Hedgehog signaling governs the development of otic sensory epithelium and its associated innervation in zebrafish

The inner ear is responsible for the perception of motion and sound in vertebrates. Its functional unit, the sensory patch, contains mechanosensory hair cells innervated by sensory neurons from the statoacoustic ganglion (SAG) that project to the corresponding nuclei in the brainstem. How hair cells develop at specific positions, and how otic neurons are sorted to specifically innervate each endorgan and to convey the extracted information to the hindbrain is not completely understood. In this work, we study the generation of macular sensory patches and investigate the role of Hedgehog (Hh) signaling in the production of their neurosensory elements. Using zebrafish transgenic lines to visualize the dynamics of hair cell and neuron production, we show that the development of the anterior and posterior maculae is asynchronic, suggesting they are independently regulated. Tracing experiments demonstrate the SAG is topologically organized in two different neuronal subpopulations, which are spatially segregated and innervate specifically each macula. Functional experiments identify the Hh pathway as crucial in coordinating the production of hair cells in the posterior macula, and the formation of its specific innervation. Finally, gene expression analyses suggest that Hh influences the balance between different SAG neuronal subpopulations. These results lead to a model in which Hh orients functionally the development of inner ear towards an auditory fate in all vertebrate species.

Effective Structural Concrete Repair, Volume 1 of 3, Repair of Impact Damaged Prestressed Concrete Beams with CFRP, March 2004

Structural concrete is one of the most commonly used construction materials in the United States. However, due to changes in design specifications, aging, vehicle impact, etc. – there is a need for new procedures for repairing concrete (reinforced or pretressed) superstructures and substructures. Thus, the overall objective of this investigation was to develop innovative cost effective repair methods for various concrete elements. In consultation with the project advisory committee, it was decided to evaluate the following three repair methods: • Carbon fiber reinforced polymers (CFRPs) for use in repairing damaged prestressed concrete bridges • Fiber reinforced polymers (FRPs) for preventing chloride penetration of bridge columns • Various patch materials The initial results of these evaluations are presented in this three volume final report. Each evaluation is briefly described in the following paragraphs. A more detailed abstract of each evaluation accompanies the volume on that particular investigation.

Effective Structural Concrete Repair, Volume 2 of 3, Use of FRP to Prevent Chloride Penetration in Bridge Columns, March 2004

Structural concrete is one of the most commonly used construction materials in the United States. However, due to changes in design specifications, aging, vehicle impact, etc. – there is a need for new procedures for repairing concrete (reinforced or pretressed) superstructures and substructures. Thus, the overall objective of this investigation was to develop innovative cost effective repair methods for various concrete elements. In consultation with the project advisory committee, it was decided to evaluate the following three repair methods: • Carbon fiber reinforced polymers (CFRPs) for use in repairing damaged prestressed concrete bridges • Fiber reinforced polymers (FRPs) for preventing chloride penetration of bridge columns • Various patch materials The initial results of these evaluations are presented in this three volume final report. Each evaluation is briefly described in the following paragraphs. A more detailed abstract of each evaluation accompanies the volume on that particular investigation.

Effective Structural Concrete Repair, Volume 3 of 3, Evaluation of Repair Materials for Use in Patching Damaged Concrete, March 2004

Structural concrete is one of the most commonly used construction materials in the United States. However, due to changes in design specifications, aging, vehicle impact, etc. – there is a need for new procedures for repairing concrete (reinforced or pretressed) superstructures and substructures. Thus, the overall objective of this investigation was to develop innovative cost effective repair methods for various concrete elements. In consultation with the project advisory committee, it was decided to evaluate the following three repair methods: • Carbon fiber reinforced polymers (CFRPs) for use in repairing damaged prestressed concrete bridges • Fiber reinforced polymers (FRPs) for preventing chloride penetration of bridge columns • Various patch materials The initial results of these evaluations are presented in this three volume final report. Each evaluation is briefly described in the following paragraphs. A more detailed abstract of each evaluation accompanies the volume on that particular investigation.

Bioreporters: gfp versus lux revisited and single-cell response.

Genetically engineered organisms expressing spectroscopically active reporter molecules in response to chemical effectors display great potential as living transducers in sensing applications. Green fluorescent protein (gfp gene) bioreporters have distinct advantages over luminescent couterparts (lux gene), including applicability at the single-cell level, but are typically less sensitive. Here we describe a gfp-bearing bioreporter that is sensitive to naphthalene (a poorly water soluble pollutant behaving like a large class of hydrophobic compounds), is suitable for use in chemical assays and bioavailability studies, and has detection limits comparable to lux-bearing bioreporters for higher efficiency detection strategies. Simultaneously, we find that the exploitation of population response data from single-cell analysis is not an algorithmic conduit to enhanced signal detection and hence lower effector detection limits, as normally assumed. The assay reported functions to equal effect with or without biocide.

