Biotin-targeted Pluronic(®) P123/F127 mixed micelles delivering niclosamide: A repositioning strategy to treat drug-resistant lung cancer cells.

PubMed

Russo, Annapina; Pellosi, Diogo Silva; Pagliara, Valentina; Milone, Maria Rita; Pucci, Biagio; Caetano, Wilker; Hioka, Noboru; Budillon, Alfredo; Ungaro, Francesca; Russo, Giulia; Quaglia, Fabiana

2016-09-10

With the aim to develop alternative therapeutic tools for the treatment of resistant cancers, here we propose targeted Pluronic(®) P123/F127 mixed micelles (PMM) delivering niclosamide (NCL) as a repositioning strategy to treat multidrug resistant non-small lung cancer cell lines. To build multifunctional PMM for targeting and imaging, Pluronic(®) F127 was conjugated with biotin, while Pluronic(®) P123 was fluorescently tagged with rhodamine B, in both cases at one of the two hydroxyl end groups. This design intended to avoid any interference of rhodamine B on biotin exposition on PMM surface, which is a key fundamental for cell trafficking studies. Biotin-decorated PMM were internalized more efficiently than non-targeted PMM in A549 lung cancer cells, while very low internalization was found in NHI3T3 normal fibroblasts. Biotin-decorated PMM entrapped NCL with good efficiency, displayed sustained drug release in protein-rich media and improved cytotoxicity in A549 cells as compared to free NCL (P<0.01). To go in depth into the actual therapeutic potential of NCL-loaded PMM, a cisplatin-resistant A549 lung cancer cell line (CPr-A549) was developed and its multidrug resistance tested against common chemotherapeutics. Free NCL was able to overcome chemoresistance showing cytotoxic effects in this cell line ascribable to nucleolar stress, which was associated to a significant increase of the ribosomal protein rpL3 and consequent up-regulation of p21. It is noteworthy that biotin-decorated PMM carrying NCL at low doses demonstrated a significantly higher cytotoxicity than free NCL in CPr-A549. These results point at NCL-based regimen with targeted PMM as a possible second-line chemotherapy for lung cancer showing cisplatin or multidrug resistance. Copyright © 2016 Elsevier B.V. All rights reserved.

Using the social amoeba Dictyostelium to study the functions of proteins linked to neuronal ceroid lipofuscinosis.

PubMed

Huber, Robert J

2016-11-24

Neuronal ceroid lipofuscinosis (NCL), also known as Batten disease, is a debilitating neurological disorder that affects both children and adults. Thirteen genetically distinct genes have been identified that when mutated, result in abnormal lysosomal function and an excessive accumulation of ceroid lipofuscin in neurons, as well as other cell types outside of the central nervous system. The NCL family of proteins is comprised of lysosomal enzymes (PPT1/CLN1, TPP1/CLN2, CTSD/CLN10, CTSF/CLN13), proteins that peripherally associate with membranes (DNAJC5/CLN4, KCTD7/CLN14), a soluble lysosomal protein (CLN5), a protein present in the secretory pathway (PGRN/CLN11), and several proteins that display different subcellular localizations (CLN3, CLN6, MFSD8/CLN7, CLN8, ATP13A2/CLN12). Unfortunately, the precise functions of many of the NCL proteins are still unclear, which has made targeted therapy development challenging. The social amoeba Dictyostelium discoideum has emerged as an excellent model system for studying the normal functions of proteins linked to human neurological disorders. Intriguingly, the genome of this eukaryotic soil microbe encodes homologs of 11 of the 13 known genes linked to NCL. The genetic tractability of the organism, combined with its unique life cycle, makes Dictyostelium an attractive model system for studying the functions of NCL proteins. Moreover, the ability of human NCL proteins to rescue gene-deficiency phenotypes in Dictyostelium suggests that the biological pathways regulating NCL protein function are likely conserved from Dictyostelium to human. In this review, I will discuss each of the NCL homologs in Dictyostelium in turn and describe how future studies can exploit the advantages of the system by testing new hypotheses that may ultimately lead to effective therapy options for this devastating and currently untreatable neurological disorder.

Effect of solvent and temperature on the size distribution of casein micelles measured by dynamic light scattering.

PubMed

Beliciu, C M; Moraru, C I

2009-05-01

The objectives of this study were to investigate the effect of the solvent on the accuracy of casein micelle particle size determination by dynamic light scattering (DLS) at different temperatures and to establish a clear protocol for these measurements. Dynamic light scattering analyses were performed at 6, 20, and 50 degrees C using a 90Plus Nanoparticle Size Analyzer (Brookhaven Instruments, Holtsville, NY). Raw and pasteurized skim milk were used as sources of casein micelles. Simulated milk ultrafiltrate, ultrafiltered water, and permeate obtained by ultrafiltration of skim milk using a 10-kDa cutoff membrane were used as solvents. The pH, ionic concentration, refractive index, and viscosity of all solvents were determined. The solvents were evaluated by DLS to ensure that they did not have a significant influence on the results of the particle size measurements. Experimental protocols were developed for accurate measurement of particle sizes in all solvents and experimental conditions. All measurements had good reproducibility, with coefficients of variation below 5%. Both the solvent and the temperature had a significant effect on the measured effective diameter of the casein micelles. When ultrafiltered permeate was used as a solvent, the particle size and polydispersity of casein micelles decreased as temperature increased. The effective diameter of casein micelles from raw skim milk diluted with ultrafiltered permeate was 176.4 +/- 5.3 nm at 6 degrees C, 177.4 +/- 1.9 nm at 20 degrees C, and 137.3 +/- 2.7 nm at 50 degrees C. This trend was justified by the increased strength of hydrophobic bonds with increasing temperature. Overall, the results of this study suggest that the most suitable solvent for the DLS analyses of casein micelles was casein-depleted ultrafiltered permeate. Dilution with water led to micelle dissociation, which significantly affected the DLS measurements, especially at 6 and 20 degrees C. Simulated milk ultrafiltrate seemed to give accurate results only at 20 degrees C. Results obtained in simulated milk ultrafiltrate at 6 degrees C could not be explained based on the known effects of temperature on the casein micelle, whereas at 50 degrees C, precipitation of amorphous calcium phosphate affected the DLS measurement.

OAI and NASA's Scientific and Technical Information.

ERIC Educational Resources Information Center

Nelson, Michael L.; Rocker, JoAnne; Harrison, Terry L.

2003-01-01

Details NASA's (National Aeronautics & Space Administration (USA)) involvement in defining and testing the Open Archives Initiative (OAI) Protocol for Metadata Harvesting (OAI-PMH) and experience with adapting existing NASA distributed searching DLs (digital libraries) to use the OAI-PMH and metadata harvesting. Discusses some new digital…

Conjunction of Vocal Production and Perception Regulates Expression of the Immediate Early Gene ZENK in a Novel Cortical Region of Songbirds

PubMed Central

Alderete, Tanya L.; Chang, Daniel

2010-01-01

The cortical nucleus LMAN (lateral magnocellular nucleus of the anterior nidopallium) provides the output of a basal ganglia pathway that is necessary for acquisition of learned vocal behavior during development in songbirds. LMAN is composed of two subregions, a core and a surrounding shell, that give rise to independent pathways that traverse the forebrain in parallel. The LMANshell pathway forms a recurrent loop that includes a cortical region, the dorsal region of the caudolateral nidopallium (dNCL), hitherto unknown to be involved with learned vocal behavior. Here we show that vocal production strongly induces the IEG product ZENK in dNCL of zebra finches. Hearing tutor song while singing is more effective at inducing expression in dNCL of juvenile birds during the auditory–motor integration stage of vocal learning than is hearing conspecific song. In contrast, hearing conspecific song is relatively more effective at inducing expression in adult birds, regardless of whether they are producing song. Furthermore, ZENK+ neurons in dNCL include projection neurons that are part of the LMANshell recurrent loop and a high proportion of dNCL projection neurons express ZENK in singing juvenile birds that hear tutor song. Thus juvenile birds that are actively refining their vocal pattern to imitate a tutor song show high levels of ZENK induction in dNCL neurons when they are singing while hearing the song of their tutor and low levels when they hear a novel conspecific. This pattern indicates that dNCL is a novel brain region involved with vocal learning and that its function is developmentally regulated. PMID:20107119

Learning Recruits Neurons Representing Previously Established Associations in the Corvid Endbrain.

PubMed

Veit, Lena; Pidpruzhnykova, Galyna; Nieder, Andreas

2017-10-01

Crows quickly learn arbitrary associations. As a neuronal correlate of this behavior, single neurons in the corvid endbrain area nidopallium caudolaterale (NCL) change their response properties during association learning. In crows performing a delayed association task that required them to map both familiar and novel sample pictures to the same two choice pictures, NCL neurons established a common, prospective code for associations. Here, we report that neuronal tuning changes during learning were not distributed equally in the recorded population of NCL neurons. Instead, such learning-related changes relied almost exclusively on neurons which were already encoding familiar associations. Only in such neurons did behavioral improvements during learning of novel associations coincide with increasing selectivity over the learning process. The size and direction of selectivity for familiar and newly learned associations were highly correlated. These increases in selectivity for novel associations occurred only late in the delay period. Moreover, NCL neurons discriminated correct from erroneous trial outcome based on feedback signals at the end of the trial, particularly in newly learned associations. Our results indicate that task-relevant changes during association learning are not distributed within the population of corvid NCL neurons but rather are restricted to a specific group of association-selective neurons. Such association neurons in the multimodal cognitive integration area NCL likely play an important role during highly flexible behavior in corvids.

Human pathology in NCL.

PubMed

Anderson, Glenn W; Goebel, Hans H; Simonati, Alessandro

2013-11-01

In childhood the neuronal ceroid lipofuscinoses (NCL) are the most frequent lysosomal diseases and the most frequent neurodegenerative diseases but, in adulthood, they represent a small fraction among the neurodegenerative diseases. Their morphology is marked by: (i) loss of neurons, foremost in the cerebral and cerebellar cortices resulting in cerebral and cerebellar atrophy; (ii) an almost ubiquitous accumulation of lipopigments in nerve cells, but also in extracerebral tissues. Loss of cortical neurons is selective, indiscriminate depletion in early childhood forms occurring only at an advanced stage, whereas loss of neurons in subcortical grey-matter regions has not been quantitatively documented. Among the fourteen different forms of NCL described to date, CLN1 and CLN10 are marked by granular lipopigments, CLN2 by curvilinear profiles (CVPs), CLN3 by fingerprint profiles (FPPs), and other forms by a combination of these features. Among extracerebral tissues, lymphocytes, skin, rectum, skeletal muscle and, occasionally, conjunctiva are possible guiding targets for diagnostic identification, the precise type of NCL then requiring molecular analysis within the clinical and morphological context. Autosomal-recessive adult NCL has been linked molecularly to different childhood forms, i.e. CLN1, CLN5, and CLN6, whilst autosomal-dominant adult NCL, now designated as CLN4, is caused by a newly identified separate gene, DNAJC5. This article is part of a Special Issue entitled: The Neuronal Ceroid Lipofuscinoses or Batten Disease. Copyright © 2012 Elsevier B.V. All rights reserved.

Niclosamide methanol solvate and niclosamide hydrate: structure, solvent inclusion mode and implications for properties.

PubMed

Harriss, Bethany I; Wilson, Claire; Radosavljevic Evans, Ivana

2014-08-01

Structural studies have been carried out of two solid forms of niclosamide [5-chloro-N-(2-chloro-4-nitrophenyl)-2-hydroxybenzamide, NCL], a widely used anthelmintic drug, namely niclosamide methanol monosolvate, C13H8Cl2N2O4·CH3OH or NCL·MeOH, and niclosamide monohydrate, denoted HA. The structure of the methanol solvate obtained from single-crystal X-ray diffraction is reported for the first time, elucidating the key host-guest hydrogen-bonding interactions which lead to solvate formation. The essentially planar NCL host molecules interact via π-stacking and pack in a herringbone-type arrangement, giving rise to channels along the crystallographic a axis in which the methanol guest molecules are located. The methanol and NCL molecules interact via short O-H...O hydrogen bonds. Laboratory powder X-ray diffraction (PXRD) measurements reveal that the initially phase-pure NCL·MeOH solvate readily transforms into NCL monohydrate within hours under ambient conditions. PXRD further suggests that the NCL monohydrate, HA, is isostructural with the NCL·MeOH solvate. This is consistent with the facile transformation of the methanol solvate into the hydrate when stored in air. The crystal packing and the topology of guest-molecule inclusion are compared with those of other NCL solvates for which the crystal structures are known, giving a consistent picture which correlates well with known experimentally observed desolvation properties.

A Genetic Cascade of let-7-ncl-1-fib-1 Modulates Nucleolar Size and rRNA Pool in Caenorhabditis elegans

PubMed Central

Chiou, Pey-Tsyr; Chen, Po-Hsiang; Lee, Ching-Ming; Chu, Yu-De; Yu, Hsiang; Hsiung, Kuei-Ching; Tsai, Yi-Tzang; Lee, Chi-Chang; Chang, Yu-Sun; Chan, Shih-Peng; Tan, Bertrand Chin-Ming; Lo, Szecheng J.

2015-01-01

Ribosome biogenesis takes place in the nucleolus, the size of which is often coordinated with cell growth and development. However, how metazoans control nucleolar size remains largely unknown. Caenorhabditis elegans provides a good model to address this question owing to distinct tissue distribution of nucleolar sizes and a mutant, ncl-1, which exhibits larger nucleoli than wild-type worms. Here, through a series of loss-of-function analyses, we report that the nucleolar size is regulated by a circuitry composed of microRNA let-7, translation repressor NCL-1, and a major nucleolar pre-rRNA processing protein FIB-1/fibrillarin. In cooperation with RNA binding proteins PUF and NOS, NCL-1 suppressed the translation of FIB-1/fibrillarin, while let-7 targeted the 3’UTR of ncl-1 and inhibited its expression. Consequently, the abundance of FIB-1 is tightly controlled and correlated with the nucleolar size. Together, our findings highlight a novel genetic cascade by which post-transcriptional regulators interplay in developmental control of nucleolar size and function. PMID:26492166

Evaluation of robenidine analog NCL195 as a novel broad-spectrum antibacterial agent.

PubMed

Ogunniyi, Abiodun D; Khazandi, Manouchehr; Stevens, Andrew J; Sims, Sarah K; Page, Stephen W; Garg, Sanjay; Venter, Henrietta; Powell, Andrew; White, Karen; Petrovski, Kiro R; Laven-Law, Geraldine; Tótoli, Eliane G; Salgado, Hérida R; Pi, Hongfei; Coombs, Geoffrey W; Shinabarger, Dean L; Turnidge, John D; Paton, James C; McCluskey, Adam; Trott, Darren J

2017-01-01

The spread of multidrug resistance among bacterial pathogens poses a serious threat to public health worldwide. Recent approaches towards combating antimicrobial resistance include repurposing old compounds with known safety and development pathways as new antibacterial classes with novel mechanisms of action. Here we show that an analog of the anticoccidial drug robenidine (4,6-bis(2-((E)-4-methylbenzylidene)hydrazinyl)pyrimidin-2-amine; NCL195) displays potent bactericidal activity against Streptococcus pneumoniae and Staphylococcus aureus by disrupting the cell membrane potential. NCL195 was less cytotoxic to mammalian cell lines than the parent compound, showed low metabolic degradation rates by human and mouse liver microsomes, and exhibited high plasma concentration and low plasma clearance rates in mice. NCL195 was bactericidal against Acinetobacter spp and Neisseria meningitidis and also demonstrated potent activity against A. baumannii, Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae and Enterobacter spp. in the presence of sub-inhibitory concentrations of ethylenediaminetetraacetic acid (EDTA) and polymyxin B. These findings demonstrate that NCL195 represents a new chemical lead for further medicinal chemistry and pharmaceutical development to enhance potency, solubility and selectivity against serious bacterial pathogens.

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

Savukoski, M.; Peltonen, L.; Santavuori, P.

We demonstrate here that at least four genetically separate loci are involved in the pathogenesis of human neuronal ceroid lipofuscinoses (NCLs), fatal brain disorders of children. Earlier the assignments of the infantile and juvenile subtypes of NCL to 1p32 and 16p12 had revealed two loci; and here a variant subtype of the late-infantile form of NCL is mapped to a well-defined region on 13q21.1-q32, whereas the clinically similar, classical form of late-infantile NCL was found to represent the fourth, yet-unidentified NCL locus. The linkage disequilibrium was crucial for locus assignment in our highly limited family material, and the data exemplifymore » the significance of this phenomenon in the random mapping of rare human diseases. 22 refs., 4 figs., 3 tabs.« less

Differential effects of neural inactivation of the dorsolateral striatum on response and latent extinction.

PubMed

Goodman, Jarid; Gabriele, Amanda; Packard, Mark G

2017-04-01

The present study examined the role of the dorsolateral striatum (DLS) in extinction behavior. Male Long-Evans rats were initially trained on the straight alley maze, in which they were reinforced to traverse a straight runway and retrieve food reward at the opposite end of the maze. After initial acquisition, animals were given extinction training using 1 of 2 distinct protocols: response extinction or latent extinction. For response extinction, the animal was released from the same starting position and had the opportunity to perform the originally reinforced approach response to the goal end of the maze, which no longer contained food. For latent extinction, the animal was confined to the original goal location without food, allowing the animal to form a new cognitive expectation (i.e., that the goal location is no longer reinforced). Immediately before response or latent extinction training, animals received bilateral intra-DLS administration of the sodium channel blocker bupivacaine or control injections of physiological saline. Results indicated that neural inactivation of the DLS with bupivacaine impaired response extinction, but did not influence latent extinction. The dissociation observed indicates that the DLS selectively mediates extinction mechanisms involving suppression of the original response, as opposed to cognitive mechanisms involving a change in expectation. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Neuronal ceroid lipofuscinoses (NCL)

MedlinePlus

... problems with the brain's ability to remove and recycle proteins. Lipofuscinoses are inherited as autosomal recessive traits. ... is recommended if your family has a known history of NCL. Prenatal tests, or a test called ...

Development of transferrin targeted NCL-240 micelles and their evaluation using in-vitro 3D cancer cell culture (spheroid) models

NASA Astrophysics Data System (ADS)

Nagelli, Srikar Goud

The main objective of this project was to develop targeted micellar delivery systems of a novel cytotoxic drug (NCL-240; a second generation DM-PIT-1 analog) and to evaluate their efficacy using optimized 3D cell culture spheroid models. Spheroids were optimized for several cancer cell lines using a range of techniques such as non-adhesive liquid overlay method, hanging drop method, and co-culturing. Transferrin (Tf)-conjugated NCL-240 micelles were prepared with varying Tf amounts and their cytotoxicities were evaluated using the optimized spheroid models. The uptake and penetration of the formulations were also studied using confocal microscopy. The results indicated that the concentration of NCL-240 micelles required to achieve the same cytotoxicity was relatively higher in spheroids compared to the monolayers. Also, In NCI-ADR-RES, Tf-targeted NCL-240 micelles were shown to have a significant increase in cytotoxicity compared to untargeted NCL-240 micelles. Even the penetration and uptake studies indicated that targeting improves the uptake and penetration of formulations. However, in U87-MG spheroids, there was a significant difference in cell viability among micelles compared to free drug but no significant benefit due to targeting was observed. The same formulations penetrated lesser in U87-MG spheroids compared to NCI-ADR-RES spheroids. This study thereby emphasizes the importance of drug screening in spheroid models as the penetration dynamics are varying from cell line to cell line because of the 3D structure.

Exome sequencing is an efficient tool for variant late-infantile neuronal ceroid lipofuscinosis molecular diagnosis.

PubMed

Patiño, Liliana Catherine; Battu, Rajani; Ortega-Recalde, Oscar; Nallathambi, Jeyabalan; Anandula, Venkata Ramana; Renukaradhya, Umashankar; Laissue, Paul

2014-01-01

The neuronal ceroid-lipofuscinoses (NCL) is a group of neurodegenerative disorders characterized by epilepsy, visual failure, progressive mental and motor deterioration, myoclonus, dementia and reduced life expectancy. Classically, NCL-affected individuals have been classified into six categories, which have been mainly defined regarding the clinical onset of symptoms. However, some patients cannot be easily included in a specific group because of significant variation in the age of onset and disease progression. Molecular genetics has emerged in recent years as a useful tool for enhancing NCL subtype classification. Fourteen NCL genetic forms (CLN1 to CLN14) have been described to date. The variant late-infantile form of the disease has been linked to CLN5, CLN6, CLN7 (MFSD8) and CLN8 mutations. Despite advances in the diagnosis of neurodegenerative disorders mutations in these genes may cause similar phenotypes, which rends difficult accurate candidate gene selection for direct sequencing. Three siblings who were affected by variant late-infantile NCL are reported in the present study. We used whole-exome sequencing, direct sequencing and in silico approaches to identify the molecular basis of the disease. We identified the novel c.1219T>C (p.Trp407Arg) and c.1361T>C (p.Met454Thr) MFSD8 pathogenic mutations. Our results highlighted next generation sequencing as a novel and powerful methodological approach for the rapid determination of the molecular diagnosis of NCL. They also provide information regarding the phenotypic and molecular spectrum of CLN7 disease.

Adipose-Derived Stem-Cell-Seeded Non-Cross-Linked Porcine Acellular Dermal Matrix Increases Cellular Infiltration, Vascular Infiltration, and Mechanical Strength of Ventral Hernia Repairs

PubMed Central

Iyyanki, Tejaswi S.; Dunne, Lina W.; Zhang, Qixu; Hubenak, Justin; Turza, Kristin C.

2015-01-01

Adipose-derived stem cells (ASCs) facilitate wound healing by improving cellular and vascular recruitment to the wound site. Therefore, we investigated whether ASCs would augment a clinically relevant bioprosthetic mesh—non-cross-linked porcine acellular dermal matrix (ncl-PADM)—used for ventral hernia repairs in a syngeneic animal model. ASCs were isolated from the subcutaneous adipose tissue of Brown Norway rats, expanded, and labeled with green fluorescent protein. ASCs were seeded (2.5×104 cells/cm2) onto ncl-PADM for 24 h before surgery. In vitro ASC adhesion to ncl-PADM was assessed at 0.5, 1, and 2 h after seeding, and cell morphology on ncl-PADM was visualized by scanning electron microscopy. Ventral hernia defects (2×4 cm) were created and repaired with ASC-seeded (n=31) and control (n=32) ncl-PADM. Explants were harvested at 1, 2, and 4 weeks after surgery. Explant remodeling outcomes were evaluated using gross evaluation (bowel adhesions, surface area, and grade), histological analysis (hematoxylin and eosin and Masson's trichrome staining), immunohistochemical analysis (von Willebrand factor VIII), fluorescent microscopy, and mechanical strength measurement at the tissue-bioprosthetic mesh interface. Stem cell markers CD29, CD90, CD44, and P4HB were highly expressed in cultured ASCs, whereas endothelial and hematopoietic cell markers, such as CD31, CD90, and CD45 had low expression. Approximately 85% of seeded ASCs adhered to ncl-PADM within 2 h after seeding, which was further confirmed by scanning electron microcopy examination. Gross evaluation of the hernia repairs revealed weak omental adhesion in all groups. Ultimate tensile strength was not significantly different in control and treatment groups. Conversely, elastic modulus was significantly greater at 4 weeks postsurgery in the ASC-seeded group (p<0.001). Cellular infiltration was significantly higher in the ASC-seeded group at all time points (p<0.05). Vascular infiltration was significantly greater at 4 weeks postsurgery in the ASC-seeded group (p<0.001). The presence of ASCs improved remodeling outcomes by yielding an increase in cellular infiltration and vascularization of ncl-PADM and enhanced the elastic modulus at the ncl-PADM-tissue interface. With the ease of harvesting adipose tissues that are rich in ASCs, this strategy may be clinically translatable for improving ncl-PADM ventral hernia repair outcomes. PMID:25156009

Adipose-derived stem-cell-seeded non-cross-linked porcine acellular dermal matrix increases cellular infiltration, vascular infiltration, and mechanical strength of ventral hernia repairs.

