analyst takes into account the features of the warning model by means of ten input parameters, which are used to identify and classify landslide and warning events according to their spatial and temporal characteristics. In the second step, the analyst computes a time-based duration matrix having a number of rows and columns equal to the number of classes defined for the warning and landslide events, respectively. In the third step, the analyst computes a series of model performance indicators derived from a set of performance criteria, which need to be defined by considering, once again, the features of the warning model. The proposed method is based on a framework clearly distinguishing between local and regional landslide early warning systems as well as among correlation laws, warning models and warning systems. The applicability, potentialities and limitations of the EDuMaP method are tested and discussed using real landslides and warnings data from the municipal early warning system operating in Rio de Janeiro (Brazil).

Assessing the performance of regional landslide early warning models: the EDuMaP method

NASA Astrophysics Data System (ADS)

Calvello, M.; Piciullo, L.

2016-01-01

A schematic of the components of regional early warning systems for rainfall-induced landslides is herein proposed, based on a clear distinction between warning models and warning systems. According to this framework an early warning system comprises a warning model as well as a monitoring and warning strategy, a communication strategy and an emergency plan. The paper proposes the evaluation of regional landslide warning models by means of an original approach, called the "event, duration matrix, performance" (EDuMaP) method, comprising three successive steps: identification and analysis of the events, i.e., landslide events and warning events derived from available landslides and warnings databases; definition and computation of a duration matrix, whose elements report the time associated with the occurrence of landslide events in relation to the occurrence of warning events, in their respective classes; evaluation of the early warning model performance by means of performance criteria and indicators applied to the duration matrix. During the first step the analyst identifies and classifies the landslide and warning events, according to their spatial and temporal characteristics, by means of a number of model parameters. In the second step, the analyst computes a time-based duration matrix with a number of rows and columns equal to the number of classes defined for the warning and landslide events, respectively. In the third step, the analyst computes a series of model performance indicators derived from a set of performance criteria, which need to be defined by considering, once again, the features of the warning model. The applicability, potentialities and limitations of the EDuMaP method are tested and discussed using real landslides and warning data from the municipal early warning system operating in Rio de Janeiro (Brazil).

[Operative treatment strategies for multiple trauma patients : early total care versus damage control].

PubMed

Klüter, T; Lippross, S; Oestern, S; Weuster, M; Seekamp, A

2013-09-01

The treatment of multiple trauma patients is a great challenge for an interdisciplinary team. After preclinical care and subsequent treatment in the emergency room the order of the interventions is prioritized depending of the individual risk stratification. For planning the surgery management it is essential to distinguish between absolutely essential operations to prevent life-threatening situations for the patient and interventions with shiftable indications, depending on the general condition of the patient. All interventions need to be done without causing significant secondary damage to prohibit hyperinflammation and systemic inflammatory response syndrome. The challenge consists in determination of the appropriate treatment at the right point in time. In general the early primary intervention, early total care, is differentiated from the damage control concept.

44 CFR 9.13 - Particular types of temporary housing.

Code of Federal Regulations, 2010 CFR

2010-10-01

...-rise areas. (5) FEMA shall comply with Step 2 Early Public Notice (§ 9.8(c)) and Step 7 Final Public... to flooding, a rejection of a non-floodplain location alternative and of the no-action alternative...

A construction of standardized near infrared hyper-spectral teeth database: a first step in the development of reliable diagnostic tool for quantification and early detection of caries

NASA Astrophysics Data System (ADS)

Bürmen, Miran; Usenik, Peter; Fidler, Aleš; Pernuš, Franjo; Likar, Boštjan

2011-03-01

Dental caries is a disease characterized by demineralization of enamel crystals leading to the penetration of bacteria into the dentin and pulp. If left untreated, the disease can lead to pain, infection and tooth loss. Early detection of enamel demineralization resulting in increased enamel porosity, commonly known as white spots, is a difficult diagnostic task. Several papers reported on near infrared (NIR) spectroscopy to be a potentially useful noninvasive spectroscopic technique for early detection of caries lesions. However, the conducted studies were mostly qualitative and did not include the critical assessment of the spectral variability of the sound and carious dental tissues and influence of the water content. Such assessment is essential for development and validation of reliable qualitative and especially quantitative diagnostic tools based on NIR spectroscopy. In order to characterize the described spectral variability, a standardized diffuse reflectance hyper-spectral database was constructed by imaging 12 extracted human teeth with natural lesions of various degrees in the spectral range from 900 to 1700 nm with spectral resolution of 10 nm. Additionally, all the teeth were imaged by digital color camera. The influence of water content on the acquired spectra was characterized by monitoring the teeth during the drying process. The images were assessed by an expert, thereby obtaining the gold standard. By analyzing the acquired spectra we were able to accurately model the spectral variability of the sound dental tissues and identify the advantages and limitations of NIR hyper-spectral imaging.

microRNA expression profiling on individual breast cancer patients identifies novel panel of circulating microRNA for early detection.

PubMed

Hamam, Rimi; Ali, Arwa M; Alsaleh, Khalid A; Kassem, Moustapha; Alfayez, Musaed; Aldahmash, Abdullah; Alajez, Nehad M

2016-05-16

Breast cancer (BC) is the most common cancer type and the second cause of cancer-related death among women. Therefore, better understanding of breast cancer tumor biology and the identification of novel biomarkers is essential for the early diagnosis and for better disease stratification and management choices. Herein we developed a novel approach which relies on the isolation of circulating microRNAs through an enrichment step using speed-vacuum concentration which resulted in 5-fold increase in microRNA abundance. Global miRNA microarray expression profiling performed on individual samples from 23 BC and 9 normals identified 18 up-regulated miRNAs in BC patients (p(corr) < 0.05). Nine miRNAs (hsa-miR-4270, hsa-miR-1225-5p, hsa-miR-188-5p, hsa-miR-1202, hsa-miR-4281, hsa-miR-1207-5p, hsa-miR-642b-3p, hsa-miR-1290, and hsa-miR-3141) were subsequently validated using qRT-PCR in a cohort of 46 BC and 14 controls. The expression of those microRNAs was overall higher in patients with stage I, II, and III, compared to stage IV, with potential utilization for early detection. The expression of this microRNA panel was slightly higher in the HER2 and TN compared to patients with luminal subtype. Therefore, we developed a novel approach which led to the identification of a novel microRNA panel which was upregulated in BC patients with potential utilization in disease diagnosis and stratification.

Assessing the Effectiveness of First Step to Success: Are Short-Term Results the First Step to Long-Term Behavioral Improvements?

ERIC Educational Resources Information Center

Sumi, W. Carl; Woodbridge, Michelle W.; Javitz, Harold S.; Thornton, S. Patrick; Wagner, Mary; Rouspil, Kristen; Yu, Jennifer W.; Seeley, John R.; Walker, Hill M.; Golly, Annemieke; Small, Jason W.; Feil, Edward G.; Severson, Herbert H.

2013-01-01

This article reports on the effectiveness of First Step to Success, a secondary-level intervention appropriate for students in early elementary school who experience moderate to severe behavior problems and are at risk for academic failure. The authors demonstrate the intervention's short-term effects on multiple behavioral and academic outcomes…

"Cast Your Net Widely": Three Steps to Expanding and Refining Your Problem before Action Learning Application

ERIC Educational Resources Information Center

Reese, Simon R.

2015-01-01

This paper reflects upon a three-step process to expand the problem definition in the early stages of an action learning project. The process created a community-powered problem-solving approach within the action learning context. The simple three steps expanded upon in the paper create independence, dependence, and inter-dependence to aid the…

Emotional influences on locomotor behavior.

PubMed

Naugle, Kelly M; Joyner, Jessica; Hass, Chris J; Janelle, Christopher M

2010-12-01

Emotional responses to appetitive and aversive stimuli motivate approach and avoidance behaviors essential for survival. The purpose of the current study was to determine the impact of specific emotional stimuli on forward, approach-oriented locomotion. Steady state walking was assessed while participants walked toward pictures varying in emotional content (erotic, happy people, attack, mutilation, contamination, and neutral). Step length and step velocity were calculated for the first two steps following picture onset. Exposure to the mutilation and contamination pictures shortened the lengths of step one and step two compared to the erotic pictures. Additionally, step velocity was greater during exposure to the erotic pictures compared to (1) the contamination and mutilation pictures for step one and (2) all other picture categories for step two. These findings suggest that locomotion is facilitated when walking toward approach-oriented emotional stimuli but compromised when walking toward aversive emotional stimuli. The data extend our understanding of fundamental interactions among motivational orientations, emotional reactions, and resultant actions. Theoretical and practical implications are discussed. Copyright © 2010 Elsevier Ltd. All rights reserved.

4 Steps for Redesigning Time for Student and Teacher Learning

ERIC Educational Resources Information Center

Nazareno, Lori

2017-01-01

Everybody complains about a lack of time in school, but few are prepared to do anything about it. Laying the foundation before making such a shift is essential to the success of the change. Once a broad-based team has been chosen to do the work, they can follow a process explained in four steps with the apt acronym of T.I.M.E.: Taking stock,…

The WOPR Protein Ros1 Is a Master Regulator of Sporogenesis and Late Effector Gene Expression in the Maize Pathogen Ustilago maydis

PubMed Central

Tollot, Marie; Assmann, Daniela; Becker, Christian; Altmüller, Janine; Dutheil, Julien Y.; Wegner, Carl-Eric; Kahmann, Regine

2016-01-01

The biotrophic basidiomycete fungus Ustilago maydis causes smut disease in maize. Hallmarks of the disease are large tumors that develop on all aerial parts of the host in which dark pigmented teliospores are formed. We have identified a member of the WOPR family of transcription factors, Ros1, as major regulator of spore formation in U. maydis. ros1 expression is induced only late during infection and hence Ros1 is neither involved in plant colonization of dikaryotic fungal hyphae nor in plant tumor formation. However, during late stages of infection Ros1 is essential for fungal karyogamy, massive proliferation of diploid fungal cells and spore formation. Premature expression of ros1 revealed that Ros1 counteracts the b-dependent filamentation program and induces morphological alterations resembling the early steps of sporogenesis. Transcriptional profiling and ChIP-seq analyses uncovered that Ros1 remodels expression of about 30% of all U. maydis genes with 40% of these being direct targets. In total the expression of 80 transcription factor genes is controlled by Ros1. Four of the upregulated transcription factor genes were deleted and two of the mutants were affected in spore development. A large number of b-dependent genes were differentially regulated by Ros1, suggesting substantial changes in this regulatory cascade that controls filamentation and pathogenic development. Interestingly, 128 genes encoding secreted effectors involved in the establishment of biotrophic development were downregulated by Ros1 while a set of 70 “late effectors” was upregulated. These results indicate that Ros1 is a master regulator of late development in U. maydis and show that the biotrophic interaction during sporogenesis involves a drastic shift in expression of the fungal effectome including the downregulation of effectors that are essential during early stages of infection. PMID:27332891

Early Warning Signals of Ecological Transitions: Methods for Spatial Patterns

PubMed Central

Brock, William A.; Carpenter, Stephen R.; Ellison, Aaron M.; Livina, Valerie N.; Seekell, David A.; Scheffer, Marten; van Nes, Egbert H.; Dakos, Vasilis

2014-01-01

A number of ecosystems can exhibit abrupt shifts between alternative stable states. Because of their important ecological and economic consequences, recent research has focused on devising early warning signals for anticipating such abrupt ecological transitions. In particular, theoretical studies show that changes in spatial characteristics of the system could provide early warnings of approaching transitions. However, the empirical validation of these indicators lag behind their theoretical developments. Here, we summarize a range of currently available spatial early warning signals, suggest potential null models to interpret their trends, and apply them to three simulated spatial data sets of systems undergoing an abrupt transition. In addition to providing a step-by-step methodology for applying these signals to spatial data sets, we propose a statistical toolbox that may be used to help detect approaching transitions in a wide range of spatial data. We hope that our methodology together with the computer codes will stimulate the application and testing of spatial early warning signals on real spatial data. PMID:24658137

Early Warning Systems: Re-Engaging Chronic Truants

ERIC Educational Resources Information Center

Chorneau, Tom

2012-01-01

School attendance can be an early indicator that something is going wrong with a student. Gathering, analyzing, and acting on attendance information is a first step toward school improvement. Meanwhile, the majority of the states are moving to build and enhance what are called "early warning systems," intended to flag at-risk students during their…

Ethical Behavior in Early Childhood Education.

ERIC Educational Resources Information Center

Katz, Lilian G.; Ward, Evangeline H.

This booklet contains two essays on ethics for early childhood educators. The first essay discusses the meaning of a code of ethics, the importance of a code of ethics for working with preschool children, ethical conflicts in day care and preschool work, and steps which may be taken to help early childhood workers resolve these conflicts. Ethical…

Demographic Factors Associated with the Early Identification of Children with Special Needs

ERIC Educational Resources Information Center

Guarino, Cassandra M.; Buddin, Richard; Pham, Chung; Cho, Michelle

2010-01-01

Early and accurate identification of special needs, coupled with an appropriate course of treatment and educational plan, is important to academic progress, in particular for economically disadvantaged children with fewer family resources to catch up if they fall behind. A first step in improving mechanisms to promote early identification is to…

Effectiveness of the Preschool Version of the First Step to Success Early Intervention Program for Preventing Antisocial Behaviors

ERIC Educational Resources Information Center

Çelik, Seçil; Arikan, Azru; Diken, Ibrahim H.; Aksoy, Funda; Çolak, Aysun; Tomris, Gözde

2016-01-01

Preventing antisocial behaviors appearing at an early age--before they become chronic--through effective early intervention programs, has become an important issue in recent years. In Turkey, the increase in the number of children at risk of antisocial behavior makes it necessary to get these behaviors under control at an early age through some…

The Necessary Art of Persuasion.

ERIC Educational Resources Information Center

Conger, Jay A.

1998-01-01

Discusses the importance of persuasion in business and offers four essential steps to effective persuasion: establish credibility, identify common ground, use vivid language and compelling evidence, and connect emotionally with the audience. (JOW)

The Development and Testing of a New Measure of Early Childhood Education Organizational Conditions

ERIC Educational Resources Information Center

Ehrlich, Stacy B.; Pacchiano, Debra M.; Luppescu, Stuart; Stein, Amanda

2016-01-01

The current study sought to scientifically adapt the existing five essentials teacher survey and develop a new parent survey, and pilot test them for use in early childhood education settings. The adaptation and development of these "Early Education Surveys" occurred in 2014-15, was based strongly on Bryk et al.'s (2010) existing…

Early Childhoods in a Changing World

ERIC Educational Resources Information Center

Clark, Margaret M., Ed.; Tucker, Stanley, Ed.

2010-01-01

This book challenges taken for granted views of early childhood across the globe. It deepens and broadens our understanding of what it means to be a child today and of the challenges children face in different parts of the world. It will be essential reading for all who work with young children or are students of early years education and…

Early Childhood Teachers at the Center: A Qualitative Case Study of Professional Development in an Urban District

ERIC Educational Resources Information Center

Baker, Megina

2018-01-01

Professional development for early childhood educators (ECE PD) is an essential component of supporting a professional early childhood workforce. Yet research on ECE PD frequently centers on narrow fidelity data, while teachers' individual voices and teaching contexts are only rarely considered in order to understand teacher experiences with PD…

Early Childhood Preservice Teachers' Knowledge and Application of Social Emotional Assessment and Intervention Practices

ERIC Educational Resources Information Center

Pribble, Lois Marie

2013-01-01

Social emotional competence is an essential developmental skill recognized as the most critical for school and later success. Rising rates in behavioral referrals and preschool expulsion have brought increased attention to the importance of helping children develop social-emotional skills in the early years. In early childhood education a central…

Understanding the Steiner Waldorf Approach: Early Years Education in Practice. Understanding the... Approach

ERIC Educational Resources Information Center

Nicol, Janni; Taplin, Jill

2012-01-01

Understanding the Steiner Waldorf Approach is a much needed source of information for those wishing to extend and consolidate their understanding of the Steiner Waldorf High Scope Approach. It will enable the reader to analyse the essential elements of the Steiner Waldorf Approach to early childhood and its relationship to quality early years…

"Look, I Have My Ears Open": Resilience and Early School Experiences among Children in an Economically Deprived Suburban Area in Ireland

ERIC Educational Resources Information Center

Tatlow-Golden, Mimi; O'Farrelly, Christine; Booth, Ailbhe; O'Rourke, Claire; Doyle, Orla

2016-01-01

Children from economically disadvantaged communities frequently lack the socio-emotional, cognitive and behavioural skills needed for successful early school adjustment. Assessments of early school experience often rely on parent and teacher perspectives, yet children's views are essential to design effective, resilience-promoting school…

Understanding the HighScope Approach: Early Years Education in Practice. Understanding the... Approach

ERIC Educational Resources Information Center

Wiltshire, Monica

2011-01-01

"Understanding the HighScope Approach" is a much needed source of information for those wishing to extend and consolidate their understanding of the HighScope Approach. It will enable the reader to analyse the essential elements of the HighScope Approach to early childhood and its relationship to quality early years practice. Exploring…

Subsurface oxide plays a critical role in CO 2 activation by Cu(111) surfaces to form chemisorbed CO 2, the first step in reduction of CO 2

DOE PAGES

Favaro, Marco; Xiao, Hai; Cheng, Tao; ...

2017-06-12

A national priority is to convert CO 2 into high-value chemical products such as liquid fuels. Because current electrocatalysts are not adequate, we aim to discover new catalysts by obtaining a detailed understanding of the initial steps of CO 2 electroreduction on copper surfaces, the best current catalysts. Using ambient pressure X-ray photoelectron spectroscopy interpreted with quantum mechanical prediction of the structures and free energies, we show that the presence of a thin suboxide structure below the copper surface is essential to bind the CO 2 in the physisorbed configuration at 298 K, and we show that this suboxide ismore » essential for converting to the chemisorbed CO 2 in the presence of water as the first step toward CO 2 reduction products such as formate and CO. This optimum suboxide leads to both neutral and charged Cu surface sites, providing fresh insights into how to design improved carbon dioxide reduction catalysts.« less

Glutathione transferases P1/P2 regulate the timing of signaling pathway activations and cell cycle progression during mouse liver regeneration

PubMed Central

Pajaud, J; Ribault, C; Ben Mosbah, I; Rauch, C; Henderson, C; Bellaud, P; Aninat, C; Loyer, P; Morel, F; Corlu, A

2015-01-01

Glutathione transferases (GST) are phase II enzymes catalyzing the detoxification of endogenous noxious compounds and xenobiotics. They also regulate phosphorylation activities of MAPKinases in a catalytic-independent manner. Previous studies have demonstrated the regulation of JNK-dependent pathway by GSTP1/2. Considering the crucial role of JNK in the early steps of the hepatocyte cell cycle, we sought to determine whether GSTP1/2 were essential for hepatocyte proliferation following partial hepatectomy (PH). Using a conventional double knockout mouse model for the Gstp1 and Gstp2 genes, we found that the lack of GSTP1/P2 reduced the rate of DNA replication and mitotic index during the first wave of hepatocyte proliferation. The lowered proliferation was associated with the decrease in TNFalpha and IL-6 plasma concentrations, reduced hepatic HGF expression and delayed and/or altered activation of STAT3, JNK and ERK1/2 signaling pathways. In addition, the expression and/or activation of cell cycle regulators such as Cyclin D1, CDK4, E2F1 and MCM7 was postponed demonstrating that the absence of GSTP1/2 delayed the entry into and progression through the G1 phase of the cell cycle and impaired the synchrony of proliferation in hepatocytes following PH. Furthermore, while JNK and its downstream targets c-Jun and ATF2 were activated during the early steps of the liver regeneration in wild-type animals, the constitutively active JNK found in the quiescent liver of Gstp1/2 knockout mice underwent a decrease in its activity after PH. Transient induction of antioxidant enzymes and nitric oxide synthase were also delayed or repressed during the regenerative response. Altogether our results demonstrate that GSTP1/2 are a critical regulators of hepatocyte proliferation in the initial phases of liver regeneration. PMID:25590808

FAA Loran early implementation project

DOT National Transportation Integrated Search

1990-03-01

The Early Implementation Project (EIP), established by FAA Administrator Admiral : Donald C. Engen, was the initial step in the process of Loran integration into the : National Airsace System (NAS). The EIP was designed to give the FAA and the Loran ...

Locomotor training improves reciprocal and nonreciprocal inhibitory control of soleus motoneurons in human spinal cord injury

PubMed Central

Smith, Andrew C.; Mummidisetty, Chaithanya K.

2015-01-01

Pathologic reorganization of spinal networks and activity-dependent plasticity are common neuronal adaptations after spinal cord injury (SCI) in humans. In this work, we examined changes of reciprocal Ia and nonreciprocal Ib inhibition after locomotor training in 16 people with chronic SCI. The soleus H-reflex depression following common peroneal nerve (CPN) and medial gastrocnemius (MG) nerve stimulation at short conditioning-test (C-T) intervals was assessed before and after training in the seated position and during stepping. The conditioned H reflexes were normalized to the unconditioned H reflex recorded during seated. During stepping, both H reflexes were normalized to the maximal M wave evoked at each bin of the step cycle. In the seated position, locomotor training replaced reciprocal facilitation with reciprocal inhibition in all subjects, and Ib facilitation was replaced by Ib inhibition in 13 out of 14 subjects. During stepping, reciprocal inhibition was decreased at early stance and increased at midswing in American Spinal Injury Association Impairment Scale C (AIS C) and was decreased at midstance and midswing phases in AIS D after training. Ib inhibition was decreased at early swing and increased at late swing in AIS C and was decreased at early stance phase in AIS D after training. The results of this study support that locomotor training alters postsynaptic actions of Ia and Ib inhibitory interneurons on soleus motoneurons at rest and during stepping and that such changes occur in cases with limited or absent supraspinal inputs. PMID:25609110

The Next Step in Understanding Impaired Reactive Balance Control in People With Stroke: The Role of Defective Early Automatic Postural Responses.

PubMed

de Kam, Digna; Roelofs, Jolanda M B; Bruijnes, Amber K B D; Geurts, Alexander C H; Weerdesteyn, Vivian

2017-08-01

Postural muscle responses are often impaired after stroke. We aimed to identify the contribution of deficits in very early postural responses to poorer reactive balance capacity, with a particular focus on reactive stepping as a key strategy for avoiding falls. A total of 34 chronic stroke survivors and 17 controls were subjected to translational balance perturbations in 4 directions. We identified the highest perturbation intensity that could be recovered without stepping (single stepping threshold [SST]) and with maximally 1 step (multiple stepping threshold [MST]). We determined onset latencies and response amplitudes of 7 leg muscles bilaterally and identified associations with balance capacity. People with stroke had a lower MST than controls in all directions. Side steps resulted in a higher lateral MST than crossover steps but were less common toward the paretic side. Postural responses were delayed and smaller in amplitude on the paretic side only. We observed the strongest associations between gluteus medius (GLUT) onset and amplitude and MST toward the paretic side ( R 2 = 0.33). Electromyographic variables were rather weakly associated with forward and backward MSTs ( R 2 = 0.10-0.22) and with SSTs ( R 2 = 0.08-0.15). Delayed and reduced paretic postural responses are associated with impaired reactive stepping after stroke. Particularly, fast and vigorous activity of the GLUT is imperative for overcoming large sideways perturbations, presumably because it facilitates the effective use of side steps. Because people with stroke often fall toward the paretic side, this finding indicates an important target for training.