Portland Cement Concrete Patching Techniques vs. Performance and Traffic Delay, January 2004

Standards for the construction of full-depth patching in portland cement concrete pavement usually require replacement of all deteriorated based materials with crushed stone, up to the bottom of the existing pavement layer. In an effort to reduce the time of patch construction and costs, the Iowa Department of Transportation and the Department of Civil, Construction and Environmental Engineering at Iowa State University studied the use of extra concrete depth as an option for base construction. This report compares the impact of additional concrete patching material depth on rate of strength gain, potential for early opening to traffic, patching costs, and long-term patch performance. This report also compares those characteristics in terms of early setting and standard concrete mixes. The results have the potential to change the method of Portland cement concrete pavement patch construction in Iowa.

Neonatal Minimally Invasive Surgery for Congenital Diaphragmatic Hernias: a multicenter study using thoracoscopy or laparoscopy.

BACKGROUND: Minimally invasive surgery (MIS) for late-presenting congenital diaphragmatic hernia (CDH) has been described previously, but few neonatal cases of CDH have been reported. This study aimed to report the multicenter experience of these rare cases and to compare the laparoscopic and thoracoscopic approaches. METHODS: Using MIS procedures, 30 patients (16 boys and 14 girls) from nine centers underwent surgery for CDH within the first month of life, 26 before day 5. Only one patient had associated malformations. There were 10 preterm patients (32-36 weeks of gestational age). Their weight at birth ranged from 1,800 to 3,800 g, with three patients weighing less than 2,600 g. Of the 30 patients, 18 were intubated at birth. RESULTS: The MIS procedures were performed in 18 cases by a thoracoscopic approach and in 12 cases by a laparoscopic approach. No severe complication was observed. For 20 patients, reduction of the intrathoracic contents was achieved easily with 15 thoracoscopies and 5 laparoscopies. In six cases, the reduction was difficult, proving to be impossible for the four remaining patients: one treated with thoracoscopy and three with laparoscopy. The reasons for the inability to reduce the thoracic contents were difficulty of liver mobilization (1 left CDH and 2 right CDH) and the presence of a dilated stomach in the thorax. Reductions were easier for cases of wide diaphragmatic defects using thoracoscopy. There were 10 conversions (5 laparoscopies and 5 thoracoscopies). The reported reasons for conversion were inability to reduce (n = 4), need for a patch (n = 5), lack of adequate vision (n = 4), narrow working space (n = 1), associated bowel malrotation (n = 1), and an anesthetic problem (n = 1). Five defects were too large for direct closure and had to be closed with a patch. Four required conversion, with one performed through video-assisted thoracic surgery. The recurrences were detected after two primer thoracoscopic closures, one of which was managed by successful reoperation using thoracoscopy. CONCLUSIONS: In the neonatal period, CDH can be safely closed using MIS procedures. The overall success rate in this study was 67%. The indication for MIS is not related to weeks of gestational age, to weight at birth (if >2,600 g), or to the extent of the immediate neonatal care. Patients with no associated anomaly who are hemodynamically stabilized can benefit from MIS procedures. Reduction of the herniated organs is easier using thoracoscopy. Right CDH, liver lobe herniation, and the need for a patch closure are the most frequent reasons for conversion.

Ultra-Thin PCC Overlays, January 2005

· Evaluate conventional methods of slab removal and asphalt surface preparation for subsequent overlays of portland cement concrete (PCC) in the “remove and replace” areas. · Evaluate existing asphaltic concrete surface under the “remove and patch” areas of rehabilitation areas and evaluate joint formation in the areas of patching. · Evaluate polypropylene fiber enhanced concrete at the three-inch depth to determine the cost/benefit of its inclusion. · Evaluate the performance of the rehabilitated ultra-thin whitetopping sections and the extended performance of the existing ultra-thin sections with and without patching. · Validate existing ultra-thin whitetopping design procedures of the Portland Cement Association (PCA) and American Concrete Pavement Association (ACPA) for application in Iowa.

Characterization of the ligand-binding site of the serotonin 5-HT3 receptor: the role of glutamate residues 97, 224, AND 235.

Ligand-gated ion channels of the Cys loop family are receptors for small amine-containing neurotransmitters. Charged amino acids are strongly conserved in the ligand-binding domain of these receptor proteins. To investigate the role of particular residues in ligand binding of the serotonin 5-HT3AS receptor (5-HT3R), glutamate amino acid residues at three different positions, Glu97, Glu224, and Glu235, in the extracellular N-terminal domain were substituted with aspartate and glutamine using site-directed mutagenesis. Wild type and mutant receptor proteins were expressed in HEK293 cells and analyzed by electrophysiology, radioligand binding, fluorescence measurements, and immunochemistry. A structural model of the ligand-binding domain of the 5-HT3R based on the acetylcholine binding protein revealed the position of the mutated amino acids. Our results demonstrate that mutations of Glu97, distant from the ligand-binding site, had little effect on the receptor, whereas mutations Glu224 and Glu235, close to the predicted binding site, are indeed important for ligand binding. Mutations E224Q, E224D, and E235Q decreased EC50 and Kd values 5-20-fold, whereas E235D was functionally expressed at a low level and had a more than 100-fold increased EC50 value. Comparison of the fluorescence properties of a fluorescein-labeled antagonist upon binding to wild type 5-HT3R and E235Q, allowed us to localize Glu235 within a distance of 1 nm around the ligand-binding site, as proposed by our model.