PubMed

Iyyanki, Tejaswi S; Dunne, Lina W; Zhang, Qixu; Hubenak, Justin; Turza, Kristin C; Butler, Charles E

2015-02-01

Adipose-derived stem cells (ASCs) facilitate wound healing by improving cellular and vascular recruitment to the wound site. Therefore, we investigated whether ASCs would augment a clinically relevant bioprosthetic mesh-non-cross-linked porcine acellular dermal matrix (ncl-PADM)-used for ventral hernia repairs in a syngeneic animal model. ASCs were isolated from the subcutaneous adipose tissue of Brown Norway rats, expanded, and labeled with green fluorescent protein. ASCs were seeded (2.5×10(4) cells/cm(2)) onto ncl-PADM for 24 h before surgery. In vitro ASC adhesion to ncl-PADM was assessed at 0.5, 1, and 2 h after seeding, and cell morphology on ncl-PADM was visualized by scanning electron microscopy. Ventral hernia defects (2×4 cm) were created and repaired with ASC-seeded (n=31) and control (n=32) ncl-PADM. Explants were harvested at 1, 2, and 4 weeks after surgery. Explant remodeling outcomes were evaluated using gross evaluation (bowel adhesions, surface area, and grade), histological analysis (hematoxylin and eosin and Masson's trichrome staining), immunohistochemical analysis (von Willebrand factor VIII), fluorescent microscopy, and mechanical strength measurement at the tissue-bioprosthetic mesh interface. Stem cell markers CD29, CD90, CD44, and P4HB were highly expressed in cultured ASCs, whereas endothelial and hematopoietic cell markers, such as CD31, CD90, and CD45 had low expression. Approximately 85% of seeded ASCs adhered to ncl-PADM within 2 h after seeding, which was further confirmed by scanning electron microcopy examination. Gross evaluation of the hernia repairs revealed weak omental adhesion in all groups. Ultimate tensile strength was not significantly different in control and treatment groups. Conversely, elastic modulus was significantly greater at 4 weeks postsurgery in the ASC-seeded group (p<0.001). Cellular infiltration was significantly higher in the ASC-seeded group at all time points (p<0.05). Vascular infiltration was significantly greater at 4 weeks postsurgery in the ASC-seeded group (p<0.001). The presence of ASCs improved remodeling outcomes by yielding an increase in cellular infiltration and vascularization of ncl-PADM and enhanced the elastic modulus at the ncl-PADM-tissue interface. With the ease of harvesting adipose tissues that are rich in ASCs, this strategy may be clinically translatable for improving ncl-PADM ventral hernia repair outcomes.

Evaluation of robenidine analog NCL195 as a novel broad-spectrum antibacterial agent

PubMed Central

Sims, Sarah K.; Page, Stephen W.; Garg, Sanjay; Venter, Henrietta; Powell, Andrew; White, Karen; Petrovski, Kiro R.; Laven-Law, Geraldine; Tótoli, Eliane G.; Salgado, Hérida R.; Pi, Hongfei; Coombs, Geoffrey W.; Shinabarger, Dean L.; Turnidge, John D.; Paton, James C.; McCluskey, Adam; Trott, Darren J.

2017-01-01

The spread of multidrug resistance among bacterial pathogens poses a serious threat to public health worldwide. Recent approaches towards combating antimicrobial resistance include repurposing old compounds with known safety and development pathways as new antibacterial classes with novel mechanisms of action. Here we show that an analog of the anticoccidial drug robenidine (4,6-bis(2-((E)-4-methylbenzylidene)hydrazinyl)pyrimidin-2-amine; NCL195) displays potent bactericidal activity against Streptococcus pneumoniae and Staphylococcus aureus by disrupting the cell membrane potential. NCL195 was less cytotoxic to mammalian cell lines than the parent compound, showed low metabolic degradation rates by human and mouse liver microsomes, and exhibited high plasma concentration and low plasma clearance rates in mice. NCL195 was bactericidal against Acinetobacter spp and Neisseria meningitidis and also demonstrated potent activity against A. baumannii, Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae and Enterobacter spp. in the presence of sub-inhibitory concentrations of ethylenediaminetetraacetic acid (EDTA) and polymyxin B. These findings demonstrate that NCL195 represents a new chemical lead for further medicinal chemistry and pharmaceutical development to enhance potency, solubility and selectivity against serious bacterial pathogens. PMID:28873428

Chemical vapor transport of layer structured crystal β-ZrNCl

NASA Astrophysics Data System (ADS)

Ohashi, M.; Yamanaka, S.; Hattori, M.

1988-12-01

A layer structured compound β-ZrNCl is transported to a higher temperature zone with the aid of ammonium chloride as the transporting agent in the temperature range of 823-1173 K. The transport mechanism can be explained by the formation of a volatile compound (NH 4) 2ZrCl 6: β- ZrNCl+5 NH4Cl→( NH4) 2ZrCl6+4 NH3. The measurements of the vapor pressure and the mass spectrum revealed that (NH 4) 2ZrCl 6 decomposed congruently according to the equation: ( NH4) 2ZrCl6( s)→ ZrCl4( g)+2 NH3( g)+2 HCl( g) The enthalpy change for the decomposition was determined to be 533 kJ/mol. By combining the above two equations, a simplified transport equation is derived: β- ZrNCl( s)+3 HCl( g)⇌ ZrCl4( g+ NH3( g) .

Exome Sequencing Is an Efficient Tool for Variant Late-Infantile Neuronal Ceroid Lipofuscinosis Molecular Diagnosis

PubMed Central

Ortega-Recalde, Oscar; Nallathambi, Jeyabalan; Anandula, Venkata Ramana; Renukaradhya, Umashankar; Laissue, Paul

2014-01-01

The neuronal ceroid-lipofuscinoses (NCL) is a group of neurodegenerative disorders characterized by epilepsy, visual failure, progressive mental and motor deterioration, myoclonus, dementia and reduced life expectancy. Classically, NCL-affected individuals have been classified into six categories, which have been mainly defined regarding the clinical onset of symptoms. However, some patients cannot be easily included in a specific group because of significant variation in the age of onset and disease progression. Molecular genetics has emerged in recent years as a useful tool for enhancing NCL subtype classification. Fourteen NCL genetic forms (CLN1 to CLN14) have been described to date. The variant late-infantile form of the disease has been linked to CLN5, CLN6, CLN7 (MFSD8) and CLN8 mutations. Despite advances in the diagnosis of neurodegenerative disorders mutations in these genes may cause similar phenotypes, which rends difficult accurate candidate gene selection for direct sequencing. Three siblings who were affected by variant late-infantile NCL are reported in the present study. We used whole-exome sequencing, direct sequencing and in silico approaches to identify the molecular basis of the disease. We identified the novel c.1219T>C (p.Trp407Arg) and c.1361T>C (p.Met454Thr) MFSD8 pathogenic mutations. Our results highlighted next generation sequencing as a novel and powerful methodological approach for the rapid determination of the molecular diagnosis of NCL. They also provide information regarding the phenotypic and molecular spectrum of CLN7 disease. PMID:25333361

Biogenic unmodified gold nanoparticles for selective and quantitative detection of cerium using UV-vis spectroscopy and photon correlation spectroscopy (DLS).

PubMed

Priyadarshini, E; Pradhan, N; Panda, P K; Mishra, B K

2015-06-15

The ability of self-functionalized biogenic GNPs towards highly selective colorimetric detection of rare earth element cerium is being reported for the first time. GNPs underwent rapid aggregation on addition of cerium indicated by red shift of SPR peak followed by complete precipitation. Hereby, this concept of co-ordination of cerium ions onto the GNP surface has been utilized for detection of cerium. The remarkable capacity of GNPs to sensitively detect Ce without proves beneficial compared to previous reports of colorimetric sensing. MDL was 15 and 35 ppm by DLS and UV-vis spectroscopy respectively, suggesting DLS to be highly sensitive and a practical alternative in ultrasensitive detection studies. The sensing system showed a good linear fit favouring feasible detection of cerium in range of 2-50 ppm. Similar studies further showed the superior selectivity of biogenic GNPs compared to chemically synthesized counterparts. The sensing system favours on-site analysis as it overcomes need of complex instrumentation, lengthy protocols and surface modification of GNP. Copyright © 2015 Elsevier B.V. All rights reserved.

Niclosamide as an adjuvant to etanercept in treatment patients with active rheumatoid arthritis: an 8-week randomized controlled pilot study.

PubMed

Al-Gareeb, Ali Ismail A; Gorial, Faiq Isho; Mahmood, Ahmed S

2018-06-07

This study designed to identify the therapeutic efficacy of niclosamide (NCL) in Iraqi patients suffering from active rheumatoid arthritis (RA) who were using etanercept (ETN) for more than 3 months and still had high or moderate active RA. One hundred ten patients suffering from active rheumatoid arthritis (RA) who were using etanercept (ETN) for more than 3 months and still had high or moderate active RA were allocated randomly into two equal groups: one of them treated with 1000 mg/day NCL and the other treated with 1000 mg/day lactose in capsule dosage form. The study duration was 8 weeks. Clinical efficacy of the NCL was measured depending on scoring of the 28-joint Disease Activity Score (DAS28), simple disease activity index (SDAI), clinical disease activity index (CDAI), and Health Assessment Questionnaire Disability Index (HAQ-DI) at the baseline and at the end of the 8-week treatment period. Moreover, blood sample were taken from the patients at baseline and at after 8 weeks of treatment for measurement of the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), interleukin 1β (IL-1 β), interleukin-6, tumor necrosis factor (TNF-α), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin. At the end of the clinical study, patients had good response to NCL when added to the ETN with a high significant improvement in the SJC, TJC, DAS-28, CDAI, SDAI, and HAQ-DI compared to patients who were received placebo drug. In addition to that, 33% of patients achieved an ACR 20% response (ACR20) on NCL and ETN. Of these, 4% achieved ACR50 and another 4% achieved ACR70 response. While those group treated by placebo + ETN, 5% achieved ACR20 response and no one reached to ACR50 or ACR70 response. Twenty-seven percent of RA patients who have taken the NCL achieved moderate EULAR score while only 17% from the group that taken placebo with ETN achieved moderate response. On the other hand, no significant reduction was found in CRP, ESR, TNF-α, and IL-6, while IL-1 β reduced significantly after treatment with NCL. Treatment with NCL also exerts a significant lowering in the serum level of the E-selectin, ICAM1, and VCAM1 when compared to their value in baseline level. In RA disease, the use of NCL as adjuvant with ETN has resulted in a marked reduction in clinical assessment scoring indices and significantly decreased the E-selectin, ICAM-1, and VCAM-1 with marked improvement in the quality of life of patients.

Measurement of bovine body and scrotal temperature using implanted temperature sensitive radio transmitters, data loggers and infrared thermography

NASA Astrophysics Data System (ADS)

Wallage, A. L.; Gaughan, J. B.; Lisle, A. T.; Beard, L.; Collins, C. W.; Johnston, S. D.

2017-07-01

Synchronous and continuous measurement of body (BT) and scrotal temperature (ST) without adverse welfare or behavioural interference is essential for understanding thermoregulation of the bull testis. This study compared three technologies for their efficacy for long-term measurement of the relationship between BT and ST by means of (1) temperature sensitive radio transmitters (RT), (2) data loggers (DL) and (3) infrared imaging (IRI). After an initial pilot study on two bulls to establish a surgical protocol, RTs and DLs were implanted into the flank and mid-scrotum of six Wagyu bulls for between 29 and 49 days. RT frequencies were scanned every 15 min, whilst DLs logged every 30 min. Infrared imaging of the body (flank) and scrotum of each bull was recorded hourly for one 24-h period and compared to RT and DL data. After a series of subsequent heat stress studies, bulls were castrated and testicular tissue samples processed for evidence of histopathology. Radio transmitters were less reliable than DLs; RTs lost >11 % of data, whilst 11 of the 12 DLs had 0 % data loss. IRI was only interpretable in 35.8 % of images recorded. Pearson correlations between DL and RT were strong for both BT ( r > 0.94, P < 0.001) and ST ( r > 0.80, P < 0.001). Surgery produced temporary minor inflammation and scrotal hematoma in two animals post-surgery. Whilst scar tissue was observed at all surgical sutured sites when bulls were castrated, there was no evidence of testicular adhesion and normal active spermatogenesis was observed in six of the eight implanted testicles. There was no significant correlation of IRI with either DL or RT. We conclude that DLs provided to be a reliable continuous source of data for synchronous measurement of BT and ST.

Progressive thalamocortical neuron loss in Cln5 deficient mice: distinct effects in Finnish variant late infantile NCL

PubMed Central

von Schantz, Carina; Kielar, Catherine; Hansen, Stine N; Pontikis, Charlie C; Alexander, Noreen A; Kopra, Outi; Jalanko, Anu; Cooper, Jonathan D

2009-01-01

Finnish variant LINCL (vLINCLFin) is the result of mutations in the CLN5 gene. To gain insights into the pathological staging of this fatal pediatric disorder, we have undertaken a stereological analysis of the CNS of Cln5 deficient mice (Cln5-/-) at different stages of disease progression. Consistent with human vLINCLFin, these Cln5-/- mice displayed a relatively late onset regional atrophy and generalized cortical thinning and synaptic pathology, preceded by early and localized glial responses within the thalamocortical system. However, in marked contrast to other forms of NCL, neuron loss in Cln5-/- mice began in the cortex and only subsequently occurred within thalamic relay nuclei. Nevertheless, as in other NCL mouse models, this progressive thalamocortical neuron loss was still most pronounced within the visual system. These data provide unexpected evidence for a distinctive sequence of neuron loss in the thalamocortical system of Cln5-/- mice, diametrically opposed to that seen in other forms of NCL. PMID:19385065

Progressive thalamocortical neuron loss in Cln5 deficient mice: Distinct effects in Finnish variant late infantile NCL.

PubMed

von Schantz, Carina; Kielar, Catherine; Hansen, Stine N; Pontikis, Charlie C; Alexander, Noreen A; Kopra, Outi; Jalanko, Anu; Cooper, Jonathan D

2009-05-01

Finnish variant LINCL (vLINCL(Fin)) is the result of mutations in the CLN5 gene. To gain insights into the pathological staging of this fatal pediatric disorder, we have undertaken a stereological analysis of the CNS of Cln5 deficient mice (Cln5-/-) at different stages of disease progression. Consistent with human vLINCL(Fin), these Cln5-/- mice displayed a relatively late onset regional atrophy and generalized cortical thinning and synaptic pathology, preceded by early and localized glial responses within the thalamocortical system. However, in marked contrast to other forms of NCL, neuron loss in Cln5-/- mice began in the cortex and only subsequently occurred within thalamic relay nuclei. Nevertheless, as in other NCL mouse models, this progressive thalamocortical neuron loss was still most pronounced within the visual system. These data provide unexpected evidence for a distinctive sequence of neuron loss in the thalamocortical system of Cln5-/- mice, diametrically opposed to that seen in other forms of NCL.

A Dynamic Approach to Make CDS/ISIS Databases Interoperable over the Internet Using the OAI Protocol

ERIC Educational Resources Information Center

Jayakanth, F.; Maly, K.; Zubair, M.; Aswath, L.

2006-01-01

Purpose: A dynamic approach to making legacy databases, like CDS/ISIS, interoperable with OAI-compliant digital libraries (DLs). Design/methodology/approach: There are many bibliographic databases that are being maintained using legacy database systems. CDS/ISIS is one such legacy database system. It was designed and developed specifically for…

The neuronal ceroid lipofuscinoses program: A translational research experience in Argentina.

PubMed

Kohan, Romina; Pesaola, Favio; Guelbert, Norberto; Pons, Patricia; Oller-Ramírez, Ana María; Rautenberg, Gisela; Becerra, Adriana; Sims, Katherine; Xin, Winnie; Cismondi, Inés Adriana; Noher de Halac, Inés

2015-10-01

The Argentinean program was initiated more than a decade ago as the first experience of systematic translational research focused on NCL in Latin America. The aim was to overcome misdiagnoses and underdiagnoses in the region. 216 NCL suspected individuals from 8 different countries and their direct family members. Clinical assessment, enzyme testing, electron microscopy, and DNA screening. 1) The study confirmed NCL disease in 122 subjects. Phenotypic studies comprised epileptic seizures and movement disorders, ophthalmology, neurophysiology, image analysis, rating scales, enzyme testing, and electron microscopy, carried out under a consensus algorithm; 2) DNA screening and validation of mutations in genes PPT1 (CLN1), TPP1 (CLN2), CLN3, CLN5, CLN6, MFSD8 (CLN7), and CLN8: characterization of variant types, novel/known mutations and polymorphisms; 3) Progress of the epidemiological picture in Latin America; and 4) NCL-like pathology studies in progress. The Translational Research Program was highly efficient in addressing the misdiagnosis/underdiagnosis in the NCL disorders. The study of "orphan diseases" in a public administrated hospital should be adopted by the health systems, as it positively impacts upon the family's quality of life, the collection of epidemiological data, and triggers research advances. This article is part of a Special Issue entitled: "Current Research on the Neuronal Ceroid Lipofuscinoses (Batten Disease)". Copyright © 2015 Elsevier B.V. All rights reserved.

Removal of Arsenic, Iron, Manganese, and Ammonia in Drinking Water: Nagaoka International Corporation CHEMILES NCL Series Water Treatment System

EPA Science Inventory

The Nagaoka International Corporation CHEMILES NCL Series system was tested to verify its performance for the reduction of multiple contaminants including: arsenic, ammonia, iron, and manganese. The objectives of this verification, as operated under the conditions at the test si...

Single Location Key to NCL's Operation | Poster

Cancer.gov

By Nancy Parrish, Staff Writer For the first time, the Nanotechnology Characterization Laboratory (NCL) is under one roof, as a result of their move to the Advanced Technology Research Facility (ATRF).  The move is expected to streamline their work as well as provide greater opportunities for collaboration with other researchers, both internal and external.

UV-induced effects on chlorination of creatinine.

PubMed

Weng, Shih Chi; Li, Jing; Wood, Karl V; Kenttämaa, Hilkka I; Williams, Peggy E; Amundson, Lucas M; Blatchley, Ernest R

2013-09-15

Ultraviolet (UV) irradiation is commonly employed for water treatment in swimming pools to complement conventional chlorination, and to reduce the concentration of inorganic chloramine compounds. The approach of combining UV irradiation and chlorination has the potential to improve water quality, as defined by microbial composition. However, relatively little is known about the effects of this process on water chemistry. To address this issue, experiments were conducted to examine the effects of sequential UV254 irradiation/chlorination, as will occur in recirculating system of swimming pools, on disinfection byproduct (DBP) formation. Creatinine, which is present in human sweat and urine, was selected as the target precursor for these experiments. Enhanced formation of dichloromethylamine (CH3NCl2) and inorganic chloramines was observed to result from post-chlorination of UV-irradiated samples. Chlorocreatinine was found to be more sensitive to UV254 irradiation than creatinine; UV254 irradiation of chlorocreatinine resulted in opening of the ring structure, thereby yielding a series of intermediates that were more susceptible to free chlorine attack than their parent compound. The quantum yields for photodegradation of creatinine and chlorocreatinine at 254 nm were estimated at 0.011 ± 0.002 mol/E and 0.144 ± 0.011 mol/E, respectively. The N-Cl bond was found to be common to UV-sensitive chlorinated compounds (e.g., inorganic chloramines, CH3NCl2, and chlorocreatinine); compounds that were less susceptible to UV-based attack generally lacked the N-Cl bond. This suggested that the N-Cl bond is susceptible to UV254 irradiation, and cleavage of the N-Cl bond appears to open or promote reaction pathways that involve free chlorine, thereby enhancing formation of some DBPs and promoting loss of free chlorine. Proposed reaction mechanisms to describe this behavior based on creatinine as a precursor are presented. Copyright © 2013 Elsevier Ltd. All rights reserved.

Sensory and Working Memory Representations of Small and Large Numerosities in the Crow Endbrain.

PubMed

Ditz, Helen M; Nieder, Andreas

2016-11-23

Neurons in the avian nidopallium caudolaterale (NCL), an endbrain structure that originated independently from the mammalian neocortex, process visual numerosities. To clarify the code for number in this anatomically distinct endbrain area in birds, neuronal responses to a broad range of numerosities were analyzed. We recorded single-neuron activity from the NCL of crows performing a delayed match-to-sample task with visual numerosities as discriminanda. The responses of >20% of randomly selected neurons were modulated significantly by numerosities ranging from one to 30 items. Numerosity-selective neurons showed bell-shaped tuning curves with one of the presented numerosities as preferred numerosity regardless of the physical appearance of the items. The resulting labeled-line code exhibited logarithmic compression obeying the Weber-Fechner law for magnitudes. Comparable proportions of selective neurons were found, not only during stimulus presentation, but also in the delay phase, indicating a dominant role of the NCL in numerical working memory. Both during sensory encoding and memorization of numerosities in working memory, NCL activity predicted the crows' number discrimination performance. These neuronal data reveal striking similarities across vertebrate taxa in their code for number despite convergently evolved and anatomically distinct endbrain structures. Birds are known for their capabilities to process numerical quantity. However, birds lack a six-layered neocortex that enables primates with numerical competence. We aimed to decipher the neuronal code for numerical quantity in the independently and distinctly evolved endbrain of birds. We recorded the activity of neurons in an endbrain association area termed nidopallium caudolaterale (NCL) from crows that assessed and briefly memorized numerosities from one to 30 dots. We report a neuronal code for sensory representation and working memory of numerosities in the crow NCL exhibiting several characteristics that are surprisingly similar to the ones found in primates. Our data suggest a common code for number in two different vertebrate taxa that has evolved based on convergent evolution. Copyright © 2016 the authors 0270-6474/16/3612044-09$15.00/0.

Neuronal ceroid lipofuscinosis associated with an MFSD8 mutation in Chihuahuas.

PubMed

Ashwini, Akanksha; D'Angelo, Antonio; Yamato, Osamu; Giordano, Cristina; Cagnotti, Giulia; Harcourt-Brown, Tom; Mhlanga-Mutangadura, Tendai; Guo, Juyuan; Johnson, Gary S; Katz, Martin L

2016-08-01

The neuronal ceroid lipofuscinoses (NCLs) are hereditary neurodegenerative disorders characterized by progressive declines in neurological functions, seizures, and premature death. NCLs result from mutations in at least 13 different genes. Canine versions of the NCLs can serve as important models in developing effective therapeutic interventions for these diseases. NCLs have been described in a number of dog breeds, including Chihuahuas. Studies were undertaken to further characterize the pathology of Chihuahua NCL and to verify its molecular genetic basis. Four unrelated client owned Chihuahuas from Japan, Italy and England that exhibited progressive neurological signs consistent with a diagnosis of NCL underwent neurological examinations. Brain and in some cases also retinal and heart tissues were examined postmortem for the presence of lysosomal storage bodies characteristic of NCL. The affected dogs exhibited massive accumulation of autofluorescent lysosomal storage bodies in the brain, retina and heart accompanied by brain atrophy and retinal degeneration. The dogs were screened for known canine NCL mutations previously reported in a variety of dog breeds. All 4 dogs were homozygous for the MFSD8 single base pair deletion (MFSD8:c.843delT) previously associated with NCL in a Chinese Crested dog and in 2 affected littermate Chihuahuas from Scotland. The dogs were all homozygous for the normal alleles at the other genetic loci known to cause different forms of canine NCL. The MFSD8:c.843delT mutation was not present in 57 Chihuahuas that were either clinically normal or suffered from unrelated diseases or in 1761 unaffected dogs representing 186 other breeds. Based on these data it is almost certain that the MFSD8:c.843delT mutation is the cause of NCL in Chihuahuas. Because the disorder occurred in widely separated geographic locations or in unrelated dogs from the same country, it is likely that the mutant allele is widespread among Chihuahuas. Genetic testing for this mutation in other Chihuahuas is therefore likely to identify intact dogs with the mutant allele that could be used to establish a research colony that could be used to test potential therapeutic interventions for the corresponding human disease. Copyright © 2016 Shire Human Genetic Therapies. Published by Elsevier Inc. All rights reserved.