Enhancing the population impact of collaborative care interventions: Mixed method development and implementation of stepped care targeting posttraumatic stress disorder and related comorbidities after acute trauma

PubMed Central

Zatzick, Douglas; Rivara, Frederick; Jurkovich, Gregory; Russo, Joan; Trusz, Sarah Geiss; Wang, Jin; Wagner, Amy; Stephens, Kari; Dunn, Chris; Uehara, Edwina; Petrie, Megan; Engel, Charles; Davydow, Dimitri; Katon, Wayne

2011-01-01

Objective To develop and implement a stepped collaborative care intervention targeting PTSD and related co-morbidities to enhance the population impact of early trauma-focused interventions. Method We describe the design and implementation of the Trauma Survivors Outcomes & Support Study (TSOS II). An interdisciplinary treatment development team was comprised of trauma surgical, clinical psychiatric and mental health services “change agents” who spanned the boundaries between front-line trauma center clinical care and acute care policy. Mixed method clinical epidemiologic and clinical ethnographic studies informed the development of PTSD screening and intervention procedures. Results Two-hundred and seven acutely injured trauma survivors with high early PTSD symptom levels were randomized into the study. The stepped collaborative care model integrated care management (i.e., posttraumatic concern elicitation and amelioration, motivational interviewing, and behavioral activation) with cognitive behavioral therapy and pharmacotherapy targeting PTSD. The model was feasibly implemented by front-line acute care MSW and ARNP providers. Conclusions Stepped care protocols targeting PTSD may enhance the population impact of early interventions developed for survivors of individual and mass trauma by extending the reach of collaborative care interventions to acute care medical settings and other non-specialty posttraumatic contexts. PMID:21596205

Augmentation of Voluntary Locomotor Activity by Transcutaneous Spinal Cord Stimulation in Motor-Incomplete Spinal Cord-Injured Individuals.

PubMed

Hofstoetter, Ursula S; Krenn, Matthias; Danner, Simon M; Hofer, Christian; Kern, Helmut; McKay, William B; Mayr, Winfried; Minassian, Karen

2015-10-01

The level of sustainable excitability within lumbar spinal cord circuitries is one of the factors determining the functional outcome of locomotor therapy after motor-incomplete spinal cord injury. Here, we present initial data using noninvasive transcutaneous lumbar spinal cord stimulation (tSCS) to modulate this central state of excitability during voluntary treadmill stepping in three motor-incomplete spinal cord-injured individuals. Stimulation was applied at 30 Hz with an intensity that generated tingling sensations in the lower limb dermatomes, yet without producing muscle reflex activity. This stimulation changed muscle activation, gait kinematics, and the amount of manual assistance required from the therapists to maintain stepping with some interindividual differences. The effect on motor outputs during treadmill-stepping was essentially augmentative and step-phase dependent despite the invariant tonic stimulation. The most consistent modification was found in the gait kinematics, with the hip flexion during swing increased by 11.3° ± 5.6° across all subjects. This preliminary work suggests that tSCS provides for a background increase in activation of the lumbar spinal locomotor circuitry that has partially lost its descending drive. Voluntary inputs and step-related feedback build upon the stimulation-induced increased state of excitability in the generation of locomotor activity. Thus, tSCS essentially works as an electrical neuroprosthesis augmenting remaining motor control. Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Essential Services Act of 2013

THOMAS, 113th Congress

Sen. Blunt, Roy [R-MO

2013-04-15

Senate - 04/15/2013 Read twice and referred to the Committee on Homeland Security and Governmental Affairs. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

Macroscopic brain dynamics during verbal and pictorial processing of affective stimuli.

PubMed

Keil, Andreas

2006-01-01

Emotions can be viewed as action dispositions, preparing an individual to act efficiently and successfully in situations of behavioral relevance. To initiate optimized behavior, it is essential to accurately process the perceptual elements indicative of emotional relevance. The present chapter discusses effects of affective content on neural and behavioral parameters of perception, across different information channels. Electrocortical data are presented from studies examining affective perception with pictures and words in different task contexts. As a main result, these data suggest that sensory facilitation has an important role in affective processing. Affective pictures appear to facilitate perception as a function of emotional arousal at multiple levels of visual analysis. If the discrimination between affectively arousing vs. nonarousing content relies on fine-grained differences, amplification of the cortical representation may occur as early as 60-90 ms after stimulus onset. Affectively arousing information as conveyed via visual verbal channels was not subject to such very early enhancement. However, electrocortical indices of lexical access and/or activation of semantic networks showed that affectively arousing content may enhance the formation of semantic representations during word encoding. It can be concluded that affective arousal is associated with activation of widespread networks, which act to optimize sensory processing. On the basis of prioritized sensory analysis for affectively relevant stimuli, subsequent steps such as working memory, motor preparation, and action may be adjusted to meet the adaptive requirements of the situation perceived.

Precompetitive cooperative research: the culture of the '90s

NASA Astrophysics Data System (ADS)

Holton, William C.

1991-03-01

In the current worldwide technology environment, it is essential for the U.S. microelectronics industry. and especially for the integrated circuit portion of that industry, that precompeutive cooperative research alliances be formed and funded at a level that emables them to be effective in rapidly advancing technology. It is important to realize that technology advances with or without our direct participation. If we do not aggressively participate we are quickly left behind. Increasing complexity and miniaturization have been the themes in semiconductor technology. Many are aware that what began in the early 60's with a few masking steps and minimum dimensions measured in mils. has now evolved to a level of sophistication requiring a 100 MW workstation for IC design and the investment of nearly S400 million dollars in fab cost to produce today's microchips. The leading nations of the world have come to realize that their future well-being is closely tied to their ability to compete in this hi-tech environment. Industry coalitions have been formed to exploit the early ramifications of emeging technologies. Improvements in overseas manufacturing have been made and continue unabated with new producLs, new processes, and new services being introduced at an increasing rate. Many foreign governments are now actively involved in formulating and conducting industrial and technology policies to aid their hi-tech industry. To meet these challenges, U.S. firms, with U. S. government cooperation, must respond.

Multi-walled carbon nanotubes applied through seed-priming influence early germination, root hair, growth and yield of bread wheat (Triticum aestivum L.).

PubMed

Joshi, Anjali; Kaur, Simranjeet; Dharamvir, Keya; Nayyar, Harsh; Verma, Gaurav

2018-06-01

Reports of multi-walled carbon nanotubes (MWCNTs) incorporated into plants have indicated better yield and productivity, yet the phenomena need in-depth understanding especially when agricultural crops are tested. We primed wheat seeds with MWCNTs to understand the effects on germination, growth, anatomy, physiology and yield. This study, carried out in field conditions, is a step forward over the previous reports. Early germination, excessive root hair, denser stomata and larger root length result in faster growth and higher yield of wheat plants. Denser root hair facilitated the uptake of both water and essential minerals such as phosphorus (P) and potassium (K), which boosted the crop yield by significantly improving grain yield per plant from 1.53 to 2.5 g, a 63% increase. Increase in cell elongation by 80% was recorded, while xylem and phloem sizes dilated to almost 83% and 85% of control, thus enhancing their capacity to conduct water and nutrients. Augmented growth of MWCNT-primed wheat, enhancement in grain number, biomass, stomatal density, xylem-phloem size, epidermal cells, and water uptake is observed while finding no DNA damage. This opens up an entirely new aspect to using cost-effective nanomaterials (the MWCNTs were produced in-house) for enhancing the performance of crop plants. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

The dimerization of the yeast cytochrome bc1 complex is an early event and is independent of Rip1.

PubMed

Conte, Annalea; Papa, Benedetta; Ferramosca, Alessandra; Zara, Vincenzo

2015-05-01

In Saccharomyces cerevisiae the mature cytochrome bc1 complex exists as an obligate homo-dimer in which each monomer consists of ten distinct protein subunits inserted into or bound to the inner mitochondrial membrane. Among them, the Rieske iron-sulfur protein (Rip1), besides its catalytic role in electron transfer, may be implicated in the bc1 complex dimerization. Indeed, Rip1 has the globular domain containing the catalytic center in one monomer while the transmembrane helix interacts with the adjacent monomer. In addition, the lack of Rip1 leads to the accumulation of an immature bc1 intermediate, only loosely associated with cytochrome c oxidase. In this study we have investigated the biogenesis of the yeast cytochrome bc1 complex using epitope tagged proteins to purify native assembly intermediates. We showed that the dimerization process is an early event during bc1 complex biogenesis and that the presence of Rip1, differently from previous proposals, is not essential for this process. We also investigated the multi-step model of bc1 assembly thereby lending further support to the existence of bona fide subcomplexes during bc1 maturation in the inner mitochondrial membrane. Finally, a new model of cytochrome bc1 complex assembly, in which distinct intermediates sequentially interact during bc1 maturation, has been proposed. Copyright © 2015 Elsevier B.V. All rights reserved.

On the enigmatic birth of the Pacific Plate within the Panthalassa Ocean

PubMed Central

Boschman, Lydian M.; van Hinsbergen, Douwe J. J.

2016-01-01

The oceanic Pacific Plate started forming in Early Jurassic time within the vast Panthalassa Ocean that surrounded the supercontinent Pangea, and contains the oldest lithosphere that can directly constrain the geodynamic history of the circum-Pangean Earth. We show that the geometry of the oldest marine magnetic anomalies of the Pacific Plate attests to a unique plate kinematic event that sparked the plate’s birth at virtually a point location, surrounded by the Izanagi, Farallon, and Phoenix Plates. We reconstruct the unstable triple junction that caused the plate reorganization, which led to the birth of the Pacific Plate, and present a model of the plate tectonic configuration that preconditioned this event. We show that a stable but migrating triple junction involving the gradual cessation of intraoceanic Panthalassa subduction culminated in the formation of an unstable transform-transform-transform triple junction. The consequent plate boundary reorganization resulted in the formation of a stable triangular three-ridge system from which the nascent Pacific Plate expanded. We link the birth of the Pacific Plate to the regional termination of intra-Panthalassa subduction. Remnants thereof have been identified in the deep lower mantle of which the locations may provide paleolongitudinal control on the absolute location of the early Pacific Plate. Our results constitute an essential step in unraveling the plate tectonic evolution of “Thalassa Incognita” that comprises the comprehensive Panthalassa Ocean surrounding Pangea. PMID:29713683

Rationale for Implementation of Warm Cardiac Surgery in Pediatrics

PubMed Central

Durandy, Yves

2016-01-01

Cardiac surgery was developed thanks to the introduction of hypothermia and cardiopulmonary bypass in the early 1950s. The deep hypothermia protective effect has been essential to circulatory arrest complex cases repair. During the early times of open-heart surgery, a major concern was to decrease mortality and to improve short-term outcomes. Both mortality and morbidity dramatically decreased over a few decades. As a consequence, the drawbacks of deep hypothermia, with or without circulatory arrest, became more and more apparent. The limitation of hypothermia was particularly evident for the brain and regional perfusion was introduced as a response to this problem. Despite a gain in popularity, the results of regional perfusion were not fully convincing. In the 1990s, warm surgery was introduced in adults and proved to be safe and reliable. This option eliminates the deleterious effect of ischemia–reperfusion injuries through a continuous, systemic coronary perfusion with warm oxygenated blood. Intermittent warm blood cardioplegia was introduced later, with impressive results. We were convinced by the easiness, safety, and efficiency of warm surgery and shifted to warm pediatric surgery in a two-step program. This article outlines the limitations of hypothermic protection and the basic reasons that led us to implement pediatric warm surgery. After tens of thousands of cases performed across several centers, this reproducible technique proved a valuable alternative to hypothermic surgery. PMID:27200324

Rationale for Implementation of Warm Cardiac Surgery in Pediatrics.

PubMed

Durandy, Yves

2016-01-01

Cardiac surgery was developed thanks to the introduction of hypothermia and cardiopulmonary bypass in the early 1950s. The deep hypothermia protective effect has been essential to circulatory arrest complex cases repair. During the early times of open-heart surgery, a major concern was to decrease mortality and to improve short-term outcomes. Both mortality and morbidity dramatically decreased over a few decades. As a consequence, the drawbacks of deep hypothermia, with or without circulatory arrest, became more and more apparent. The limitation of hypothermia was particularly evident for the brain and regional perfusion was introduced as a response to this problem. Despite a gain in popularity, the results of regional perfusion were not fully convincing. In the 1990s, warm surgery was introduced in adults and proved to be safe and reliable. This option eliminates the deleterious effect of ischemia-reperfusion injuries through a continuous, systemic coronary perfusion with warm oxygenated blood. Intermittent warm blood cardioplegia was introduced later, with impressive results. We were convinced by the easiness, safety, and efficiency of warm surgery and shifted to warm pediatric surgery in a two-step program. This article outlines the limitations of hypothermic protection and the basic reasons that led us to implement pediatric warm surgery. After tens of thousands of cases performed across several centers, this reproducible technique proved a valuable alternative to hypothermic surgery.

HCPCS Coding: An Integral Part of Your Reimbursement Strategy.

PubMed

Nusgart, Marcia

2013-12-01

The first step to a successful reimbursement strategy is to ensure that your wound care product has the most appropriate Healthcare Common Procedure Coding System (HCPCS) code (or billing) for your product. The correct HCPCS code plays an essential role in patient access to new and existing technologies. When devising a strategy to obtain a HCPCS code for its product, companies must consider a number of factors as follows: (1) Has the product gone through the Food and Drug Administration (FDA) regulatory process or does it need to do so? Will the FDA code designation impact which HCPCS code will be assigned to your product? (2) In what "site of service" do you intend to market your product? Where will your customers use the product? Which coding system (CPT ® or HCPCS) applies to your product? (3) Does a HCPCS code for a similar product already exist? Does your product fit under the existing HCPCS code? (4) Does your product need a new HCPCS code? What is the linkage, if any, between coding, payment, and coverage for the product? Researchers and companies need to start early and place the same emphasis on a reimbursement strategy as it does on a regulatory strategy. Your reimbursement strategy staff should be involved early in the process, preferably during product research and development and clinical trial discussions.

On the Enigmatic Birth of the Pacific Plate within the Panthalassa Ocean

NASA Astrophysics Data System (ADS)

Boschman, L.; Van Hinsbergen, D. J. J.

2016-12-01

The oceanic Pacific Plate started forming in Early Jurassic time within the vast Panthalassa Ocean that surrounded the supercontinent Pangea and contains the oldest lithosphere that can directly constrain the geodynamic history of the circum-Pangean Earth. Here, we show that the geometry of the oldest marine magnetic anomalies of the Pacific Plate attests of a unique plate kinematic event that sparked the plate's birth in virtually a point location, surrounded by the Izanagi, Farallon and Phoenix Plates. We reconstruct the unstable triple junction that caused the plate reorganization leading to the birth of the Pacific Plate and present a model of the plate tectonic configuration that preconditioned this event. We show that a stable, but migrating triple junction involving the gradual cessation of intra-oceanic Panthalassa subduction culminated in the formation of an unstable transform-transform-transform triple junction. The consequent plate boundary reorganization resulted in the formation of a stable triangular three-ridge system from which the nascent Pacific Plate expanded. We link the birth of the Pacific Plate to the regional termination of intra-Panthalassa subduction. Remnants thereof have been identified in the deep lower mantle of which the locations may provide paleolongitudinal control on the absolute location of the early Pacific Plate. Our results constitute an essential step in unraveling the plate tectonic evolution of `Thalassa Incognita' comprising the comprehensive Panthalassa Ocean surrounding Pangea.

Comprehensive Evaluation of Streptococcus sanguinis Cell Wall-Anchored Proteins in Early Infective Endocarditis▿ †

PubMed Central

Turner, Lauren Senty; Kanamoto, Taisei; Unoki, Takeshi; Munro, Cindy L.; Wu, Hui; Kitten, Todd

2009-01-01

Streptococcus sanguinis is a member of the viridans group of streptococci and a leading cause of the life-threatening endovascular disease infective endocarditis. Initial contact with the cardiac infection site is likely mediated by S. sanguinis surface proteins. In an attempt to identify the proteins required for this crucial step in pathogenesis, we searched for surface-exposed, cell wall-anchored proteins encoded by S. sanguinis and then used a targeted signature-tagged mutagenesis (STM) approach to evaluate their contributions to virulence. Thirty-three predicted cell wall-anchored proteins were identified—a number much larger than those found in related species. The requirement of each cell wall-anchored protein for infective endocarditis was assessed in the rabbit model. It was found that no single cell wall-anchored protein was essential for the development of early infective endocarditis. STM screening was also employed for the evaluation of three predicted sortase transpeptidase enzymes, which mediate the cell surface presentation of cell wall-anchored proteins. The sortase A mutant exhibited a modest (∼2-fold) reduction in competitiveness, while the other two sortase mutants were indistinguishable from the parental strain. The combined results suggest that while cell wall-anchored proteins may play a role in S. sanguinis infective endocarditis, strategies designed to interfere with individual cell wall-anchored proteins or sortases would not be effective for disease prevention. PMID:19703977

Comprehensive evaluation of Streptococcus sanguinis cell wall-anchored proteins in early infective endocarditis.

PubMed

Turner, Lauren Senty; Kanamoto, Taisei; Unoki, Takeshi; Munro, Cindy L; Wu, Hui; Kitten, Todd

2009-11-01

Streptococcus sanguinis is a member of the viridans group of streptococci and a leading cause of the life-threatening endovascular disease infective endocarditis. Initial contact with the cardiac infection site is likely mediated by S. sanguinis surface proteins. In an attempt to identify the proteins required for this crucial step in pathogenesis, we searched for surface-exposed, cell wall-anchored proteins encoded by S. sanguinis and then used a targeted signature-tagged mutagenesis (STM) approach to evaluate their contributions to virulence. Thirty-three predicted cell wall-anchored proteins were identified-a number much larger than those found in related species. The requirement of each cell wall-anchored protein for infective endocarditis was assessed in the rabbit model. It was found that no single cell wall-anchored protein was essential for the development of early infective endocarditis. STM screening was also employed for the evaluation of three predicted sortase transpeptidase enzymes, which mediate the cell surface presentation of cell wall-anchored proteins. The sortase A mutant exhibited a modest (approximately 2-fold) reduction in competitiveness, while the other two sortase mutants were indistinguishable from the parental strain. The combined results suggest that while cell wall-anchored proteins may play a role in S. sanguinis infective endocarditis, strategies designed to interfere with individual cell wall-anchored proteins or sortases would not be effective for disease prevention.

Question 2: Raman spectroscopic approach to analytical astrobiology: the detection of key biomolecular markers in the search for life.

PubMed

Edwards, Howell G M

2007-10-01

The recognition of extinct or extant life signatures in the terrestrial geological record is fundamentally dependent upon the understanding of both the structural morphology and chemical composition of relict biomaterials; the identification of cyanobacterial colonies that have adapted biogeologically their mineral matrices in early evolutionary processes is a fundamental step in the acquisition of analytical data from remote planetary probes designed for life-detection experiments, particularly on Mars and on the planetary satellite moons, Europa and Titan. A key factor in the assessment of early life signatures is the molecular presence of chemicals designed to protect the emerging organisms from the damaging effect of radiation exposure and of desiccation and temperature changes; in this respect the non-destructive capability of Raman spectroscopy to delineate the interfacial interactions between substrates and endolithic biology is now deemed an essential part of the ExoMars life-detection suite of instrumentation planned by the European Space Agency in the AURORA programme. A description of the scientific basis for the biogeological discrimination offered by Raman spectroscopy between organic and inorganic moieties in specimens from terrestrial Mars analogue sites is followed by selected examples of the type of analytical information provided, which will be complementary to the elementary and microscopic data obtained from other instrumentation on the same mission.

On the enigmatic birth of the Pacific Plate within the Panthalassa Ocean.

PubMed

Boschman, Lydian M; van Hinsbergen, Douwe J J

2016-07-01

The oceanic Pacific Plate started forming in Early Jurassic time within the vast Panthalassa Ocean that surrounded the supercontinent Pangea, and contains the oldest lithosphere that can directly constrain the geodynamic history of the circum-Pangean Earth. We show that the geometry of the oldest marine magnetic anomalies of the Pacific Plate attests to a unique plate kinematic event that sparked the plate's birth at virtually a point location, surrounded by the Izanagi, Farallon, and Phoenix Plates. We reconstruct the unstable triple junction that caused the plate reorganization, which led to the birth of the Pacific Plate, and present a model of the plate tectonic configuration that preconditioned this event. We show that a stable but migrating triple junction involving the gradual cessation of intraoceanic Panthalassa subduction culminated in the formation of an unstable transform-transform-transform triple junction. The consequent plate boundary reorganization resulted in the formation of a stable triangular three-ridge system from which the nascent Pacific Plate expanded. We link the birth of the Pacific Plate to the regional termination of intra-Panthalassa subduction. Remnants thereof have been identified in the deep lower mantle of which the locations may provide paleolongitudinal control on the absolute location of the early Pacific Plate. Our results constitute an essential step in unraveling the plate tectonic evolution of "Thalassa Incognita" that comprises the comprehensive Panthalassa Ocean surrounding Pangea.

Does First Step to Success Have Long-Term Impacts on Student Behavior? An Analysis of Efficacy Trial Data

ERIC Educational Resources Information Center

Woodbridge, Michelle W.; Sumi, W. Carl; Wagner, Mary M.; Javitz, Harold S.; Seeley, John R.; Walker, Hill M.; Small, Jason W.; Golly, Annemieke; Feil, Edward G.; Severson, Herbert H.