Oxytocin selectively gates fear responses through distinct outputs from the central amygdala.

Central amygdala (CeA) projections to hypothalamic and brain stem nuclei regulate the behavioral and physiological expression of fear, but it is unknown whether these different aspects of the fear response can be separately regulated by the CeA. We combined fluorescent retrograde tracing of CeA projections to nuclei that modulate fear-related freezing or cardiovascular responses with in vitro electrophysiological recordings and with in vivo monitoring of related behavioral and physiological parameters. CeA projections emerged from separate neuronal populations with different electrophysiological characteristics and different response properties to oxytocin. In vivo, oxytocin decreased freezing responses in fear-conditioned rats without affecting the cardiovascular response. Thus, neuropeptidergic signaling can modulate the CeA outputs through separate neuronal circuits and thereby individually steer the various aspects of the fear response.

Thiazolidinedione-induced fluid retention is independent of collecting duct alphaENaC activity.

Thiazolidinediones are agonists of peroxisome proliferator-activated receptor gamma (PPARgamma) that can induce fluid retention and weight gain through unclear mechanisms. To test a proposed role for the epithelial sodium channel ENaC in thiazolidinedione-induced fluid retention, we used mice with conditionally inactivated alphaENaC in the collecting duct (Scnn1a(loxloxCre) mice). In control mice, rosiglitazone did not alter plasma aldosterone levels or protein expression of ENaC subunits in the kidney, but did increase body weight, plasma volume, and the fluid content of abdominal fat pads, and decreased hematocrit. Scnn1a(loxloxCre) mice provided functional evidence for blunted Na+ uptake in the collecting duct, but still exhibited rosiglitazone-induced fluid retention. Moreover, treatment with rosiglitazone or pioglitazone did not significantly alter the open probability or number of ENaC channels per patch in isolated, split-open cortical collecting ducts of wild-type mice. Finally, patch-clamp studies in primary mouse inner medullary collecting duct cells did not detect ENaC activity but did detect a nonselective cation channel upregulated by pioglitazone. These data argue against a primary and critical role of ENaC in thiazolidinedione-induced fluid retention.

Cricotracheal resection for laryngeal invasion by thyroid carcinoma: our experience.

Invasion of the laryngeal framework by thyroid carcinoma requires specific surgical techniques and carries a higher rate of complications that deserve to be highlighted. We reviewed our data from 1995 to 2012 and found six patients with laryngotracheal invasion by thyroid carcinoma. All underwent total thyroidectomy and single-stage cricotracheal resection, plus anterolateral neck dissection. Three had airway obstruction that necessitated prior endoscopic debulking. None of the patients needed a tracheotomy. There were four cases of papillary carcinoma, and two cases of undifferentiated carcinoma. One patient died of complications of the procedure (anastomotic dehiscence and tracheo-innominate artery fistula). Another died 2 months after the procedure from local recurrence and aspiration pneumonia. One case presented recurrence at 15 months, which was managed by re-excision and adjuvant radiotherapy; after 26 months of follow-up, he has no evidence of locoregional recurrence. The three other patients are alive without evidence of disease at 6, 18 and 41 months, respectively. Cricotracheal resection for subglottic invasion by thyroid carcinoma is an effective procedure, but carries significant risks of complications. This could be attributed to the devascularisation of the tracheal wall due to the simultaneous neck dissection, sacrifice of the strap muscles or of a patch of oesophageal muscle layer. We advocate a sternocleidomastoid flap to cover the anastomosis. Cricotracheal resection for subglottic invasion can be curative with good functional outcomes, even for the advanced stages of thyroid cancer. Endoscopic debulking of the airway prior to the procedure avoids tracheotomy.

Inhibitory effects of (2S, 3S)-3-[3-[4-(trifluoromethyl)benzoylamino]benzyloxy]aspartate (TFB-TBOA) on the astrocytic sodium responses to glutamate.