Negative correlation learning for customer churn prediction: a comparison study.

PubMed

Rodan, Ali; Fayyoumi, Ayham; Faris, Hossam; Alsakran, Jamal; Al-Kadi, Omar

2015-01-01

Recently, telecommunication companies have been paying more attention toward the problem of identification of customer churn behavior. In business, it is well known for service providers that attracting new customers is much more expensive than retaining existing ones. Therefore, adopting accurate models that are able to predict customer churn can effectively help in customer retention campaigns and maximizing the profit. In this paper we will utilize an ensemble of Multilayer perceptrons (MLP) whose training is obtained using negative correlation learning (NCL) for predicting customer churn in a telecommunication company. Experiments results confirm that NCL based MLP ensemble can achieve better generalization performance (high churn rate) compared with ensemble of MLP without NCL (flat ensemble) and other common data mining techniques used for churn analysis.

Figure12

EPA Pesticide Factsheets

NCL script: cmaq_ensemble_isam_4panels_subdomain.nclNetcdf input file for NCL script, containing ensemble means and standard deviation of ISAM SO4 and O3 contributions from IPM: test.ncPlot (ps): maps_isam_mean_std_lasthour_ipm_so4_o3_east.psPlot (pdf): maps_isam_mean_std_lasthour_ipm_so4_o3_east.pdfPlot (ncgm): maps_isam_mean_std_lasthour_ipm_so4_o3_east.ncgmThis dataset is associated with the following publication:Gilliam , R., C. Hogrefe , J. Godowitch, S. Napelenok , R. Mathur , and S.T. Rao. Impact of inherent meteorology uncertainty on air quality model predictions. JOURNAL OF GEOPHYSICAL RESEARCH-ATMOSPHERES. American Geophysical Union, Washington, DC, USA, 120(23): 12,259–12,280, (2015).

Amygdala central nucleus interacts with dorsolateral striatum to regulate the acquisition of habits

PubMed Central

Lingawi, Nura W.; Balleine, Bernard W.

2012-01-01

The role of the amygdala central nucleus (CeN) in habit learning was assessed in two experiments. First we examined the effects of bilateral lesions of the anterior CeN on an overtraining-induced lever press habit evaluated using an outcome devaluation protocol. Overtraining generated habitual performance and rendered sham lesioned rats insensitive to outcome devaluation, an effect that was also found in rats given control lesions of the posterior CeN. In contrast, rats with lesions of the anterior CeN did not show normal habit acquisition and their performance remained goal-directed and sensitive to outcome devaluation. Nevertheless, lesions of either the posterior or the anterior CeN abolished the general excitatory influence of a Pavlovian CS on instrumental performance. Next we assessed the functional interaction between the CeN and dorsolateral striatum (DLS), a region previously implicated in the acquisition of habits, using asymmetrical lesions to disconnect these structures. Rats were given a unilateral lesion of anterior CeN and a unilateral lesion of the DLS, made either ipsilateral (control) or contralateral (disconnection) to the CeN lesion, and given overtraining followed by outcome devaluation. Although the ipsilateral lesioned rats were insensitive to devaluation, the contralateral CeN-DLS lesion impaired habit acquisition rendering performance sensitive to the devaluation treatment. These results are the first to implicate the CeN and its connection with a circuit involving DLS in habit learning. They imply that, in instrumental conditioning, regions of amygdala parse the instrumental outcome into the reward and reinforcement signals mediating goal-directed and habitual actions, respectively. PMID:22262905

Targeting Host Cell Surface Nucleolin for RSV Therapy: Challenges and Opportunities.

PubMed

Mastrangelo, Peter; Norris, Michael J; Duan, Wenming; Barrett, Edward G; Moraes, Theo J; Hegele, Richard G

2017-09-19

Nucleolin (NCL) has been reported as a cellular receptor for the human respiratory syncytial virus (RSV). We studied the effects of re-purposing AS1411, an anti-cancer compound that binds cell surface NCL, as a possible novel strategy for RSV therapy in vitro and in vivo. AS1411 was administered to RSV-infected cultures of non-polarized (HEp-2) and polarized (MDCK) epithelial cells and to virus-infected mice and cotton rats. Results of in vitro experiments showed that AS1411, used in micromolar concentrations, was associated with decreases in the number of virus-positive cells. Intranasal administration of AS1411 (50 mg/kg) to RSV-infected mice and cotton rats was associated with partial reductions in lung viral titers, decreased virus-associated airway inflammation, and decreased IL-4/IFN-γ ratios when compared to untreated, infected animals. In conclusion, our findings indicate that therapeutic use of AS1411 has modest effects on RSV replication and host response. While the results underscore the challenges of targeting cell surface NCL as a potential novel strategy for RSV therapy, they also highlight the potential of cell surface NCL as a therapeutic target.

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

Wenliang Yan; Ozelius, L.; Breakefield, X.O.

The neuronal ceroid lipofuscinoses (NCL) are a group of progressive neurodegenerative disorders characterized by the deposition of autofluorescent proteinaceous fingerprint or curvilinear bodies. The authors have found that CLN3, the gene underlying the juvenile form of NCL, is very tightly linked to the dinucleotide repeat marker D16S285 on chromosome 16. Integration of D16S285 into the genetic map of chromosome 16 by using the Centre d'Etude du Polymorphisme Humain panel of reference pedigrees yielded a favored marker order in the CLN3 region of qtel-D16S150-.08-D16S285-.04-D16S148-.02-D16S67-ptel. The most likely location of the disease gene, near D16S285 in the D16S150-D16S148 interval, was favored bymore » odds of greater than 10[sup 4]:1 over the adjacent D16S148-D16S67 interval, which was recently reported as the minimum candidate region. Analysis of D16S285 in pedigrees with late-infantile NCL virtually excluded the CLN3 region, suggesting that these two forms of NCL are genetically distinct. 23 refs., 3 figs., 2 tabs.« less

Negative Correlation Learning for Customer Churn Prediction: A Comparison Study

PubMed Central

Faris, Hossam

2015-01-01

Recently, telecommunication companies have been paying more attention toward the problem of identification of customer churn behavior. In business, it is well known for service providers that attracting new customers is much more expensive than retaining existing ones. Therefore, adopting accurate models that are able to predict customer churn can effectively help in customer retention campaigns and maximizing the profit. In this paper we will utilize an ensemble of Multilayer perceptrons (MLP) whose training is obtained using negative correlation learning (NCL) for predicting customer churn in a telecommunication company. Experiments results confirm that NCL based MLP ensemble can achieve better generalization performance (high churn rate) compared with ensemble of MLP without NCL (flat ensemble) and other common data mining techniques used for churn analysis. PMID:25879060

Human versus non-cross-linked porcine acellular dermal matrix used for ventral hernia repair: comparison of in vivo fibrovascular remodeling and mechanical repair strength.

PubMed

Campbell, Kristin Turza; Burns, Nadja K; Rios, Carmen N; Mathur, Anshu B; Butler, Charles E

2011-06-01

Human acellular dermal matrix (HADM) and non-cross-linked porcine acellular dermal matrix (ncl-PADM) are clinically useful for complex ventral hernia repair. Direct comparisons between the two in vivo are lacking, however. This study compared clinically relevant early outcomes with these bioprosthetic materials when used for ventral hernia repair. Seventy-two guinea pigs underwent inlay repair of surgically created hernias with HADM (n = 37) or ncl-PADM (n = 35). Repair sites were harvested at 1, 2, or 4 weeks postoperatively. Adhesions were graded and quantified. Mechanical testing and histologic and immunohistologic (factor VIII) analyses of cellular and vascular infiltration were performed. No infections or recurrent hernias occurred. No difference was observed in mean adhesion surface area or tenacity between groups. Mean cellular infiltration (p < 0.002, weeks 1 and 4; p < 0.006, week 2) and vascular infiltration (p < 0.0003, week 1; p < 0.0001, weeks 2 and 4) were greater in HADM. Ultimate tensile strength at the implant-musculofascia interface increased over time with both materials, but no difference was observed at 4 weeks. The mean ultimate tensile strength of explanted ncl-PADM itself was consistently greater than that of HADM. The elastic modulus (stiffness) did not differ between groups at the interface but was greater in explanted ncl-PADM (p < 0.0001, weeks 1 and 2; p < 0.02, week 4). Both HADM and ncl-PADM become infiltrated with host cells and blood vessels within 4 weeks and have similar musculofascia-bioprosthetic interface strength. However, HADM has greater cellular and vascular infiltration. Longer-term studies will help determine whether later differences in material strength, stiffness, and remodeling affect hernia and/or bulge incidence.

Evaluation of the Effect of Low Dietary Fermentable Carbohydrate Content on Growth Performance, Nutrient Digestibility, Blood Characteristics, and Meat Quality in Finishing Pigs

PubMed Central

Hong, S. M.; Hwang, J. H.; Kim, I. H.

2012-01-01

A total of 96 pigs (49.23±3.20 kg) were used in an 11 wk growth trial to evaluate the effect of fermentable carbohydrate (FC) content on growth performance, apparent total tract digestibility (ATTD) of nutrient, blood profile, and meat quality. The dietary treatments were: i) negative control (NC), basal diet, ii) positive control (PC), NC+antibiotics (positive control diet with 5 ppm flavomycin), iii) PCL, PC-13% lower FC, and iv) NCL, NC-13% lower FC. The growth performance (average daily gain, average daily feed intake, and gain/feed) didn’t differ among treatments through the whole experiment. These pigs fed the PCL diet had the greater (p<0.05) apparent total tract digestibility (ATTD) of dry matter than those from PC and NC treatment at the end of the experiment. No differences were observed in white blood cell (WBC), red blood cell (RBC), and lymphocyte concentration among different treatments. After the feeding period, meat samples were collected from the pigs at slaughter. The pigs in NCL and PCL treatments had greater (p<0.05) backfat thickness and lower lean percentage. The color value of loin was higher (p<0.05) in NCL treatment compared to PCL treatment. Also, the NCL treatment had higher (p<0.05) marbling value than PC treatment. The drip loss was depressed by PCL and NCL treatment comapared to NC treatments. The water holding capacity (WHC) was higher (p<0.05) in NC and PCL treatment. In conclusion, the low FC can improve digestibility and meat quality of finishing pigs. PMID:25049693

Safety and potential efficacy of gemfibrozil as a supportive treatment for children with late infantile neuronal ceroid lipofuscinosis and other lipid storage disorders.

PubMed

Kim, Kyeongsoon; Kleinman, Hynda K; Lee, Hahn-Jun; Pahan, Kalipada

2017-06-17

Neuronal Ceroid Lipofuscinosis (NCL), also known as Batten disease, is a group of genetically distinct lysosomal disorders that mainly affect the central nervous system, resulting in progressive motor and cognitive decline primarily in children. Multiple distinct genes involved in the metabolism of lipids have been identified to date with various mutations in this family of diseases. There is no cure for these diseases but some new therapeutic approaches have been tested that offer more hope than the standard palliative care. Many of the therapeutic advances require invasive procedures but some progress in slowing the disease has been found and more options can be expected in the future. We also review the literature on children with disease/conditions other than NCL for the non-invasive use, safety, and tolerability of a lipid-lowering drug, gemfibrozil, as a potential treatment for NCLs. Gemfibrozil has shown efficacy in an animal model of NCL known as CLN2 (late infantile classic juvenile) and has been shown to be safe for lowering lipids in children. Among the 200 non-NCL children found in the published literature who were treated with gemfibrozil for NCL-related problems, only 3 experienced adverse events, including 2 with muscle pain and 1 with localized linear IgA bullous dermatitis. We conclude that gemfibrozil is safe for long-term use in children, causes minimal adverse events, is well tolerated, and may delay the progression of NCLs. Gemfibrozil may potentially be an alternative to more invasive therapeutic approaches currently under investigation and has the potential to be used in combination with other therapeutic approaches.

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

Frecker, M.F.; Jacob, J.C.; Ives, E.J.

The neuronal ceroid lipofuscinoses (NCL) are a group of recessively inherited neurodegenerative disorders. The most common type found in Newfoundland is late infantile NCL; 1 in 63 of the population is estimated to be a carrier. The incidence has decreased over the years with fewer affected siblings born in families and migration away from smaller communities. For the 30 late infantile cases (24 families), most presented with generalized convulsive seizures; all had curvilinear inclusion bodies in several cell types. The mean age at onset was 2.8 {plus_minus} 0.6 yr and they lived a mean of 7.5 {plus_minus} 2.1 yr. Threemore » of these families have been used to exclude linkage to markers on chromosome 1 and 16. There is one typical juvenile NCL family; it has been used to further define the localization of the gene on chromosome 16p. Genetic counseling for carrier status has been offered in this family. A single case of adult NCL (Kufs) has been identified. Reevaluation of the cases indicated that there are many who have clinical and neuropathological features of both late infantile and juvenile NCL. Unusual findings in these 13 cases (11 families) included the coexistence of both types of inclusion bodies. In patients with juvenile fingerprint inclusion bodies, atypical presentations were delayed milestones at age 8 mo, visual loss before 4 yr, psychomotor retardation before loss of vision and an enhanced response to photic stimulation on EEG. Molecular studies will determine the basis for this heterogeneity. Extensive family histories showed only 53% (19/36) of families were consanguinous or interelated indicating that the frequency of the gene is probably quite high.« less

Neuronal ceroid lipofuscinosis in Border Collie dogs in Japan: clinical and molecular epidemiological study (2000-2011).

PubMed

Mizukami, Keijiro; Kawamichi, Takuji; Koie, Hiroshi; Tamura, Shinji; Matsunaga, Satoru; Imamoto, Shigeki; Saito, Miyoko; Hasegawa, Daisuke; Matsuki, Naoaki; Tamahara, Satoshi; Sato, Shigenobu; Yabuki, Akira; Chang, Hye-Sook; Yamato, Osamu

2012-01-01

Neuronal ceroid lipofuscinosis (NCL) is an inherited, neurodegenerative lysosomal disease that causes premature death. The present study describes the clinical and molecular epidemiologic findings of NCL in Border Collies in Japan for 12 years, between 2000 and 2011. The number of affected dogs was surveyed, and their clinical characteristics were analyzed. In 4 kennels with affected dogs, the dogs were genotyped. The genetic relationships of all affected dogs and carriers identified were analyzed. The survey revealed 27 affected dogs, but there was a decreasing trend at the end of the study period. The clinical characteristics of these affected dogs were updated in detail. The genotyping survey demonstrated a high mutant allele frequency in examined kennels (34.8%). The pedigree analysis demonstrated that all affected dogs and carriers in Japan are related to some presumptive carriers imported from Oceania and having a common ancestor. The current high prevalence in Japan might be due to an overuse of these carriers by breeders without any knowledge of the disease. For NCL control and prevention, it is necessary to examine all breeding dogs, especially in kennels with a high prevalence. Such endeavors will reduce NCL prevalence and may already be contributing to the recent decreasing trend in Japan.

Neuronal Ceroid Lipofuscinosis in Border Collie Dogs in Japan: Clinical and Molecular Epidemiological Study (2000–2011)

PubMed Central

Mizukami, Keijiro; Kawamichi, Takuji; Koie, Hiroshi; Tamura, Shinji; Matsunaga, Satoru; Imamoto, Shigeki; Saito, Miyoko; Hasegawa, Daisuke; Matsuki, Naoaki; Tamahara, Satoshi; Sato, Shigenobu; Yabuki, Akira; Chang, Hye-Sook; Yamato, Osamu

2012-01-01

Neuronal ceroid lipofuscinosis (NCL) is an inherited, neurodegenerative lysosomal disease that causes premature death. The present study describes the clinical and molecular epidemiologic findings of NCL in Border Collies in Japan for 12 years, between 2000 and 2011. The number of affected dogs was surveyed, and their clinical characteristics were analyzed. In 4 kennels with affected dogs, the dogs were genotyped. The genetic relationships of all affected dogs and carriers identified were analyzed. The survey revealed 27 affected dogs, but there was a decreasing trend at the end of the study period. The clinical characteristics of these affected dogs were updated in detail. The genotyping survey demonstrated a high mutant allele frequency in examined kennels (34.8%). The pedigree analysis demonstrated that all affected dogs and carriers in Japan are related to some presumptive carriers imported from Oceania and having a common ancestor. The current high prevalence in Japan might be due to an overuse of these carriers by breeders without any knowledge of the disease. For NCL control and prevention, it is necessary to examine all breeding dogs, especially in kennels with a high prevalence. Such endeavors will reduce NCL prevalence and may already be contributing to the recent decreasing trend in Japan. PMID:22919312

Portuguese family with the co-occurrence of frontotemporal lobar degeneration and neuronal ceroid lipofuscinosis phenotypes due to progranulin gene mutation.

PubMed

Almeida, Maria R; Macário, Maria C; Ramos, Lina; Baldeiras, Inês; Ribeiro, Maria H; Santana, Isabel

2016-05-01

We and others have reported heterozygous progranulin mutations as an important cause of frontotemporal lobar degeneration (FTLD). It has been identified a complete progranulin deficiency because of a homozygous mutation in a sibling pair with neuronal ceroid lipofuscinosis (NCL). Here, we describe the first case of NCL caused by a homozygous progranulin mutation segregating in a family with neuropathological confirmed FTLD. In this FTLD-NCL family, we detail the clinical phenotype, neuropsychological evaluation and imaging data of our proband harboring a homozygous mutation, c.900_901dupGT, with serum progranulin level (<6 ng/mL). Symptoms included rapidly progressive visual deficit, slightly dysarthria, and cerebellar ataxia. The electroretinogram confirmed a severe attenuation of rod and cone responses compatible with retinal dystrophy diagnosis and magnetic resonance imaging showed severe global cerebellar atrophy. In contrast, heterozygous relatives presented behavioral variant of frontotemporal dementia (FTD) and some also developed extrapyramidal features compatible with corticobasal syndrome. Our findings suggest the importance of assessing serum progranulin levels in suspected recessive adult-onset NCL cases. Overall, a more holistic neurologic intervention is needed to guarantee a proper genetic counseling in cases like the present family where two distinct phenotypes are generated according to the individuals' mutation state. Copyright © 2016 Elsevier Inc. All rights reserved.

Protein chemical synthesis by α-ketoacid-hydroxylamine ligation.

PubMed

Harmand, Thibault J; Murar, Claudia E; Bode, Jeffrey W

2016-06-01

Total chemical synthesis of proteins allows researchers to custom design proteins without the complex molecular biology that is required to insert non-natural amino acids or the biocontamination that arises from methods relying on overexpression in cells. We describe a detailed procedure for the chemical synthesis of proteins with the α-ketoacid-hydroxylamine (KAHA ligation), using (S)-5-oxaproline (Opr) as a key building block. This protocol comprises two main parts: (i) the synthesis of peptide fragments by standard fluorenylmethoxycarbonyl (Fmoc) chemistry and (ii) the KAHA ligation between fragments containing Opr and a C-terminal peptide α-ketoacid. This procedure provides an alternative to native chemical ligation (NCL) that could be valuable for the synthesis of proteins, particularly targets that do not contain cysteine residues. The ligation conditions-acidic DMSO/H2O or N-methyl-2-pyrrolidinone (NMP)/H2O-are ideally suited for solubilizing peptide segments, including many hydrophobic examples. The utility and efficiency of the protocol is demonstrated by the total chemical synthesis of the mature betatrophin (also called ANGPTL8), a 177-residue protein that contains no cysteine residues. With this protocol, the total synthesis of the betatrophin protein has been achieved in around 35 working days on a multimilligram scale.

Analytical validation of a flow cytometric protocol for quantification of platelet microparticles in dogs.

PubMed

Cremer, Signe E; Krogh, Anne K H; Hedström, Matilda E K; Christiansen, Liselotte B; Tarnow, Inge; Kristensen, Annemarie T

2018-06-01

Platelet microparticles (PMPs) are subcellular procoagulant vesicles released upon platelet activation. In people with clinical diseases, alterations in PMP concentrations have been extensively investigated, but few canine studies exist. This study aims to validate a canine flow cytometric protocol for PMP quantification and to assess the influence of calcium on PMP concentrations. Microparticles (MP) were quantified in citrated whole blood (WB) and platelet-poor plasma (PPP) using flow cytometry. Anti-CD61 antibody and Annexin V (AnV) were used to detect platelets and phosphatidylserine, respectively. In 13 healthy dogs, CD61 + /AnV - concentrations were analyzed with/without a calcium buffer. CD61 + /AnV - , CD61 + /AnV + , and CD61 - /AnV + MP quantification were validated in 10 healthy dogs. The coefficient of variation (CV) for duplicate (intra-assay) and parallel (inter-assay) analyses and detection limits (DLs) were calculated. CD61 + /AnV - concentrations were higher in calcium buffer; 841,800 MP/μL (526,000-1,666,200) vs without; 474,200 MP/μL (278,800-997,500), P < .05. In WB, PMP were above DLs and demonstrated acceptable (<20%) intra-assay and inter-assay CVs in 9/10 dogs: 1.7% (0.5-8.9) and 9.0% (0.9-11.9), respectively, for CD61 + /AnV - and 2.4% (0.2-8.7) and 7.8% (0.0-12.8), respectively, for CD61 + /AnV + . Acceptable CVs were not seen for the CD61 - /AnV + MP. In PPP, quantifications were challenged by high inter-assay CV, overlapping DLs and hemolysis and lipemia interfered with quantification in 5/10 dogs. Calcium induced higher in vitro PMP concentrations, likely due to platelet activation. PMP concentrations were reliably quantified in WB, indicating the potential for clinical applications. PPP analyses were unreliable due to high inter-CV and DL overlap, and not obtainable due to hemolysis and lipemia interference. © 2018 American Society for Veterinary Clinical Pathology.

A novel bioscaffold with naturally-occurring extracellular matrix promotes hepatocyte survival and vessel patency in mouse models of heterologous transplantation.