2014-01-01

First Step to Success (First Step; Walker et al., 1997, 1998) is a secondary-level intervention for students with behavior problems in early elementary school. The purposes of this study were to assess whether effects in student behavior and academics at posttest shown in a recent efficacy trial (Walker et al., 2009) were maintained at follow-up…

Step 6: Does Not Routinely Employ Practices, Procedures Unsupported by Scientific Evidence

PubMed Central

Goer, Henci; Sagady Leslie, Mayri; Romano, Amy

2007-01-01

Step 6 of the Ten Steps of Mother-Friendly Care addresses two issues: 1) the routine use of interventions (shaving, enemas, intravenous drips, withholding food and fluids, early rupture of membranes, and continuous electronic fetal monitoring; and 2) the optimal rates of induction, episiotomy, cesareans, and vaginal births after cesarean. Rationales for compliance and systematic reviews are presented. PMID:18523680

A More Flexible Approach to Valuing Flexibility

DTIC Science & Technology

2011-04-01

remaining life of the program? Almost certainly. Next is the cost assessment step. This is executed in the context of whatever design options we...methodology is essentially a modifi- cation of the current life cycle model and is premised on the notion that the need for capabili- ty changes in a program...valuing the inherent ability of a system or design to accommodate change. The proposed methodology is essentially a modifi-cation of the current life

Transcriptome Analysis of Honeybee (Apis Mellifera) Haploid and Diploid Embryos Reveals Early Zygotic Transcription during Cleavage

PubMed Central

Pires, Camilla Valente; Freitas, Flávia Cristina de Paula; Cristino, Alexandre S.; Dearden, Peter K.; Simões, Zilá Luz Paulino

2016-01-01

In honeybees, the haplodiploid sex determination system promotes a unique embryogenesis process wherein females develop from fertilized eggs and males develop from unfertilized eggs. However, the developmental strategies of honeybees during early embryogenesis are virtually unknown. Similar to most animals, the honeybee oocytes are supplied with proteins and regulatory elements that support early embryogenesis. As the embryo develops, the zygotic genome is activated and zygotic products gradually replace the preloaded maternal material. The analysis of small RNA and mRNA libraries of mature oocytes and embryos originated from fertilized and unfertilized eggs has allowed us to explore the gene expression dynamics in the first steps of development and during the maternal-to-zygotic transition (MZT). We localized a short sequence motif identified as TAGteam motif and hypothesized to play a similar role in honeybees as in fruit flies, which includes the timing of early zygotic expression (MZT), a function sustained by the presence of the zelda ortholog, which is the main regulator of genome activation. Predicted microRNA (miRNA)-target interactions indicated that there were specific regulators of haploid and diploid embryonic development and an overlap of maternal and zygotic gene expression during the early steps of embryogenesis. Although a number of functions are highly conserved during the early steps of honeybee embryogenesis, the results showed that zygotic genome activation occurs earlier in honeybees than in Drosophila based on the presence of three primary miRNAs (pri-miRNAs) (ame-mir-375, ame-mir-34 and ame-mir-263b) during the cleavage stage in haploid and diploid embryonic development. PMID:26751956

ASSOCIATION BETWEEN VISUAL FUNCTION AND SUBRETINAL DRUSENOID DEPOSITS IN NORMAL AND EARLY AGE-RELATED MACULAR DEGENERATION EYES.

PubMed

Neely, David; Zarubina, Anna V; Clark, Mark E; Huisingh, Carrie E; Jackson, Gregory R; Zhang, Yuhua; McGwin, Gerald; Curcio, Christine A; Owsley, Cynthia

2017-07-01

To examine the association between subretinal drusenoid deposits (SDDs) identified by multimodal retinal imaging and visual function in older eyes with normal macular health or in the earliest phases of age-related macular degeneration (AMD). Age-related macular degeneration status for each eye was defined according to the Age-Related Eye Disease Study (AREDS) 9-step classification system (normal = Step 1, early AMD = Steps 2-4) based on color fundus photographs. Visual functions measured were best-corrected photopic visual acuity, contrast and light sensitivity, mesopic visual acuity, low-luminance deficit, and rod-mediated dark adaptation. Subretinal drusenoid deposits were identified through multimodal imaging (color fundus photographs, infrared reflectance and fundus autofluorescence images, and spectral domain optical coherence tomography). The sample included 1,202 eyes (958 eyes with normal health and 244 eyes with early AMD). In normal eyes, SDDs were not associated with any visual function evaluated. In eyes with early AMD, dark adaptation was markedly delayed in eyes with SDDs versus no SDD (a 4-minute delay on average), P = 0.0213. However, this association diminished after age adjustment, P = 0.2645. Other visual functions in early AMD eyes were not associated with SDDs. In a study specifically focused on eyes in normal macular health and in the earliest phases of AMD, early AMD eyes with SDDs have slower dark adaptation, largely attributable to the older ages of eyes with SDD; they did not exhibit deficits in other visual functions. Subretinal drusenoid deposits in older eyes in normal macular health are not associated with any visual functions evaluated.

Optimizing identification and management of COPD patients - reviewing the role of the community pharmacist.

PubMed

van der Molen, Thys; van Boven, Job F M; Maguire, Terence; Goyal, Pankaj; Altman, Pablo

2017-01-01

The aim of this paper was to propose key steps for community pharmacist integration into a patient care pathway for chronic obstructive pulmonary disease (COPD) management. A literature search was conducted to identify publications focusing on the role of the community pharmacist in identification and management of COPD. The literature search highlighted evidence supporting an important role for pharmacists at each of the four key steps in the patient care pathway for COPD management. Step 1 (primary prevention): pharmacists are ideally placed to provide information on disease awareness and risk prevention campaigns, and to encourage lifestyle interventions, including smoking cessation. Step 2 (early detection/case finding): pharmacists are often the first point of contact between the patient and the healthcare system and can therefore play an important role in the early identification of patients with COPD. Step 3 (management and ongoing support): pharmacists can assist patients by providing advice and education on dosage, inhaler technique, treatment expectations and the importance of adherence, and by supporting self-management, including recognition and treatment of COPD exacerbations. Step 4 (review and follow-up): pharmacists can play an important role in monitoring adherence and ongoing inhaler technique in patients with COPD. In summary, pharmacists are ideally positioned to play a vital role in all key stages of an integrated COPD patient care pathway from early disease detection to the support of management plans, including advice and counselling regarding medications, inhaler technique and treatment adherence. Areas requiring additional consideration include pharmacist training, increasing awareness of the pharmacist role, administration and reimbursement, and increasing physician-pharmacist collaboration. © 2016 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

A solver for General Unilateral Polynomial Matrix Equation with Second-Order Matrices Over Prime Finite Fields

NASA Astrophysics Data System (ADS)

Burtyka, Filipp

2018-03-01

The paper firstly considers the problem of finding solvents for arbitrary unilateral polynomial matrix equations with second-order matrices over prime finite fields from the practical point of view: we implement the solver for this problem. The solver’s algorithm has two step: the first is finding solvents, having Jordan Normal Form (JNF), the second is finding solvents among the rest matrices. The first step reduces to the finding roots of usual polynomials over finite fields, the second is essentially exhaustive search. The first step’s algorithms essentially use the polynomial matrices theory. We estimate the practical duration of computations using our software implementation (for example that one can’t construct unilateral matrix polynomial over finite field, having any predefined number of solvents) and answer some theoretically-valued questions.

Inhibitors of amino acids biosynthesis as antifungal agents.

PubMed

Jastrzębowska, Kamila; Gabriel, Iwona

2015-02-01

Fungal microorganisms, including the human pathogenic yeast and filamentous fungi, are able to synthesize all proteinogenic amino acids, including nine that are essential for humans. A number of enzymes catalyzing particular steps of human-essential amino acid biosynthesis are fungi specific. Numerous studies have shown that auxotrophic mutants of human pathogenic fungi impaired in biosynthesis of particular amino acids exhibit growth defect or at least reduced virulence under in vivo conditions. Several chemical compounds inhibiting activity of one of these enzymes exhibit good antifungal in vitro activity in minimal growth media, which is not always confirmed under in vivo conditions. This article provides a comprehensive overview of the present knowledge on pathways of amino acids biosynthesis in fungi, with a special emphasis put on enzymes catalyzing particular steps of these pathways as potential targets for antifungal chemotherapy.

The Components of Effective Teacher Training in the Use of Three-Dimensional Immersive Virtual Worlds for Learning and Instruction Purposes: A Literature Review

ERIC Educational Resources Information Center

Nussli, Natalie; Oh, Kevin

2014-01-01

The overarching question that guides this review is to identify the key components of effective teacher training in virtual schooling, with a focus on three-dimensional (3D) immersive virtual worlds (IVWs). The process of identifying the essential components of effective teacher training in the use of 3D IVWs will be described step-by-step. First,…

Tangible Steps Toward Tomorrow: New Designs for Early Education, Ages 0-8

ERIC Educational Resources Information Center

W. K. Kellogg Foundation, 2007

2007-01-01

This publication, developed by W.K. Kellogg Foundation in collaboration with IDEO, details a human-centered approach to evolving the system of early education for the needs and possibilities of the 21st century. It provides a set of ideas or "thought-starters" on transforming early education to ensure school readiness and success for the…

State of Early Child Development Research, Practice, and Policy for Most Vulnerable Children: A Global Perspective

ERIC Educational Resources Information Center

Young, Mary Eming

2017-01-01

Interventions to enhance development of children ages 0-6 have profound benefits for children, families, and societies. The benefits are well documented, recognized internationally, and supportive of policies and programs targeting early child development (ECD). Intervening in the early years is a critical first step toward alleviating poverty,…

Supporting Online Learners: Blending High-Tech with High-Touch

ERIC Educational Resources Information Center

Dolan, Sean; Donohue, Chip; Holstrom, Lisa; Pernell, Latonia; Sachdev, Anu

2009-01-01

Effective and easily accessible student support services are essential to the success of adult learners. A student-centered approach is especially important in the design and delivery of online courses, professional certificates, and degree programs for early childhood professionals. A student-first approach is essential for non-traditional adult…

FOCUS: Essential Elements of Quality for State-Funded Preschool Programs

ERIC Educational Resources Information Center

New Mexico Public Education Department, 2016

2016-01-01

The "FOCUS: Essential Elements of Quality, New Mexico's Tiered Quality Rating and Improvement System (TQRIS)," provides early childhood program personnel with the criteria, tools, and resources they need to improve the quality of their program. These quality improvements focus on children's growth, development, and learning--so that each…

A Practical Approach to Early Technical Education

ERIC Educational Resources Information Center

Chijioke, M. O.

1973-01-01

A minimum of technological awareness is essential to Black Africa in its efforts to modernize itself. The young grow up deprived of an environment where they are made to feel at home with gadgets and machines. Elementary technical training and orderly exposure to mathematics are essential to child's education. (EB)

Start Early to Build a Healthy Future: The Research Linking Early Learning and Health. Summary

ERIC Educational Resources Information Center

Fisher, Brooke; Hanson, Ann; Raden, Tony

2014-01-01

Every child deserves a fair chance. A chance to learn, grow, explore possibilities, persevere and achieve his or her potential. The Ounce of Prevention Fund believes that no child's potential should be limited by poor health. Good health in early childhood is an essential component of school readiness. The benefits of health and learning are…

Using PulpMotion Videos as Instructional Anchors for Pre-Service Teachers Learning about Early Childhood Special Education

ERIC Educational Resources Information Center

Chapman, Denise N. J.

2014-01-01

Providing pre-service early childhood general educators with a strong knowledge base of key aspects of early childhood special education is essential in the United States as US federal law mandates it. Specifically, the Individuals with Disabilities Education Act (IDEA) stipulates that children with special needs must to be placed in the least…

Earlier School Start Times as a Risk Factor for Poor School Performance: An Examination of Public Elementary Schools in the Commonwealth of Kentucky

ERIC Educational Resources Information Center

Keller, Peggy S.; Smith, Olivia A.; Gilbert, Lauren R.; Bi, Shuang; Haak, Eric A.; Buckhalt, Joseph A.

2015-01-01

Adequate sleep is essential for child learning. However, school systems may inadvertently be promoting sleep deprivation through early school start times. The current study examines the potential implications of early school start times for standardized test scores in public elementary schools in Kentucky. Associations between early school start…

Hepatitis B "e" antigen-mediated inhibition of HBV replication fitness and transcription efficiency in vitro.

PubMed

Samal, Jasmine; Kandpal, Manish; Vivekanandan, Perumal

2015-10-01

A mutation at nucleotide 1896 (G1896A) is the most common cause for the loss of HBeAg. In contrast to clinical data, cell culture studies report a high-replicating phenotype for the G1896A mutant. Differences between the wild-type and the G1896A mutant in early steps of HBV replication including the synthesis of pre-genomic RNA and transcripts have not been investigated. The G1896A mutant is associated with higher replication fitness, transcription efficiency and higher levels of secreted HBsAg than the wild-type. Interestingly, trans-complementation of the G1896A mutant with HBeAg lowers the replication fitness and transcriptionefficiency to levels comparable to that of the wild-type. Our results highlight the role of HBeAg in modulating the early steps in HBV replication. In sum, our findings highlight the role of HBeAg in regulating hepatitis B virus replication fitness and transcription efficiency and new insights on the early steps of replication in the G1896A mutant. Copyright © 2015 Elsevier Inc. All rights reserved.

Pseudomonas aeruginosa essentials: an update on investigation of essential genes.

PubMed

Juhas, Mario

2015-11-01

Pseudomonas aeruginosa is the leading cause of nosocomial infections, particularly in immunocompromised, cancer, burn and cystic fibrosis patients. Development of novel antimicrobials against P. aeruginosa is therefore of the highest importance. Although the first reports on P. aeruginosa essential genes date back to the early 2000s, a number of more sensitive genomic approaches have been used recently to better define essential genes in this organism. These analyses highlight the evolution of the definition of an 'essential' gene from the traditional to the context-dependent. Essential genes, particularly those indispensable under the clinically relevant conditions, are considered to be promising targets of novel antibiotics against P. aeruginosa. This review provides an update on the investigation of P. aeruginosa essential genes. Special focus is on recently identified P. aeruginosa essential genes and their exploitation for the development of antimicrobials.

Getting Ready for College Early: A Handbook for Parents of Students in the Middle and Junior High School Years.

ERIC Educational Resources Information Center

Department of Education, Washington, DC. Planning and Evaluation Service.

Steps that parents and children can take to ensure that students properly prepare for college are covered in this guidebook. The guidebook is divided into four steps. In step one, reasons why it is important to go to college are covered. Some of these reasons include better job opportunities, more earning potential, and the increased variety of…

The impact of a public health department's expansion from a one-step to a two-step refugee screening process on the detection and initiation of treatment of latent tuberculosis.

PubMed

Einterz, E M; Younge, O; Hadi, C

2018-06-01

To determine, subsequent to the expansion of a county health department's refugee screening process from a one-step to a two-step process, the change in early loss to follow-up and time to initiation of treatment of new refugees with latent tuberculosis infection (LTBI). Quasi-experimental, quantitative. Review of patient medical records. Among 384 refugees who met the case definition of LTBI without prior tuberculosis (TB) classification, the number of cases lost to early follow-up fell from 12.5% to 0% after expansion to a two-step screening process. The average interval between in-country arrival and initiation of LTBI treatment was shortened by 41.4%. The addition of a second step to the refugee screening process was correlated with significant improvements in the county's success in tracking and treating cases of LTBI in refugees. Given the disproportionate importance of foreign-born cases of LTBI to the incidence of TB disease in low-incidence countries, these improvements could have a substantial impact on overall TB control, and the process described could serve as a model for other local health department refugee screening programs. Copyright © 2018 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

Anticoagulative strategies in reconstructive surgery – clinical significance and applicability

PubMed Central

Jokuszies, Andreas; Herold, Christian; Niederbichler, Andreas D.; Vogt, Peter M.

2012-01-01

Advanced strategies in reconstructive microsurgery and especially free tissue transfer with advanced microvascular techniques have been routinely applied and continously refined for more than three decades in day-to-day clinical work. Bearing in mind the success rates of more than 95%, the value of these techniques in patient care and comfort (one-step reconstruction of even the most complex tissue defects) cannot be underestimated. However, anticoagulative protocols and practices are far from general acceptance and – most importantly – lack the benchmark of evidence basis while the reconstructive and microsurgical methods are mostly standardized. Therefore, the aim of our work was to review the actual literature and synoptically lay out the mechanisms of action of the plethora of anticoagulative substances. The pharmacologic prevention and the surgical intervention of thrombembolic events represent an established and essential part of microsurgery. The high success rates of microvascular free tissue transfer as of today are due to treatment of patients in reconstructive centers where proper patient selection, excellent microsurgical technique, tissue transfer to adequate recipient vessels, and early anastomotic revision in case of thrombosis is provided. Whether the choice of antithrombotic agents is a factor of success remains still unclear. Undoubtedly however the lack of microsurgical experience and bad technique can never be compensated by any regimen of antithrombotic therapy. All the more, the development of consistent standards and algorithms in reconstructive microsurgery is absolutely essential to optimize clinical outcomes and increase multicentric and international comparability of postoperative results and complications. PMID:22294976

Engineering design constraints of the lunar surface environment

NASA Technical Reports Server (NTRS)

Morrison, D. A.

1992-01-01

Living and working on the lunar surface will be difficult. Design of habitats, machines, tools, and operational scenarios in order to allow maximum flexibility in human activity will require paying attention to certain constraints imposed by conditions at the surface and the characteristics of lunar material. Primary design drivers for habitat, crew health and safety, and crew equipment are: ionizing radiation, the meteoroid flux, and the thermal environment. Secondary constraints for engineering derive from: the physical and chemical properties of lunar surface materials, rock distributions and regolith thicknesses, topography, electromagnetic properties, and seismicity. Protection from ionizing radiation is essential for crew health and safety. The total dose acquired by a crew member will be the sum of the dose acquired during EVA time (when shielding will be least) plus the dose acquired during time spent in the habitat (when shielding will be maximum). Minimizing the dose acquired in the habitat extends the time allowable for EVA's before a dose limit is reached. Habitat shielding is enabling, and higher precision in predicting secondary fluxes produced in shielding material would be desirable. Means for minimizing dose during a solar flare event while on extended EVA will be essential. Early warning of the onset of flare activity (at least a half-hour is feasible) will dictate the time available to take mitigating steps. Warning capability affects design of rovers (or rover tools) and site layout. Uncertainty in solar flare timing is a design constraint that points to the need for quickly accessible or constructible safe havens.

Engineering design constraints of the lunar surface environment

NASA Astrophysics Data System (ADS)

Morrison, D. A.

1992-02-01

Living and working on the lunar surface will be difficult. Design of habitats, machines, tools, and operational scenarios in order to allow maximum flexibility in human activity will require paying attention to certain constraints imposed by conditions at the surface and the characteristics of lunar material. Primary design drivers for habitat, crew health and safety, and crew equipment are: ionizing radiation, the meteoroid flux, and the thermal environment. Secondary constraints for engineering derive from: the physical and chemical properties of lunar surface materials, rock distributions and regolith thicknesses, topography, electromagnetic properties, and seismicity. Protection from ionizing radiation is essential for crew health and safety. The total dose acquired by a crew member will be the sum of the dose acquired during EVA time (when shielding will be least) plus the dose acquired during time spent in the habitat (when shielding will be maximum). Minimizing the dose acquired in the habitat extends the time allowable for EVA's before a dose limit is reached. Habitat shielding is enabling, and higher precision in predicting secondary fluxes produced in shielding material would be desirable. Means for minimizing dose during a solar flare event while on extended EVA will be essential. Early warning of the onset of flare activity (at least a half-hour is feasible) will dictate the time available to take mitigating steps. Warning capability affects design of rovers (or rover tools) and site layout. Uncertainty in solar flare timing is a design constraint that points to the need for quickly accessible or constructible safe havens.

CTC1-mediated C-strand fill-in is an essential step in telomere length maintenance

PubMed Central

Feng, Xuyang; Hsu, Shih-Jui; Kasbek, Christopher; Chaiken, Mary

2017-01-01

Abstract To prevent progressive telomere shortening as a result of conventional DNA replication, new telomeric DNA must be added onto the chromosome end. The de novo DNA synthesis involves elongation of the G-rich strand of the telomere by telomerase. In human cells, the CST complex (CTC1-STN1-TEN1) also functions in telomere replication. CST first aids in duplication of the telomeric dsDNA. Then after telomerase has extended the G-rich strand, CST facilitates fill-in synthesis of the complementary C-strand. Here, we analyze telomere structure after disruption of human CTC1 and demonstrate that functional CST is essential for telomere length maintenance due to its role in mediating C-strand fill-in. Removal of CTC1 results in elongation of the 3΄ overhang on the G-rich strand. This leads to accumulation of RPA and telomeric DNA damage signaling. G-overhang length increases with time after CTC1 disruption and at early times net G-strand growth is apparent, indicating telomerase-mediated G-strand extension. In contrast, C-strand length decreases continuously, indicating a deficiency in C-strand fill-in synthesis. The lack of C-strand maintenance leads to gradual shortening of the telomeric dsDNA, similar to that observed in cells lacking telomerase. Thus, telomerase-mediated G-strand extension and CST-mediated C-strand fill-in are equally important for telomere length maintenance. PMID:28334750

Report of the Governor's Blue Ribbon Transportation Task Force

DOT National Transportation Integrated Search

1982-12-01

Governor Ray appointed the Blue Ribbon Transportation Task Force to provide guidance concerning specific steps that can be taken to: achieve maximum efficiency in the utilization of transportation resources; preserve essential transportation services...

Genetics Home Reference: hidradenitis suppurativa

MedlinePlus

... proteins, which is an important step in several chemical signaling pathways. One of these pathways, known as Notch signaling, is essential for the normal maturation and division of hair follicle cells and other types of skin cells. ...

EMG1 is essential for mouse pre-implantation embryo development.

PubMed

Wu, Xiaoli; Sandhu, Sumit; Patel, Nehal; Triggs-Raine, Barbara; Ding, Hao

2010-09-21

Essential for mitotic growth 1 (EMG1) is a highly conserved nucleolar protein identified in yeast to have a critical function in ribosome biogenesis. A mutation in the human EMG1 homolog causes Bowen-Conradi syndrome (BCS), a developmental disorder characterized by severe growth failure and psychomotor retardation leading to death in early childhood. To begin to understand the role of EMG1 in mammalian development, and how its deficiency could lead to Bowen-Conradi syndrome, we have used mouse as a model. The expression of Emg1 during mouse development was examined and mice carrying a null mutation for Emg1 were generated and characterized. Our studies indicated that Emg1 is broadly expressed during early mouse embryonic development. However, in late embryonic stages and during postnatal development, Emg1 exhibited specific expression patterns. To assess a developmental role for EMG1 in vivo, we exploited a mouse gene-targeting approach. Loss of EMG1 function in mice arrested embryonic development prior to the blastocyst stage. The arrested Emg1-/- embryos exhibited defects in early cell lineage-specification as well as in nucleologenesis. Further, loss of p53, which has been shown to rescue some phenotypes resulting from defects in ribosome biogenesis, failed to rescue the Emg1-/- pre-implantation lethality. Our data demonstrate that Emg1 is highly expressed during mouse embryonic development, and essential for mouse pre-implantation development. The absolute requirement for EMG1 in early embryonic development is consistent with its essential role in yeast. Further, our findings also lend support to the previous study that showed Bowen-Conradi syndrome results from a partial EMG1 deficiency. A complete deficiency would not be expected to be compatible with a live birth.