Astrocytes are responsible for the majority of the clearance of extracellular glutamate released during neuronal activity. dl-threo-beta-benzyloxyaspartate (TBOA) is extensively used as inhibitor of glutamate transport activity, but suffers from relatively low affinity for the transporter. Here, we characterized the effects of (2S, 3S)-3-[3-[4-(trifluoromethyl)benzoylamino]benzyloxy]aspartate (TFB-TBOA), a recently developed inhibitor of the glutamate transporter on mouse cortical astrocytes in primary culture. The glial Na(+)-glutamate transport system is very efficient and its activation by glutamate causes rapid intracellular Na(+) concentration (Na(+)(i)) changes that enable real time monitoring of transporter activity. Na(+)(i) was monitored by fluorescence microscopy in single astrocytes using the fluorescent Na(+)-sensitive probe sodium-binding benzofuran isophtalate. When applied alone, TFB-TBOA, at a concentration of 1 muM, caused small alterations of Na(+)(i). TFB-TBOA inhibited the Na(+)(i) response evoked by 200 muM glutamate in a concentration-dependent manner with IC(50) value of 43+/-9 nM, as measured on the amplitude of the Na(+)(i) response. The maximum inhibition of glutamate-evoked Na(+)(i) increase by TFB-TBOA was >80%, but was only partly reversible. The residual response persisted in the presence of the AMPA/kainate receptor antagonist CNQX. TFB-TBOA also efficiently inhibited Na(+)(i) elevations caused by the application of d-aspartate, a transporter substrate that does not activate non-NMDA ionotropic receptors. TFB-TBOA was found not to influence the membrane properties of cultured cortical neurons recorded in whole-cell patch clamp. Thus, TFB-TBOA, with its high potency and its apparent lack of neuronal effects, appears to be one of the most useful pharmacological tools available so far for studying glial glutamate transporters.

VIKI : a semiotic-based system for multilingual knowledge retrieval

Abstract Since its creation, the Internet has permeated our daily life. The web is omnipresent for communication, research and organization. This exploitation has resulted in the rapid development of the Internet. Nowadays, the Internet is the biggest container of resources. Information databases such as Wikipedia, Dmoz and the open data available on the net are a great informational potentiality for mankind. The easy and free web access is one of the major feature characterizing the Internet culture. Ten years earlier, the web was completely dominated by English. Today, the web community is no longer only English speaking but it is becoming a genuinely multilingual community. The availability of content is intertwined with the availability of logical organizations (ontologies) for which multilinguality plays a fundamental role. In this work we introduce a very high-level logical organization fully based on semiotic assumptions. We thus present the theoretical foundations as well as the ontology itself, named Linguistic Meta-Model. The most important feature of Linguistic Meta-Model is its ability to support the representation of different knowledge sources developed according to different underlying semiotic theories. This is possible because mast knowledge representation schemata, either formal or informal, can be put into the context of the so-called semiotic triangle. In order to show the main characteristics of Linguistic Meta-Model from a practical paint of view, we developed VIKI (Virtual Intelligence for Knowledge Induction). VIKI is a work-in-progress system aiming at exploiting the Linguistic Meta-Model structure for knowledge expansion. It is a modular system in which each module accomplishes a natural language processing task, from terminology extraction to knowledge retrieval. VIKI is a supporting system to Linguistic Meta-Model and its main task is to give some empirical evidence regarding the use of Linguistic Meta-Model without claiming to be thorough.

International nursing : cultivating a culture of empowerment

International nursing has been a growing phenomenon throughout the globe. International nurses have been found to be an asset to healthcare organizations and an important part of the health care team. However, growing concern for the plight of international nurses facing obstacles such as professional stagnation and exploitation has spurred the development of strategies to mitigate and ameliorate the experiences of nurses working abroad. In this respect, the purpose of this study was to explore the management-influenced factors and the nurse team-influenced factors that promote the empowerment of the international nurse in the health care setting. The methodology used in this study was a systemic review. After a rigorous search for relevant empirical studies using OVID database, eight empirical research studies were selected using systematic review methodology to collect, analyze and synthesize data. The selected eight empirical studies were then subjected to a content analysis. The results suggested that the empowerment of an international nurse is inseparable from the empowerment of the health care organization. Based on the findings in this study, strategies to promote international nurses were found to mirror strategies evidenced to empower the nursing organization. Some of the management-influenced factors which were found to facilitate empowerment included a diversity rich work culture, transformational leadership at the management level, and a responsibility to foster the values of the organization. The team-influenced factors which were found to contribute to the empowerment of the international nurse included a united mutually-interdependent nurse team, shared accountability among the members of the nurse team, and the building of trust in work relationships. To conlude, this study indicates that efforts to empower international nurses without considering the work culture and the organization as a whole are futile because empowerment cannot take place in an environment that lacks antecedent conditions. Strategies to empower the international nurse should not focus on the deficits and special needs of the international nurse, but should focus on the similarities and commonalities of the nursing body. Empowerment of the international nurse mean open honest communication, supportive work environment, and a firm policy to quell disruptive elements that threaten the organization's values, mission, and philosophy of care.