PubMed

Yang, Wei; Chen, Quanyu; Xia, Renpei; Zhang, Yujun; Shuai, Ling; Lai, Jiejuan; You, Xiaolin; Jiang, Yan; Bie, Ping; Zhang, Leida; Zhang, Hongyu; Bai, Lianhua

2018-05-28

Naïve decellularized liver scaffold (nDLS)-based tissue engineering has been impaired by the lack of a suitable extracellular matrix (ECM) to provide "active micro-environmental" support. The present study aimed to examine whether a novel, regenerative DLS (rDLS) with an active ECM improves primary hepatocyte survival and prevents thrombosis. rDLS was obtained from a 30-55% partial hepatectomy that was maintained in vivo for 3-5 days and then perfused with detergent in vitro. Compared to nDLS generated from normal livers, rDLS possesses bioactive molecules due to the regenerative period in vivo. Primary mouse hepatocyte survival was evaluated by staining for Ki-67 and Trypan blue exclusion. Thrombosis was assessed by immunohistochemistry and ex vivo diluted whole-blood perfusion. Hemocompatibility was determined by near-infrared laser-Doppler flowmetry and heterotopic transplantation. After recellularization, rDLS contained more Ki-67-positive primary hepatocytes than nDLS. rDLS had a higher oxygen saturation and blood flow velocity and a lower expression of integrin αIIb and α4 than nDLS. Tumor necrosis factor-α, hepatocyte growth factor, interleukin-10, interleukin-6 and interleukin-1β were highly expressed throughout the rDLS, whereas expression of collagen-I, collagen-IV and thrombopoietin were lower in rDLS than in nDLS. Improved blood vessel patency was observed in rDLS both in vitro and in vivo. The results in mice were confirmed in large animals (pigs). rDLS is an effective DLS with an "active microenvironment" that supports primary hepatocyte survival and promotes blood vessel patency. This is the first study to demonstrate a rDLS with a blood microvessel network that promotes hepatocyte survival and resists thrombosis. Copyright © 2018 Elsevier Ltd. All rights reserved.

Late onset neurodegeneration in the Cln3-/- mouse model of juvenile neuronal ceroid lipofuscinosis is preceded by low level glial activation.

PubMed

Pontikis, Charlie C; Cella, Claire V; Parihar, Nisha; Lim, Ming J; Chakrabarti, Shubhodeep; Mitchison, Hannah M; Mobley, William C; Rezaie, Payam; Pearce, David A; Cooper, Jonathan D

2004-10-15

Mouse models of neuronal ceroid lipofuscinosis (NCL) exhibit many features of the human disorder, with widespread regional atrophy and significant loss of GABAergic interneurons in the hippocampus and neocortex. Reactive gliosis is a characteristic of all forms of NCL, but it is unclear whether glial activation precedes or is triggered by neuronal loss. To explore this issue we undertook detailed morphological characterization of the Cln3 null mutant (Cln3(-/-)) mouse model of juvenile NCL (JNCL) that revealed a delayed onset neurodegenerative phenotype with no significant regional atrophy, but with widespread loss of hippocampal interneurons that was first evident at 14 months of age. Quantitative image analysis demonstrated upregulation of markers of astrocytic and microglial activation in presymptomatic Cln3(-/-) mice at 5 months of age, many months before significant neuronal loss occurs. These data provide evidence for subtle glial responses early in JNCL pathogenesis.

Acyl donors for native chemical ligation.

PubMed

Yan, Bingjia; Shi, Weiwei; Ye, Linzhi; Liu, Lei

2018-04-11

Native chemical ligation (NCL) has become one of the most important methods in chemical syntheses of proteins. Recently, in order to expand its scope, considerable effort has been devoted to tuning the C-terminal acyl donor thioesters used in NCL. This article reviews the recent advances in the design of C-terminal acyl donors, their precursors and surrogates, and highlights some noteworthy progress that may lead the future direction of protein chemical synthesis. Copyright © 2018 Elsevier Ltd. All rights reserved.

Immobilization methods for the rapid total chemical synthesis of proteins on microtiter plates.

PubMed

Zitterbart, Robert; Krumrey, Michael; Seitz, Oliver

2017-07-01

The chemical synthesis of proteins typically involves the solid-phase peptide synthesis of unprotected peptide fragments that are stitched together in solution by native chemical ligation (NCL). The process is slow, and throughput is limited because of the need for repeated high performance liquid chromatography purification steps after both solid-phase peptide synthesis and NCL. With an aim to provide faster access to functional proteins and to accelerate the functional analysis of synthetic proteins by parallelization, we developed a method for the high performance liquid chromatography-free synthesis of proteins on the surface of microtiter plates. The method relies on solid-phase synthesis of unprotected peptide fragments, immobilization of the C-terminal fragment and on-surface NCL with an unprotected peptide thioester in crude form. Herein, we describe the development of a suitable immobilization chemistry. We compared (i) formation of nickel(II)-oligohistidine complexes, (ii) Cu-based [2 + 3] alkine-azide cycloaddition and (iii) hydrazone ligation. The comparative study identified the hydrazone ligation as most suitable. The sequence of immobilization via hydrazone ligation, on-surface NCL and radical desulfurization furnished the targeted SH3 domains in near quantitative yield. The synthetic proteins were functional as demonstrated by an on-surface fluorescence-based saturation binding analysis. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.

Final Report for the Development of the NASA Technical Report Server (NTRS)

NASA Technical Reports Server (NTRS)

Nelson, Michael L.

2005-01-01

The author performed a variety of research, development and consulting tasks for NASA Langley Research Center in the area of digital libraries (DLs) and supporting technologies, such as the Open Archives Initiative Protocol for Metadata Harvesting (OAI-PMH). In particular, the development focused on the NASA Technical Report Server (NTRS) and its transition from a distributed searching model to one that uses the OAI-PMH. The Open Archives Initiative (OAI) is an international consortium focused on furthering the interoperability of DLs through the use of "metadata harvesting". The OAI-PMH version of NTRS went into public production on April 28, 2003. Since that time, it has been extremely well received. In addition to providing the NTRS user community with a higher level of service than the previous, distributed searching version of NTRS, it has provided more insight into how the user community uses NTRS in a variety of deployment scenarios. This report details the design, implementation and maintenance of the NTRS. Source code is included in the appendices.

Impact of TCFA on Unanticipated Ischemic Events in Medically Treated Diabetes Mellitus: Insights From the PROSPECT Study.

PubMed

Kedhi, Elvin; Kennedy, Mark W; Maehara, Akiko; Lansky, Alexandra J; McAndrew, Thomas C; Marso, Steven P; De Bruyne, Bernard; Serruys, Patrick W; Stone, Gregg W

2017-04-01

This study sought to investigate the relationship between thin-cap fibroatheromas (TCFAs) on major adverse cardiac events (MACEs) arising from medically treated nonculprit lesions (NCLs) in patients with acute coronary syndromes (ACS) with and without diabetes mellitus (DM). MACEs occur frequently in patients with DM and ACS. The impact of plaque composition on subsequent MACEs in DM patients with ACS is unknown. In the PROSPECT (Providing Regional Observations Study Predictors of Events in the Coronary Tree) study, using 3-vessel radiofrequency intravascular ultrasound, we analyzed the incidence of NCL-MACE in 2 propensity-matched groups according to the presence of DM and TCFA. Among 697 patients, 119 (17.7%) had DM. The 3-year total MACE rate (29.4% vs. 18.8%; p = 0.01) was significantly higher in patients with versus without DM, driven by a higher rate of NCL-MACE in DM (18.7% vs. 10.4%; p = 0.02). Propensity score matching generated 2 balanced groups with and without DM of 82 patients each. Among DM patients, the presence of ≥1 TCFA was associated with higher NCL-MACE at 3 years (27.8% vs. 8.9% in patients without a TCFA, hazard ratio: 3.56; 95% confidence interval: 0.98 to 12.96; p = 0.04). DM patients without a TCFA had a similar 3-year rate of NCL-MACE as patients without DM (8.9% vs. 8.9%; hazard ratio: 1.09; 95% confidence interval: 0.27 to 4.41; p = 0.90). ACS patients with DM and ≥1 TCFA have a high rate of NCL-MACE at 3 years. In contrast, the prognosis of ACS patients with DM but no TCFAs is favorable and similar to patients without DM. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Nanotechnology Laboratory Continues Partnership with FDA and National Institute of Standards and Technology | Poster

Cancer.gov

The NCI-funded Nanotechnology Characterization Laboratory (NCL)—a leader in evaluating promising nanomedicines to fight cancer—recently renewed its collaboration with the U.S. Food and Drug Administration (FDA) and the National Institute of Standards and Technology (NIST) to continue its groundbreaking work on characterizing nanomedicines and moving them toward the clinic. In partnership with NIST and the FDA, NCL has laid a solid, scientific foundation for using the power of nanotechnology to increase the potency and target the delivery

Characterization of hepatocellular carcinoma (HCC) in non-alcoholic fatty liver disease (NAFLD) patients without cirrhosis.

PubMed

Mohamad, Bashar; Shah, Vaishal; Onyshchenko, Mykola; Elshamy, Mohammed; Aucejo, Federico; Lopez, Rocio; Hanouneh, Ibrahim A; Alhaddad, Razan; Alkhouri, Naim

2016-07-01

The incidence of hepatocellular carcinoma (HCC) has increased significantly in United States over the last few decades in parallel with the epidemic of nonalcoholic fatty liver disease (NAFLD). Limited data suggests that HCC could arise in steatotic liver without the presence of cirrhosis. The present study was conducted to characterize patients with NAFLD presenting with HCC in non-cirrhotic liver (NCL) compared to the NAFLD- HCC patients in association with cirrhotic liver (CL). A retrospective analysis of all patients diagnosed with HCC and NAFLD diagnosis seen at our institution between 2003 and 2012 was done. The patients were characterized based on demographic and clinical variables as well as histological and tumor features. Comparisons between the NCL and CL groups were done using analysis of variance (ANOVA) or the non-parametric Kruskal-Wallis tests and Pearson's chi-square tests or Fisher's Exact tests as appropriate. P value of <0.05 was considered statistically significant. Thirty-six patients with NAFLD and HCC in NCL (HCC-NCL group) were identified and compared to 47 patients with NAFLD-HCC and Liver Cirrhosis (HCC-LC group). Liver fibrosis was not present in 55.9 % of patients in the HCC-NCL group (F0), stage 1 was present in 17.6 %, stage 2 in 8.8 % and stage 3 in 17.6 %. Lobular inflammation was present in 63.6 % of non-cirrhotic patients. Patients in the HCC-NCL were older (67.5 ± 12.3 vs. 62.7 ± 8.1 years), and less likely to be obese (52 % vs. 83 %) or have type 2 diabetes (38 % vs. 83 %), with p value <0.05 for all. More importantly, compared with the HCC-CL group, those in the HCC-NCL group were more likely to present with a single nodule (80.6 % vs. 52.2 %), larger nodule size (>5 cm) (77.8 % vs. 10.6 %), and receive hepatic resection as the modality of HCC treatment (66.7 % vs. 17 %); and were less likely to receive loco-regional therapy (22.3 % vs. 61.7 %) or orthotopic liver transplantation (OLT) (0 % vs. 72.3 %), with p value <0.001 for all. Furthermore, 86 % of patients without cirrhosis had HCC recurrence compared to only 14 % in patients with cirrhosis (p < 0.001). Unadjusted analysis indicates that non-cirrhotics had worse survival with mortality rate of 47 % vs. 28 % in CL group (p = 0.03); however this difference in survival between two groups was not significant after adjusting for age or OLT (p > 0.05). Patients with HCC in the absence of liver cirrhosis are more likely to present at an older age with larger tumor and have higher rates of tumor recurrence. Studies to assess the cost-effectiveness of HCC surveillance in this group should be conducted.

Associative learning rapidly establishes neuronal representations of upcoming behavioral choices in crows

PubMed Central

Veit, Lena; Pidpruzhnykova, Galyna; Nieder, Andreas

2015-01-01

The ability to form associations between behaviorally relevant sensory stimuli is fundamental for goal-directed behaviors. We investigated neuronal activity in the telencephalic area nidopallium caudolaterale (NCL) while two crows (Corvus corone) performed a delayed association task. Whereas some paired associates were familiar to the crows, novel associations had to be learned and mapped to the same target stimuli within a single session. We found neurons that prospectively encoded the chosen test item during the delay for both familiar and newly learned associations. These neurons increased their selectivity during learning in parallel with the crows' increased behavioral performance. Thus, sustained activity in the NCL actively processes information for the upcoming behavioral choice. These data provide new insights into memory representations of behaviorally meaningful stimuli in birds, and how such representations are formed during learning. The findings suggest that the NCL plays a role in learning arbitrary associations, a cornerstone of corvids’ remarkable behavioral flexibility and adaptability. PMID:26598669

Reactions between atomic chlorine and pyridine in solid para-hydrogen: infrared spectrum of the 1-chloropyridinyl (C5H5N-Cl) radical.

PubMed

Das, Prasanta; Bahou, Mohammed; Lee, Yuan-Pern

2013-02-07

With infrared absorption spectra we investigated the reaction between Cl atom and pyridine (C(5)H(5)N) in a para-hydrogen (p-H(2)) matrix. Pyridine and Cl(2) were co-deposited with p-H(2) at 3.2 K; a planar C(5)H(5)N-Cl(2) complex was identified from the observed infrared spectrum of the Cl(2)/C(5)H(5)N/p-H(2) matrix. Upon irradiation at 365 nm to generate Cl atom in situ and annealing at 5.1 K for 3 min to induce secondary reaction, the 1-chloropyridinyl radical (C(5)H(5)N-Cl) was identified as the major product of the reaction Cl + C(5)H(5)N in solid p-H(2); absorption lines at 3075.9, 1449.7, 1200.6, 1148.8, 1069.3, 1017.4, 742.9, and 688.7 cm(-1) were observed. The assignments are based on comparison of observed vibrational wavenumbers and relative IR intensities with those predicted using the B3PW91/6-311++G(2d, 2p) method. The observation of the preferential addition of Cl to the N-site of pyridine to form C(5)H(5)N-Cl radical but not 2-, 3-, or 4-chloropyridine (ClC(5)H(5)N) radicals is consistent with the reported theoretical prediction that formation of the former proceeds via a barrierless path.

Is an observed non-co-linear RNA product spliced in trans, in cis or just in vitro?

PubMed Central

Yu, Chun-Ying; Liu, Hsiao-Jung; Hung, Li-Yuan; Kuo, Hung-Chih; Chuang, Trees-Juen

2014-01-01

Global transcriptome investigations often result in the detection of an enormous number of transcripts composed of non-co-linear sequence fragments. Such ‘aberrant’ transcript products may arise from post-transcriptional events or genetic rearrangements, or may otherwise be false positives (sequencing/alignment errors or in vitro artifacts). Moreover, post-transcriptionally non-co-linear (‘PtNcl’) transcripts can arise from trans-splicing or back-splicing in cis (to generate so-called ‘circular RNA’). Here, we collected previously-predicted human non-co-linear RNA candidates, and designed a validation procedure integrating in silico filters with multiple experimental validation steps to examine their authenticity. We showed that >50% of the tested candidates were in vitro artifacts, even though some had been previously validated by RT-PCR. After excluding the possibility of genetic rearrangements, we distinguished between trans-spliced and circular RNAs, and confirmed that these two splicing forms can share the same non-co-linear junction. Importantly, the experimentally-confirmed PtNcl RNA events and their corresponding PtNcl splicing types (i.e. trans-splicing, circular RNA, or both sharing the same junction) were all expressed in rhesus macaque, and some were even expressed in mouse. Our study thus describes an essential procedure for confirming PtNcl transcripts, and provides further insight into the evolutionary role of PtNcl RNA events, opening up this important, but understudied, class of post-transcriptional events for comprehensive characterization. PMID:25053845

Variability of single-leg versus double-leg stance radiographs in the varus knee.

PubMed

Chen, Andrew; Rich, Valerie; Bain, Elizabeth; Sterett, William I

2009-07-01

We evaluated measured radiographic parameter variability between single-leg stance (SLS) and double-leg stance (DLS) radiographs in patients with varus knee malalignment, indicated for high tibial osteotomy. Fifty-three consecutive knees (mean, 49 years; range, 18-79 years) were evaluated for varus thrust. SLS and DLS radiographs were obtained. A single blinded observer measured mechanical axis angles and weight-bearing line (WBL) deviation using a goniometer. Mechanical axis angles averaged 9.1 degrees (DLS) and 11.3 degrees (SLS). SLS radiographs averaged 9% greater WBL medialization than did DLS. Medial opening averaged 16.4 mm (DLS) and 18.8 mm (SLS). DLS and SLS radiographs showed no significant differences in patients without varus thrust. Patients with varus thrust demonstrated differences in mechanical axis angles (DLS, 9.4 degrees; SLS, 12.2 degrees), WBL deviation (12.1% less), medialization (DLS), and medial opening necessary for correction (DLS, 16.6 mm; SLS, 20.3 mm). In varus thrust, SLS radiographs more closely replicate dynamic knee malalignment, possibly providing more accurate measurements of angular deformity.

Neuronal ceroid lipofuscinosis (NCL) is caused by the entire deletion of CLN8 in the Alpenländische Dachsbracke dog.

PubMed

Hirz, M; Drögemüller, M; Schänzer, A; Jagannathan, V; Dietschi, E; Goebel, H H; Hecht, W; Laubner, S; Schmidt, M J; Steffen, F; Hilbe, M; Köhler, K; Drögemüller, C; Herden, C

2017-03-01

Neuronal ceroid lipofuscinoses (NCLs) are inherited lysosomal storage diseases that have been described in a variety of dog breeds, where they are caused by different mutations in different genes. However, the causative gene defect in the breed Alpenländische Dachsbracke remained unknown so far. Here we present two confirmed cases of NCL in Alpenländische Dachsbracke dogs from different litters of the same sire with a different dam harboring the same underlying novel mutation in the CLN8 gene. Case 1, a 2-year-old male Alpenländische Dachsbracke was presented with neurological signs including disorientation, character changes including anxiety states and aggressiveness, sudden blindness and reduction of food intake. Magnetic resonance imaging (MRI) scans showed cerebral atrophy with dilation of all cerebral ventricles, thinning of the intermediate mass of the thalamus and widening of the cerebral sulci. Postmortem examination of the central nervous system (CNS) showed neuronal loss in the cerebral cortex, cerebellum and spinal cord with massive intracellular deposits of ceroid pigment. Additional ceroid-lipofuscin deposits were observed in the enteric nervous system and in macrophages within spleen, lymph nodes and lung. Ultrastructural analyses confirmed NCL with the presence of osmiophilic membrane bounded lamellar-like structures. Case 2, a 1,5-year old female Alpenländische Dachsbracke was presented with progressive generalized forebrain disease including mental changes such as fearful reactions to various kinds of external stimuli and disorientation. The dog also displayed seizures, absence of menace reactions and negative cotton-ball test with normal pupillary light reactions. The clinical and post mortem examination yielded similar results in the brain as in Case 1. Whole genome sequencing of Case 1 and PCR results of both cases revealed a homozygous deletion encompassing the entire CLN8 gene as the most likely causative mutation for the NCL form observed in both cases. The deletion follows recessive inheritance since the dam and a healthy male littermate of Case 1 were tested as heterozygous carriers. This is the first detailed description of CLN8 gene associated NCL in Alpenländische Dachsbracke dogs and thus provides a novel canine CLN8 model for this lysosomal storage disease. The presence of ceroid lipofuscin in extracerebral tissues may help to confirm the diagnosis of NCL in vivo, especially in new dog breeds where the underlying mutation is not known. Copyright © 2016 Elsevier Inc. All rights reserved.

Identification and validation nucleolin as a target of curcumol in nasopharyngeal carcinoma cells.

PubMed

Wang, Juan; Wu, Jiacai; Li, Xumei; Liu, Haowei; Qin, Jianli; Bai, Zhun; Chi, Bixia; Chen, Xu

2018-06-30

Identification of the specific protein target(s) of a drug is a critical step in unraveling its mechanisms of action (MOA) in many natural products. Curcumol, isolated from well known Chinese medicinal plant Curcuma zedoary, has been shown to possess multiple biological activities. It can inhibit nasopharyngeal carcinoma (NPC) proliferation and induce apoptosis, but its target protein(s) in NPC cells remains unclear. In this study, we employed a mass spectrometry-based chemical proteomics approach reveal the possible protein targets of curcumol in NPC cells. Cellular thermal shift assay (CETSA), molecular docking and cell-based assay was used to validate the binding interactions. Chemical proteomics capturing uncovered that NCL is a target of curcumol in NPC cells, Molecular docking showed that curcumol bound to NCL with an -7.8 kcal/mol binding free energy. Cell function analysis found that curcumol's treatment leads to a degradation of NCL in NPC cells, and it showed slight effects on NP69 cells. In conclusion, our results providing evidences that NCL is a target protein of curcumol. We revealed that the anti-cancer effects of curcumol in NPC cells are mediated, at least in part, by NCL inhibition. Many natural products showed high bioactivity, while their mechanisms of action (MOA) are very poor or completely missed. Understanding the MOA of natural drugs can thoroughly exploit their therapeutic potential and minimize their adverse side effects. Identification of the specific protein target(s) of a drug is a critical step in unraveling its MOA. Compound-centric chemical proteomics is a classic chemical proteomics approach which integrates chemical synthesis with cell biology and mass spectrometry (MS) to identify protein targets of natural products determine the drug mechanism of action, describe its toxicity, and figure out the possible cause of off-target. It is an affinity-based chemical proteomics method to identify small molecule-protein interactions through affinity chromatography approach coupled with mass spectrometry, has been conventionally used to identify target proteins and has yielded good results. Curcumol, has shown effective inhibition on Nasopharyngeal Carcinoma (NPC) Cells, interacted with NCL and then initiated the anti-tumor biological effect. This research demonstrated the effectiveness of chemical proteomics approaches in natural drugs molecular target identification, revealing and understanding of the novel mechanism of actions of curcumol is crucial for cancer prevention and treatment in nasopharynx cancer. Copyright © 2018 Elsevier B.V. All rights reserved.

Progranulin Gene Therapy Improves Lysosomal Dysfunction and Microglial Pathology Associated with Frontotemporal Dementia and Neuronal Ceroid Lipofuscinosis.

PubMed

Arrant, Andrew E; Onyilo, Vincent C; Unger, Daniel E; Roberson, Erik D

2018-02-28

Loss-of-function mutations in progranulin, a lysosomal glycoprotein, cause neurodegenerative disease. Progranulin haploinsufficiency causes frontotemporal dementia (FTD) and complete progranulin deficiency causes CLN11 neuronal ceroid lipofuscinosis (NCL). Progranulin replacement is a rational therapeutic strategy for these disorders, but there are critical unresolved mechanistic questions about a progranulin gene therapy approach, including its potential to reverse existing pathology. Here, we address these issues using an AAV vector (AAV- Grn ) to deliver progranulin in Grn -/- mice (both male and female), which model aspects of NCL and FTD pathology, developing lysosomal dysfunction, lipofuscinosis, and microgliosis. We first tested whether AAV- Grn could improve preexisting pathology. Even with treatment after onset of pathology, AAV- Grn reduced lipofuscinosis in several brain regions of Grn -/- mice. AAV- Grn also reduced microgliosis in brain regions distant from the injection site. AAV-expressed progranulin was only detected in neurons, not in microglia, indicating that the microglial activation in progranulin deficiency can be improved by targeting neurons and thus may be driven at least in part by neuronal dysfunction. Even areas with sparse transduction and almost undetectable progranulin showed improvement, indicating that low-level replacement may be sufficiently effective. The beneficial effects of AAV- Grn did not require progranulin binding to sortilin. Finally, we tested whether AAV- Grn improved lysosomal function. AAV-derived progranulin was delivered to the lysosome, ameliorated the accumulation of LAMP-1 in Grn -/- mice, and corrected abnormal cathepsin D activity. These data shed light on progranulin biology and support progranulin-boosting therapies for NCL and FTD due to GRN mutations. SIGNIFICANCE STATEMENT Heterozygous loss-of-function progranulin ( GRN ) mutations cause frontotemporal dementia (FTD) and homozygous mutations cause neuronal ceroid lipofuscinosis (NCL). Here, we address several mechanistic questions about the potential of progranulin gene therapy for these disorders. GRN mutation carriers with NCL or FTD exhibit lipofuscinosis and Grn -/- mouse models develop a similar pathology. AAV-mediated progranulin delivery reduced lipofuscinosis in Grn -/- mice even after the onset of pathology. AAV delivered progranulin only to neurons, not microglia, but improved microgliosis in several brain regions, indicating cross talk between neuronal and microglial pathology. Its beneficial effects were sortilin independent. AAV-derived progranulin was delivered to lysosomes and corrected lysosomal abnormalities. These data provide in vivo support for the efficacy of progranulin-boosting therapies for FTD and NCL. Copyright © 2018 the authors 0270-6474/18/382342-18$15.00/0.