Foot Placement Characteristics and Plantar Pressure Distribution Patterns during Stepping on Ground in Neonates

PubMed Central

Sylos-Labini, F.; Magnani, S.; Cappellini, G.; La Scaleia, V.; Fabiano, A.; Picone, S.; Paolillo, P.; Di Paolo, A.; Lacquaniti, F.; Ivanenko, Y.

2017-01-01

Stepping on ground can be evoked in human neonates, though it is rather irregular and stereotyped heel-to-toe roll-over pattern is lacking. Such investigations can provide insights into the role of contact- or load-related proprioceptive feedback during early development of locomotion. However, the detailed characteristics of foot placements and their association with motor patterns are still incompletely documented. We elicited stepping in 33 neonates supported on a table. Unilateral limb kinematics, bilateral plantar pressure distribution and EMG activity from up to 11 ipsilateral leg muscles were recorded. Foot placement characteristics in neonates showed a wide variation. In ~25% of steps, the swinging foot stepped onto the contralateral foot due to generally small step width. In the remaining steps with separate foot placements, the stance phase could start with forefoot (28%), midfoot (47%), or heel (25%) touchdowns. Despite forefoot or heel initial contacts, the kinematic and loading patterns markedly differed relatively to toe-walking or adult-like two-peaked vertical force profile. Furthermore, while the general stepping parameters (cycle duration, step length, range of motion of proximal joints) were similar, the initial foot contact was consistently associated with specific center-of-pressure excursion, range of motion in the ankle joint, and the center-of-activity of extensor muscles (being shifted by ~5% of cycle toward the end of stance in the “heel” relative to “forefoot” condition). In sum, we found a variety of footfall patterns in conjunction with associated changes in motor patterns. These findings suggest the potential contribution of load-related proprioceptive feedback and/or the expression of variations in the locomotor program already during early manifestations of stepping on ground in human babies. PMID:29066982

Chagas disease diagnostic applications: present knowledge and future steps

PubMed Central

Balouz, Virginia; Agüero, Fernán; Buscaglia, Carlos A.

2017-01-01

Chagas disease, caused by the protozoan Trypanosoma cruzi, is a life-long and debilitating illness of major significance throughout Latin America, and an emergent threat to global public health. Being a neglected disease, the vast majority of Chagasic patients have limited access to proper diagnosis and treatment, and there is only a marginal investment into R&D for drug and vaccine development. In this context, identification of novel biomarkers able to transcend the current limits of diagnostic methods surfaces as a main priority in Chagas disease applied research. The expectation is that these novel biomarkers will provide reliable, reproducible and accurate results irrespective of the genetic background, infecting parasite strain, stage of disease, and clinical-associated features of Chagasic populations. In addition, they should be able to address other still unmet diagnostic needs, including early detection of congenital T. cruzi transmission, rapid assessment of treatment efficiency or failure, indication/prediction of disease progression and direct parasite typification in clinical samples. The lack of access of poor and neglected populations to essential diagnostics also stress the necessity of developing new methods operational in Point-of-Care (PoC) settings. In summary, emergent diagnostic tests integrating these novel and tailored tools should provide a significant impact on the effectiveness of current intervention schemes and on the clinical management of Chagasic patients. In this chapter, we discuss the present knowledge and possible future steps in Chagas disease diagnostic applications, as well as the opportunity provided by recent advances in high-throughput methods for biomarker discovery. PMID:28325368

National Security Technology Incubator Evaluation Process

DOE Office of Scientific and Technical Information (OSTI.GOV)

None, None

This report describes the process by which the National Security Technology Incubator (NSTI) will be evaluated. The technology incubator is being developed as part of the National Security Preparedness Project (NSPP), funded by a Department of Energy (DOE)/National Nuclear Security Administration (NNSA) grant. This report includes a brief description of the components, steps, and measures of the proposed evaluation process. The purpose of the NSPP is to promote national security technologies through business incubation, technology demonstration and validation, and workforce development. The NSTI will focus on serving businesses with national security technology applications by nurturing them through critical stages ofmore » early development. An effective evaluation process of the NSTI is an important step as it can provide qualitative and quantitative information on incubator performance over a given period. The vision of the NSTI is to be a successful incubator of technologies and private enterprise that assist the NNSA in meeting new challenges in national safety and security. The mission of the NSTI is to identify, incubate, and accelerate technologies with national security applications at various stages of development by providing hands-on mentoring and business assistance to small businesses and emerging or growing companies. To achieve success for both incubator businesses and the NSTI program, an evaluation process is essential to effectively measure results and implement corrective processes in the incubation design if needed. The evaluation process design will collect and analyze qualitative and quantitative data through performance evaluation system.« less

Development and current applications of assisted fertilization.

PubMed

Palermo, Gianpiero D; Neri, Queenie V; Monahan, Devin; Kocent, Justin; Rosenwaks, Zev

2012-02-01

Since the very early establishment of in vitro insemination, it became clear that one of the limiting steps is the achievement of fertilization. Among the different assisted fertilization methods, intracytoplasmic sperm injection emerged as the ultimate technique to allow fertilization with ejaculated, epididymal, and testicular spermatozoa. This work describes the early steps that brought forth the development of intracytoplasmic sperm injection and its role in assisted reproductive techniques. The current methods to select the preferential male gamete will be elucidated and the concerns related to the offspring of severe male factor couples will be discussed. Copyright © 2012. Published by Elsevier Inc.

Utilization of a cognitive task analysis for laparoscopic appendectomy to identify differentiated intraoperative teaching objectives.

PubMed

Smink, Douglas S; Peyre, Sarah E; Soybel, David I; Tavakkolizadeh, Ali; Vernon, Ashley H; Anastakis, Dimitri J

2012-04-01

Experts become automated when performing surgery, making it difficult to teach complex procedures to trainees. Cognitive task analysis (CTA) enables experts to articulate operative steps and cognitive decisions in complex procedures such as laparoscopic appendectomy, which can then be used to identify central teaching points. Three local surgeon experts in laparoscopic appendectomy were interviewed using critical decision method-based CTA methodology. Interview transcripts were analyzed, and a cognitive demands table (CDT) was created for each expert. The individual CDTs were reviewed by each expert for completeness and then combined into a master CDT. Percentage agreement on operative steps and decision points was calculated for each expert. The experts then participated in a consensus meeting to review the master CDT. Each surgeon expert was asked to identify in the master CDT the most important teaching objectives for junior-level and senior-level residents. The experts' responses for junior-level and senior-level residents were compared using a χ(2) test. The surgeon experts identified 24 operative steps and 27 decision points. Eighteen of the 24 operative steps (75%) were identified by all 3 surgeon experts. The percentage of operative steps identified was high for each surgeon expert (96% for surgeon 1, 79% for surgeon 2, and 83% for surgeon 3). Of the 27 decision points, only 5 (19%) were identified by all 3 surgeon experts. The percentage of decision points identified varied by surgeon expert (78% for surgeon 1, 59% for surgeon 2, and 48% for surgeon 3). When asked to identify key teaching points, the surgeon experts were more likely to identify operative steps for junior residents (9 operative steps and 6 decision points) and decision points for senior residents (4 operative steps and 13 decision points) (P < .01). CTA can deconstruct the essential operative steps and decision points associated with performing a laparoscopic appendectomy. These results provide a framework to identify key teaching principles to guide intraoperative instruction. These learning objectives could be used to guide resident level-appropriate teaching of an essential general surgery procedure. Copyright © 2012 Elsevier Inc. All rights reserved.

A suite of essential biodiversity variables for detecting critical biodiversity change.

PubMed

Schmeller, Dirk S; Weatherdon, Lauren V; Loyau, Adeline; Bondeau, Alberte; Brotons, Lluis; Brummitt, Neil; Geijzendorffer, Ilse R; Haase, Peter; Kuemmerlen, Mathias; Martin, Corinne S; Mihoub, Jean-Baptiste; Rocchini, Duccio; Saarenmaa, Hannu; Stoll, Stefan; Regan, Eugenie C

2018-02-01

Key global indicators of biodiversity decline, such as the IUCN Red List Index and the Living Planet Index, have relatively long assessment intervals. This means they, due to their inherent structure, function as late-warning indicators that are retrospective, rather than prospective. These indicators are unquestionably important in providing information for biodiversity conservation, but the detection of early-warning signs of critical biodiversity change is also needed so that proactive management responses can be enacted promptly where required. Generally, biodiversity conservation has dealt poorly with the scattered distribution of necessary detailed information, and needs to find a solution to assemble, harmonize and standardize the data. The prospect of monitoring essential biodiversity variables (EBVs) has been suggested in response to this challenge. The concept has generated much attention, but the EBVs themselves are still in development due to the complexity of the task, the limited resources available, and a lack of long-term commitment to maintain EBV data sets. As a first step, the scientific community and the policy sphere should agree on a set of priority candidate EBVs to be developed within the coming years to advance both large-scale ecological research as well as global and regional biodiversity conservation. Critical ecological transitions are of high importance from both a scientific as well as from a conservation policy point of view, as they can lead to long-lasting biodiversity change with a high potential for deleterious effects on whole ecosystems and therefore also on human well-being. We evaluated candidate EBVs using six criteria: relevance, sensitivity to change, generalizability, scalability, feasibility, and data availability and provide a literature-based review for eight EBVs with high sensitivity to change. The proposed suite of EBVs comprises abundance, allelic diversity, body mass index, ecosystem heterogeneity, phenology, range dynamics, size at first reproduction, and survival rates. The eight candidate EBVs provide for the early detection of critical and potentially long-lasting biodiversity change and should be operationalized as a priority. Only with such an approach can science predict the future status of global biodiversity with high certainty and set up the appropriate conservation measures early and efficiently. Importantly, the selected EBVs would address a large range of conservation issues and contribute to a total of 15 of the 20 Aichi targets and are, hence, of high biological relevance. © 2017 Cambridge Philosophical Society.

Drastic changes of (p,t) analyzing powers for the isotopes /sup 58,60,62,64/Ni and marked incident-energy dependence of the analyzing powers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Toba Y.; Yagi, K.

1984-01-01

Drastic changes of (p,t) analyzing powers for the four Ni isotopes in ground-state transitions were observed. The changes are not explained by direct one-step processes but are interpreted by including strong two-step (p,d) (d,t) processes. Interference between the two processes of comparable intensities is essential. Marked incident-energy dependence of the analyzing powers is interpreted similarly.

Expression of Bacillus anthracis Protective Antigen in Bacillus megaterium

DTIC Science & Technology

2004-03-01

was easily purified to homogeneity in a single step by ion exchange chromatography. N-terminal amino acid sequencing of the final product confirmed...and this material was purified in a single step by ion-exchange chromatography. N-terminal amino acid sequencing definitively proved that the rPA was...production of a poly-D-glutamic acid capsule, encoded by pXO2, is essential for immune evasion and cellular survival in the host [3,4]. The lethal effects

Minimizing cows' stress when calves were early weaned using the two-step method with nose flaps.

PubMed

Ungerfeld, R; Quintans, G; Hötzel, M J

2016-11-01

Early weaning may be used in beef cattle production to improve reproduction rates in range conditions. However, weaning causes a stress response in cows, which may be especially strong in early weaning management, as the bond between the cow and the calf is still strong. We hypothesized that weaning calves in two steps, with the aid of anti-sucking devices (nose flaps) would reduce the behavioural stress response in the cows separated from their calves 2 months after parturition. We compared the behaviour frequency and weight change in cows that were weaned abruptly, by separation of the calf on day 0 of the study, or in two steps, consisting of the use of anti-sucking nose flaps for 5 days before permanent separation; a third group was not weaned to serve as control. Thirty-six crossbred multiparous Aberdeen Angus×Hereford cows and their calves (n=12/treatment) were managed in three paddocks with similar pasture availability, with four dyads from each treatment per paddock. Cows' behaviour was observed by direct visual instantaneous sampling, at 10 min intervals from days -3 to 11. Weaning the calves in two steps clearly attenuated the behavioural stress response observed in abruptly weaned cows, which included reductions in grazing and lying, and increases in pacing, walking and vocalizing. Our results corroborate those previously shown for cows nursing older calves, and indicate that step weaning can reduce the behavioural stress response of cows at weaning, even when the calf is weaned shortly after birth, when the bond between the cow and calf is still very strong.

Orthodontic-orthognathic interventions in orthognathic surgical cases: “Paper surgery” and “model surgery” concepts in surgical orthodontics

PubMed Central

Gandedkar, Narayan H.; Chng, Chai Kiat; Yeow, Vincent Kok Leng

2016-01-01

Thorough planning and execution is the key for successful treatment of dentofacial deformity involving surgical orthodontics. Presurgical planning (paper surgery and model surgery) are the most essential prerequisites of orthognathic surgery, and orthodontist is the one who carries out this procedure by evaluating diagnostic aids such as crucial clinical findings and radiographic assessments. However, literature pertaining to step-by-step orthognathic surgical guidelines is limited. Hence, this article makes an attempt to provide an insight and nuances involved in the planning and execution. The diagnostic information revealed from clinical findings and radiographic assessments is integrated in the “paper surgery” to establish “surgical-plan.” Furthermore, the “paper surgery” is emulated in “model surgery” such that surgical bite-wafers are created, which aid surgeon to preview the final outcome and make surgical movements that are deemed essential for the desired skeletal and dental outcomes. Skeletal complexities are corrected by performing “paper surgery” and an occlusion is set up during “model surgery” for the fabrication of surgical bite-wafers. Further, orthodontics is carried out for the proper settling and finishing of occlusion. Article describes the nuances involved in the treatment of Class III skeletal deformity individuals treated with orthognathic surgical approach and illustrates orthodontic-orthognathic step-by-step procedures from “treatment planning” to “execution” for successful management of aforementioned dentofacial deformity. PMID:27630506

Arbitrarily high-order time-stepping schemes based on the operator spectrum theory for high-dimensional nonlinear Klein-Gordon equations

NASA Astrophysics Data System (ADS)

Liu, Changying; Wu, Xinyuan

2017-07-01

In this paper we explore arbitrarily high-order Lagrange collocation-type time-stepping schemes for effectively solving high-dimensional nonlinear Klein-Gordon equations with different boundary conditions. We begin with one-dimensional periodic boundary problems and first formulate an abstract ordinary differential equation (ODE) on a suitable infinity-dimensional function space based on the operator spectrum theory. We then introduce an operator-variation-of-constants formula which is essential for the derivation of our arbitrarily high-order Lagrange collocation-type time-stepping schemes for the nonlinear abstract ODE. The nonlinear stability and convergence are rigorously analysed once the spatial differential operator is approximated by an appropriate positive semi-definite matrix under some suitable smoothness assumptions. With regard to the two dimensional Dirichlet or Neumann boundary problems, our new time-stepping schemes coupled with discrete Fast Sine / Cosine Transformation can be applied to simulate the two-dimensional nonlinear Klein-Gordon equations effectively. All essential features of the methodology are present in one-dimensional and two-dimensional cases, although the schemes to be analysed lend themselves with equal to higher-dimensional case. The numerical simulation is implemented and the numerical results clearly demonstrate the advantage and effectiveness of our new schemes in comparison with the existing numerical methods for solving nonlinear Klein-Gordon equations in the literature.

Effective Partnering of State Agencies to Achieve Early Hearing Detection and Intervention Benchmarks

ERIC Educational Resources Information Center

Corwin, Joanne

2011-01-01

Relative to Early Hearing Detection and Intervention (EHDI), New Mexico struggles with multiple points of referral into early intervention in the same way most states do. Referrals are not systematized through a single point of entry. The Step*Hi (statewide Parent-Infant) Program of the New Mexico School for the Deaf (NMSD) receives referrals from…

New Hampshire Early Childhood Professional Development System: Guide to Early Childhood Careers.

ERIC Educational Resources Information Center

McDonnell, Tessa, Ed.

The community of child care providers in New Hampshire has adopted the Early Childhood Professional Development System as an initial step toward assuring quality care and education for children. This guide describes the components of that system and is presented in eight sections. Section 1 of the guide introduces the system based on a set of two…

State Initiatives To Promote Early Learning: Next Steps in Coordinating Subsidized Child Care, Head Start, and State Prekindergarten. Full Report.

ERIC Educational Resources Information Center

Schumacher, Rachel; Greenberg, Mark; Lombardi, Joan

While current early education and care funding still reaches only a fraction of preschool children, some states now have considerable experience in coordinating subsidized child care, Head Start, and state prekindergarten initiatives to enhance early education and learning opportunities for young children. Drawing on the experiences of Georgia,…

Photodynamic therapy (PDT) utilizing PhotofrinR for treatment of early esophageal cancer

NASA Astrophysics Data System (ADS)

Overholt, Bergein F.; Panjehpour, Masoud; Teffeteller, Elmeria; Rose, S. Mark

1993-06-01

Four lesions of early carcinoma of the esophagus found during endoscopic biopsies in three patients were treated with photodynamic therapy. Follow-up biopsies over 9 - 24 months remain negative for carcinoma. Endoscopic ultrasonography is essential for proper staging and treatment planning for these patients. Photodynamic therapy may provide an alternative to surgical resection for early esophageal carcinoma or severe dysplasia in Barrett's esophagus.

The Principal's Role in Literacy

ERIC Educational Resources Information Center

Kinney, Patti

2009-01-01

"Breaking Ranks II" and "Breaking Ranks in the Middle" both call for students to master "academically rigorous essential learnings" that have been established by the school, and students need a strong foundation in reading and writing if this is to happen. There is no doubt that literacy instruction in the early grades is an essential beginning,…

Non-coding stem-bulge RNAs are required for cell proliferation and embryonic development in C. elegans

PubMed Central

Kowalski, Madzia P.; Baylis, Howard A.; Krude, Torsten

2015-01-01

ABSTRACT Stem bulge RNAs (sbRNAs) are a family of small non-coding stem-loop RNAs present in Caenorhabditis elegans and other nematodes, the function of which is unknown. Here, we report the first functional characterisation of nematode sbRNAs. We demonstrate that sbRNAs from a range of nematode species are able to reconstitute the initiation of chromosomal DNA replication in the presence of replication proteins in vitro, and that conserved nucleotide sequence motifs are essential for this function. By functionally inactivating sbRNAs with antisense morpholino oligonucleotides, we show that sbRNAs are required for S phase progression, early embryonic development and the viability of C. elegans in vivo. Thus, we demonstrate a new and essential role for sbRNAs during the early development of C. elegans. sbRNAs show limited nucleotide sequence similarity to vertebrate Y RNAs, which are also essential for the initiation of DNA replication. Our results therefore establish that the essential function of small non-coding stem-loop RNAs during DNA replication extends beyond vertebrates. PMID:25908866

Object Relations and the Development of Values.

ERIC Educational Resources Information Center

Gazda, George M.; Sedgwick, Charlalee

1990-01-01

Claims acquisition of values is related to successes and failures of early relationships. Describes steps person goes through in making identifications, explaining steps that move person toward construction of value system. Refers to works of Heinz Kohut to explain how child's idealizing has within it necessary components for child's growth in…

Safety in the Chemical Laboratory: Flood Control.

ERIC Educational Resources Information Center

Pollard, Bruce D.

1983-01-01

Describes events leading to a flood in the Wehr Chemistry Laboratory at Marquette University, discussing steps taken to minimize damage upon discovery. Analyzes the problem of flooding in the chemical laboratory and outlines seven steps of flood control: prevention; minimization; early detection; stopping the flood; evaluation; clean-up; and…

Sox5 is a DNA binding co-factor for BMP R-Smads that directs target specificity during patterning of the early ectoderm

PubMed Central

Nordin, Kara; LaBonne, Carole

2014-01-01

SUMMARY The SoxD factor, Sox5, is expressed in ectodermal cells at times and places where BMP signaling is active, including the cells of the animal hemisphere at blastula stages, and the neural plate border (NPB) and neural crest (NC) at neurula stages. Sox5 is required for proper ectoderm development, and deficient embryos display patterning defects characteristic of perturbations of BMP signaling, including loss of neural crest and epidermis and expansion of the neural plate. We show that Sox5 is essential for activation of BMP target genes in embryos and explants, that it physically interacts with BMP R-Smads, and that it is essential for recruitment of Smad1/4 to BMP regulatory elements. Our findings identify Sox5 as the long sought DNA binding partner for BMP R-Smads essential to plasticity and pattern in the early ectoderm. PMID:25453832

Chromatin condensation of Xist genomic loci during oogenesis in mice.

PubMed

Fukuda, Atsushi; Mitani, Atsushi; Miyashita, Toshiyuki; Umezawa, Akihiro; Akutsu, Hidenori

2015-12-01

Repression of maternal Xist (Xm-Xist) during preimplantation in mouse embryos is essential for establishing imprinted X chromosome inactivation. Nuclear transplantation (NT) studies using nuclei derived from non-growing (ng) and full-grown (fg) oocytes have indicated that maternal-specific repressive modifications are imposed on Xm-Xist during oogenesis, as well as on autosomal imprinted genes. Recent studies have revealed that histone H3 lysine 9 trimethylation (H3K9me3) enrichments on Xm-Xist promoter regions are involved in silencing at the preimplantation stages. However, whether H3K9me3 is imposed on Xm-Xist during oogenesis is not known. Here, we dissected the chromatin states in ng and fg oocytes and early preimplantation stage embryos. Chromatin immunoprecipitation experiments against H3K9me3 revealed that there was no significant enrichment within the Xm-Xist region during oogenesis. However, NT embryos with ng nuclei (ngNT) showed extensive Xm-Xist derepression and H3K9me3 hypomethylation of the promoter region at the 4-cell stage, which corresponds to the onset of paternal Xist expression. We also found that the chromatin state at the Xist genomic locus became markedly condensed as oocyte growth proceeded. Although the condensed Xm-Xist genomic locus relaxed during early preimplantation phases, the extent of the relaxation across Xm-Xist loci derived from normally developed oocytes was significantly smaller than those of paternal-Xist and ngNT-Xist genomic loci. Furthermore, Xm-Xist from 2-cell metaphase nuclei became derepressed following NT. We propose that chromatin condensation is associated with imprinted Xist repression and that skipping of the condensation step by NT leads to Xist activation during the early preimplantation phase. © 2015. Published by The Company of Biologists Ltd.

Lineage-associated tracts defining the anatomy of the Drosophila first instar larval brain

PubMed Central

Hartenstein, Volker; Younossi-Hartenstein, Amelia; Lovick, Jennifer; Kong, Angel; Omoto, Jaison; Ngo, Kathy; Viktorin, Gudrun

2015-01-01

Fixed lineages derived from unique, genetically specified neuroblasts form the anatomical building blocks of the Drosophila brain. Neurons belonging to the same lineage project their axons in a common tract, which is labeled by neuronal markers. In this paper, we present a detailed atlas of the lineage-associated tracts forming the brain of the early Drosophila larva, based on the use of global markers (anti-Neuroglian, anti-Neurotactin, Inscuteable-Gal4>UAS-chRFP-Tub) and lineage-specific reporters. We describe 68 discrete fiber bundles that contain axons of one lineage or pairs/small sets of adjacent lineages. Bundles enter the neuropil at invariant locations, the lineage tract entry portals. Within the neuropil, these fiber bundles form larger fascicles that can be classified, by their main orientation, into longitudinal, transverse, and vertical (ascending/descending) fascicles. We present 3D digital models of lineage tract entry portals and neuropil fascicles, set into relationship to commonly used, easily recognizable reference structures such as the mushroom body, the antennal lobe, the optic lobe, and the Fasciclin II-positive fiber bundles that connect the brain and ventral nerve cord. Correspondences and differences between early larval tract anatomy and the previously described late larval and adult lineage patterns are highlighted. Our L1 neuro-anatomical atlas of lineages constitutes an essential step towards following morphologically defined lineages to the neuroblasts of the early embryo, which will ultimately make it possible to link the structure and connectivity of a lineage to the expression of genes in the particular neuroblast that gives rise to that lineage. Furthermore, the L1 atlas will be important for a host of ongoing work that attempts to reconstruct neuronal connectivity at the level of resolution of single neurons and their synapses. PMID:26141956

Lineage-associated tracts defining the anatomy of the Drosophila first instar larval brain.

PubMed

Hartenstein, Volker; Younossi-Hartenstein, Amelia; Lovick, Jennifer K; Kong, Angel; Omoto, Jaison J; Ngo, Kathy T; Viktorin, Gudrun

2015-10-01

Fixed lineages derived from unique, genetically specified neuroblasts form the anatomical building blocks of the Drosophila brain. Neurons belonging to the same lineage project their axons in a common tract, which is labeled by neuronal markers. In this paper, we present a detailed atlas of the lineage-associated tracts forming the brain of the early Drosophila larva, based on the use of global markers (anti-Neuroglian, anti-Neurotactin, inscuteable-Gal4>UAS-chRFP-Tub) and lineage-specific reporters. We describe 68 discrete fiber bundles that contain axons of one lineage or pairs/small sets of adjacent lineages. Bundles enter the neuropil at invariant locations, the lineage tract entry portals. Within the neuropil, these fiber bundles form larger fascicles that can be classified, by their main orientation, into longitudinal, transverse, and vertical (ascending/descending) fascicles. We present 3D digital models of lineage tract entry portals and neuropil fascicles, set into relationship to commonly used, easily recognizable reference structures such as the mushroom body, the antennal lobe, the optic lobe, and the Fasciclin II-positive fiber bundles that connect the brain and ventral nerve cord. Correspondences and differences between early larval tract anatomy and the previously described late larval and adult lineage patterns are highlighted. Our L1 neuro-anatomical atlas of lineages constitutes an essential step towards following morphologically defined lineages to the neuroblasts of the early embryo, which will ultimately make it possible to link the structure and connectivity of a lineage to the expression of genes in the particular neuroblast that gives rise to that lineage. Furthermore, the L1 atlas will be important for a host of ongoing work that attempts to reconstruct neuronal connectivity at the level of resolution of single neurons and their synapses. Copyright © 2015 Elsevier Inc. All rights reserved.

miRNA regulation in the early development of barley seed

PubMed Central

2012-01-01

Background During the early stages of seed development many genes are under dynamic regulation to ensure the proper differentiation and establishment of the tissue that will constitute the mature grain. To investigate how miRNA regulation contributes to this process in barley, a combination of small RNA and mRNA degradome analyses were used to identify miRNAs and their targets. Results Our analysis identified 84 known miRNAs and 7 new miRNAs together with 96 putative miRNA target genes regulated through a slicing mechanism in grain tissues during the first 15 days post anthesis. We also identified many potential miRNAs including several belonging to known miRNA families. Our data gave us evidence for an increase in miRNA-mediated regulation during the transition between pre-storage and storage phases. Potential miRNA targets were found in various signalling pathways including components of four phytohormone pathways (ABA, GA, auxin, ethylene) and the defence response to powdery mildew infection. Among the putative miRNA targets we identified were two essential genes controlling the GA response, a GA3oxidase1 and a homolog of the receptor GID1, and a homolog of the ACC oxidase which catalyses the last step of ethylene biosynthesis. We found that two MLA genes are potentially miRNA regulated, establishing a direct link between miRNAs and the R gene response. Conclusion Our dataset provides a useful source of information on miRNA regulation during the early development of cereal grains and our analysis suggests that miRNAs contribute to the control of development of the cereal grain, notably through the regulation of phytohormone response pathways. PMID:22838835

Disulfide bond rearrangement during formation of the chorionic gonadotropin beta-subunit cystine knot in vivo.

PubMed

Wilken, Jason A; Bedows, Elliott

2004-05-04

The intracellular kinetic folding pathway of the human chorionic gonadotropin beta-subunit (hCG-beta) reveals the presence of a disulfide between Cys residues 38-57 that is not detected by X-ray analysis of secreted hCG-beta. This led us to propose that disulfide rearrangement is an essential feature of cystine knot formation during CG-beta folding. To test this, we used disulfide bond formation to monitor progression of intracellular folding intermediates of a previously uncharacterized protein, the CG-beta subunit of cynomolgous macaque (Macaca fascicularis). Like its human counterpart hCG-beta with which it shares 81% identity, macaque (m)CG-beta is a cystine knot-containing subunit that assembles with an alpha-subunit common to all glycoprotein hormone members of its species to form a biologically active heterodimer, mCG, which, like hCG, is required for pregnancy maintenance. An early mCG-beta folding intermediate, mpbeta1, contained two disulfide bonds, one between Cys34 and Cys88 and the other between Cys38 and Cys57. The subsequent folding intermediate, mpbeta2-early, was represented by an ensemble of folding forms that, in addition to the two disulfides mentioned above, included disulfide linkages between Cys9 and Cys57 and between Cys38 and Cys90. These latter two disulfides are those contained within the beta-subunit cystine knot and reveal that a disulfide exchange occurred during the mpbeta2-early folding step leading to formation of the mCG-beta knot. Thus, while defining the intracellular kinetic protein folding pathway of a monkey homologue of CG-beta, we detected the previously predicted disulfide exchange event crucial for CG-beta cystine knot formation and attainment of CG-beta assembly competence.

Time-Resolved Records of Magnetic Activity on the Pallasite Parent Body and Psyche

NASA Astrophysics Data System (ADS)

Bryson, J. F. J.; Nichols, C. I. O.; Herrero-Albillos, J.; Kronast, F.; Kasama, T.; Alimadadi, H.; van der Laan, G.; Nimmo, F.; Harrison, R. J.

2014-12-01

Although many small bodies apparently generated dynamo fields in the early solar system, the nature and temporal evolution of these fields has remained enigmatic. Time-resolved records of the Earth's planetary field have been essential in understanding the dynamic history of our planet, and equivalent information from asteroids could provide a unique insight into the development of the solar system. Here we present time-resolved records of magnetic activity on the main-group pallasite parent body and (16) Psyche, obtained using newly-developed nanomagnetic imaging techniques. For the pallasite parent body, the inferred field direction remained relatively constant and the intensity was initially stable at ~100 μT before it decreased in two discrete steps down to 0 μT. We interpret this behaviour as due to vigorous dynamo activity driven by compositional convection in the core, ultimately transitioning from a dipolar to multipolar field as the inner core grew from the bottom-up. For Psyche (measured from IVA iron meteorites), the inferred field direction reversed, while the intensity remained stable at >50 μT. Psyche cooled rapidly as an unmantled core, although the resulting thermal convection alone cannot explain these observations. Instead, this behaviour required top-down core solidification, and is attributed either to compositional convection (if the core also solidified from the bottom-up) or convection generated directly by top-down solidification (e.g. Fe-snow). The mechanism governing convection in small body cores is an open question (due partly to uncertainties in the direction of core solidification), and these observations suggest that unconventional (i.e. not thermal) mechanisms acted in the early solar system. These mechanisms are very efficient at generating convection, implying a long-lasting and widespread epoch of dynamo activity among small bodies in the early solar system.

TraJ-dependent Escherichia coli K1 interactions with professional phagocytes are important for early systemic dissemination of infection in the neonatal rat.

PubMed

Hill, Val T; Townsend, Stacy M; Arias, Robyn S; Jenabi, Jasmine M; Gomez-Gonzalez, Ignacio; Shimada, Hiroyuki; Badger, Julie L

2004-01-01

Escherichia coli is a major cause of neonatal bacterial sepsis and meningitis. We recently identified a gene, traJ, which contributes to the ability of E. coli K1 to penetrate the blood-brain barrier in the neonatal rat. Because very little is known regarding the most critical step in disease progression, translocation to the gut and dissemination to the lymphoid tissues after a natural route of infection, we assessed the ability of a traJ mutant to cause systemic disease in the neonatal rat. Our studies determined that the traJ mutant is significantly less virulent than the wild type in the neonatal rat due to a decreased ability to disseminate from the mesenteric lymph nodes to the deeper tissues of the liver and spleen and to the blood during the early stages of systemic disease. Histopathologic studies determined that although significantly less or no mutant bacteria were recovered from the spleen and livers of infected neonatal rats, the inflammatory response was considerably greater than that in wild-type-colonized tissues. In vitro studies revealed that macrophages internalize the traJ mutant less frequently than they do the wild type and by a morphologically distinct process. Furthermore, we determined that tissue macrophages and dendritic cells within the liver and spleen are the major cellular targets of E. coli K1 and that TraJ significantly contributes to the predominantly intracellular nature of E. coli K1 within these professional phagocytes exclusively during the early stages of systemic disease. These data indicate that, contrary to earlier indications, E. coli K1 resides within professional phagocytes, and this is essential for the efficient progression of systemic disease.

Sall4-Gli3 system in early limb progenitors is essential for the development of limb skeletal elements.

PubMed

Akiyama, Ryutaro; Kawakami, Hiroko; Wong, Julia; Oishi, Isao; Nishinakamura, Ryuichi; Kawakami, Yasuhiko

2015-04-21

Limb skeletal elements originate from the limb progenitor cells, which undergo expansion and patterning to develop each skeletal element. Posterior-distal skeletal elements, such as the ulna/fibula and posterior digits develop in a Sonic hedgehog (Shh)-dependent manner. However, it is poorly understood how anterior-proximal elements, such as the humerus/femur, the radius/tibia and the anterior digits, are developed. Here we show that the zinc finger factors Sall4 and Gli3 cooperate for proper development of the anterior-proximal skeletal elements and also function upstream of Shh-dependent posterior skeletal element development. Conditional inactivation of Sall4 in the mesoderm before limb outgrowth caused severe defects in the anterior-proximal skeletal elements in the hindlimb. We found that Gli3 expression is reduced in Sall4 mutant hindlimbs, but not in forelimbs. This reduction caused posteriorization of nascent hindlimb buds, which is correlated with a loss of anterior digits. In proximal development, Sall4 integrates Gli3 and the Plzf-Hox system, in addition to proliferative expansion of cells in the mesenchymal core of nascent hindlimb buds. Whereas forelimbs developed normally in Sall4 mutants, further genetic analysis identified that the Sall4-Gli3 system is a common regulator of the early limb progenitor cells in both forelimbs and hindlimbs. The Sall4-Gli3 system also functions upstream of the Shh-expressing ZPA and the Fgf8-expressing AER in fore- and hindlimbs. Therefore, our study identified a critical role of the Sall4-Gli3 system at the early steps of limb development for proper development of the appendicular skeletal elements.

Cancer heterogeneity: converting a limitation into a source of biologic information.

PubMed

Rübben, Albert; Araujo, Arturo

2017-09-08

Analysis of spatial and temporal genetic heterogeneity in human cancers has revealed that somatic cancer evolution in most cancers is not a simple linear process composed of a few sequential steps of mutation acquisitions and clonal expansions. Parallel evolution has been observed in many early human cancers resulting in genetic heterogeneity as well as multilineage progression. Moreover, aneuploidy as well as structural chromosomal aberrations seems to be acquired in a non-linear, punctuated mode where most aberrations occur at early stages of somatic cancer evolution. At later stages, the cancer genomes seem to get stabilized and acquire only few additional rearrangements. While parallel evolution suggests positive selection of driver mutations at early stages of somatic cancer evolution, stabilization of structural aberrations at later stages suggests that negative selection takes effect when cancer cells progressively lose their tolerance towards additional mutation acquisition. Mixing of genetically heterogeneous subclones in cancer samples reduces sensitivity of mutation detection. Moreover, driver mutations present only in a fraction of cancer cells are more likely to be mistaken for passenger mutations. Therefore, genetic heterogeneity may be considered a limitation negatively affecting detection sensitivity of driver mutations. On the other hand, identification of subclones and subclone lineages in human cancers may lead to a more profound understanding of the selective forces which shape somatic cancer evolution in human cancers. Identification of parallel evolution by analyzing spatial heterogeneity may hint to driver mutations which might represent additional therapeutic targets besides driver mutations present in a monoclonal state. Likewise, stabilization of cancer genomes which can be identified by analyzing temporal genetic heterogeneity might hint to genes and pathways which have become essential for survival of cancer cell lineages at later stages of cancer evolution. These genes and pathways might also constitute patient specific therapeutic targets.

Baseline demographic, anthropometric, psychosocial, and behavioral characteristics of rural, Southern women in early pregnacy

USDA-ARS?s Scientific Manuscript database

Beginning life in a healthy uterine environment is essential for future well-being, particularly as it relates to chronic disease risk. Baseline (early pregnancy) demographic, anthropometric (height and weight), psychosocial (depression and perceived stress), and behavioral (diet and exercise) char...

Fostering Social Expertise in Early Childhood

ERIC Educational Resources Information Center

Porath, Marion

2009-01-01

Social competence is an essential capability to bring to school because of its relationship to academic success. Development and consolidation of social understanding in early childhood ensures that young children have a solid foundation of social expertise when they begin formal schooling. Social expertise, conceptualized within the framework of…

Paramyxovirus Glycoproteins and the Membrane Fusion Process.

PubMed

Aguilar, Hector C; Henderson, Bryce A; Zamora, J Lizbeth; Johnston, Gunner P

2016-09-01

The family Paramyxoviridae includes many viruses that significantly affect human and animal health. An essential step in the paramyxovirus life cycle is viral entry into host cells, mediated by virus-cell membrane fusion. Upon viral entry, infection results in expression of the paramyxoviral glycoproteins on the infected cell surface. This can lead to cell-cell fusion (syncytia formation), often linked to pathogenesis. Thus membrane fusion is essential for both viral entry and cell-cell fusion and an attractive target for therapeutic development. While there are important differences between viral-cell and cell-cell membrane fusion, many aspects are conserved. The paramyxoviruses generally utilize two envelope glycoproteins to orchestrate membrane fusion. Here, we discuss the roles of these glycoproteins in distinct steps of the membrane fusion process. These findings can offer insights into evolutionary relationships among Paramyxoviridae genera and offer future targets for prophylactic and therapeutic development.

Paramyxovirus Glycoproteins and the Membrane Fusion Process

PubMed Central

Aguilar, Hector C.; Henderson, Bryce A.; Zamora, J. Lizbeth; Johnston, Gunner P.

2016-01-01

The family Paramyxoviridae includes many viruses that significantly affect human and animal health. An essential step in the paramyxovirus life cycle is viral entry into host cells, mediated by virus-cell membrane fusion. Upon viral entry, infection results in expression of the paramyxoviral glycoproteins on the infected cell surface. This can lead to cell-cell fusion (syncytia formation), often linked to pathogenesis. Thus membrane fusion is essential for both viral entry and cell-cell fusion and an attractive target for therapeutic development. While there are important differences between viral-cell and cell-cell membrane fusion, many aspects are conserved. The paramyxoviruses generally utilize two envelope glycoproteins to orchestrate membrane fusion. Here, we discuss the roles of these glycoproteins in distinct steps of the membrane fusion process. These findings can offer insights into evolutionary relationships among Paramyxoviridae genera and offer future targets for prophylactic and therapeutic development. PMID:28138419

DOE Office of Scientific and Technical Information (OSTI.GOV)

Favaro, Marco; Xiao, Hai; Cheng, Tao

A national priority is to convert CO 2 into high-value chemical products such as liquid fuels. Because current electrocatalysts are not adequate, we aim to discover new catalysts by obtaining a detailed understanding of the initial steps of CO 2 electroreduction on copper surfaces, the best current catalysts. Using ambient pressure X-ray photoelectron spectroscopy interpreted with quantum mechanical prediction of the structures and free energies, we show that the presence of a thin suboxide structure below the copper surface is essential to bind the CO 2 in the physisorbed configuration at 298 K, and we show that this suboxide ismore » essential for converting to the chemisorbed CO 2 in the presence of water as the first step toward CO 2 reduction products such as formate and CO. This optimum suboxide leads to both neutral and charged Cu surface sites, providing fresh insights into how to design improved carbon dioxide reduction catalysts.« less

Contraceptive Vaccines Targeting Factors Involved in Establishment of Pregnancy

PubMed Central

Lemons, Angela R.; Naz, Rajesh K.

2011-01-01

Problem Current methods of contraception lack specificity and are accompanied with serious side effects. A more specific method of contraception is needed. Contraceptive vaccines can provide most, if not all, the desired characteristics of an ideal contraceptive. Approach This article reviews several factors involved in the establishment of pregnancy, focusing on those that are essential for successful implantation. Factors that are both essential and pregnancy-specific can provide potential targets for contraception. Conclusion Using database search, 76 factors (cytokines/chemokines/growth factors/others) were identified that are involved in various steps of the establishment of pregnancy. Among these factors, three, namely chorionic gonadotropin (CG), leukemia inhibitory factor (LIF), and preimplantation factor (PIF), are found to be unique and exciting molecules. Human CG is a well-known pregnancy-specific protein that has undergone phase I and phase II clinical trials, in women, as a contraceptive vaccine with encouraging results. LIF and PIF are pregnancy-specific and essential for successful implantation. These molecules are intriguing and may provide viable targets for immunocontraception. A multiepitope vaccine combining factors/antigens involved in various steps of the fertilization cascade and pregnancy establishment, may provide a highly immunogenic and efficacious modality for contraception in humans. PMID:21481058

The Intra-Cloud Lightning Fraction in the Contiguous United States

NASA Technical Reports Server (NTRS)

Medici, Gina; Cummins, Kenneth L.; Koshak, William J.; Rudlosky, Scott D.; Blakeslee, Richard J.; Goodman, Steven J.; Cecil, Daniel J.; Bright, David R.

2015-01-01

Lightning is dangerous and destructive; cloud-to-ground (CG) lightning flashes can start fires, interrupt power delivery, destroy property and cause fatalities. Its rate-of-occurrence reflects storm kinematics and microphysics. For decades lightning research has been an important focus, and advances in lightning detection technology have been essential contributors to our increasing knowledge of lightning. A significant step in detection technology is the Geostationary Lightning Mapper (GLM) to be onboard the Geostationary Operational Environment Satellite R-Series (GOES-R) to be launched in early 2016. GLM will provide continuous "Total Lightning" observations [CG and intra-cloud lightning (IC)] with near-uniform spatial resolution over the Americas by measuring radiance at the cloud tops from the different types of lightning. These Total Lightning observations are expected to significantly improve our ability to nowcast severe weather. It may be important to understand the long-term regional differences in the relative occurrence of IC and CG lightning in order to understand and properly use the short-term changes in Total Lightning flash rate for evaluating individual storms.

A novel method for segmentation of Infrared Scanning Laser Ophthalmoscope (IR-SLO) images of retina.

PubMed

Ajaz, Aqsa; Aliahmad, Behzad; Kumar, Dinesh K

2017-07-01

Retinal vessel segmentation forms an essential element of automatic retinal disease screening systems. The development of multimodal imaging system with IR-SLO and OCT could help in studying the early stages of retinal disease. The advantages of IR-SLO to examine the alterations in the structure of retina and direct correlation with OCT can be useful for assessment of various diseases. This paper presents an automatic method for segmentation of IR-SLO fundus images based on the combination of morphological filters and image enhancement techniques. As a first step, the retinal vessels are contrasted using morphological filters followed by background exclusion using Contrast Limited Adaptive Histogram Equalization (CLAHE) and Bilateral filtering. The final segmentation is obtained by using Isodata technique. Our approach was tested on a set of 26 IR-SLO images and results were compared to two set of gold standard images. The performance of the proposed method was evaluated in terms of sensitivity, specificity and accuracy. The system has an average accuracy of 0.90 for both the sets.

Principles of neuroanesthesia in aneurysmal subarachnoid hemorrhage: The Helsinki experience.

PubMed

Randell, Tarja; Niemelä, Mika; Kyttä, Juha; Tanskanen, Päivi; Määttänen, Markku; Karatas, Ayse; Ishii, Keisuke; Dashti, Reza; Shen, Hu; Hernesniemi, Juha

2006-10-01

Aneurysmal subarachnoid hemorrhage is a devastating disease that is followed by a marked stress response affecting other organs besides the brain. The aim in the management of patients with aSAH is not only to prevent rebleedings by treating the aneurysm by either microneurosurgery or endovascular surgery, but also to evacuate acute space-occupying hematomas and to treat hydrocephalus. This review is based on the experience of the authors in the management of more than 7500 patients with aSAH treated in the Department of Neurosurgery at Helsinki University Central Hospital, Finland. The role of the neuroanesthesiologist together with the neurosurgeon may begin in the emergency department to assess and stabilize the general medical and neurologic status of the patients. Early preoperative management of patients in the NICU, prevention of rebleeding, and providing a slack brain during microneurosurgical procedures are further steps. Postoperative management, prevention, and treatment of possible medical complications and cerebrovascular spasm are as necessary as high-quality microsurgery. Multidisciplinary and professional teamwork is essential in the management of patients with cerebral aneurysms.