DNA-magnetic Particle Binding Analysis by Dynamic and Electrophoretic Light Scattering.

PubMed

Haddad, Yazan; Dostalova, Simona; Kudr, Jiri; Zitka, Ondrej; Heger, Zbynek; Adam, Vojtech

2017-11-09

Isolation of DNA using magnetic particles is a field of high importance in biotechnology and molecular biology research. This protocol describes the evaluation of DNA-magnetic particles binding via dynamic light scattering (DLS) and electrophoretic light scattering (ELS). Analysis by DLS provides valuable information on the physicochemical properties of particles including particle size, polydispersity, and zeta potential. The latter describes the surface charge of the particle which plays major role in electrostatic binding of materials such as DNA. Here, a comparative analysis exploits three chemical modifications of nanoparticles and microparticles and their effects on DNA binding and elution. Chemical modifications by branched polyethylenimine, tetraethyl orthosilicate and (3-aminopropyl)triethoxysilane are investigated. Since DNA exhibits a negative charge, it is expected that zeta potential of particle surface will decrease upon binding of DNA. Forming of clusters should also affect particle size. In order to investigate the efficiency of these particles in isolation and elution of DNA, the particles are mixed with DNA in low pH (~6), high ionic strength and dehydration environment. Particles are washed on magnet and then DNA is eluted by Tris-HCl buffer (pH = 8). DNA copy number is estimated using quantitative polymerase chain reaction (PCR). Zeta potential, particle size, polydispersity and quantitative PCR data are evaluated and compared. DLS is an insightful and supporting method of analysis that adds a new perspective to the process of screening of particles for DNA isolation.

The role of controllable lifestyle in the choice of specialisation among Hungarian medical doctors.

PubMed

Girasek, Edmond; Szócska, Miklós; Kovács, Eszter; Gaál, Péter

2017-11-13

Hungary has been serious facing human resources crisis in health care, as a result of a massive emigration of health workers. The resulting shortage is unevenly distributed among medical specialisations. The findings of research studies are consistent in that the most important motivating factor of the choice of the medical career and of medical specialisations is professional interest. Beyond this, it is important to examine other reasons of why students do or do not choose certain specialisations. The lifestyle determined by the chosen speciality is one such factor described in the literature. Using convenient sampling, first year resident medical doctors from each of the four Hungarian universities with a medical faculty were asked to participate in the study in 2008. In total 391 first year resident medical doctors completed the self-administered questionnaire indicating a 57.3% response rate. On the basis of the work of Schwartz et al. (Acad Med 65(3):207-210, 1990), the specialisation fields were divided into the two main categories of non-controllable (NCL) or controllable lifestyles (CL). We carried out a factor analysis on motivating factors and set up an explanatory model regarding the choice of CL and NCL specialisations. Two maximum likelihood factors were extracted from the motivational questions: "lifestyle and income" and "professional interest and consciousness". The explanatory model on specialisation choice shows that the "professional interest and consciousness" factor increases the likelihood of choosing NCL specialisations. In contrast the "lifestyle and income" factor has no significant impact on the choice of CL/NCL specialisations in the model. Our results confirm the important role of professional interest in the choice of medical specializations in Hungary. On the other hand, it seems surprising that we found no significant difference in the "lifestyle and income" related motivation among those medical residents, who opted for CL as opposed to those, who opted for NCL specialisations. This does not necessarily mean that lifestyle is not an important motivating factor, but that it is equally important for both groups of medical residents.

Impact of positive and negative lesion site remodeling on clinical outcomes: insights from PROSPECT.

PubMed

Inaba, Shinji; Mintz, Gary S; Farhat, Naim Z; Fajadet, Jean; Dudek, Dariusz; Marzocchi, Antonio; Templin, Barry; Weisz, Giora; Xu, Ke; de Bruyne, Bernard; Serruys, Patrick W; Stone, Gregg W; Maehara, Akiko

2014-01-01

This study investigated coronary artery remodeling patterns associated with clinical outcomes. In the prospective, multicenter PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree: An Imaging Study in Patients With Unstable Atherosclerotic Lesions) study, reported predictors of nonculprit lesion (NCL) major adverse cardiac events (MACE) were an intravascular ultrasound (IVUS) minimal lumen area (MLA) ≤4 mm(2), a plaque burden ≥70%, and a IVUS-virtual histology (VH) thin-cap fibroatheroma (TCFA), but not lesion site remodeling. Overall, 697 consecutive patients with an acute coronary syndrome were enrolled and underwent 3-vessel gray-scale and IVUS-VH; 3,223 NCLs were identified by IVUS. The remodeling index (RI) was calculated as the external elastic membrane area at the MLA site divided by the average of the proximal and distal reference external elastic membrane areas. First, one third of the patients were randomly selected to determine RI cutoffs related to NCL MACE (development cohort). Receiver-operating characteristic analysis showed that there were 2 separate cut points that predicted NCL MACE: RI = 0.8789 and RI = 1.0046 (area under the curve = 0.663). These cut points were used to define negative remodeling as an RI <0.88, intermediate remodeling as an RI of 0.88 to 1.00, and positive remodeling as an RI >1.00. Second, we used the remaining two-thirds of patients to validate these cut points with respect to lesion morphology and clinical outcomes (validation cohort). Kaplan-Meier curve analysis in the validation cohort showed that NCL MACE occurred more frequent (and equally) in negative and positive remodeling lesions compared with intermediate remodeling lesions. In this cohort, negative remodeling lesions had the smallest MLA, positive remodeling lesions had the largest plaque burden, and VH TCFA, especially VH TCFA with multiple necrotic cores, was most common in negatively remodeling lesions. The present study showed the novel concept that positive and negative lesion site remodeling was associated with unanticipated NCL MACE in the PROSPECT study. ( An Imaging Study in Patients With Unstable Atherosclerotic Lesions [PROSPECT]; NCT00180466). Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Cortical inter-hemispheric circuits for multimodal vocal learning in songbirds.

PubMed

Paterson, Amy K; Bottjer, Sarah W

2017-10-15

Vocal learning in songbirds and humans is strongly influenced by social interactions based on sensory inputs from several modalities. Songbird vocal learning is mediated by cortico-basal ganglia circuits that include the SHELL region of lateral magnocellular nucleus of the anterior nidopallium (LMAN), but little is known concerning neural pathways that could integrate multimodal sensory information with SHELL circuitry. In addition, cortical pathways that mediate the precise coordination between hemispheres required for song production have been little studied. In order to identify candidate mechanisms for multimodal sensory integration and bilateral coordination for vocal learning in zebra finches, we investigated the anatomical organization of two regions that receive input from SHELL: the dorsal caudolateral nidopallium (dNCL SHELL ) and a region within the ventral arcopallium (Av). Anterograde and retrograde tracing experiments revealed a topographically organized inter-hemispheric circuit: SHELL and dNCL SHELL , as well as adjacent nidopallial areas, send axonal projections to ipsilateral Av; Av in turn projects to contralateral SHELL, dNCL SHELL , and regions of nidopallium adjacent to each. Av on each side also projects directly to contralateral Av. dNCL SHELL and Av each integrate inputs from ipsilateral SHELL with inputs from sensory regions in surrounding nidopallium, suggesting that they function to integrate multimodal sensory information with song-related responses within LMAN-SHELL during vocal learning. Av projections share this integrated information from the ipsilateral hemisphere with contralateral sensory and song-learning regions. Our results suggest that the inter-hemispheric pathway through Av may function to integrate multimodal sensory feedback with vocal-learning circuitry and coordinate bilateral vocal behavior. © 2017 Wiley Periodicals, Inc.

The effect of previous soft contact lens wear on corneal refractive surgery outcomes.

PubMed

Lloyd-McKernan, Aoife; Simo Mannion, Luisa; O'Dwyer, Veronica

2017-10-01

To examine the influence of previous soft contact lens (SCL) wear on corneal refractive surgery (CRS) outcomes when SCL wear is ceased for two weeks versus twenty-four hours, and also when compared to no wear, prior to CRS. A retrospective examination of CRS patient records was carried out for two groups of patients- who ceased SCL wear for two weeks (n=45) and for twenty-four hours (n=49) prior to CRS and compared to a non-contact lens (NCL) control group (n=45 and n=49, respectively). CRS outcomes (efficacy, predictability, visual acuity and refractive error) were compared pre-operatively and one and six months post-operatively. One month post-operative results found unaided distance visual acuity (UDVA) was significantly better for LASEK/PRK patients who had ceased SCL wear for two weeks prior to CRS (-0.05±0.09), compared with the NCL group (0.02±0.09; p=0.04). Furthermore, six month post-operative results found UDVA was significantly better for both LASIK and LASEK/PRK patients who had ceased SCL wear for two weeks prior to CRS, and for LASEK/PRK patients who had ceased SCL wear for twenty-four hours prior to CRS compared with the NCL group. Given the current setup and methods followed, it was concluded that previous SCL wear had no negative impact on visual outcomes following CRS compared with a NCL control group, regardless of previous SCL cessation time prior to CRS. Copyright © 2017 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

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

Andermann, F.; Andermann, E.; Carpenter, S.

Most forms of neuronal ceroid lipofuscinosis (NCL) are autosomal recessive, and three genes have already been mapped: the infantile form (CLN 1); the juvenile form (CLN 3); and the early juvenile variant (CLN 5) on chromosomes 1, 16 and 13, respectively. Kufs` disease or adolescent-adult onset NCL is usually inherited as an autosomal recessive trait, and presents as three distinct clinical syndromes: progressive myoclonus epilepsy (PME) with onset in the early teens or around age 30; and onset of dementia with motor disability in the 30s. We have studied three families originating from different parts of the USA manifesting dominantlymore » inherited Kufs` disease. Granular osmophilic deposits (GROD) were found in brain, but storage in skin was not an obligatory feature. Six dominantly inherited PME families have been ascertained from three different regions of Spain. No storage was found in skin or muscle in any of these families. The mean age of onset in the American families is earlier, the clinical manifestations more severe, and the progression much more rapid that in the Spanish families. These findings would suggest the possibility of genetic heterogeneity involving two or more loci, or different mutations at the same gene locus. Genetic linkage studies have been carried out in a six-generation New Jersey family in an attempt to characterize the gene(s) responsible for this disorder. The infantile NCL locus on chromosome 1p (CLN1) and the juvenile NCL locus on chromosome 16p (CLN 3) have been excluded in this family. Further clinical, pathological and molecular genetic studies should lead to the clarification of the diagnostic approaches in this disorder.« less

Pesticide mobility and leachate toxicity in two abandoned mine soils. Effect of organic amendments.

PubMed

Rodríguez-Liébana, José Antonio; Mingorance, M Dolores; Peña, Aránzazu

2014-11-01

Abandoned mine areas, used in the past for the extraction of minerals, constitute a degraded landscape which needs to be reintegrated to productive or leisure activities. However these soils, mainly composed by silt or sand and with low organic matter content, are vulnerable to organic and inorganic pollutants posing a risk to the surrounding ecosystems and groundwater. Soils from two mining areas from Andalusia were evaluated: one from Nerva (NCL) in the Iberian Pyrite Belt (SW Andalusia) and another one from the iron Alquife mine (ALQ) (SE Andalusia). To improve soil properties and fertility two amendments, stabilised sewage sludge (SSL) and composted sewage sludge (CSL), were selected. The effect of amendment addition on the mobility of two model pesticides, thiacloprid and fenarimol, was assessed using soil columns under non-equilibrium conditions. Fenarimol, more hydrophobic than thiacloprid, only leached from native ALQ, a soil with lower organic carbon (OC) content than NCL (0.21 and 1.4%, respectively). Addition of amendments affected differently pesticide mobility: thiacloprid in the leachates was reduced by 14% in NCL-SSL and by 4% in ALQ-CSL. Soil OC and dissolved OC were the parameters which explained pesticide residues in soil. Chemical analysis revealed that leachates from the different soil columns did not contain toxic element levels, except As in NCL soil. Finally ecotoxicological data showed moderate toxicity in the initial leachates, with an increase coinciding with pesticide maximum concentration. The addition of SSL slightly reduced the toxicity towards Vibrio fischeri, likely due to enhanced retention of pesticides by amended soils. Copyright © 2014 Elsevier B.V. All rights reserved.

Combined crystal chemistry and DFT studies of ThNCl and Th2N2X (X: chalcogen) behaving as pseudo-binaries

NASA Astrophysics Data System (ADS)

Matar, Samir F.; Kfoury, Charbel N.

2018-02-01

Common features and peculiar differentiations characterize binary and ternary thorium nitride Th3N4, thorium nitride chloride ThNCl and the family of thorium nitride chalcogenides Th2N2X (X = O, S, Se, Te) investigated in the framework of the quantum density functional theory DFT. Particularly the dominant effect of the Th-N covalent bond stronger than ionic Th-Cl/Th-X ones as identified from analyses of bonding from overlap integral, electron localization function mapping, electronic density of states and charge transfer, is found at the origin of the layered-like structural arrangements in Th-N monolayers within ThNCl (Cl / [ThN]/ Cl) and Th-N double layers in Th2N2X (X / [Th2N2] / X) with the result of pseudo binary compounds: [ThN]+Cl- and [Th2N2] 2+X2-. All compounds are found semi-conducting with ∼2 eV band gap. It is claimed that such insights into Solid State Chemistry can help rationalizing complex compounds more comprehensively (two examples given).

High-pressure study of layered nitride superconductors

NASA Astrophysics Data System (ADS)

Taguchi, Y.; Hisakabe, M.; Ohishi, Y.; Yamanaka, S.; Iwasa, Y.

2004-09-01

Pressure dependence of critical temperature, lattice constant, and phonon frequency has been investigated for layered nitride superconductors, ZrNCl0.7 and Li0.5(THF)yHfNCl . The analysis of the data in terms of MacMillan’s theory indicated that the relevant phonon frequencies are low ( ≈50 and 100cm-1 , respectively), and that the electron-phonon coupling constant λ is larger than 3 in both compounds in sharp contrast with previous experimental and theoretical results. This result may suggest a possibility that other bosonic excitation than phonon additionally contributes to the pairing interaction in these materials.

High pressure study on layered nitride superconductors

NASA Astrophysics Data System (ADS)

Taguchi, Y.; Hisakabe, M.; Ohishi, Y.; Yamanaka, S.; Iwasa, Y.

2004-03-01

Pressure dependence of critical temperature, lattice constant, and phonon frequency has been investigated for layered nitride superconductors, Li_0.5(THF)_yHfNCl and ZrNCl_0.7. The data have been analyzed in terms of MacMillan's theory, and electron-phonon coupling constant λ (=1.3), Coulomb pseudopotential μ^* (=0.31), and relevant phonon frequency (=630 cm-1) have been extracted. The obtained value of λ exceeds 1 in contrast with previous experimental and theoretical results. The present result indicates that, if the superconductivity is within a MacMillan scheme, it is mediated by high frequency phonons in a strong coupling regime.

Maximum-Likelihood Parameter Estimation of a Generalized Gumbel Distribution

DTIC Science & Technology

1989-03-24

Calculate the roots of g(.) and ht .) IERR = 0 CALL R0UTG( XROOT ,YROUT,IEHRJ IF (LERR.NE.0) GOTO 900 Calculate the value of b TEMP1 = OLOG( YROOT) - PSI(YRGOT...TEMP2 = XBAR - XROOT OVAL = TEMP2 / TEMP1 RLAM = XROOT - DSHIF1 ELSE C Scale 8VAL to match HOOTH routine IF (XC(NCL).GT.70.D0) THEN ALPHA - XC NCL...ICNT) 10 CONTINUE RETURN END c C *ROOTG( XROOT ,YROOT,IERR) C 31 Aug 88 C *Res. Dir., C E Hall, Jr. SUBROUTINE ROOTG( XRDOT , ROOT ,IERRJ IMPLICIT DOUBLE

CK13 in craniopharyngioma versus related odontogenic neoplasms and human enamel organ.

PubMed

el-Sissy, N A; Rashad, N A

1999-05-01

The monoclonal antibody NCL-CK13 was studied in specimens of craniopharyngioma, ameloblastoma and calcifying odontogenic cyst neoplasms and the mandible and maxillae of normal human fetuses. There was a decrease in NCL-CK13 as the dental lamina developed, with a complete loss in the enamel organ. The neoplastic epithelia of the neoplasms revealed a clear phenotypic and immunohistochemical reactive relationship to the stratified embroyonic mucosa, away from the enamel organ. This suggests that these neoplasms might have their histogenesis from early stage epithelium, the oral part of the dental lamina or its remnants.

The cell line NCl-H441 is a useful in vitro model for transport studies of human distal lung epithelial barrier.

PubMed

Salomon, Johanna J; Muchitsch, Viktoria E; Gausterer, Julia C; Schwagerus, Elena; Huwer, Hanno; Daum, Nicole; Lehr, Claus-Michael; Ehrhardt, Carsten

2014-03-03

The lack of a well characterized, continuously growing in vitro model of human distal lung epithelial phenotype constitutes a serious limitation in the area of inhalation biopharmaceutics, particularly in the context of transepithelial transport studies. Here, we investigated if a human lung adenocarcinoma cell line, NCl-H441, has potential to serve as an in vitro model of human distal lung epithelium. The development of barrier properties was studied by immunocytochemistry (ICC) against the junction proteins zonula occludens protein 1 (ZO-1) and E-cadherin and measurement of transepithelial electrical resistance (TEER). Moreover, transport studies with the paracellular marker compounds fluorescein sodium and fluorescein isothiocyanate (FITC)-labeled dextrans of molecular weights ranging from 4 to 70 kDa were carried out. The expression of P-glycoprotein (P-gp; ABCB1) and organic cation transporters (OCT/Ns; SLC22A1-A5) was investigated by ICC and immunoblot. P-gp function was assessed by monolayer release and bidirectional transport studies using rhodamine 123 (Rh123) and the inhibitors verapamil and LY335979. Uptake of 4-(4-(dimethylamino)styryl)-N-methylpyridinium iodide (ASP(+)) was measured, in order to assess organic cation transporter function in vitro. Furthermore, the inhibitory potential of several organic cations on ASP(+) uptake was studied. NCl-H441 cells, when grown under liquid-covered conditions, formed confluent, electrically tight monolayers with peak TEER values of approximately 1000 Ω·cm(2), after 8-12 days in culture. These monolayers were able to differentiate paracellularly transported substrates according to their molecular weight. Presence of P-gp, OCT1, OCT2, OCT3, OCTN1, and OCTN2 was confirmed by Western blot and ICC and was similar to data from freshly isolated human alveolar epithelial cells in primary culture. Rh123 release from NCI-H441 monolayers was time-dependent and showed low, albeit significant attenuation by both inhibitors. In transport studies, Rh123 exhibited net secretion, which again was inhibitable by bona fide P-gp modulators. The uptake of ASP(+) was time- and temperature-dependent with Km = 881.2 ± 195.3 μM and Vmax = 2.07 ± 0.26 nmol/min/mg protein. TEA, amantadine, quinidine, and verapamil significantly inhibited ASP(+) uptake into NCl-H441 cells, whereas the effect of d- and l-carnitine and ergothioneine, two OCTN substrates, was less pronounced. NCl-H441 cells are the first cell line of human distal lung epithelial origin with the ability to form monolayers with appreciable barrier properties. Moreover, drug transporter expression and activity in NCl-H441 cells was consistent with what has been reported for human alveolar epithelial cells in primary culture.

Sagittal plane analysis of the spine and pelvis in degenerative lumbar scoliosis.

PubMed

Han, Fei; Weishi, Li; Zhuoran, Sun; Qingwei, Ma; Zhongqiang, Chen

2017-01-01

Previous studies have reported the normative values of pelvic sagittal parameters, but no study has analyzed the sagittal spino-pelvic alignment in degenerative lumbar scoliosis (DLS) and its role in the pathogenesis. Retrospective analysis was applied to 104 patients with DLS, together with 100 cases of asymptomatic young adults as a control group and another control group consisting of 145 cases with cervical spondylosis. The coronal and sagittal parameters were measured on the anteroposterior and lateral radiograph of the whole spine in the DLS group as well as in the two control groups. Statistical analysis showed that the DLS group had a higher pelvic incidence (PI) value (50.5° ± 10.2°), than the normal control group (with PI 47.2° ± 8.8°) and the cervical spondylosis group (46.9° ± 9.1°). In DLS group, there were 38 cases (36.5%) complicated with degenerative lumbar spondylolisthesis, who had higher PI values than patients without it. Besides, the lumbar lordosis (LL) and sacral slope (SS) of DLS group were lower; the scoliosis Cobb's angle was correlated with pelvic tilt (PT); thoracic kyphosis was correlated with LL, SS, and PT; and LL was correlated with other sagittal parameters. Patients with DLS may have a higher PI, which may impact the pathogenesis of DLS. A high PI value is probably associated with the high prevalence of degenerative lumbar spondylolisthesis among DLS patients. In DLS patients, the lumbar spine maintains the ability of regulating the sagittal balance, and the regulation depends more on thoracic curve.

Repeated whisker stimulation evokes invariant neuronal responses in the dorsolateral striatum of anesthetized rats: a potential correlate of sensorimotor habits

PubMed Central

Mowery, Todd M.; Harrold, Jon B.

2011-01-01

The dorsolateral striatum (DLS) receives extensive projections from primary somatosensory cortex (SI), but very few studies have used somesthetic stimulation to characterize the sensory coding properties of DLS neurons. In this study, we used computer-controlled whisker deflections to characterize the extracellular responses of DLS neurons in rats lightly anesthetized with isoflurane. When multiple whiskers were synchronously deflected by rapid back-and-forth movements, whisker-sensitive neurons in the DLS responded to both directions of movement. The latency and magnitude of these neuronal responses displayed very little variation with changes in the rate (2, 5, or 8 Hz) of whisker stimulation. Simultaneous recordings in SI barrel cortex and the DLS revealed important distinctions in the neuronal responses of these serially connected brain regions. In contrast to DLS neurons, SI neurons were activated by the initial deflection of the whiskers but did not respond when the whiskers moved back to their original position. As the rate of whisker stimulation increased, SI responsiveness declined, and the latencies of the responses increased. In fact, when whiskers were deflected at 5 or 8 Hz, many neurons in the DLS responded before the SI neurons. These results and earlier anatomic findings suggest that a component of the sensory-induced response in the DLS is mediated by inputs from the thalamus. Furthermore, the lack of sensory adaptation in the DLS may represent a critical part of the neural mechanism by which the DLS encodes stimulus-response associations that trigger motor habits and other stimulus-evoked behaviors that are not contingent on rewarded outcomes. PMID:21389309

Repeated whisker stimulation evokes invariant neuronal responses in the dorsolateral striatum of anesthetized rats: a potential correlate of sensorimotor habits.

PubMed

Mowery, Todd M; Harrold, Jon B; Alloway, Kevin D

2011-05-01

The dorsolateral striatum (DLS) receives extensive projections from primary somatosensory cortex (SI), but very few studies have used somesthetic stimulation to characterize the sensory coding properties of DLS neurons. In this study, we used computer-controlled whisker deflections to characterize the extracellular responses of DLS neurons in rats lightly anesthetized with isoflurane. When multiple whiskers were synchronously deflected by rapid back-and-forth movements, whisker-sensitive neurons in the DLS responded to both directions of movement. The latency and magnitude of these neuronal responses displayed very little variation with changes in the rate (2, 5, or 8 Hz) of whisker stimulation. Simultaneous recordings in SI barrel cortex and the DLS revealed important distinctions in the neuronal responses of these serially connected brain regions. In contrast to DLS neurons, SI neurons were activated by the initial deflection of the whiskers but did not respond when the whiskers moved back to their original position. As the rate of whisker stimulation increased, SI responsiveness declined, and the latencies of the responses increased. In fact, when whiskers were deflected at 5 or 8 Hz, many neurons in the DLS responded before the SI neurons. These results and earlier anatomic findings suggest that a component of the sensory-induced response in the DLS is mediated by inputs from the thalamus. Furthermore, the lack of sensory adaptation in the DLS may represent a critical part of the neural mechanism by which the DLS encodes stimulus-response associations that trigger motor habits and other stimulus-evoked behaviors that are not contingent on rewarded outcomes.

Dorsolateral Striatum Engagement Interferes with Early Discrimination Learning.

PubMed

Bergstrom, Hadley C; Lipkin, Anna M; Lieberman, Abby G; Pinard, Courtney R; Gunduz-Cinar, Ozge; Brockway, Emma T; Taylor, William W; Nonaka, Mio; Bukalo, Olena; Wills, Tiffany A; Rubio, F Javier; Li, Xuan; Pickens, Charles L; Winder, Danny G; Holmes, Andrew

2018-05-22

In current models, learning the relationship between environmental stimuli and the outcomes of actions involves both stimulus-driven and goal-directed systems, mediated in part by the DLS and DMS, respectively. However, though these models emphasize the importance of the DLS in governing actions after extensive experience has accumulated, there is growing evidence of DLS engagement from the onset of training. Here, we used in vivo photosilencing to reveal that DLS recruitment interferes with early touchscreen discrimination learning. We also show that the direct output pathway of the DLS is preferentially recruited and causally involved in early learning and find that silencing the normal contribution of the DLS produces plasticity-related alterations in a PL-DMS circuit. These data provide further evidence suggesting that the DLS is recruited in the construction of stimulus-elicited actions that ultimately automate behavior and liberate cognitive resources for other demands, but with a cost to performance at the outset of learning. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Streptomyces lonarensis sp. nov., isolated from Lonar Lake, a meteorite salt water lake in India.

PubMed

Sharma, Trupti K; Mawlankar, Rahul; Sonalkar, Vidya V; Shinde, Vidhya K; Zhan, Jing; Li, Wen-Jun; Rele, Meenakshi V; Dastager, Syed G; Kumar, Lalitha Sunil

2016-02-01

A novel alkaliphilic actinomycete, strain NCL716(T), was isolated from a soil sample collected from the vicinity of Lonar Lake, an alkaline salt water meteorite lake in Buldhana district of Maharashtra State in India. The strain was characterised using a polyphasic taxonomic approach which confirmed that it belongs to the genus Streptomyces. Growth was observed over a pH range of 7-11 at 28 °C. The cell wall was found to contain LL-diaminopimelic acid and traces of meso-diaminopimelic acid. The major fatty acid components were identified as iso-C16:0 (46.8 %), C17:1 (12.4 %), anteiso-C15:0 (5.1 %) and anteiso-C17:1 (4.8 %). The major polar lipids were identified as diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol and phosphatidylinositol. The major menaquinones were determined to be MK-9 (H6) (70.3 %), MK-9 (H4) (15.5 %) and MK-9 (H8) (7.2 %). The G+C content of the DNA of the type strain was determined to be 71.4 mol %. The 16S rRNA gene sequence has been deposited in GenBank with accession number FJ919811. Although the 16S rRNA gene sequence analysis revealed that strain NCL716(T) shares >99 % similarity with that of Streptomyces bohaiensis strain 11A07(T), DNA-DNA hybridization revealed only 33.2 ± 3.0 % relatedness between them. Moreover, these two strains can be readily distinguished by some distinct phenotypic characteristics. Hence, on the basis of phenotypic and genetic analyses, it is proposed that strain NCL716(T) represents a novel species of the genus Streptomyces, for which the name Streptomyces lonarensis sp. nov., is proposed. The type strain is NCL 716(T) (=DSM 42084(T) = MTCC 11708(T) = KCTC 39684(T)).

Dynamic light scattering in ophthalmology: results of in vitro and in vivo experiments.

PubMed

Fankhauser, Franz

2006-01-01

To calibrate new dynamic light scattering (DLS) devices in defined solutions and post mortem porcine and human eyes. To examine all segments of the eye and to become familiar with the usage of the technique in living subjects. METHODS, DESIGN: Three new DLS devices for the usage in patients were developed. Mono-disperse solutions, poly-disperse solutions, gels, post mortem porcine and human eyes as well as healthy volunteers were studied. The detected signals were inverted into autocorrelation functions. We constructed three DLS devices appropriate for in vitro as well as in vivo examinations. In mono disperse solution precise disintegration rates could be calculated. In poly-disperse solutions, in gel and in the vitreous the results did not correlate with movements of individual particles but we could calculate characteristics of the complete scattering system. In vivo measurements demonstrated that DLS can be used in all human eye segments. DLS is a unique technique. With DLS the molecular composition of eye segments can be studied in living subjects. This can be used to understand the molecular basis of severe eye diseases. The presented data demonstrate that DLS delivers reproducible data from all eye segments. It is possible to study the molecular structures of eye segments in living subjects. The developed devices were proved successfully in vitro as well as in vivo. Limitations are the low specificity of DLS and its sensitivity to background noise. Now clinical studies are necessary to demonstrate potential diagnostic benefits of DLS in specific eye diseases.

Differential implication of dorsolateral and dorsomedial srtiatum in encoding and recovery processes of latent inhibition.

PubMed

Díaz, Estrella; Vargas, Juan Pedro; Quintero, Esperanza; Gonzalo de la Casa, Luis; O'Donnell, Patricio; Lopez, Juan Carlos

2014-05-01

The dorsal striatum has been ascribed to different behavioral roles. While the lateral area (dls) is implicated in habitual actions, its medial part (dms) is linked to goal expectancy. According to this model, dls function includes representation of stimulus-response associations, but not of goals. Dls function has been typically analyzed with regard to movement, and there is no data indicating whether this region could processes specific stimulus-outcome associations. To test this possibility, we analyzed the effects of dls and dms inactivation on the retrieval phase, and dms lesion on the acquisition phase of a latent inhibition procedure using two conditions, long and short presentations of the future conditioned stimulus. Contrary to current theories of basal ganglia function, we report evidence in favor of the dls involvement in cognitive processes of learning and retrieval. Moreover, we provide data about the sequential relationship between dms and dls, in which the dms could be involved, but it would not be critical, in new learning and the dls could be subsequently involved in consolidating cognitive routines. Copyright © 2014 Elsevier Inc. All rights reserved.

The effects of nidopallium caudolaterale inactivation on serial-order behaviour in pigeons (Columba livia).

PubMed

Johnston, Melissa Jane; Clarkson, Andrew N; Gowing, Emma K; Scarf, Damian; Colombo, Mike

2018-06-06

Serial-order behaviour is the ability to complete a sequence of responses in a predetermined order to achieve a reward. In birds, serial-order behaviour is thought to be impaired by damage to the nidopallium caudolaterale (NCL). In the current study, we examined the role of the NCL in serial-order behaviour by training pigeons on a 4-item serial-order task and a go/no-go discrimination task. Following training, pigeons were received infusions of 1μl of either tetrodotoxin (TTX) or saline. Saline infusions had no impact on serial-order behaviour whereas TTX infusions resulted in a significant decrease in performance. The serial-order impairments, however, were not the results of errors of any specific error at any specific list item. With respect to the go/no-go discrimination task, saline infusions also had no impact on performance whereas TTX infusions impaired pigeons' discrimination abilities. Given the impairments on the go/no-go discrimination task, which does not require processing of serial-order information, we tentatively conclude that damage to the NCL does not impair serial-order behaviour per se, but rather results in a more generalised impairment that may impact performance across a range of tasks.

Lysosomal storage disease upon disruption of the neuronal chloride transport protein ClC-6

PubMed Central

Poët, Mallorie; Kornak, Uwe; Schweizer, Michaela; Zdebik, Anselm A.; Scheel, Olaf; Hoelter, Sabine; Wurst, Wolfgang; Schmitt, Anja; Fuhrmann, Jens C.; Planells-Cases, Rosa; Mole, Sara E.; Hübner, Christian A.; Jentsch, Thomas J.

2006-01-01

Mammalian CLC proteins function as Cl− channels or as electrogenic Cl−/H+ exchangers and are present in the plasma membrane and intracellular vesicles. We now show that the ClC-6 protein is almost exclusively expressed in neurons of the central and peripheral nervous systems, with a particularly high expression in dorsal root ganglia. ClC-6 colocalized with markers for late endosomes in neuronal cell bodies. The disruption of ClC-6 in mice reduced their pain sensitivity and caused moderate behavioral abnormalities. Neuronal tissues showed autofluorescence at initial axon segments. At these sites, electron microscopy revealed electron-dense storage material that caused a pathological enlargement of proximal axons. These deposits were positive for several lysosomal proteins and other marker proteins typical for neuronal ceroid lipofuscinosis (NCL), a lysosomal storage disease. However, the lysosomal pH of Clcn6−/− neurons appeared normal. CLCN6 is a candidate gene for mild forms of human NCL. Analysis of 75 NCL patients identified ClC-6 amino acid exchanges in two patients but failed to prove a causative role of CLCN6 in that disease. PMID:16950870

Distinct patterns of serum immunoreactivity as evidence for multiple brain-directed autoantibodies in juvenile neuronal ceroid lipofuscinosis.

PubMed

Lim, M J; Beake, J; Bible, E; Curran, T M; Ramirez-Montealegre, D; Pearce, D A; Cooper, J D

2006-10-01

Autoantibodies to glutamic acid decarboxylase (GAD65) have been reported in sera from the Cln3(-/-) mouse model of juvenile neuronal ceroid lipofuscinosis (JNCL), and in individuals with this fatal paediatric neurodegenerative disorder. To investigate the existence of other circulating autoreactive antibodies, we used sera from patients with JNCL and other forms of neuronal ceroid lipofuscinosis (NCL) as primary antisera to stain rat and human central nervous system sections. JNCL sera displayed characteristic patterns of IgG, but not IgA, IgE or IgM immunoreactivity that was distinct from the other forms of NCL. Immunoreactivity of JNCL sera was not confined to GAD65-positive (GABAergic) neurons, but also stained multiple other cell populations. Preadsorption of JNCL sera with recombinant GAD65 reduced the intensity of the immunoreactivity, but did not significantly change its staining pattern. Moreover, sera from Stiff Person Syndrome and Type I Diabetes, disorders in which GAD65 autoantibodies are present, stained with profiles that were markedly different from JNCL sera. Collectively, these studies provide evidence of the presence of autoreactive antibodies within multiple forms of NCL, and are not exclusively directed towards GAD65.

Modeling solubility and acid-base properties of some amino acids in aqueous NaCl and (CH3)4NCl aqueous solutions at different ionic strengths and temperatures.

PubMed

Bretti, Clemente; Giuffrè, Ottavia; Lando, Gabriele; Sammartano, Silvio

2016-01-01

New potentiometric experiments have been performed in NaCl and in (CH3)4NCl media, to determine the protonation constants, the protonation enthalpy changes and the solubility of six natural α-amino acids, namely Glycine (Gly), Alanine (Ala), Valine (Val), Leucine (Leu), Serine (Ser) and Phenylalanine (Phe). The aim of the work is the rationalization of the protonation thermodynamics (log [Formula: see text], solubility and [Formula: see text]) in NaCl, determining recommended, tentative or provisional values in selected experimental conditions and to report, for the first time, data in a weak interacting medium, as (CH3)4NCl. Literature data analysis was performed selecting the most reliable values, analyzed together with new data here reported. Significant trends and similarities were observed in the behavior of the six amino acids, and in some cases it was possible to determine common parameters for the ionic strength and temperature dependence. In general, the first protonation step, relative to the amino group, is significantly exothermic (average value is [Formula: see text] = -44.5 ± 0.4 kJ mol(-1) at infinite dilution and T = 298.15 K), and the second, relative to the carboxylate group, is fairly close to zero ([Formula: see text] = -2.5 ± 1.6, same conditions). In both cases, the main contribution to the proton binding reaction is mainly entropic in nature. For phenylalanine and leucine, solubility measurements at different concentrations of supporting electrolyte allowed to determine total and specific solubility values, then used to obtain the Setschenow and the activity coefficients of all the species involved in the protonation equilibria. The values of the first protonation constant in (CH3)4NCl are lower than the corresponding values in NaCl, due to the weak interaction between the deprotonated amino group and (CH3)4N(+). In this light, differences between the protonation functions in NaCl and (CH3)4NCl were used for the quantification of the stability of the weak [(CH3)4N(+)-L(-)] complexes that resulted log K = -0.38 ± 0.07 as an average value for the six amino acids.

STM/STS Observation on Layered Nitride Superconductor α-(DDA)xTiNCl

NASA Astrophysics Data System (ADS)

Sugimoto, Akira; Ukita, Ryuichi; Ekino, Toshikazu; Zheng, Zhanfeng; Yamanaka, Shoji

2012-12-01

Scanning tunneling microscopy/spectroscopy (STM/STS) measurements on α-(DDA)xTiNCl (DDA=H2N-(CH2)10-NH2, Tc=16 K) have been carried out. The STM topography exhibits simple rectangular shaped atomic lattice with the periods of |a|=0.38 nm and |b| =0.33 nm. The averaged dI / dV spectrum shows the gap value of Δ ~ 9 meV, giving an unusual large gap ratio 2Δ/kBTc ≃ 13. The STS results show the bar-shaped domain structures along the b-axis direction in the bias range of V = +5 ~ +15 mV, demonstrating the possible existence of intercalated molecules.

Enhancement of pairing interaction and magnetic fluctuations toward a band insulator in an electron-doped Li(x)ZrNCl Superconductor.

PubMed

Kasahara, Yuichi; Kishiume, Tsukasa; Takano, Takumi; Kobayashi, Katsuki; Matsuoka, Eiichi; Onodera, Hideya; Kuroki, Kazuhiko; Taguchi, Yasujiro; Iwasa, Yoshihiro

2009-08-14

The doping dependence of specific heat and magnetic susceptibility has been investigated for Li(x)ZrNCl superconductors derived from a band insulator. As the carrier concentration is decreased, the anisotropy of superconducting gap changes from highly anisotropic to almost isotropic. It was also found that, upon reducing carrier density, the superconducting coupling strength and the magnetic susceptibility are concomitantly enhanced in parallel with T(c), while the density of states at the Fermi level is kept almost constant. Theoretical calculations taking into account the on-site Coulomb interaction reproduced the experimental results, suggesting a possible pairing mediated by magnetic fluctuations, even in the doped band insulators.

Neurons in the pigeon caudolateral nidopallium differentiate Pavlovian conditioned stimuli but not their associated reward value in a sign-tracking paradigm

PubMed Central

Kasties, Nils; Starosta, Sarah; Güntürkün, Onur; Stüttgen, Maik C.

2016-01-01

Animals exploit visual information to identify objects, form stimulus-reward associations, and prepare appropriate behavioral responses. The nidopallium caudolaterale (NCL), an associative region of the avian endbrain, contains neurons exhibiting prominent response modulation during presentation of reward-predicting visual stimuli, but it is unclear whether neural activity represents valuation signals, stimulus properties, or sensorimotor contingencies. To test the hypothesis that NCL neurons represent stimulus value, we subjected pigeons to a Pavlovian sign-tracking paradigm in which visual cues predicted rewards differing in magnitude (large vs. small) and delay to presentation (short vs. long). Subjects’ strength of conditioned responding to visual cues reliably differentiated between predicted reward types and thus indexed valuation. The majority of NCL neurons discriminated between visual cues, with discriminability peaking shortly after stimulus onset and being maintained at lower levels throughout the stimulus presentation period. However, while some cells’ firing rates correlated with reward value, such neurons were not more frequent than expected by chance. Instead, neurons formed discernible clusters which differed in their preferred visual cue. We propose that this activity pattern constitutes a prerequisite for using visual information in more complex situations e.g. requiring value-based choices. PMID:27762287

The impact of multichannel microelectrode recording (MER) in deep brain stimulation of the basal ganglia.

PubMed

Kinfe, Thomas M; Vesper, Jan

2013-01-01

Deep brain stimulation (DBS) of the basal ganglia (Ncl. subthalamicus, Ncl. ventralis intermedius thalami, globus pallidus internus) has become an evidence-based and well-established treatment option in otherwise refractory movement disorders. The Ncl. subthalamicus (STN) is the target of choice in Parkinson's disease.However, a considerable discussion is currently ongoing with regard to the necessity for micro-electrode recording (MER) in DBS surgery.The present review provides an overview on deep brain stimulation and (MER) of the STN in patients with Parkinson's disease. Detailed description is given concerning the multichannel MER systems nowadays available for DBS of the basal ganglia, especially of the STN, as a useful tool for target refinement. Furthermore, an overview is given of the historical aspects, spatial mapping of the STN by MER, and its impact for accuracy and precision in current functional stereotactic neurosurgery.The pros concerning target refinement by MER means on the one hand, and cons including increased bleeding risk, increased operation time, local or general anesthesia, and single versus multichannel microelectrode recording are discussed in detail. Finally, the authors favor the use of MER with intraoperative testing combined with imaging to achieve a more precise electrode placement, aiming to ameliorate clinical outcome in therapy-resistant movement disorders.

Neural stem cells for disease modeling and evaluation of therapeutics for infantile (CLN1/PPT1) and late infantile (CLN2/TPP1) neuronal ceroid lipofuscinoses.

PubMed

Sima, Ni; Li, Rong; Huang, Wei; Xu, Miao; Beers, Jeanette; Zou, Jizhong; Titus, Steven; Ottinger, Elizabeth A; Marugan, Juan J; Xie, Xing; Zheng, Wei

2018-04-10

Infantile and late infantile neuronal ceroid lipofuscinoses (NCLs) are lysosomal storage diseases affecting the central nervous system (CNS). The infantile NCL (INCL) is caused by mutations in the PPT1 gene and late-infantile NCL (LINCL) is due to mutations in the TPP1 gene. Deficiency in PPT1 or TPP1 enzyme function results in lysosomal accumulation of pathological lipofuscin-like material in the patient cells. There is currently no small-molecular drug treatment for NCLs. We have generated induced pluripotent stem cells (iPSC) from three patient dermal fibroblast lines and further differentiated them into neural stem cells (NSCs). Using these new disease models, we evaluated the effect of δ-tocopherol (DT) and hydroxypropyl-β-cyclodextrin (HPBCD) with the enzyme replacement therapy as the control. Treatment with the relevant recombinant enzyme or DT significantly ameliorated the lipid accumulation and lysosomal enlargement in the disease cells. A combination therapy of δ-tocopherol and HPBCD further improved the effect compared to that of either drug used as a single therapy. The results demonstrate that these patient iPSC derived NCL NSCs are valid cell- based disease models with characteristic disease phenotypes that can be used for study of disease pathophysiology and drug development.

Progressive Retinal Degeneration and Accumulation of Autofluorescent Lipopigments in Progranulin Deficient Mice

PubMed Central

Hafler, Brian P.; Klein, Zoe A.; Zhou, Z. Jimmy; Strittmatter, Stephen M.

2014-01-01

Prior investigations have shown that patients with neuronal ceroid lipofuscinosis (NCL) develop neurodegeneration characterized by vision loss, motor dysfunction, seizures, and often early death. Neuropathological analysis of patients with NCL shows accumulation of intracellular autofluorescent storage material, lipopigment, throughout neurons in the central nervous system including in the retina. A recent study of a sibling pair with adult onset NCL and retinal degeneration showed linkage to the region of the progranulin (GRN) locus and a homozygous mutation was demonstrated in GRN. In particular, the sibling pair with a mutation in GRN developed retinal degeneration and optic atrophy. This locus for this form of adult onset neuronal ceroid lipofuscinosis was designated neuronal ceroid lipofuscinosis-11 (CLN11). Based on these clinical observations, we wished to determine whether Grn-null mice develop accumulation of autofluorescent particles and retinal degeneration. Retinas of both wild-type and Progranulin deficient mice were examined by immunostaining and autofluorescence. Accumulation of autofluorescent material was present in Progranulin deficient mice at 12 months. Degeneration of multiple classes of neurons including photoreceptors and retinal ganglion cells was noted in mice at 12 and 18 months. Our data shows that Grn−/− mice develop degenerative pathology similar to features of human CLN11. PMID:25234724

Integration of health services improves multiple healthcare outcomes among HIV-infected people who inject drugs in Ukraine.

PubMed

Bachireddy, Chethan; Soule, Michael C; Izenberg, Jacob M; Dvoryak, Sergey; Dumchev, Konstantin; Altice, Frederick L

2014-01-01

People who inject drugs (PWID) experience poor outcomes and fuel HIV epidemics in middle-income countries in Eastern Europe and Central Asia. We assess integrated/co-located (ICL) healthcare for HIV-infected PWID, which despite international recommendations, is neither widely available nor empirically examined. A 2010 cross-sectional study randomly sampled 296 HIV-infected opioid-dependent PWID from two representative HIV-endemic regions in Ukraine where ICL, non-co-located (NCL) and harm reduction/outreach (HRO) settings are available. ICL settings provide onsite HIV, addiction, and tuberculosis services, NCLs only treat addiction, and HROs provide counseling, needles/syringes, and referrals, but no opioid substitution therapy (OST). The primary outcome was receipt of quality healthcare, measured using a quality healthcare indicator (QHI) composite score representing percentage of eight guidelines-based recommended indicators met for HIV, addiction and tuberculosis treatment. The secondary outcomes were individual QHIs and health-related quality-of-life (HRQoL). On average, ICL-participants had significantly higher QHI composite scores compared to NCL- and HRO-participants (71.9% versus 54.8% versus 37.0%, p<0.001) even after controlling for potential confounders. Compared to NCL-participants, ICL-participants were significantly more likely to receive antiretroviral therapy (49.5% versus 19.2%, p<0.001), especially if CD4 ≤ 200 (93.8% versus 62.5% p<0.05); guideline-recommended OST dosage (57.3% versus 41.4%, p<0.05); and isoniazid preventive therapy (42.3% versus 11.2%, p<0.001). Subjects receiving OST had significantly higher HRQoL than those not receiving it (p<0.001); however, HRQoL did not differ significantly between ICL- and NCL-participants. These findings suggest that OST alone improves quality-of-life, while receiving care in integrated settings collectively and individually improves healthcare quality indicators for PWID. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Integration of Health Services Improves Multiple Healthcare Outcomes Among HIV-infected People Who Inject Drugs in Ukraine

PubMed Central

Bachireddy, Chethan; Soule, Michael C.; Izenberg, Jacob M.; Dvoryak, Sergey; Dumchev, Konstantin; Altice, Frederick L.