Concurrent Engineering Working Group White Paper Distributed Collaborative Design: The Next Step in Aerospace Concurrent Engineering

NASA Technical Reports Server (NTRS)

Hihn, Jairus; Chattopadhyay, Debarati; Karpati, Gabriel; McGuire, Melissa; Panek, John; Warfield, Keith; Borden, Chester

2011-01-01

As aerospace missions grow larger and more technically complex in the face of ever tighter budgets, it will become increasingly important to use concurrent engineering methods in the development of early conceptual designs because of their ability to facilitate rapid assessments and trades of performance, cost and schedule. To successfully accomplish these complex missions with limited funding, it is essential to effectively leverage the strengths of individuals and teams across government, industry, academia, and international agencies by increased cooperation between organizations. As a result, the existing concurrent engineering teams will need to increasingly engage in distributed collaborative concurrent design. The purpose of this white paper is to identify a near-term vision for the future of distributed collaborative concurrent engineering design for aerospace missions as well as discuss the challenges to achieving that vision. The white paper also documents the advantages of creating a working group to investigate how to engage the expertise of different teams in joint design sessions while enabling organizations to maintain their organizations competitive advantage.

Rethinking the outpatient medication list: increasing patient activation and education while architecting for centralization and improved medication reconciliation.

PubMed

Pandolfe, Frank; Wright, Adam; Slack, Warner V; Safran, Charles

2018-05-17

Identify barriers impacting the time consuming and error fraught process of medication reconciliation. Design and implement an electronic medication management system where patient and trusted healthcare proxies can participate in establishing and maintaining an inclusive and up-to-date list of medications. A patient-facing electronic medication manager was deployed within an existing research project focused on elder care management funded by the AHRQ, InfoSAGE, allowing patients and patients' proxies the ability to build and maintain an accurate and up-to-date medication list. Free and open-source tools available from the U.S. government were used to embed the tenets of centralization, interoperability, data federation, and patient activation into the design. Using patient-centered design and free, open-source tools, we implemented a web and mobile enabled patient-facing medication manager for complex medication management. Patient and caregiver participation are essential to improve medication safety. Our medication manager is an early step towards a patient-facing medication manager that has been designed with data federation and interoperability in mind.

Genital surgery for disorders of sex development: implementing a shared decision-making approach.

PubMed

Karkazis, Katrina; Tamar-Mattis, Anne; Kon, Alexander A

2010-08-01

Ongoing controversy surrounds early genital surgery for children with disorders of sex development, making decisions about these procedures extraordinarily complex. Professional organizations have encouraged healthcare providers to adopt shared decision-making due to its broad potential to improve the decision-making process, perhaps most so when data are lacking, when there is no clear "best-choice" treatment, when decisions involve more than one choice, where each choice has both advantages and disadvantages, and where the ranking of options depends heavily on the decision-maker's values. We present a 6-step model for shared decision-making in decisions about genital surgery for disorders of sex development: (1) Set the stage and develop an appropriate team; (2) Establish preferences for information and roles in decision-making; (3) Perceive and address emotions; (4) Define concerns and values; (5) Identify options and present evidence; and (6) Share responsibility for making a decision. As long as controversy persists regarding surgery for DSD, an SDM process can facilitate the increased sharing of relevant information essential for making important health care decisions.

Birth order dependent growth cone segregation determines synaptic layer identity in the Drosophila visual system

PubMed Central

Kulkarni, Abhishek; Ertekin, Deniz; Lee, Chi-Hon; Hummel, Thomas

2016-01-01

The precise recognition of appropriate synaptic partner neurons is a critical step during neural circuit assembly. However, little is known about the developmental context in which recognition specificity is important to establish synaptic contacts. We show that in the Drosophila visual system, sequential segregation of photoreceptor afferents, reflecting their birth order, lead to differential positioning of their growth cones in the early target region. By combining loss- and gain-of-function analyses we demonstrate that relative differences in the expression of the transcription factor Sequoia regulate R cell growth cone segregation. This initial growth cone positioning is consolidated via cell-adhesion molecule Capricious in R8 axons. Further, we show that the initial growth cone positioning determines synaptic layer selection through proximity-based axon-target interactions. Taken together, we demonstrate that birth order dependent pre-patterning of afferent growth cones is an essential pre-requisite for the identification of synaptic partner neurons during visual map formation in Drosophila. DOI: http://dx.doi.org/10.7554/eLife.13715.001 PMID:26987017

The tight-adhesion proteins TadGEF of Bradyrhizobium diazoefficiens USDA 110 are involved in cell adhesion and infectivity on soybean roots.

PubMed

Mongiardini, Elías J; Parisi, Gustavo D; Quelas, Juan I; Lodeiro, Aníbal R

2016-01-01

Adhesion of symbiotic bacteria to host plants is an essential early step of the infection process that leads to the beneficial interaction. In the Bradyrhizobium diazoefficiens-soybean symbiosis few molecular determinants of adhesion are known. Here we identified the tight-adhesion gene products TadGEF in the open-reading frames blr3941-blr3943 of the B. diazoefficiens USDA 110 complete genomic sequence. Predicted structure of TadG indicates a transmembrane domain and two extracytosolic domains, from which the C-terminal has an integrin fold. TadE and TadF are also predicted as bearing transmembrane segments. Mutants in tadG or the small cluster tadGEF were impaired in adhesion to soybean roots, and the root infection was delayed. However, nodule histology was not compromised by the mutations, indicating that these effects were restricted to the earliest contact of the B. diazoefficiens and root surfaces. Knowledge of preinfection determinants is important for development of inoculants that are applied to soybean crops worldwide. Copyright © 2015 Elsevier GmbH. All rights reserved.

Artifact removal algorithms for stroke detection using a multistatic MIST beamforming algorithm.

PubMed

Ricci, E; Di Domenico, S; Cianca, E; Rossi, T

2015-01-01

Microwave imaging (MWI) has been recently proved as a promising imaging modality for low-complexity, low-cost and fast brain imaging tools, which could play a fundamental role to efficiently manage emergencies related to stroke and hemorrhages. This paper focuses on the UWB radar imaging approach and in particular on the processing algorithms of the backscattered signals. Assuming the use of the multistatic version of the MIST (Microwave Imaging Space-Time) beamforming algorithm, developed by Hagness et al. for the early detection of breast cancer, the paper proposes and compares two artifact removal algorithms. Artifacts removal is an essential step of any UWB radar imaging system and currently considered artifact removal algorithms have been shown not to be effective in the specific scenario of brain imaging. First of all, the paper proposes modifications of a known artifact removal algorithm. These modifications are shown to be effective to achieve good localization accuracy and lower false positives. However, the main contribution is the proposal of an artifact removal algorithm based on statistical methods, which allows to achieve even better performance but with much lower computational complexity.

The Nuclear Pore-Associated TREX-2 Complex Employs Mediator to Regulate Gene Expression

PubMed Central

Schneider, Maren; Hellerschmied, Doris; Schubert, Tobias; Amlacher, Stefan; Vinayachandran, Vinesh; Reja, Rohit; Pugh, B. Franklin; Clausen, Tim; Köhler, Alwin

2015-01-01

Summary Nuclear pore complexes (NPCs) influence gene expression besides their established function in nuclear transport. The TREX-2 complex localizes to the NPC basket and affects gene-NPC interactions, transcription, and mRNA export. How TREX-2 regulates the gene expression machinery is unknown. Here, we show that TREX-2 interacts with the Mediator complex, an essential regulator of RNA Polymerase (Pol) II. Structural and biochemical studies identify a conserved region on TREX-2, which directly binds the Mediator Med31/Med7N submodule. TREX-2 regulates assembly of Mediator with the Cdk8 kinase and is required for recruitment and site-specific phosphorylation of Pol II. Transcriptome and phenotypic profiling confirm that TREX-2 and Med31 are functionally interdependent at specific genes. TREX-2 additionally uses its Mediator-interacting surface to regulate mRNA export suggesting a mechanism for coupling transcription initiation and early steps of mRNA processing. Our data provide mechanistic insight into how an NPC-associated adaptor complex accesses the core transcription machinery. PMID:26317468

A Novel Association between Two Trypanosome-Specific Factors and the Conserved L5-5S rRNA Complex

PubMed Central

Ciganda, Martin; Prohaska, Kimberly; Hellman, Kristina; Williams, Noreen

2012-01-01

P34 and P37 are two previously identified RNA binding proteins in the flagellate protozoan Trypanosoma brucei. RNA interference studies have determined that the proteins are involved in and essential for ribosome biogenesis. The proteins interact with the 5S rRNA with nearly identical binding characteristics. We have shown that this interaction is achieved mainly through the LoopA region of the RNA, but P34 and P37 also protect the L5 binding site located on LoopC. We now provide evidence to show that these factors form a novel pre-ribosomal particle through interactions with both 5S rRNA and the L5 ribosomal protein. Further in silico and in vitro analysis of T. brucei L5 indicates a lower affinity for 5S rRNA than expected, based on other eukaryotic L5 proteins. We hypothesize that P34 and P37 complement L5 and bridge the interaction with 5S rRNA, stabilizing it and aiding in the early steps of ribosome biogenesis. PMID:22859981

Kinetics of Doubletime Kinase-dependent Degradation of the Drosophila Period Protein*

PubMed Central

Syed, Sheyum; Saez, Lino; Young, Michael W.

2011-01-01

Robust circadian oscillations of the proteins PERIOD (PER) and TIMELESS (TIM) are hallmarks of a functional clock in the fruit fly Drosophila melanogaster. Early morning phosphorylation of PER by the kinase Doubletime (DBT) and subsequent PER turnover is an essential step in the functioning of the Drosophila circadian clock. Here using time-lapse fluorescence microscopy we study PER stability in the presence of DBT and its short, long, arrhythmic, and inactive mutants in S2 cells. We observe robust PER degradation in a DBT allele-specific manner. With the exception of doubletime-short (DBTS), all mutants produce differential PER degradation profiles that show direct correspondence with their respective Drosophila behavioral phenotypes. The kinetics of PER degradation with DBTS in cell culture resembles that with wild-type DBT and posits that, in flies DBTS likely does not modulate the clock by simply affecting PER degradation kinetics. For all the other tested DBT alleles, the study provides a simple model in which the changes in Drosophila behavioral rhythms can be explained solely by changes in the rate of PER degradation. PMID:21659538

naked cuticle targets dishevelled to antagonize Wnt signal transduction

PubMed Central

Rousset, Raphaël; Mack, Judith A.; Wharton, Keith A.; Axelrod, Jeffrey D.; Cadigan, Ken M.; Fish, Matthew P.; Nusse, Roel; Scott, Matthew P.

2001-01-01

In Drosophila embryos the protein Naked cuticle (Nkd) limits the effects of the Wnt signal Wingless (Wg) during early segmentation. nkd loss of function results in segment polarity defects and embryonic death, but how nkd affects Wnt signaling is unknown. Using ectopic expression, we find that Nkd affects, in a cell-autonomous manner, a transduction step between the Wnt signaling components Dishevelled (Dsh) and Zeste-white 3 kinase (Zw3). Zw3 is essential for repressing Wg target-gene transcription in the absence of a Wg signal, and the role of Wg is to relieve this inhibition. Our double-mutant analysis shows that, in contrast to Zw3, Nkd acts when the Wg pathway is active to restrain signal transduction. Yeast two hybrid and in vitro experiments indicate that Nkd directly binds to the basic-PDZ region of Dsh. Specially timed Nkd overexpression is capable of abolishing Dsh function in a distinct signaling pathway that controls planar-cell polarity. Our results suggest that Nkd acts directly through Dsh to limit Wg activity and thus determines how efficiently Wnt signals stabilize Armadillo (Arm)/β-catenin and activate downstream genes. PMID:11274052

APC sets the Wnt tone necessary for cerebral cortical progenitor development

PubMed Central

Nakagawa, Naoki; Li, Jingjun; Yabuno-Nakagawa, Keiko; Eom, Tae-Yeon; Cowles, Martis; Mapp, Tavien; Taylor, Robin; Anton, E.S.

2017-01-01

Adenomatous polyposis coli (APC) regulates the activity of β-catenin, an integral component of Wnt signaling. However, the selective role of the APC–β-catenin pathway in cerebral cortical development is unknown. Here we genetically dissected the relative contributions of APC-regulated β-catenin signaling in cortical progenitor development, a necessary early step in cerebral cortical formation. Radial progenitor-specific inactivation of the APC–β-catenin pathway indicates that the maintenance of appropriate β-catenin-mediated Wnt tone is necessary for the orderly differentiation of cortical progenitors and the resultant formation of the cerebral cortex. APC deletion deregulates β-catenin, leads to high Wnt tone, and disrupts Notch1 signaling and primary cilium maintenance necessary for radial progenitor functions. β-Catenin deregulation directly disrupts cilium maintenance and signaling via Tulp3, essential for intraflagellar transport of ciliary signaling receptors. Surprisingly, deletion of β-catenin or inhibition of β-catenin activity in APC-null progenitors rescues the APC-null phenotype. These results reveal that APC-regulated β-catenin activity in cortical progenitors sets the appropriate Wnt tone necessary for normal cerebral cortical development. PMID:28916710

Maternal Gdf3 is an obligatory cofactor in Nodal signaling for embryonic axis formation in zebrafish

PubMed Central

Bisgrove, Brent W; Su, Yi-Chu

2017-01-01

Zebrafish Gdf3 (Dvr1) is a member of the TGFβ superfamily of cell signaling ligands that includes Xenopus Vg1 and mammalian Gdf1/3. Surprisingly, engineered homozygous mutants in zebrafish have no apparent phenotype. Elimination of Gdf3 in oocytes of maternal-zygotic mutants results in embryonic lethality that can be fully rescued with gdf3 RNA, demonstrating that Gdf3 is required only early in development, beyond which mutants are viable and fertile. Gdf3 mutants are refractory to Nodal ligands and Nodal repressor Lefty1. Signaling driven by TGFβ ligand Activin and constitutively active receptors Alk4 and Alk2 remain intact in gdf3 mutants, indicating that Gdf3 functions at the same pathway step as Nodal. Targeting gdf3 and ndr2 RNA to specific lineages indicates that exogenous gdf3 is able to fully rescue mutants only when co-expressed with endogenous Nodal. Together, these findings demonstrate that Gdf3 is an essential cofactor of Nodal signaling during establishment of the embryonic axis. PMID:29140249

Phosphoglycerolipids are master players in plant hormone signal transduction.

PubMed

Janda, Martin; Planchais, Severine; Djafi, Nabila; Martinec, Jan; Burketova, Lenka; Valentova, Olga; Zachowski, Alain; Ruelland, Eric

2013-06-01

Phosphoglycerolipids are essential structural constituents of membranes and some also have important cell signalling roles. In this review, we focus on phosphoglycerolipids that are mediators in hormone signal transduction in plants. We first describe the structures of the main signalling phosphoglycerolipids and the metabolic pathways that generate them, namely the phospholipase and lipid kinase pathways. In silico analysis of Arabidopsis transcriptome data provides evidence that the genes encoding the enzymes of these pathways are transcriptionally regulated in responses to hormones, suggesting some link with hormone signal transduction. The involvement of phosphoglycerolipid signalling in the early responses to abscisic acid, salicylic acid and auxins is then detailed. One of the most important signalling lipids in plants is phosphatidic acid. It can activate or inactivate protein kinases and/or protein phosphatases involved in hormone signalling. It can also activate NADPH oxidase leading to the production of reactive oxygen species. We will interrogate the mechanisms that allow the activation/deactivation of the lipid pathways, in particular the roles of G proteins and calcium. Mediating lipids thus appear as master players of cell signalling, modulating, if not controlling, major transducing steps of hormone signals.

Impurity effects in crystal growth from solutions: Steady states, transients and step bunch motion

NASA Astrophysics Data System (ADS)

Ranganathan, Madhav; Weeks, John D.

2014-05-01

We analyze a recently formulated model in which adsorbed impurities impede the motion of steps in crystals grown from solutions, while moving steps can remove or deactivate adjacent impurities. In this model, the chemical potential change of an atom on incorporation/desorption to/from a step is calculated for different step configurations and used in the dynamical simulation of step motion. The crucial difference between solution growth and vapor growth is related to the dependence of the driving force for growth of the main component on the size of the terrace in front of the step. This model has features resembling experiments in solution growth, which yields a dead zone with essentially no growth at low supersaturation and the motion of large coherent step bunches at larger supersaturation. The transient behavior shows a regime wherein steps bunch together and move coherently as the bunch size increases. The behavior at large line tension is reminiscent of the kink-poisoning mechanism of impurities observed in calcite growth. Our model unifies different impurity models and gives a picture of nonequilibrium dynamics that includes both steady states and time dependent behavior and shows similarities with models of disordered systems and the pinning/depinning transition.

Promoting Sound Ethical Decisions in the Air Force: CGO Solutions to Air Force Moral and Ethical Lapses

DTIC Science & Technology

2014-07-01

The second step is to create a Cross Check program—essentially franchising the Think Tank process in smaller groups across the Air Force as a forum...accessed 20 July 2014). 32  Cross Check Think Tank 14D proposes the implementation of “Cross Check” programs—essentially franchising the Think Tank...Tank Franchise , the meetings would be action-oriented, and networked together throughout the Air Force to provide lessons-learned, 33  resources

Drama: Narrative Pedagogy and Socially Challenged Children

ERIC Educational Resources Information Center

Peter, Melanie

2009-01-01

Melanie Peter, Senior Lecturer in Education and Early Childhood at Anglia Ruskin University, argues that the ability to engage in narrative stems from early interactive play formats and is essential for perceiving patterns and sequences in life--the fabric of social understanding. Developing themes set out in her earlier work, this article…

Investing in Early Career General Staff

ERIC Educational Resources Information Center

Graham, Carroll

2009-01-01

With the greying of the Australian population, it has been widely recognised that active career development for early career academics is essential to the future capacities of universities (Hugo, Daysh, Morris & Rudd, 2004). However, the same has not been acknowledged for general staff, despite general staff comprising more than 50% of staff…

From Universalism to Selectivity? The Background, Discourses and Ideas of Recent Early Childhood Education and Care Reforms in Finland

ERIC Educational Resources Information Center

Lundkvist, Marina; Nyby, Josefine; Autto, Janne; Nygård, Mikael

2017-01-01

Universal public childcare for children under seven has been central in Finland since the mid-1990s, capacitating both gender equality and children's human capital and wellbeing. In 2015, as a further step in the development of this system, early learning and childhood pedagogy was strengthened through the early childhood education and care (ECEC)…

Early Childhood Educator Competencies: A Literature Review of Current Best Practices, and a Public Input Process on Next Steps for California. Research Report

ERIC Educational Resources Information Center

Center for the Study of Child Care Employment, University of California at Berkeley, 2008

2008-01-01

In recent years, growing knowledge of the critical importance of early childhood development for lifelong learning and growth had led to increased calls for the professionalism of early childhood educators, including higher standards for their training and education. As part of this attention to professional development, many states are…

Towards a smart glove: arousal recognition based on textile Electrodermal Response.

PubMed

Valenza, Gaetano; Lanata, Antonio; Scilingo, Enzo Pasquale; De Rossi, Danilo

2010-01-01

This paper investigates the possibility of using Electrodermal Response, acquired by a sensing fabric glove with embedded textile electrodes, as reliable means for emotion recognition. Here, all the essential steps for an automatic recognition system are described, from the recording of physiological data set to a feature-based multiclass classification. Data were collected from 35 healthy volunteers during arousal elicitation by means of International Affective Picture System (IAPS) pictures. Experimental results show high discrimination after twenty steps of cross validation.

Children with Disabilities Are Often Misdiagnosed Initially and Children with Neuropsychiatric Disorders Are Referred to Adequate Resources 30 Months Later than Children with Other Disabilities

ERIC Educational Resources Information Center

Tuominen-Eriksson, Alli-Marie; Svensson, Yvonne; Gunnarsson, Ronny K.

2013-01-01

Disabilities in a child may lead to low self-esteem and social problems. The lives of parents and siblings are also affected. Early intervention may decrease these consequences. To promote early intervention early referral to adequate resources is essential. In a longitudinal retrospective observational study it was found that children with…

The Head Start Child Development and Early Learning Framework: Promoting Positive Outcomes in Early Childhood Programs Serving Children 3-5 Years Old

ERIC Educational Resources Information Center

Office of Head Start, US Department of Health and Human Services, 2010

2010-01-01

This report presents a revision of the Head Start Child Outcomes Framework (2000), renamed The Head Start Child Development and Learning Framework: Promoting Positive Outcomes in Early Childhood Programs Serving Children 3-5 Years Old. The Framework outlines the essential areas of development and learning that are to be used by Head Start programs…

Customer service: the key to market differentiation.

PubMed

Stahl, D A

1997-06-01

Fierce competition in the subacute care environment makes customer service orientation essential. Four steps help to achieve quality customer service are: (1) institute core values; (2) identify your customers; (3) understand human resources; and (4) establish an efficient system.

Essential Transportation Worker Identification Credential Assessment Act

THOMAS, 113th Congress

Rep. Jackson Lee, Sheila [D-TX-18

2013-09-27

Senate - 07/29/2014 Received in the Senate and Read twice and referred to the Committee on Commerce, Science, and Transportation. (All Actions) Tracker: This bill has the status Passed HouseHere are the steps for Status of Legislation:

Cross-sectional observational assessment of quality of newborn care immediately after birth in health facilities across six sub-Saharan African countries.

PubMed

de Graft-Johnson, Joseph; Vesel, Linda; Rosen, Heather E; Rawlins, Barbara; Abwao, Stella; Mazia, Goldy; Bozsa, Robert; Mwebesa, Winifrede; Khadka, Neena; Kamunya, Rosemary; Getachew, Ashebir; Tibaijuka, Gaudiosa; Rakotovao, Jean Pierre; Tekleberhan, Alemnesh

2017-03-27

To present information on the quality of newborn care services and health facility readiness to provide newborn care in 6 African countries, and to advocate for the improvement of providers' essential newborn care knowledge and skills. Cross-sectional observational health facility assessment. Ethiopia, Kenya, Madagascar, Mozambique, Rwanda and Tanzania. Health workers in 643 facilities. 1016 health workers were interviewed, and 2377 babies were observed in the facilities surveyed. Indicators of quality of newborn care included (1) provision of immediate essential newborn care: thermal care, hygienic cord care, and early and exclusive initiation of breast feeding; (2) actual and simulated resuscitation of asphyxiated newborn infants; and (3) knowledge of health workers on essential newborn care, including resuscitation. Sterile or clean cord cutting instruments, suction devices, and tables or firm surfaces for resuscitation were commonly available. 80% of newborns were immediately dried after birth and received clean cord care in most of the studied facilities. In all countries assessed, major deficiencies exist for essential newborn care supplies and equipment, as well as for health worker knowledge and performance of key routine newborn care practices, particularly for immediate skin-to-skin contact and breastfeeding initiation. Of newborns who did not cry at birth, 89% either recovered on their own or through active steps taken by the provider through resuscitation with initial stimulation and/or ventilation. 11% of newborns died. Assessment of simulated resuscitation using a NeoNatalie anatomic model showed that less than a third of providers were able to demonstrate ventilation skills correctly. The findings shared in this paper call attention to the critical need to improve health facility readiness to provide quality newborn care services and to ensure that service providers have the necessary equipment, supplies, knowledge and skills that are critical to save newborn lives. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Essential, Not Optional: Education for Sustainability in Early Childhood Centres

ERIC Educational Resources Information Center

Elliott, Sue

2010-01-01

As the impact of humans on the Earth and on its ecological systems that sustain people become more visible--in terms of climate change, resource depletion, and species extinctions--so, too, it is becoming clearer that living sustainably is essential, not optional. To live sustainably requires a mind shift for many people. Education for…

Fundamentos para Asociados en Desarrollo Infantil quienes trabajan con Ninos Pequenos (Essentials for Child Development Associates Working with Young Children).

ERIC Educational Resources Information Center

Phillips, Carol Brunson, Ed.

A study guide for the Child Development Associate (CDA) Professional Preparation Program, this Spanish-language guidebook contains essential information on the basics of good professional practice for early childhood educators. It includes self-study activities, checklists, and resources for additional information. Unit 1 provides an overview of…

Chloroplast targeting of FtsHprotease is essential for chloroplast development and thylakoid stability at elevated temperatures in plants

USDA-ARS?s Scientific Manuscript database

AtFtsH11 is a chloroplast and mitochondria dual targeted metalloprotease, identified as essential for Arabidopsis plant to survive at moderate high temperatures at all developmental stages. Our study showed that FtsH11 plays critical roles in both the early stages of chloroplast biogenesis and main...

Functional Integrity of the Retrosplenial Cortex Is Essential for Rapid Consolidation and Recall of Fear Memory

ERIC Educational Resources Information Center

Katche, Cynthia; Dorman, Guido; Slipczuk, Leandro; Cammarota, Martin; Medina, Jorge H.

2013-01-01

Memory storage is a temporally graded process involving different phases and different structures in the mammalian brain. Cortical plasticity is essential to store stable memories, but little is known regarding its involvement in memory processing. Here we show that fear memory consolidation requires early post-training macromolecular synthesis in…

[Cardiopulmonary resuscitation: the essential of 2015 guidelines].

PubMed

Maudet, Ludovic; Carron, Pierre-Nicolas; Trueb, Lionel

2016-02-10

Cardiopulmonary resuscitation (CPR) guidelines have been updated in October 2015. The 2010 guidelines are reaffirmed: immediate call for help via the local dispatch center, high quality CPR (frequency between 100 and 120/min, compression depth between 5 and 6 cm) and early defibrillation improve patient's survival chances. This article reviews the essential elements of resuscitation and recommended advanced measures.

Planning energy-efficient bipedal locomotion on patterned terrain

NASA Astrophysics Data System (ADS)

Zamani, Ali; Bhounsule, Pranav A.; Taha, Ahmad

2016-05-01

Energy-efficient bipedal walking is essential in realizing practical bipedal systems. However, current energy-efficient bipedal robots (e.g., passive-dynamics-inspired robots) are limited to walking at a single speed and step length. The objective of this work is to address this gap by developing a method of synthesizing energy-efficient bipedal locomotion on patterned terrain consisting of stepping stones using energy-efficient primitives. A model of Cornell Ranger (a passive-dynamics inspired robot) is utilized to illustrate our technique. First, an energy-optimal trajectory control problem for a single step is formulated and solved. The solution minimizes the Total Cost Of Transport (TCOT is defined as the energy used per unit weight per unit distance travelled) subject to various constraints such as actuator limits, foot scuffing, joint kinematic limits, ground reaction forces. The outcome of the optimization scheme is a table of TCOT values as a function of step length and step velocity. Next, we parameterize the terrain to identify the location of the stepping stones. Finally, the TCOT table is used in conjunction with the parameterized terrain to plan an energy-efficient stepping strategy.

Automated microaneurysm detection in diabetic retinopathy using curvelet transform

NASA Astrophysics Data System (ADS)

Ali Shah, Syed Ayaz; Laude, Augustinus; Faye, Ibrahima; Tang, Tong Boon

2016-10-01

Microaneurysms (MAs) are known to be the early signs of diabetic retinopathy (DR). An automated MA detection system based on curvelet transform is proposed for color fundus image analysis. Candidates of MA were extracted in two parallel steps. In step one, blood vessels were removed from preprocessed green band image and preliminary MA candidates were selected by local thresholding technique. In step two, based on statistical features, the image background was estimated. The results from the two steps allowed us to identify preliminary MA candidates which were also present in the image foreground. A collection set of features was fed to a rule-based classifier to divide the candidates into MAs and non-MAs. The proposed system was tested with Retinopathy Online Challenge database. The automated system detected 162 MAs out of 336, thus achieved a sensitivity of 48.21% with 65 false positives per image. Counting MA is a means to measure the progression of DR. Hence, the proposed system may be deployed to monitor the progression of DR at early stage in population studies.

Automated microaneurysm detection in diabetic retinopathy using curvelet transform.

PubMed

Ali Shah, Syed Ayaz; Laude, Augustinus; Faye, Ibrahima; Tang, Tong Boon

2016-10-01

Microaneurysms (MAs) are known to be the early signs of diabetic retinopathy (DR). An automated MA detection system based on curvelet transform is proposed for color fundus image analysis. Candidates of MA were extracted in two parallel steps. In step one, blood vessels were removed from preprocessed green band image and preliminary MA candidates were selected by local thresholding technique. In step two, based on statistical features, the image background was estimated. The results from the two steps allowed us to identify preliminary MA candidates which were also present in the image foreground. A collection set of features was fed to a rule-based classifier to divide the candidates into MAs and non-MAs. The proposed system was tested with Retinopathy Online Challenge database. The automated system detected 162 MAs out of 336, thus achieved a sensitivity of 48.21% with 65 false positives per image. Counting MA is a means to measure the progression of DR. Hence, the proposed system may be deployed to monitor the progression of DR at early stage in population studies.

Towards the run and walk activity classification through step detection--an android application.

PubMed

Oner, Melis; Pulcifer-Stump, Jeffry A; Seeling, Patrick; Kaya, Tolga

2012-01-01

Falling is one of the most common accidents with potentially irreversible consequences, especially considering special groups, such as the elderly or disabled. One approach to solve this issue would be an early detection of the falling event. Towards reaching the goal of early fall detection, we have worked on distinguishing and monitoring some basic human activities such as walking and running. Since we plan to implement the system mostly for seniors and the disabled, simplicity of the usage becomes very important. We have successfully implemented an algorithm that would not require the acceleration sensor to be fixed in a specific position (the smart phone itself in our application), whereas most of the previous research dictates the sensor to be fixed in a certain direction. This algorithm reviews data from the accelerometer to determine if a user has taken a step or not and keeps track of the total amount of steps. After testing, the algorithm was more accurate than a commercial pedometer in terms of comparing outputs to the actual number of steps taken by the user.

Monitoring of human populations for early markers of cadmium toxicity: A review

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fowler, Bruce A.

2009-08-01

Exposure of human populations to cadmium (Cd) from air, food and water may produce effects in organs such as the kidneys, liver, lungs, cardiovascular, immune and reproductive systems. Since Cd has been identified as a human carcinogen, biomarkers for early detection of susceptibility to cancer are of an importance to public health. The ability to document Cd exposure and uptake of this element through biological monitoring is a first step towards understanding its health effects. Interpretation and application of biological monitoring data for predicting human health outcomes require correlation with biological measures of organ system responses to the documented exposure.more » Essential to this understanding is the detection and linkage of early biological responses toxic effects in target cell populations. Fortunately, advances in cell biology have resulted in the development of pre-clinical biological markers (biomarkers) that demonstrate measurable and characteristic molecular changes in organ systems following chemical exposures that occur prior to the onset of overt clinical disease or development of cancer. Technical advances have rendered a number of these biomarkers practical for monitoring Cd-exposed human populations. Biomarkers will be increasingly important in relation to monitoring effects from the exposure to new Cd-based high technology materials. For example, cadmium-selenium (CdSe), nano-materials made from combinations of these elements have greatly altered cellular uptake characteristics due to particle size. These differences may greatly alter effects at the target cell level and hence risks for organ toxicities from such exposures. The value of validated biomarkers for early detection of systemic Cd-induced effects in humans cannot be underestimated due to the rapid expansion of nano-material technologies. This review will attempt to briefly summarize the applications, to date, of biomarker endpoints for assessing target organ system effects in humans and experimental systems from Cd exposure. Further, it will attempt to provide a prospective look at the possible future of biomarkers. The emphasis will be on the detection of early toxic effects from exposure to Cd in new products such as nano-materials and identification of populations at special risk for Cd toxicity.« less

Monitoring of human populations for early markers of cadmium toxicity: a review.

PubMed

Fowler, Bruce A

2009-08-01

Exposure of human populations to cadmium (Cd) from air, food and water may produce effects in organs such as the kidneys, liver, lungs, cardiovascular, immune and reproductive systems. Since Cd has been identified as a human carcinogen, biomarkers for early detection of susceptibility to cancer are of an importance to public health. The ability to document Cd exposure and uptake of this element through biological monitoring is a first step towards understanding its health effects. Interpretation and application of biological monitoring data for predicting human health outcomes require correlation with biological measures of organ system responses to the documented exposure. Essential to this understanding is the detection and linkage of early biological responses toxic effects in target cell populations. Fortunately, advances in cell biology have resulted in the development of pre-clinical biological markers (biomarkers) that demonstrate measurable and characteristic molecular changes in organ systems following chemical exposures that occur prior to the onset of overt clinical disease or development of cancer. Technical advances have rendered a number of these biomarkers practical for monitoring Cd-exposed human populations. Biomarkers will be increasingly important in relation to monitoring effects from the exposure to new Cd-based high technology materials. For example, cadmium-selenium (CdSe), nano-materials made from combinations of these elements have greatly altered cellular uptake characteristics due to particle size. These differences may greatly alter effects at the target cell level and hence risks for organ toxicities from such exposures. The value of validated biomarkers for early detection of systemic Cd-induced effects in humans cannot be underestimated due to the rapid expansion of nano-material technologies. This review will attempt to briefly summarize the applications, to date, of biomarker endpoints for assessing target organ system effects in humans and experimental systems from Cd exposure. Further, it will attempt to provide a prospective look at the possible future of biomarkers. The emphasis will be on the detection of early toxic effects from exposure to Cd in new products such as nano-materials and identification of populations at special risk for Cd toxicity.

Cervical necrotizing fasciitis: report of 6 cases and review of literature.

PubMed

Cruz Toro, P; Callejo Castillo, À; Tornero Saltó, J; González Compta, X; Farré, A; Maños, M

2014-12-01

Necrotizing fasciitis in the cervical region is a rare entity, characterized by a fulminant infection that causes extensive necrosis of the subcutaneous tissue and fascial planes, with high mortality and morbidity rates. The origin is generally odontogenic or pharyngeal, involving a mixed flora of microorganisms. Descending infection and mediastinal involvement are usually associated and are the main complications. The aim of the present study was to review the cases treated in our department and analyze diagnosis and treatment, supplementing the understanding of the disease. A retrospective study was performed on the clinical records of patients admitted to our center between January 2005 and June 2010 with diagnosis of necrotizing cervical fasciitis. Six clinical records were reviewed. The origin of the infection was mainly oropharyngeal and odontogenic, with a mixed flora of Prevotella, Peptostreptococcus and coagulase-negative Staphylococcus. All patients presented mediastinal involvement: superior mediastinitis in 4 patients and superior and postero-inferior mediastinitis in 2 cases. All patients underwent early drainage by bilateral cervicotomy with mediastinal drainage by a cervical approach in those with superior mediastinal affection, and associated thoracotomy, in a single surgical step, for postero-inferior mediastinitis. Temporary tracheotomy was performed in all cases. All received broad spectrum antibiotics, with a medium hospital stay of 37 days. There were no deaths reported. Concerning cervical necrotizing fasciitis, early diagnosis and surgical treatment associated to antibiotics and intensive medical care are essential to obtain a favorable outcome. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Practical aspects of the control of cardiovascular risk in type 2 diabetes mellitus and the metabolic syndrome

PubMed Central

Cerghizan, Anca; Bala, Cornelia; Nita, Cristina; Hancu, Nicolae

2007-01-01

Cardiovascular disease is unanimously recognized as the major burden in type 2 diabetes, in terms of both mortality and morbidity. There is an extensive evidence coming from epidemiological studies that supports this statement. The presence of the metabolic syndrome confers a higher risk of long-term death, and dysglycemia appears to be responsible for the most of the excess risk. The metabolic syndrome also has an essential role in the modern concept of cardiovascular prevention. Global cardiovascular risk represents the action and consequences of all risk factors that simultaneously or sequentially act on the body, leading to atherogenesis/atherosclerosis. In daily practice, a stepwise approach to control cardiovascular risk in people with type 2 diabetes has been proposed. This algorithm comprises three steps: identification of cardiovascular risk factors, interpretation of global cardiovascular risk, and intervention for all identified risk factors and diseases. In the past decades, the whole concept of diabetes and the metabolic syndrome care has undergone a radical change. From here the concept of modern management of those diseases emerged: early, multi-factorial and intensive control. This concept emphasized early and aggressive interventions for all cardiovascular risk factors in the long-term management. The model of multiple cardiovascular risk factor intervention ought to be implemented in daily practice as much as possible. This offers a unique opportunity to reduce the devastating cardiovascular morbidity and mortality in people with type 2 diabetes and the metabolic syndrome. PMID:18650987

Changes in nutritional status in nursing home residents and associated factors in nutritional status decline: a secondary data analysis.

PubMed

Bauer, Silvia; Halfens, Ruud J G; Lohrmann, Christa

2017-10-01

The aim of this study was to describe changes in the nutritional status of nursing home residents over a period of 1 year and identify factors associated with a decline in nutritional status. The maintenance of good nutritional status is important for nursing home residents. Therefore, it is essential to identify risk factors that indicate a decline in nutritional status to take early prevention steps. Secondary data analysis of repeated cross-sectional studies. Data collection was performed between 2009-2013 using the International Prevalence Measurement of Care Problems questionnaire. Data from three purposively selected nursing homes that included 157 residents were analysed. The comparison between baseline data and data collected 1 year later showed that the nutritional status declined in 22·8% of the residents and improved in 6·5% of the cases. The body mass index and changes in the body mass index were significantly different between residents with stable/improved and declined nutritional status. The multivariate logistic regression analysis showed that care dependency, length of stay, changes in body mass index and malnutrition risk at baseline were significantly associated with a decline in nutritional status. This study showed that the baseline risk of malnutrition is the most important risk factor indicating a decline in nutritional status. Therefore, healthcare professionals should identify the malnutrition risk and take action as early as possible. © 2017 John Wiley & Sons Ltd.

EST databases and web tools for EST projects.

PubMed

Shen, Yao-Qing; O'Brien, Emmet; Koski, Liisa; Lang, B Franz; Burger, Gertraud

2009-01-01

This chapter outlines key considerations for constructing and implementing an EST database. Instead of showing the technological details step by step, emphasis is put on the design of an EST database suited to the specific needs of EST projects and how to choose the most suitable tools. Using TBestDB as an example, we illustrate the essential factors to be considered for database construction and the steps for data population and annotation. This process employs technologies such as PostgreSQL, Perl, and PHP to build the database and interface, and tools such as AutoFACT for data processing and annotation. We discuss these in comparison to other available technologies and tools, and explain the reasons for our choices.

CNK1: A New Component in the Control of Insulin Signaling | Center for Cancer Research

Cancer.gov

The control of insulin release after a meal to mediate blood-glucose levels is an essential step in energy regulation. An external signal activates molecular pathways within the cell to control this process.

Brand as Relevance.

ERIC Educational Resources Information Center

Sevier, Robert A.

2001-01-01

Discusses seven steps for colleges to create effective brands: identifying essential qualities that your audiences desire; assessing how well your audience perceives you deliver on those qualities; identifying which performance and perception gaps you want to fill; responding strategically; revising and prioritizing your vivid descriptors;…

The Fractal Self at Play

ERIC Educational Resources Information Center

Marks-Tarlow, Terry

2010-01-01

In this article, the author draws on contemporary science to illuminate the relationship between early play experiences, processes of self-development, and the later emergence of the fractal self. She argues that orientation within social space is a primary function of early play and developmentally a two-step process. With other people and with…

Estimulacion Precoz para Ninos Minusvalidos (Early Stimulation for Disabled Children).

ERIC Educational Resources Information Center

Lumpkin, Garren

Written as a first step to improve early stimulation services to developmentally disabled and retarded preschool aged children in Costa Rica, the manual, in Spanish, seeks to attain the following objectives: raise consciousness and understanding of health service personnel, primary and special educators, rehabilitation personnel, and parents;…

Defining the Developmental Parameters of Temper Loss in Early Childhood: Implications for Developmental Psychopathology

ERIC Educational Resources Information Center

Wakschlag, Lauren S.; Choi, Seung W.; Carter, Alice S.; Hullsiek, Heide; Burns, James; McCarthy, Kimberly; Leibenluft, Ellen; Briggs-Gowan, Margaret J.

2012-01-01

Background: Temper modulation problems are both a hallmark of early childhood and a common mental health concern. Thus, characterizing specific behavioral manifestations of temper loss along a dimension from normative misbehaviors to clinically significant problems is an important step toward identifying clinical thresholds. Methods:…

Steps to Implementing Technology in Inclusive Early Childhood Programs

ERIC Educational Resources Information Center

Lyons, Catherine D.; Tredwell, Claire T.

2015-01-01

Twenty-first-century preschool children, with and without disabilities, may be found using technology, including assistive technologies, on a daily basis in their homes, schools, and communities. Early childhood educators are exploring opportunities to integrate technology and interactive media into the present-day curriculum. The authors suggest…

The Emergence of Ethics and Professionalism in the Early Advertising Business.

ERIC Educational Resources Information Center

Schultze, Quentin J.

In the pre-World War I era, advertising practitioners attempted to make their craft a profession. Generally agreeing that the creation of ethical codes was the most important step toward professionalism, practitioners organized the Associated Advertising Clubs of America (AACA). Early journal articles and AACA proceedings indicate that…

The Role of Meaningful Dialogue in Early Childhood Education Leadership

ERIC Educational Resources Information Center

Deakins, Eric

2007-01-01

Action research was used to study the effectiveness of Learning Organisation and Adaptive Enterprise theories for promoting organisation-wide learning and creating a more effective early childhood education organisation. This article describes the leadership steps taken to achieve shared vision via meaningful dialogue between board, management and…

A Systematic Review of Part C Early Identification Studies

ERIC Educational Resources Information Center

Barger, Brian; Rice, Catherine; Simmons, Christina Anne; Wolf, Rebecca

2018-01-01

Authors conducted a systematic literature review on early identification steps leading at-risk young children to connect with Part C services. Authors classified data collection settings as primary (settings for general population) or specialized (settings for children at risk of developmental delay) and according to the phases of early…

Patent and exclusivity status of essential medicines for non-communicable disease.

PubMed

Mackey, Tim K; Liang, Bryan A

2012-01-01

The threat of non-communicable diseases ("NCDs") is increasingly becoming a global health crisis and are pervasive in high, middle, and low-income populations resulting in an estimated 36 million deaths per year. There is a need to assess intellectual property rights ("IPRs") that may impede generic production and availability and affordability to essential NCD medicines. Using the data sources listed below, the study design systematically eliminated NCD drugs that had no patent/exclusivity provisions on API, dosage, or administration route. The first step identified essential medicines that treat certain high disease burden NCDs. A second step examined the patent and exclusivity status of active ingredient, dosage and listed route of administration using exclusion criteria outlined in this study. We examined the patent and exclusivity status of medicines listed in the World Health Organization's ("WHO") Model List of Essential Drugs (Medicines) ("MLEM") and other WHO sources for drugs treating certain NCDs. i.e., cardiovascular and respiratory disease, cancers, and diabetes. We utilized the USA Food and Drug Administration Orange Book and the USA Patent and Trademark Office databases as references given the predominant number of medicines registered in the USA. Of the 359 MLEM medicines identified, 22% (79/359) address targeted NCDs. Of these 79, only eight required in-depth patent or exclusivity assessment. Upon further review, no NCD MLEM medicines had study patent or exclusivity protection for reviewed criteria. We find that ensuring availability and affordability of potential generic formulations of NCD MLEM medicines appears to be more complex than the presence of IPRs with API, dosage, or administration patent or exclusivity protection. Hence, more sophisticated analysis of NCD barriers to generic availability and affordability should be conducted in order to ensure equitable access to global populations for these essential medicines.

Access to Cytotoxic Medicines by Children With Cancer: A Focus on Low and Middle Income Countries.

PubMed

Barr, Ronald; Robertson, Jane

2016-02-01

The Essential Medicines Working Group of the International Society of Pediatric Oncology (SIOP) has proposed a list of antineoplastic drugs that should be available in low and middle income countries. Data were extracted on the listing of 18 essential and 8 ancillary antineoplastic medicines in the national essential medicines lists (NEMLs) or national reimbursable medicines lists (NRMLs) of 135 countries with gross national income (GNI) per capita of less than US $25,000. Correlations between numbers of medicines listed and GNI per capita, annual government health expenditure (AGHE) per capita, and the number of physicians per million people were examined. Listing of the 18 essential antineoplastic drugs ranged from 27% (thioguanine) to 95% (methotrexate). The median number of medicines listed was 7 (0-18) in low income countries (n = 26) and 14 in lower-middle (n = 42), upper-middle (n = 44), and high income countries (n = 20). For the ancillary eight medicines, the median was one (0-8) across the 135 countries. Correlations with GNI per capita (r = 0.17, P = 0.0266) and physician density (r = 0.25, P = 0.0017) were statistically significant; not so for AGHE per capita (r = 0.00, P = 0.5000). There was large variability within income groups in numbers of antineoplastic agents identified as essential in NEMLs and NRMLs. While not a direct measure of availability, listing is an important step, guiding procurement for the public sector. These results focus attention on deficits in NEMLs and NMRLs as a step to improving access to effective antineoplastic medicines for cancers in children in low and middle income countries. © 2015 Wiley Periodicals, Inc.

A genomics resource for investigating regulation of essential oil production in Lavandula angustifolia.