2013-01-01

Background People who inject drugs (PWID) experience poor outcomes and fuel HIV epidemics in middle-income countries in Eastern Europe and Central Asia. We assess integrated/co-located (ICL) healthcare for HIV-infected PWID, which despite international recommendations, is neither widely available nor empirically examined. Methods A 2010 cross-sectional study randomly sampled 296 HIV-infected opioid-dependent PWID from two representative HIV-endemic regions in Ukraine where ICL, non-co-located (NCL) and harm reduction/outreach (HRO) settings are available. ICL settings provide onsite HIV, addiction, and tuberculosis services, NCLs only treat addiction, and HROs provide counseling, needles/syringes, and referrals, but no opioid substitution therapy (OST). The primary outcome was receipt of quality healthcare, measured using a quality healthcare indicator (QHI) composite score representing percentage of eight guidelines-based recommended indicators met for HIV, addiction and tuberculosis treatment. The secondary outcomes were individual QHIs and health-related quality-of-life (HRQoL). Results On average, ICL-participants had significantly higher QHI composite scores compared to NCL- and HRO-participants (71.9% versus 54.8% versus 37.0%, p<0.001) even after controlling for potential confounders. Compared to NCL-participants, ICL-participants were significantly more likely to receive antiretroviral therapy (49.5% versus 19.2%, p<0.001), especially if CD4≤200 (93.8% versus 62.5% p<0.05); guideline-recommended OST dosage (57.3% versus 41.4%, p<0.05); and isoniazid preventive therapy (42.3% versus 11.2%, p<0.001). Subjects receiving OST had significantly higher HRQoL than those not receiving it (p<0.001); however, HRQoL did not differ significantly between ICL- and NCL-participants. Conclusions These findings suggest that OST alone improves quality-of-life, while receiving care in integrated settings collectively and individually improves healthcare quality for PWID. PMID:24128379

Partial genetic suppression of a loss-of-function mutant of the neuronal ceroid lipofuscinosis-associated protease TPP1 in Dictyostelium discoideum

PubMed Central

Phillips, Jonathan E.; Gomer, Richard H.

2015-01-01

Neuronal ceroid lipofuscinosis (NCL) is the most common childhood-onset neurodegenerative disease. NCL is inevitably fatal, and there is currently no treatment available. Children with NCL show a progressive decline in movement, vision and mental abilities, and an accumulation of autofluorescent deposits in neurons and other cell types. Late-infantile NCL is caused by mutations in the lysosomal protease tripeptidyl peptidase 1 (TPP1). TPP1 cleaves tripeptides from the N-terminus of proteins in vitro, but little is known about the physiological function of TPP1. TPP1 shows wide conservation in vertebrates but it is not found in Drosophila, Caenorhabditis elegans or Saccharomyces cerevisiae. Here, we characterize ddTpp1, a TPP1 ortholog present in the social amoeba Dictyostelium discoideum. Lysates from cells lacking ddTpp1 show a reduced but not abolished ability to cleave a TPP1 substrate, suggesting that other Dictyostelium enzymes can perform this cleavage. ddTpp1 and human TPP1 localize to the lysosome in Dictyostelium, indicating conserved function and trafficking. Cells that lack ddTpp1 show precocious multicellular development and a reduced ability to form spores during development. When cultured in autophagy-stimulating conditions, cells lacking ddTpp1 rapidly decrease in size and are less viable than wild-type cells, suggesting that one function of ddTpp1 could be to limit autophagy. Cells that lack ddTpp1 exhibit strongly impaired development in the presence of the lysosome-perturbing drug chloroquine, and this phenotype can be suppressed through a secondary mutation in the gene that we name suppressor of tpp1− A (stpA), which encodes a protein with some similarity to mammalian oxysterol-binding proteins (OSBPs). Taken together, these results suggest that targeting specific proteins could be a viable way to suppress the effects of loss of TPP1 function. PMID:25540127

Techniques for Accurate Sizing of Gold Nanoparticles Using Dynamic Light Scattering with Particular Application to Chemical and Biological Sensing Based on Aggregate Formation.

PubMed

Zheng, Tianyu; Bott, Steven; Huo, Qun

2016-08-24

Gold nanoparticles (AuNPs) have found broad applications in chemical and biological sensing, catalysis, biomolecular imaging, in vitro diagnostics, cancer therapy, and many other areas. Dynamic light scattering (DLS) is an analytical tool used routinely for nanoparticle size measurement and analysis. Due to its relatively low cost and ease of operation in comparison to other more sophisticated techniques, DLS is the primary choice of instrumentation for analyzing the size and size distribution of nanoparticle suspensions. However, many DLS users are unfamiliar with the principles behind the DLS measurement and are unware of some of the intrinsic limitations as well as the unique capabilities of this technique. The lack of sufficient understanding of DLS often leads to inappropriate experimental design and misinterpretation of the data. In this study, we performed DLS analyses on a series of citrate-stabilized AuNPs with diameters ranging from 10 to 100 nm. Our study shows that the measured hydrodynamic diameters of the AuNPs can vary significantly with concentration and incident laser power. The scattered light intensity of the AuNPs has a nearly sixth order power law increase with diameter, and the enormous scattered light intensity of AuNPs with diameters around or exceeding 80 nm causes a substantial multiple scattering effect in conventional DLS instruments. The effect leads to significant errors in the reported average hydrodynamic diameter of the AuNPs when the measurements are analyzed in the conventional way, without accounting for the multiple scattering. We present here some useful methods to obtain the accurate hydrodynamic size of the AuNPs using DLS. We also demonstrate and explain an extremely powerful aspect of DLS-its exceptional sensitivity in detecting gold nanoparticle aggregate formation, and the use of this unique capability for chemical and biological sensing applications.

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

Williams, R.; McKay, T.; Mitchison, H.

The neuronal ceroid lipofuscinoses (NCLs) are a group of inherited neurodegenerative disorders characterized by the accumulation of autofluorescent lipopigment in neurons and other cell types. Inheritance is autosomal recessive. Three main childhood subtypes are recognized: Infantile (Haltia-Santavuori disease; MIM 256743), late infantile (Jansky-Bielschowsky disease; MIM 204500), and juvenile (Spielmeyer-Sjoegren-Vogt, or Batten disease; MIM 204200). The gene loci for the juvenile (CLN3) and infantile (CLN1) types have been mapped to human chromosomes 16p and 1p, respectively, by linkage analysis. Linkage analysis of 25 families segregating for late-infantile NCL has excluded these regions as the site of this disease locus (CLN2). Themore » three childhood subtypes of NCL therefore arise from mutations at distinct loci. 17 refs., 2 figs., 3 tabs.« less

Special Education Elementary Teachers' Perceptions of Daily Living Skills Instruction for Students with Autism

ERIC Educational Resources Information Center

Spencer, Jamala

2017-01-01

The question of which strategies for teaching daily living skills (DLS) are most effective for students with autism spectrum disorder (ASD) requires increased attention. Special education elementary teachers may not have the instructional strategies necessary to teach DLS to students with ASD. DLS instruction for students with ASD is important…

Enhancing and impairing extinction of habit memory through modulation of NMDA receptors in the dorsolateral striatum.

PubMed

Goodman, Jarid; Ressler, Reed L; Packard, Mark G

2017-06-03

The present experiments investigated the involvement of N-methyl-d-aspartate (NMDA) receptors of the dorsolateral striatum (DLS) in consolidation of extinction in a habit memory task. Adult male Long-Evans rats were initially trained in a food-reinforced response learning version of a plus-maze task and were subsequently given extinction training in which the food was removed from the maze. In experiment 1, immediately after the first day of extinction training, rats received bilateral intra-DLS injections of the NMDA receptor antagonist 2-amino-5-phosphonopentanoic acid (AP5; 2µg/side) or physiological saline. In experiment 2, immediately following the first day of extinction training, animals were given intra-DLS injections of NMDA receptor partial agonist d-cycloserine (DCS; 10 or 20µg/side) or saline. In both experiments, the number of perseverative trials (a trial in which a rat made the same previously reinforced body-turn response) and latency to reach the previously correct food well were used as measures of extinction behavior. Results indicated that post-training intra-DLS injections of AP5 impaired extinction. In contrast, post-training intra-DLS infusions of DCS (20µg) enhanced extinction. Intra-DLS administration of AP5 or DCS given two hours after extinction training did not influence extinction of response learning, indicating that immediate post-training administration of AP5 and DCS specifically influenced consolidation of the extinction memory. The present results indicate a critical role for DLS NMDA receptors in modulating extinction of habit memory and may be relevant to developing therapeutic approaches to combat the maladaptive habits observed in human psychopathologies in which DLS-dependent memory has been implicated (e.g. drug addiction and relapse and obsessive compulsive disorder). Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

On the generation of double layers from ion- and electron-acoustic instabilities

DOE PAGES

Fu, Xiangrong; Cowee, Misa M.; Gary, Stephen Peter; ...

2016-03-17

A plasma double layer (DL) is a nonlinear electrostatic structure that carries a uni-polar electric field parallel to the background magnetic field due to local charge separation. Past studies showed that DLs observed in space plasmas are mostly associated with the ion acoustic instability. Recent Van Allen Probes observations of parallel electric fields traveling much faster than the ion acoustic speed have motivated a computational study to test the hypothesis that a new type of DLs – electron acoustic DLs – generated from the electron acoustic instability are responsible for these electric fields. Nonlinear particle-in-cell simulations yield negative results, i.e.more » the hypothetical electron acoustic DLs cannot be formed in a way similar to ion acoustic DLs. We find that linear theory analysis and the simulations show that the frequencies of electron acoustic waves are too high for ions to respond and maintain charge separation required by DLs. However, our results do show that local density perturbations in a two-electron-component plasma can result in unipolar-like electric fields that propagate at the electron thermal speed, suggesting another potential explanation for the observations.« less

Contributions of dorsal striatal subregions to spatial alternation behavior.

PubMed

Moussa, Roula; Poucet, Bruno; Amalric, Marianne; Sargolini, Francesca

2011-07-01

Considerable evidence has shown a clear dissociation between the dorsomedial (DMS) and the dorsolateral (DLS) striatum in instrumental conditioning. In particular, DMS activity is necessary to form action-outcome associations, whereas the DLS is required for developing habitual behavior. However, few studies have investigated whether a similar dissociation exists in more complex goal-directed learning processes. The present study examined the role of the two structures in such complex learning by analyzing the effects of excitotoxic DMS and DLS lesions during the acquisition and extinction of spatial alternation behavior, in a continuous alternation T-maze task. We demonstrate that DMS and DLS lesions have opposite effects, the former impairing and the latter improving animal performance during learning and extinction. DMS lesions may impair the acquisition of spatial alternation behavior by disrupting the signal necessary to link a goal with a specific spatial sequence. In contrast, DLS lesions may accelerate goal-driven strategies by minimizing the influence of external stimuli on the response, thus increasing the impact of action-reward contingencies. Taken together, these results suggest that DMS- and DLS-mediated learning strategies develop in parallel and compete for the control of the behavioral response early in learning.

Construction of bioengineered hepatic tissue derived from human umbilical cord mesenchymal stem cells via aggregation culture in porcine decellularized liver scaffolds.

PubMed

Li, Yi; Wu, Qiong; Wang, Yujia; Li, Li; Chen, Fei; Shi, Yujun; Bao, Ji; Bu, Hong

2017-01-01

An individualized, tissue-engineered liver suitable for transplanting into a patient with liver disease would be of great benefit to the patient and the healthcare system. The tissue-engineered liver would possess the functions of the original healthy organ. Two fields of study, (i) using decellularized tissue as cell scaffolding, and (ii) stem cell differentiation into functional cells, are coming together to make this concept feasible. The decellularized liver scaffolds (DLS) can interact with cells to promote cell differentiation and signal transduction and three-dimensional (3D) stem cell aggregations can maintain the phenotypes and improve functions of stem cells after differentiation by undergoing cell-cell contact. Although the effects of DLS and stem cell aggregation culture have been intensively studied, few observations about the interaction between the two have been achieved. We established a method that combines the use of decellularized liver scaffolds and aggregation culture of MSCs (3D-DLS) and explored the effects of the two on hepatic differentiation of human umbilical cord mesenchymal stem cells (hUC-MSCs) in bioengineered hepatic tissue. A higher percentage of albumin-producing cells, higher levels of liver-specific transcripts, higher urea cycle-related transcripts, and lower levels of stem cell-specific transcripts were observed in the 3D-DLS group when compared to that of hUC-MSCs in monolayer culture (2D), aggregation culture (3D), monolayer on DLS culture (2D-DLS). The gene arrays also indicated that 3D-DLS induced the differentiation from the hUC-MSC phenotype to the PHH phenotype. Liver-specific proteins albumin, CK-18, and glycogen storage were highly positive in the 3D-DLS group. Albumin secretion and ammonia conversion to urea were more effective with a higher cell survival rate in the 3D-DLS group for 14 days. This DLS and aggregation combination culture system provides a novel method to improve hepatic differentiation, maintain phenotype of hepatocyte-like cells and sustain survival for 14 days in vitro. This is a promising strategy to use to construct bioengineered hepatic tissue. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Performance comparison of two commercial BGO-based PET/CT scanners using NEMA NU 2-2001.

PubMed

Bolard, Grégory; Prior, John O; Modolo, Luca; Delaloye, Angelika Bischof; Kosinski, Marek; Wastiel, Claude; Malterre, Jérôme; Bulling, Shelley; Bochud, François; Verdun, Francis R

2007-07-01

Combined positron emission tomography and computed tomography (PET/CT) scanners play a major role in medicine for in vivo imaging in an increasing number of diseases in oncology, cardiology, neurology, and psychiatry. With the advent of short-lived radioisotopes other than 18F and newer scanners, there is a need to optimize radioisotope activity and acquisition protocols, as well as to compare scanner performances on an objective basis. The Discovery-LS (D-LS) was among the first clinical PET/CT scanners to be developed and has been extensively characterized with older National Electrical Manufacturer Association (NEMA) NU 2-1994 standards. At the time of publication of the latest version of the standards (NU 2-2001) that have been adapted for whole-body imaging under clinical conditions, more recent models from the same manufacturer, i.e., Discovery-ST (D-ST) and Discovery-STE (D-STE), were commercially available. We report on the full characterization both in the two- and three-dimensional acquisition mode of the D-LS according to latest NEMA NU 2-2001 standards (spatial resolution, sensitivity, count rate performance, accuracy of count losses, and random coincidence correction and image quality), as well as a detailed comparison with the newer D-ST widely used and whose characteristics are already published.

Performance comparison of two commercial BGO-based PET/CT scanners using NEMA NU 2-2001

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

Bolard, Gregory; Prior, John O.; Modolo, Luca

2007-07-15

Combined positron emission tomography and computed tomography (PET/CT) scanners play a major role in medicine for in vivo imaging in an increasing number of diseases in oncology, cardiology, neurology, and psychiatry. With the advent of short-lived radioisotopes other than {sup 18}F and newer scanners, there is a need to optimize radioisotope activity and acquisition protocols, as well as to compare scanner performances on an objective basis. The Discovery-LS (D-LS) was among the first clinical PET/CT scanners to be developed and has been extensively characterized with older National Electrical Manufacturer Association (NEMA) NU 2-1994 standards. At the time of publication ofmore » the latest version of the standards (NU 2-2001) that have been adapted for whole-body imaging under clinical conditions, more recent models from the same manufacturer, i.e., Discovery-ST (D-ST) and Discovery-STE (D-STE), were commercially available. We report on the full characterization both in the two- and three-dimensional acquisition mode of the D-LS according to latest NEMA NU 2-2001 standards (spatial resolution, sensitivity, count rate performance, accuracy of count losses, and random coincidence correction and image quality), as well as a detailed comparison with the newer D-ST widely used and whose characteristics are already published.« less

Neotropical coastal lagoons: an appraisal of their biodiversity, functioning, threats and conservation management.

PubMed

Esteves, F A; Caliman, A; Santangelo, J M; Guariento, R D; Farjalla, V F; Bozelli, R L

2008-11-01

Neotropical coastal lagoons (NCL) are human-dominated ecosystems. Their distribution along densely populated coastal areas of developing countries makes these systems among the most threatened in the world. Here, we summarize some aspects of the causes and consequences of NCL biodiversity, their functioning, their importance to the surrounding populations, their fragility, and their responses to local and global anthropogenic impacts and the challenges that Neotropical countries face in conserving these systems. Although still scarce and geographically concentrated, a growing body of studies has shown that NCLs are physiographically diversified systems, which harbor a considerable and particular proportion of the Neotropical inland aquatic biodiversity. Despite the fact that coastal lagoons are ecotones that are intricately connected to surrounding environments, they develop mechanisms for structural and functional regulation, which confer to these systems higher productivity and carrying capacities than surrounding ecosystems. Such traits attract residential developments and subsidize local traditional populations with important economic and aesthetic ecosystem revenues such as fisheries and scenic beauty. However, the disorganized human occupation around NCLs are causing profound impacts such as eutrophication, salinization, exotic species introduction, as well as other effects, which are ultimately imposing major habitat degradations and biodiversity extirpations in NCLs. We argue that interdisciplinary conservation strategies, which integrate scientific expertise, government officials, private companies and the general public, are the most likely to overcome the geographic and economic obstacles to NCL conservation.

Mechanistic study on the fluorination of K[B(CN)4] with ClF enabling the high yield and large scale synthesis of K[B(CF3)4] and K[(CF3)3BCN].

PubMed

Bernhardt, Eduard; Finze, Maik; Willner, Helge

2011-10-17

The fluorination of K[B(CN)(4)] with ClF is studied by millimolar test reactions in aHF and CH(2)Cl(2) solution and by subsequent identification of intermediates such as B-CF═NCl, B-CF(2)-NCl(2), and B-CF(3) species as well as NCl(3) by (19)F, (11)B NMR, and Raman spectroscopy, respectively. At first one cyano group of K[B(CN)(4)] is converted fast into a CF(3) group, and with increasing fluorination the reaction becomes slower and several intermediates could be observed. On the basis of these results, a synthesis was developed for K[B(CF(3))(4)] on a 0.2 molar scale by treatment of K[B(CN)(4)] diluted in aHF with ClF. The course of the reactions was followed by (i) monitoring the vapor pressure inside the reactor, (ii) observing the heat dissipation during ClF uptake, and (iii) measuring the volume of the released nitrogen gas. Since the fluorination of the last cyano group proceeds very slowly, the selective synthesis of K[(CF(3))(3)BCN] on a 0.2 molar scale is possible, as well. The analysis of the mechanisms, thermodynamics, and kinetics of the fluorination reactions is supported by density functional theory (DFT) calculations.

An Exploratory Survey of Digital Libraries on the World Wide Web: Art and Literature of the Early Italian Renaissance.

ERIC Educational Resources Information Center

McKibben, Suzanne J.

This study assessed the ongoing development of digital libraries (DLs) on the World Wide Web. DLs of art and literature were surveyed for selected works from the early Italian Renaissance in order to gain insight into the current trends prevalent throughout the larger population of DLs. The following artists and authors were selected for study:…

Dynamic light scattering as an objective noninvasive method in veterinary ophthalmic diagnosis and research

NASA Astrophysics Data System (ADS)

Dubin, Stephen; Ansari, Rafat R.; Tulp, Orien; Steinberg, Sheldon; Koch, Seth; DellaVecchia, Michael A.; Cozmi, Mihaela; Victor, Mary

1999-06-01

The absence of verbal feedback, available from most human patients, is a major limitation in veterinary diagnosis in general and in the evaluation of ophthalmic lens opacity in particular. A novel compact dynamic light scattering (DLS) instrument, developed at NASA, offers significant mitigation to this limitation. It not only yields objective repeatable non-invasive estimation of lens opacity but also provides insight into the nature of chemical and physical alternations in the lens and other eye structures. For example, DLS measurements of the cataractous lens may be interpreted in terms of alpha crystalline protein size. In contrast to most conventional methods, the examination results are numerical and readily accommodate statistical analysis. We present results of DLS measurements in laboratory rabbits with naphthalene induced cataracts, rodents with genetically conditioned hypertension and/or diabetes mellitus; as well as applications of the DLS method in clinical veterinary patients. Use of DLS in examination of phacoemulsification fluid, urine and other biological materials, and potential applications in ocular toxically will also be discussed.

The Effect of a Dissipative Ladle Shroud on Mixing in Tundish: Mathematical and Experimental Modelling

NASA Astrophysics Data System (ADS)

Zhang, Jiangshan; Yang, Shufeng; Li, Jingshe; Tang, Haiyan; Jiang, Zhengyi

2018-01-01

The effect of a dissipative ladle shroud (DLS) on mixing in tundish was investigated, compared with that of a conventional ladle shroud (CLS) using mathematical and physical modelling. The tracer profiles of mathematical results, achieved using large eddy simulation, were validated by physical observations employing high-speed cinephotography. The design of a DLS dramatically changed the flow patterns and contributed the intermixing of fluid elements inside the ladle shroud. The vortex flow encouraged the turbulent mixing and was verified by tracking of physical tracer dispersion inside the DLS. Residence Time Distribution (RTD) curves were obtained in two different sized tundishes to examine the mixing behaviours. The findings indicated that the DLS benefited the tundish mixing in terms of increasing active volume. The effect seemed to be more remarkable in the smaller tundish. The DLS gave rise to a more plug-like flow pattern inside the tundish, showing potential to shorten the transition length during grade change.

Acoustic evaluation of pirfenidone on patients with combined pulmonary fibrosis emphysema syndrome.

PubMed

Charleston-Villalobos, Sonia; Castaneda-Villa, Norma; Gonzalez-Camarena, Ramon; Mejia-Avila, M; Mateos-Toledo, H; Aljama-Corrales, Tomas

2016-08-01

The combined pulmonary fibrosis emphysema syndrome (CPFES) overall has a poor prognosis with a 5-year survival of 35-80%. Consequently, to evaluate possible positive effects on patients of novel agents as pirfenidone is relevant. However, the efficacy of pirfenidone in CPFES patients is still not well-known. In this study we propose an alternative to evaluate the effects of pirfenidone treatment on CPFES patients via acoustic information. Quantitative analysis of discontinuous adventitious lung sounds (DLS), known as crackles, has been promising to detect and characterize diverse pulmonary pathologies. The present study combines independent components (ICs) analysis of LS and the automated selection of ICs associated with DLS. ICs's features as fractal dimension, entropy and sparsity produce several clusters by kmeans. Those clusters containing ICs of DLS are exclusively considered to finally estimate the number of DLS per ICs by a time-variant AR modeling. For the evaluation of the effects of pirfenidone, the 2D DLS-ICs spatial distribution in conjunction with the estimated number of DLS events are shown. The methodology is applied to two real cases of CPFES with 6 and 12 months of treatment. The acoustical evaluation indicates that pirfenidone treatment may not be satisfactory for CPFES patients but further evaluation has to be performed.

Lesions of dorsal striatum eliminate lose-switch responding but not mixed-response strategies in rats.

PubMed

Skelin, Ivan; Hakstol, Rhys; VanOyen, Jenn; Mudiayi, Dominic; Molina, Leonardo A; Holec, Victoria; Hong, Nancy S; Euston, David R; McDonald, Robert J; Gruber, Aaron J

2014-05-01

We used focal brain lesions in rats to examine how dorsomedial (DMS) and dorsolateral (DLS) regions of the striatum differently contribute to response adaptation driven by the delivery or omission of rewards. Rats performed a binary choice task under two modes: one in which responses were rewarded on half of the trials regardless of choice; and another 'competitive' one in which only unpredictable choices were rewarded. In both modes, control animals were more likely to use a predictable lose-switch strategy than animals with lesions of either DMS or DLS. Animals with lesions of DMS presumably relied more on DLS for behavioural control, and generated repetitive responses in the first mode. These animals then shifted to a random response strategy in the competitive mode, thereby performing better than controls or animals with DLS lesions. Analysis using computational models of reinforcement learning indicated that animals with striatal lesions, particularly of the DLS, had blunted reward sensitivity and less stochasticity in the choice mechanism. These results provide further evidence that the rodent DLS is involved in rapid response adaptation that is more sophisticated than that embodied by the classic notion of habit formation driven by gradual stimulus-response learning. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Side-to-side differences in lower extremity biomechanics during multi-directional jump landing in volleyball athletes.