PubMed

Lane, Alexander; Boecklemann, Astrid; Woronuk, Grant N; Sarker, Lukman; Mahmoud, Soheil S

2010-03-01

We are developing Lavandula angustifolia (lavender) as a model system for investigating molecular regulation of essential oil (a mixture of mono- and sesquiterpenes) production in plants. As an initial step toward building the necessary 'genomics toolbox' for this species, we constructed two cDNA libraries from lavender leaves and flowers, and obtained sequence information for 14,213 high-quality expressed sequence tags (ESTs). Based on homology to sequences present in GenBank, our EST collection contains orthologs for genes involved in the 1-deoxy-D: -xylulose-5-phosphate (DXP) and the mevalonic acid (MVA) pathways of terpenoid biosynthesis, and for known terpene synthases and prenyl transferases. To gain insight into the regulation of terpene metabolism in lavender flowers, we evaluated the transcriptional activity of the genes encoding for 1-deoxy-D: -xylulose-5-phosphate synthase (DXS) and HMG-CoA reductase (HMGR), which represent regulatory steps of the DXP and MVA pathways, respectively, in glandular trichomes (oil glands) by real-time PCR. While HMGR transcripts were barely detectable, DXS was heavily expressed in this tissue, indicating that essential oil constituents are predominantly produced through the DXP pathway in lavender glandular trichomes. As anticipated, the linalool synthase (LinS)-the gene responsible for the production of linalool, a major constituent of lavender essential oil-was also strongly expressed in glands. Surprisingly, the most abundant transcript in floral glandular trichomes corresponded to a sesquiterpene synthase (cadinene synthase, CadS), although sesquiterpenes are minor constituents of lavender essential oils. This result, coupled to the weak activity of the MVA pathway (the main route for sesquiterpene production) in trichomes, indicates that precursor supply may represent a bottleneck in the biosynthesis of sesquiterpenes in lavender flowers.

Targeted deletion of p97 (VCP/CDC48) in mouse results in early embryonic lethality.

PubMed

Müller, J M M; Deinhardt, K; Rosewell, I; Warren, G; Shima, D T

2007-03-09

The highly conserved AAA ATPase p97 (VCP/CDC48) has well-established roles in cell cycle progression, proteasome degradation and membrane dynamics. Gene disruption in Saccromyces cerevisiae, Drosophila melanogaster and Trypanosoma brucei demonstrated that p97 is essential in unicellular and multicellular organisms. To explore the requirement for p97 in mammalian cell function and embryogenesis, we disrupted the p97 locus by gene targeting. Heterozygous p97+/- mice were indistinguishable from their wild-type littermates, whereas homozygous mutants did not survive to birth and died at a peri-implantation stage. These results show that p97 is an essential gene for early mouse development.

On Becoming Batman: An Ethnographic Examination of Hero Imagery in Early-Career Residential Life Emergency Management

ERIC Educational Resources Information Center

Molina, Danielle K.

2016-01-01

Emergency response is an essential function of all residential life staff, but particularly for resident assistants serving on the front line. This organizational ethnography examined the role that professional identity played for early-career residential life practitioners engaged in emergency management. The data elucidated heroism as a…

Designing a Measurement Framework for Response to Intervention in Early Childhood Programs

ERIC Educational Resources Information Center

McConnell, Scott R.; Wackerle-Hollman, Alisha K.; Roloff, Tracy A.; Rodriguez, Michael

2014-01-01

The overall architecture and major components of a measurement system designed and evaluated to support Response to Intervention (RTI) in the areas of language and literacy in early childhood programs are described. Efficient and reliable measurement is essential for implementing any viable RTI system, and implementing such a system in early…

Heterogeneity in Externalizing Problems at Age 3: Association with Age 15 Biological and Environmental Outcomes

ERIC Educational Resources Information Center

Fanti, Kostas A.; Kimonis, Eva

2017-01-01

Investigating heterogeneity in antisocial behavior early in life is essential for understanding the etiology, development, prognosis, and treatment of these problems. Data from the longitudinal National Institute of Child Health and Development (NICHD) study of Early Child Care were used to identify homogeneous groups of young antisocial children…

Starting Strong 2017: Key OECD Indicators on Early Childhood Education and Care

ERIC Educational Resources Information Center

OECD Publishing, 2017

2017-01-01

Early childhood education and care (ECEC) can help lay the foundations for future skills development, well-being and learning. Having timely, reliable and comparable international information is essential to help countries improve their ECEC services and systems. For over 15 years, the OECD has been conducting policy analysis and gathering new…

The Gentle Art of Listening: Skills for Developing Family-Administrator Relationships in Early Childhood.

ERIC Educational Resources Information Center

Lam, Mei Seung

2000-01-01

Notes that relationships between parents, administrators, and teachers are essential to quality early childhood education. Examines the role of good communication skills in building positive home-school relationships. Discusses the importance of developing effective listening skills in order to understand parents' needs and concerns, and how the…

Studying the Emergence of Autism Spectrum Disorders in High-Risk Infants: Methodological and Practical Issues

ERIC Educational Resources Information Center

Zwaigenbaum, Lonnie; Thurm, Audrey; Stone, Wendy; Baranek, Grace; Bryson, Susan; Iverson, Jana; Kau, Alice; Klin, Ami; Lord, Cathy; Landa, Rebecca; Rogers, Sally; Sigman, Marian

2007-01-01

Detecting early signs of autism is essential for timely diagnosis and initiation of effective interventions. Several research groups have initiated prospective studies of high-risk populations including infant siblings, to systematically collect data on early signs within a longitudinal design. Despite the potential advantages of prospective…

Aggression and Young Children. Research in Practice Series. Volume 11, Number 1

ERIC Educational Resources Information Center

Szarkowicz, Diane Louise

2004-01-01

The "Research in Practice Series" is a practical, easy-to-read resource, offering effective new approaches for those challenging issues which arise in the care and education of young children. Early Childhood Australia's "Research in Practice Series" is an essential resource for those involved in the early childhood field.…

Relationship-Centered Practices in Early Childhood: Working with Families, Infants, and Young Children at Risk

ERIC Educational Resources Information Center

Ensher, Gail L.; Clark, David A.

2011-01-01

Strong working relationships with diverse families and children are the foundation of successful early intervention. Discover fresh, practical ways to build these relationships in this essential guidebook, every professional's blueprint for working with children and families within the specific context of their culture, family structure, and risk…

A Monitoring Tool of Infant and Toddler Movement Skills

ERIC Educational Resources Information Center

Leitschuh, Carol A.; Harring, Jeffrey R.; Dunn, Winnie

2014-01-01

Physical activity in infancy is essential for early brain development. Development in the early years is the most rapid at any time during life. Monitoring functional movement skills of infants and toddlers frequently (3-week intervals) and quickly (minutes) produces information on whether development is on track or in need of intervention. To…

Subsidizing Early Childhood Education and Care for Parents on Low Income: Moving beyond the Individualized Economic Rationale of Neoliberalism

ERIC Educational Resources Information Center

Simpson, Donald; Envy, Rose

2015-01-01

Neoliberalism and an associated "new politics of parenting" adopts a predominantly economic rationale which discursively positions early childhood education and care (ECEC) as essential to tackling several social ills by allowing individual parents (particularly young mothers) to improve their labour force participation, thus boosting…

Perspectives in Early Childhood Education: Belize, Brazil, Mexico, El Salvador and Peru

ERIC Educational Resources Information Center

McConnell-Farmer, Judith Lynne; Cook, Pamela R.; Farmer, M. W.

2012-01-01

Early childhood education (ECE) provision is becoming a growing priority. During the past twenty years, Latin America has shown a growing recognition in the provision of educational programs for young children, birth to age eight, is essential. Urban and rural populations intimated in 2009, that many countries utilizing equitable access to…

Literacy Workshops: School Social Workers Enhancing Educational Connections between Educators, Early Childhood Students, and Families

ERIC Educational Resources Information Center

Hunter, William C.; Elswick, Susan E.; Perkins, J. Helen; Heroux, JoDell R.; Harte, Helene

2017-01-01

Parents and family members play an essential role in the literacy development of their children. Research indicates that children with disabilities enrolled in early childhood programs are likely to experience marginalization in terms of receiving educational services. This research emphasizes the importance of exposing students with disabilities…

Negotiating Assimilation: Chicago Catholic High Schools' Pursuit of Accreditation in the Early Twentieth Century

ERIC Educational Resources Information Center

Ryan, Ann Marie

2006-01-01

While the national debates over the accreditation of Catholic schools remain an essential element of understanding Catholic education during the early 20th century, this study examines how individuals, groups, and institutions grappled with the perceived need for standardization and increased articulation of schools. In particular, it examines the…

Practical Applications for Using Curriculum-Based Assessment to Create Embedded Learning Opportunities for Young Children

ERIC Educational Resources Information Center

Macy, Marisa G.; Bricker, Dianer D.

2006-01-01

Meaningful assessments should inform early childhood intervention practices. The essential relationship between assessment and curriculum is an organizing principle of the Division of Early Childhood Recommended Practices. One tool that combines assessment and curriculum into a comprehensive system for supporting and serving young children and…

From Parents to Partners: Building a Family-Centered Early Childhood Program

ERIC Educational Resources Information Center

Keyser, Janis

2006-01-01

Partnering with parents is essential if an early childhood program is to succeed. "From Parents to Partners" explores the reasons and methods for developing ongoing partnerships with parents and other family members. It also provides the tools and strategies needed to build the communication and support networks within which these partnerships…

Job-Embedded Professional Learning Essential to Improving Teaching and Learning in Early Education

ERIC Educational Resources Information Center

Pacchiano, Debra; Klein, Rebecca; Hawley, Marsha Shigeyo

2016-01-01

Improving classroom teaching improves children's learning outcomes. In pursuit of those goals, the early education field has made substantial investments aimed at increasing the quality of classroom environments and teacher-child interactions. Yet, in publicly funded programs across the country, the quality of instruction remains low and…

The Application of a Transdisciplinary Model for Early Intervention Services

ERIC Educational Resources Information Center

King, Gillian; Strachan, Deborah; Tucker, Michelle; Duwyn, Betty; Desserud, Sharon; Shillington, Monique

2009-01-01

This article reviews the literature on the transdisciplinary approach to early intervention services and identifies the essential elements of this approach. A practice model describing the implementation of the approach is then presented, based on the experiences of staff members in a home visiting program for infants that has been in existence…

Preschool Education in Saudi Arabia: Past, Present, and Future

ERIC Educational Resources Information Center

Aljabreen, Haifa Hassan; Lash, Martha

2016-01-01

Despite differences in specific teaching styles, nations around the world are united in the belief that early education is essential for preparing children for success throughout their school life and beyond. This tenet is as applicable to the Saudi Arabian early childhood education (ECE) system as it is anywhere else. Yet, little is actually…

Monsters under the Bed: Critically Investigating Early Years Writing

ERIC Educational Resources Information Center

Melrose, Andrew

2012-01-01

"Monsters Under the Bed" is an essential text focussing on critical and contemporary issues surrounding writing for "early years" children. Containing a critically creative and a creatively critical investigation of the cult and culture of the child and childhood in fiction and non-fictional writing, it also contains a wealth of ideas and critical…

Two-Step Functional Innovation of the Stem-Cell Factors WUS/WOX5 during Plant Evolution

PubMed Central

Zhang, Yuzhou; Jiao, Yue; Jiao, Hengwu

2017-01-01

WUS and WOX5, which are expressed, respectively, in the organizing center (OC) and the quiescent center (QC), are essential for shoot/root apical stem-cell maintenance in flowering plants. However, little is known about how these stem-cell factors evolved their functions in flowering plants. Here, we show that the WUS/WOX5 proteins acquired two distinct capabilities by a two-step functional innovation process in the course of plant evolution. The first-step is the apical stem-cell maintenance activity of WUS/WOX5, which originated in the common ancestor of ferns and seed plants, as evidenced by the interspecies complementation experiments, showing that ectopic expression of fern Ceratopteris richardii WUS-like (CrWUL) surrounding OC/QC, or exclusive OC-/QC-expressed gymnosperms/angiosperms WUS/WOX5 in Arabidopsis wus-1 and wox5-1 mutants, could rescue their phenotypes. The second-step is the intercellular mobility that emerged in the common ancestor of seed plants after divergence from the ferns. Evidence for this includes confocal imaging of GFP fusion proteins, showing that WUS/WOX5 from seed plants, rather than from the fern CrWUL, can migrate into cells adjacent to the OC/QC. Evolutionary analysis showed that the WUS-like gene was duplicated into two copies prior to the divergence of gymnosperms/angiosperms. Then the two gene copies (WUS and WOX5) have undergone similar levels of purifying selection, which is consistent with their conserved functions in angiosperm shoot/root stem-cell maintenance and floral organ formation. Our results highlight the critical roles and the essential prerequisites that the two-step functional innovation of these genes performs and represents in the origin of flowering plants. PMID:28053005

Using Click Chemistry to Identify Potential Drug Targets in Plasmodium

DTIC Science & Technology

2015-04-01

step of the Plasmodium mammalian cycle . Inhibiting this step can block malaria at an early step. However, few anti-malarials target liver infection...points in the life cycle of malaria parasites. PLoS Biol 12: e1001806. 2. Falae A, Combe A, Amaladoss A, Carvalho T, Menard R, et al. (2010) Role of...AWARD NUMBER: W81XWH-13-1-0429 TITLE: Using "Click Chemistry" to Identify Potential Drug Targets in Plasmodium PRINCIPAL INVESTIGATOR: Dr. Purnima

[PROtocol-based MObilizaTION on intensive care units : Design of a cluster randomized pilot study].

PubMed

Nydahl, P; Diers, A; Günther, U; Haastert, B; Hesse, S; Kerschensteiner, C; Klarmann, S; Köpke, S

2017-10-12

Despite convincing evidence for early mobilization of patients on intensive care units (ICU), implementation in practice is limited. Protocols for early mobilization, including in- and exclusion criteria, assessments, safety criteria, and step schemes may increase the rate of implementation and mobilization. Patients (population) on ICUs with a protocol for early mobilization (intervention), compared to patients on ICUs without protocol (control), will be more frequently mobilized (outcome). A multicenter, stepped-wedge, cluster-randomized pilot study is presented. Five ICUs will receive an adapted, interprofessional protocol for early mobilization in randomized order. Before and after implementation, mobilization of ICU patients will be evaluated by randomized monthly one-day point prevalence surveys. Primary outcome is the percentage of patients mobilized out of bed, operationalized as a score of ≥3 on the ICU Mobility Scale. Secondary outcome parameters will be presence and/or length of mechanical ventilation, delirium, stay on ICU and in hospital, barriers to early mobilization, adverse events, and process parameters as identified barriers, used strategies, and adaptions to local conditions. Exploratory evaluation of study feasibility and estimation of effect sizes as the basis for a future explanatory study.

Age at adoption from institutional care as a window into the lasting effects of early experiences

PubMed Central

Julian, Megan M.

2013-01-01

One of the major questions of human development is how early experience impacts the course of development years later. Children adopted from institutional care experience varying levels of deprivation in their early life followed by qualitatively better care in an adoptive home, providing a unique opportunity to study the lasting effects of early deprivation and its timing. The effects of age at adoption from institutional care are discussed for multiple domains of social and behavioral development within the context of several prominent developmental hypotheses about the effects of early deprivation (cumulative effects, experience-expectant developmental programming, and experience-adaptive developmental programming). Age at adoption effects are detected in a majority of studies, particularly when children experienced global deprivation and were assessed in adolescence. For most outcomes, institutionalization beyond a certain age is associated with a step-like increase in risk for lasting social and behavioral problems, with the step occurring at an earlier age for children who experienced more severe levels of deprivation. Findings are discussed in terms of their concordance and discordance with our current hypotheses, and speculative explanations for the findings are offered. PMID:23576122

Toxic Accumulation of LPS Pathway Intermediates Underlies the Requirement of LpxH for Growth of Acinetobacter baumannii ATCC 19606

PubMed Central

Richie, Daryl L.; Takeoka, Kenneth T.; Bojkovic, Jade; Metzger, Louis E.; Rath, Christopher M.; Sawyer, William S.; Wei, Jun-Rong; Dean, Charles R.

2016-01-01

The lipid A moiety of lipopolysaccharide (LPS) is the main constituent of the outer leaflet of the Gram-negative bacterial outer membrane (OM) and is essential in many Gram-negative pathogens. An exception is Acinetobacter baumannii ATCC 19606, where mutants lacking enzymes occurring early in lipid A biosynthesis (LpxA, LpxC or LpxD), and correspondingly lacking LPS, can grow. In contrast, we show here that LpxH, an enzyme that occurs downstream of LpxD in the lipid A biosynthetic pathway, is essential for growth in this strain. Multiple attempts to disrupt lpxH on the genome were unsuccessful, and when LpxH expression was controlled by an isopropyl β-d-1-thiogalactopyranoside (IPTG) inducible promoter, cell growth under typical laboratory conditions required IPTG induction. Mass spectrometry analysis of cells shifted from LpxH-induced to uninduced (and whose growth was correspondingly slowing as LpxH was depleted) showed a large cellular accumulation of UDP-2,3-diacyl-GlcN (substrate of LpxH), a C14:0(3-OH) acyl variant of the LpxD substrate (UDP-3-O-[(R)-3-OH-C14]-GlcN), and disaccharide 1-monophosphate (DSMP). Furthermore, the viable cell counts of the LpxH depleted cultures dropped modestly, and electron microscopy revealed clear defects at the cell (inner) membrane, suggesting lipid A intermediate accumulation was toxic. Consistent with this, blocking the synthesis of these intermediates by inhibition of the upstream LpxC enzyme using CHIR-090 abrogated the requirement for IPTG induction of LpxH. Taken together, these data indicate that LpxH is essential for growth in A. baumannii ATCC19606, because, unlike earlier pathway steps like LpxA or LpxC, blockage of LpxH causes accumulation of detergent-like pathway intermediates that prevents cell growth. PMID:27526195

Utilizing Electronic Medical Records to Discover Changing Trends of Medical Behaviors Over Time*

PubMed Central

Yin, Liangying; Dong, Wei; He, Chunhua; Duan, Huilong

2017-01-01

Summary Objectives Medical behaviors are playing significant roles in the delivery of high quality and cost-effective health services. Timely discovery of changing frequencies of medical behaviors is beneficial for the improvement of health services. The main objective of this work is to discover the changing trends of medical behaviors over time. Methods This study proposes a two-steps approach to detect essential changing patterns of medical behaviors from Electronic Medical Records (EMRs). In detail, a probabilistic topic model, i.e., Latent Dirichlet allocation (LDA), is firstly applied to disclose yearly treatment patterns in regard to the risk stratification of patients from a large volume of EMRs. After that, the changing trends by comparing essential/critical medical behaviors in a specific time period are detected and analyzed, including changes of significant patient features with their values, and changes of critical treatment interventions with their occurring time stamps. Results We verify the effectiveness of the proposed approach on a clinical dataset containing 12,152 patient cases with a time range of 10 years. Totally, 135 patients features and 234 treatment interventions in three treatment patterns were selected to detect their changing trends. In particular, evolving trends of yearly occurring probabilities of the selected medical behaviors were categorized into six content changing patterns (i.e, 112 growing, 123 declining, 43 up-down, 16 down-up, 35 steady, and 40 jumping), using the proposed approach. Besides, changing trends of execution time of treatment interventions were classified into three occurring time changing patterns (i.e., 175 early-implemented, 50 steady-implemented and 9 delay-implemented). Conclusions Experimental results show that our approach has an ability to utilize EMRs to discover essential evolving trends of medical behaviors, and thus provide significant potential to be further explored for health services redesign and improvement. PMID:28474729

Early-career experts essential for planetary sustainability

USGS Publications Warehouse

Lim, Michelle; Lynch, Abigail J.; Fernández-Llamazares, Alvaro; Balint, Lenke; Basher, Zeenatul; Chan, Ivis; Jaureguiberry, Pedro; Mohamed, A.A.A.; Mwampamba, Tuyeni H.; Palomo, Ignacio; Pliscoff, Patricio; Salimov, R.A.; Samakov, Aibek; Selomane, Odirilwe; Shrestha, Uttam B.; Sidorovich, Anna A.

2017-01-01

Early-career experts can play a fundamental role in achieving planetary sustainability by bridging generational divides and developing novel solutions to complex problems. We argue that intergenerational partnerships and interdisciplinary collaboration among early-career experts will enable emerging sustainability leaders to contribute fully to a sustainable future. We review 16 international, interdisciplinary, and sustainability-focused early-career capacity building programs. We conclude that such programs are vital to developing sustainability leaders of the future and that decision-making for sustainability is likely to be best served by strong institutional cultures that promote intergenerational learning and involvement.

Growth and clinical variables in nitrogen-restricted piglets fed an adjusted essential amino acid mix: Effects using free amino acid-based diets

USDA-ARS?s Scientific Manuscript database

Excess protein intake in early life has been linked to obesity and metabolic syndrome in later life. Yet, protein, and in particular the essential amino acids (EAA), need to be present in adequate quantity to support growth. Using a piglet model restricted in dietary amino acids (AA), our objective...

The Effects of Using the Essential Skills Inventory on Teacher Perception of High-Quality Classroom Instruction

ERIC Educational Resources Information Center

Sornson, Bob

2015-01-01

This study explores the efficacy of using the Essential Skill Inventories (ESI) to increase high-quality instruction in the early learning years. Kindergarten and first- and second-grade teachers, who were identified as using the ESI with fidelity, assessed their own teaching skills and behaviors, reflecting on these before and after use of the…

Dancing with the Stars: Stepping up and Stepping out in Honors Education

ERIC Educational Resources Information Center

Dinndorf, Elizabeth A.

2015-01-01

One of the most profound statements in James Herbert's lead essay-simple as it seems at the very beginning of his piece, "Thinking and Rethinking: The Practical Value of an Honors Education," concerns his discovery early in his career that "a liberal education in honors was good preparation for life." Stressing the importance…

First Step to Success. What Works Clearinghouse Intervention Report

ERIC Educational Resources Information Center

What Works Clearinghouse, 2012

2012-01-01

"First Step to Success" is an early intervention program designed to help children who are at risk for developing aggressive or antisocial behavioral patterns. The program uses a trained behavior coach who works with each student and his or her class peers, teacher, and parents for approximately 50 to 60 hours over a three-month period.…

Early Success Is Vital in Minimal Worksite Wellness Interventions at Small Worksites

ERIC Educational Resources Information Center

Ablah, Elizabeth; Dong, Frank; Konda, Kurt; Konda, Kelly; Armbruster, Sonja; Tuttle, Becky

2015-01-01

Intervention: In an effort to increase physical activity, 15 workplaces participated in a minimal-contact 10,000-steps-a-day program sponsored by the Sedgwick County Health Department in 2007 and 2008. Pedometers were provided to measure participants' weekly steps for the 10-week intervention. Method: Participants were defined as those who…

Phonemic Awareness: A Step by Step Approach for Success in Early Reading

ERIC Educational Resources Information Center

Perez, Idalia Rodriguez

2008-01-01

This guide will help teach phonemic awareness to Pre K-3 students. It presents phonemic awareness as a sophisticated branch of phonological awareness through interactive activities that allows the student to succeed in learning the sounds represented by the letters of the alphabet. The book is designed to provide easy-to-follow suggestions for:…