PubMed

Sinsurin, Komsak; Srisangboriboon, Sarun; Vachalathiti, Roongtiwa

2017-07-01

Side-to-side differences of lower extremities may influence the likelihood of injury. Moreover, adding the complexity of jump-landing direction would help to explain lower extremity control during sport activities. The aim was to determine the effects of limb dominance and jump-landing direction on lower extremity biomechanics. Nineteen female volleyball athletes participated. Both dominant limbs (DLs) and non-dominant limbs (NLs) were examined in single-leg jump-landing tests in four directions, including forward (0°), diagonal (30° and 60°), and lateral (90°) directions. Kinematic marker trajectories and ground reaction forces were collected using a 10 camera Vicon system and an AMTI force plate. Repeated measures ANOVA (2 × 4, limb × direction) was used to analyse. The finding showed that, at peak vertical GRF, a significant interaction of limb dominance and direction effects was found in the hip flexion angle and lower extremity joint kinetics (p < .05). NLs and DLs exhibited significantly different strategies while landing in various directions. Significantly higher increase of ankle dorsiflexion angle was observed in lateral direction compared to other directions for both DLs and NLs (p < .05). Increasingly using ankle dorsiflexion was observed from the forward to the lateral direction for both DLs and NLs. However, NLs and DLs preferentially used different strategies of joint moment organization to respond to similar VGRFs in various directions. The response pattern of DLs might not be effective and may expose DLs to a higher injury risk, especially with regard to landing with awkward posture compared with NLs.

Classification of breast cancer in ultrasound imaging using a generic deep learning analysis software: a pilot study.

PubMed

Becker, Anton S; Mueller, Michael; Stoffel, Elina; Marcon, Magda; Ghafoor, Soleen; Boss, Andreas

2018-02-01

To train a generic deep learning software (DLS) to classify breast cancer on ultrasound images and to compare its performance to human readers with variable breast imaging experience. In this retrospective study, all breast ultrasound examinations from January 1, 2014 to December 31, 2014 at our institution were reviewed. Patients with post-surgical scars, initially indeterminate, or malignant lesions with histological diagnoses or 2-year follow-up were included. The DLS was trained with 70% of the images, and the remaining 30% were used to validate the performance. Three readers with variable expertise also evaluated the validation set (radiologist, resident, medical student). Diagnostic accuracy was assessed with a receiver operating characteristic analysis. 82 patients with malignant and 550 with benign lesions were included. Time needed for training was 7 min (DLS). Evaluation time for the test data set were 3.7 s (DLS) and 28, 22 and 25 min for human readers (decreasing experience). Receiver operating characteristic analysis revealed non-significant differences (p-values 0.45-0.47) in the area under the curve of 0.84 (DLS), 0.88 (experienced and intermediate readers) and 0.79 (inexperienced reader). DLS may aid diagnosing cancer on breast ultrasound images with an accuracy comparable to radiologists, and learns better and faster than a human reader with no prior experience. Further clinical trials with dedicated algorithms are warranted. Advances in knowledge: DLS can be trained classify cancer on breast ultrasound images high accuracy even with comparably few training cases. The fast evaluation speed makes real-time image analysis feasible.

Dorsolateral neostriatum contribution to incentive salience: Opioid or dopamine stimulation makes one reward cue more motivationally attractive than another

PubMed Central

DiFeliceantonio, Alexandra G.; Berridge, Kent C.

2016-01-01

Pavlovian cues for rewards can become attractive incentives: approached and ‘wanted’ as the rewards themselves. The motivational attractiveness of a previously learned cue is not fixed, but can be dynamically amplified during re-encounter by simultaneous activation of brain limbic circuitry. Here we report that opioid or dopamine microinjections in the dorsolateral quadrant of the neostriatum (DLS) of rats selectively amplify attraction toward a previously learned Pavlovian cue in an individualized fashion, at the expense of a competing cue. In an autoshaping (sign-tracking vs goal-tracking) paradigm, microinjection of the mu opioid receptor agonist (DAMGO) or dopamine indirect agonist (amphetamine) in DLS of sign-tracker individuals selectively enhanced their sign-tracking attraction toward the reward-predictive lever cue. By contrast, DAMGO or amphetamine in DLS of goal-trackers selectively enhanced prepotent attraction toward the reward-proximal cue of sucrose dish. Amphetamine also enhanced goal-tracking in some sign-tracker individuals (if they ever defected to the dish even once). That DLS enhancement of cue attraction was due to stronger motivation, not stronger habits was suggested by: 1) sign-trackers flexibly followed their cue to a new location when the lever was suddenly moved after DLS DAMGO microinjection, and 2) DAMGO in DLS also made sign-trackers work harder on a new instrumental nose-poke response required to earn presentations of their Pavlovian lever cue (instrumental conditioned reinforcement). Altogether, our results suggest that DLS circuitry can enhance the incentive salience of a Pavlovian reward cue, selectively making that cue a stronger motivational magnet. PMID:26924040

The dorsolateral striatum selectively mediates extinction of habit memory.

PubMed

Goodman, Jarid; Ressler, Reed L; Packard, Mark G

2016-12-01

Previous research has indicated a role for the dorsolateral striatum (DLS) in acquisition and retrieval of habit memory. However, the neurobiological mechanisms guiding extinction of habit memory have not been extensively investigated. The present study examined whether the dorsolateral striatum (DLS) is involved in extinction of habit memory in a food-rewarded response learning version of the plus-maze in adult male Long-Evans rats (experiment 1). In addition, to determine whether the role of this brain region in extinction is selective to habit memory, we also examined whether the DLS is required for extinction of hippocampus-dependent spatial memory in a place learning version of the plus-maze (experiment 2). Following acquisition in either task, rats received two days of extinction training, in which the food reward was removed from the maze. The number of perseverative trials (a trial in which the rat made the same previously reinforced body-turn) and latency to reach the previously correct food well were used as measures of extinction. Animals were given immediate post-training intra-DLS administration of the sodium channel blocker bupivacaine or vehicle to determine the effect of DLS inactivation on consolidation of extinction memory in each task. In the response learning task, post-training DLS inactivation impaired consolidation of extinction memory. Injections of bupivacaine delayed 2 h post-training did not affect extinction, indicating a time-dependent effect of neural inactivation on consolidation of extinction memory in this task. In contrast, post-training DLS inactivation did not impair, but instead slightly enhanced, extinction memory in the place learning task. The present findings indicate a critical role for the DLS in extinction of habit memory in the response learning task, and may be relevant to understanding the neural mechanisms through which maladaptive habits in human psychopathologies (e.g. drug addiction) may be suppressed. Copyright © 2016 Elsevier Inc. All rights reserved.

Diode Laser Stapedotomy vs Conventional Stapedotomy in Otosclerosis: A Double-Blinded Randomized Clinical Trial.

PubMed

Parida, Pradipta Kumar; Kalaiarasi, Raja; Gopalakrishnan, Surianarayana

2016-06-01

To assess and compare the efficacy of diode laser stapedotomy (DLS) and conventional manual stapedotomy (CMS) in the treatment of otosclerosis. Randomized clinical trial. Tertiary health center. We randomly assigned 60 patients with otosclerosis planned for primary stapedotomy to receive either DLS or CMS. Primary outcome measure was hearing gain measured by pure-tone audiometry (PTA) performed preoperatively and postoperatively. Hearing gain was compared within and between the groups. Secondary outcome measures were the incidence of intraoperative (bleeding and fractured footplate) and postoperative (vomiting, vertigo, sensorineural hearing loss, tinnitus, facial nerve paralysis, and hospital stay) morbidities. Sixty primary stapedotomies (30 in the CMS group and 30 in the DLS group) done for 60 patients (male, n = 42; female, n = 18) were included in the analysis. Preoperative mean air-bone (AB) gap in the DLS and CMS groups was 38.51 ± 8.643 dB and 36.42 ± 8.678 dB, respectively. Mean AB gap at 6 month was 10.86 ± 5.383 dB and 11.05 ± 5.236 dB in the CMS and DLS groups, respectively. Air conduction was improved by 24.98 ± 5.348 dB in the DLS group and 24.08 ± 5.911 dB in the CMS group at 6 months. No statistically significant differences were found in hearing gain between the 2 groups at 6 months (P > .05). A decreased rate and severity of intraoperative bleeding, postoperative vertigo, and vomiting were observed with the diode laser (0%, 6.6%, and 10%) compared with the conventional technique (16.7%, 16.7%, and 16.7%), but these differences were not statistically significant (P > .05). Hearing outcomes and complications of DLS were similar to CMS. These study findings confirm the efficacy of the diode laser in stapedotomy, but DLS offers no advantages over CMS for otosclerosis surgery. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.

Development and Validation of a Deep Learning System for Diabetic Retinopathy and Related Eye Diseases Using Retinal Images From Multiethnic Populations With Diabetes.

PubMed

Ting, Daniel Shu Wei; Cheung, Carol Yim-Lui; Lim, Gilbert; Tan, Gavin Siew Wei; Quang, Nguyen D; Gan, Alfred; Hamzah, Haslina; Garcia-Franco, Renata; San Yeo, Ian Yew; Lee, Shu Yen; Wong, Edmund Yick Mun; Sabanayagam, Charumathi; Baskaran, Mani; Ibrahim, Farah; Tan, Ngiap Chuan; Finkelstein, Eric A; Lamoureux, Ecosse L; Wong, Ian Y; Bressler, Neil M; Sivaprasad, Sobha; Varma, Rohit; Jonas, Jost B; He, Ming Guang; Cheng, Ching-Yu; Cheung, Gemmy Chui Ming; Aung, Tin; Hsu, Wynne; Lee, Mong Li; Wong, Tien Yin

2017-12-12

A deep learning system (DLS) is a machine learning technology with potential for screening diabetic retinopathy and related eye diseases. To evaluate the performance of a DLS in detecting referable diabetic retinopathy, vision-threatening diabetic retinopathy, possible glaucoma, and age-related macular degeneration (AMD) in community and clinic-based multiethnic populations with diabetes. Diagnostic performance of a DLS for diabetic retinopathy and related eye diseases was evaluated using 494 661 retinal images. A DLS was trained for detecting diabetic retinopathy (using 76 370 images), possible glaucoma (125 189 images), and AMD (72 610 images), and performance of DLS was evaluated for detecting diabetic retinopathy (using 112 648 images), possible glaucoma (71 896 images), and AMD (35 948 images). Training of the DLS was completed in May 2016, and validation of the DLS was completed in May 2017 for detection of referable diabetic retinopathy (moderate nonproliferative diabetic retinopathy or worse) and vision-threatening diabetic retinopathy (severe nonproliferative diabetic retinopathy or worse) using a primary validation data set in the Singapore National Diabetic Retinopathy Screening Program and 10 multiethnic cohorts with diabetes. Use of a deep learning system. Area under the receiver operating characteristic curve (AUC) and sensitivity and specificity of the DLS with professional graders (retinal specialists, general ophthalmologists, trained graders, or optometrists) as the reference standard. In the primary validation dataset (n = 14 880 patients; 71 896 images; mean [SD] age, 60.2 [2.2] years; 54.6% men), the prevalence of referable diabetic retinopathy was 3.0%; vision-threatening diabetic retinopathy, 0.6%; possible glaucoma, 0.1%; and AMD, 2.5%. The AUC of the DLS for referable diabetic retinopathy was 0.936 (95% CI, 0.925-0.943), sensitivity was 90.5% (95% CI, 87.3%-93.0%), and specificity was 91.6% (95% CI, 91.0%-92.2%). For vision-threatening diabetic retinopathy, AUC was 0.958 (95% CI, 0.956-0.961), sensitivity was 100% (95% CI, 94.1%-100.0%), and specificity was 91.1% (95% CI, 90.7%-91.4%). For possible glaucoma, AUC was 0.942 (95% CI, 0.929-0.954), sensitivity was 96.4% (95% CI, 81.7%-99.9%), and specificity was 87.2% (95% CI, 86.8%-87.5%). For AMD, AUC was 0.931 (95% CI, 0.928-0.935), sensitivity was 93.2% (95% CI, 91.1%-99.8%), and specificity was 88.7% (95% CI, 88.3%-89.0%). For referable diabetic retinopathy in the 10 additional datasets, AUC range was 0.889 to 0.983 (n = 40 752 images). In this evaluation of retinal images from multiethnic cohorts of patients with diabetes, the DLS had high sensitivity and specificity for identifying diabetic retinopathy and related eye diseases. Further research is necessary to evaluate the applicability of the DLS in health care settings and the utility of the DLS to improve vision outcomes.

Development and Validation of a Deep Learning System for Diabetic Retinopathy and Related Eye Diseases Using Retinal Images From Multiethnic Populations With Diabetes

PubMed Central

Ting, Daniel Shu Wei; Cheung, Carol Yim-Lui; Lim, Gilbert; Tan, Gavin Siew Wei; Quang, Nguyen D.; Gan, Alfred; Hamzah, Haslina; Garcia-Franco, Renata; San Yeo, Ian Yew; Lee, Shu Yen; Wong, Edmund Yick Mun; Sabanayagam, Charumathi; Baskaran, Mani; Ibrahim, Farah; Tan, Ngiap Chuan; Finkelstein, Eric A.; Lamoureux, Ecosse L.; Wong, Ian Y.; Bressler, Neil M.; Sivaprasad, Sobha; Varma, Rohit; Jonas, Jost B.; He, Ming Guang; Cheng, Ching-Yu; Cheung, Gemmy Chui Ming; Aung, Tin; Hsu, Wynne; Lee, Mong Li

2017-01-01

Importance A deep learning system (DLS) is a machine learning technology with potential for screening diabetic retinopathy and related eye diseases. Objective To evaluate the performance of a DLS in detecting referable diabetic retinopathy, vision-threatening diabetic retinopathy, possible glaucoma, and age-related macular degeneration (AMD) in community and clinic-based multiethnic populations with diabetes. Design, Setting, and Participants Diagnostic performance of a DLS for diabetic retinopathy and related eye diseases was evaluated using 494 661 retinal images. A DLS was trained for detecting diabetic retinopathy (using 76 370 images), possible glaucoma (125 189 images), and AMD (72 610 images), and performance of DLS was evaluated for detecting diabetic retinopathy (using 112 648 images), possible glaucoma (71 896 images), and AMD (35 948 images). Training of the DLS was completed in May 2016, and validation of the DLS was completed in May 2017 for detection of referable diabetic retinopathy (moderate nonproliferative diabetic retinopathy or worse) and vision-threatening diabetic retinopathy (severe nonproliferative diabetic retinopathy or worse) using a primary validation data set in the Singapore National Diabetic Retinopathy Screening Program and 10 multiethnic cohorts with diabetes. Exposures Use of a deep learning system. Main Outcomes and Measures Area under the receiver operating characteristic curve (AUC) and sensitivity and specificity of the DLS with professional graders (retinal specialists, general ophthalmologists, trained graders, or optometrists) as the reference standard. Results In the primary validation dataset (n = 14 880 patients; 71 896 images; mean [SD] age, 60.2 [2.2] years; 54.6% men), the prevalence of referable diabetic retinopathy was 3.0%; vision-threatening diabetic retinopathy, 0.6%; possible glaucoma, 0.1%; and AMD, 2.5%. The AUC of the DLS for referable diabetic retinopathy was 0.936 (95% CI, 0.925-0.943), sensitivity was 90.5% (95% CI, 87.3%-93.0%), and specificity was 91.6% (95% CI, 91.0%-92.2%). For vision-threatening diabetic retinopathy, AUC was 0.958 (95% CI, 0.956-0.961), sensitivity was 100% (95% CI, 94.1%-100.0%), and specificity was 91.1% (95% CI, 90.7%-91.4%). For possible glaucoma, AUC was 0.942 (95% CI, 0.929-0.954), sensitivity was 96.4% (95% CI, 81.7%-99.9%), and specificity was 87.2% (95% CI, 86.8%-87.5%). For AMD, AUC was 0.931 (95% CI, 0.928-0.935), sensitivity was 93.2% (95% CI, 91.1%-99.8%), and specificity was 88.7% (95% CI, 88.3%-89.0%). For referable diabetic retinopathy in the 10 additional datasets, AUC range was 0.889 to 0.983 (n = 40 752 images). Conclusions and Relevance In this evaluation of retinal images from multiethnic cohorts of patients with diabetes, the DLS had high sensitivity and specificity for identifying diabetic retinopathy and related eye diseases. Further research is necessary to evaluate the applicability of the DLS in health care settings and the utility of the DLS to improve vision outcomes. PMID:29234807

Ca2+/Cation Antiporters (CaCA): Identification, Characterization and Expression Profiling in Bread Wheat (Triticum aestivum L.)

PubMed Central

Taneja, Mehak; Tyagi, Shivi; Sharma, Shailesh; Upadhyay, Santosh Kumar

2016-01-01

The Ca2+/cation antiporters (CaCA) superfamily proteins play vital function in Ca2+ ion homeostasis, which is an important event during development and defense response. Molecular characterization of these proteins has been performed in certain plants, but they are still not characterized in Triticum aestivum (bread wheat). Herein, we identified 34 TaCaCA superfamily proteins, which were classified into TaCAX, TaCCX, TaNCL, and TaMHX protein families based on their structural organization and evolutionary relation with earlier reported proteins. Since the T. aestivum comprises an allohexaploid genome, TaCaCA genes were derived from each A, B, and D subgenome and homeologous chromosome (HC), except chromosome-group 1. Majority of genes were derived from more than one HCs in each family that were considered as homeologous genes (HGs) due to their high similarity with each other. These HGs showed comparable gene and protein structures in terms of exon/intron organization and domain architecture. Majority of TaCaCA proteins comprised two Na_Ca_ex domains. However, TaNCLs consisted of an additional EF-hand domain with calcium binding motifs. Each TaCaCA protein family consisted of about 10 transmembrane and two α-repeat regions with specifically conserved signature motifs except TaNCL, which had single α-repeat. Variable expression of most of the TaCaCA genes during various developmental stages suggested their specified role in development. However, constitutively high expression of a few genes like TaCAX1-A and TaNCL1-B indicated their role throughout the plant growth and development. The modulated expression of certain genes during biotic (fungal infections) and abiotic stresses (heat, drought, salt) suggested their role in stress response. Majority of TaCCX and TaNCL family genes were found highly affected during various abiotic stresses. However, the role of individual gene needs to be established. The present study unfolded the opportunity for detail functional characterization of TaCaCA proteins and their utilization in future crop improvement programs. PMID:27965686

The SNP at −592 of human IL-10 gene is associated with serum IL-10 levels and increased risk for human papillomavirus cervical lesion development

PubMed Central

2012-01-01

Background Women with Human Papilloma Virus (HPV) persistence are characterized by high levels of IL-10 at cervix. We have determined whether polymorphisms of IL-10 gene promoter might be associated with increased risk of squamous intraepithelial cervical lesions (SICL) and whether exist significative differences of IL-10 mRNA expression at cervix and systemic and serum IL-10 protein between SICL cases and non-Cervical Lesions (NCL). Methods Peripheral blood samples from SICL (n = 204) and NCL (n = 166) were used to detect IL-10 promoter polymorphisms at loci -592A/C (rs1800872), -819C/T (rs1800871), -1082A/G (rs1800896), -1352A/G (rs1800893), by allelic discrimination and to evaluate serum IL-10 protein. Cervical epithelial scrapings from NCL and biopsies from SICLs were used for HPV-typing and to evaluate IL-10 mRNA expression level. The systemic and local IL-10 mRNA expression levels were measured by real time-PCR. Genotypic and allelic frequencies of the selected polymorphisms were analyzed by logistic regression, adjusting by age and HPV-genotype, to determine the association with SICL. Results No significant differences were found between genotype frequencies at loci −819, -1082, and −1352. Individuals carrying at least one copy of risk allele A of polymorphism −592 had a two-fold increased risk of developing SICL [adjusted odds ratio (OR), 2.02 (95% CI, 1.26-3.25), p = 0.003], compared to NCL. The IL-10 mRNA expression and serum IL-10 protein, were significantly higher in SICL cases (p < 0.01), being higher in patients carrying the risk allele A. Conclusions The −592 polymorphism is associated with increased risk of SICL and can serve as a marker of genetic susceptibility to SICL among Mexican women. According to IL-10 levels found in SICL, IL-10 can be relevant factor for viral persistence and progression disease. PMID:23148667

Ca2+/Cation Antiporters (CaCA): Identification, Characterization and Expression Profiling in Bread Wheat (Triticum aestivum L.).

PubMed

Taneja, Mehak; Tyagi, Shivi; Sharma, Shailesh; Upadhyay, Santosh Kumar

2016-01-01

The Ca 2+ /cation antiporters (CaCA) superfamily proteins play vital function in Ca 2+ ion homeostasis, which is an important event during development and defense response. Molecular characterization of these proteins has been performed in certain plants, but they are still not characterized in Triticum aestivum (bread wheat). Herein, we identified 34 TaCaCA superfamily proteins, which were classified into TaCAX, TaCCX, TaNCL, and TaMHX protein families based on their structural organization and evolutionary relation with earlier reported proteins. Since the T. aestivum comprises an allohexaploid genome, TaCaCA genes were derived from each A, B, and D subgenome and homeologous chromosome (HC), except chromosome-group 1. Majority of genes were derived from more than one HCs in each family that were considered as homeologous genes (HGs) due to their high similarity with each other. These HGs showed comparable gene and protein structures in terms of exon/intron organization and domain architecture. Majority of TaCaCA proteins comprised two Na_Ca_ex domains. However, TaNCLs consisted of an additional EF-hand domain with calcium binding motifs. Each TaCaCA protein family consisted of about 10 transmembrane and two α-repeat regions with specifically conserved signature motifs except TaNCL, which had single α-repeat. Variable expression of most of the TaCaCA genes during various developmental stages suggested their specified role in development. However, constitutively high expression of a few genes like TaCAX1-A and TaNCL1-B indicated their role throughout the plant growth and development. The modulated expression of certain genes during biotic (fungal infections) and abiotic stresses (heat, drought, salt) suggested their role in stress response. Majority of TaCCX and TaNCL family genes were found highly affected during various abiotic stresses. However, the role of individual gene needs to be established. The present study unfolded the opportunity for detail functional characterization of TaCaCA proteins and their utilization in future crop improvement programs.

Total chemical synthesis of proteins without HPLC purification† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c6sc01883a Click here for additional data file.

PubMed Central

Loibl, S. F.; Harpaz, Z.; Zitterbart, R.

2016-01-01

The total chemical synthesis of proteins is a tedious and time-consuming endeavour. The typical steps involve solid phase synthesis of peptide thioesters and cysteinyl peptides, native chemical ligation (NCL) in solution, desulfurization or removal of ligation auxiliaries in the case of extended NCL as well as many intermediary and final HPLC purification steps. With an aim to facilitate and improve the throughput of protein synthesis we developed the first method for the rapid chemical total on-resin synthesis of proteins that proceeds without a single HPLC-purification step. The method relies on the combination of three orthogonal protein tags that allow sequential immobilization (via the N-terminal and C-terminal ends), extended native chemical ligation and release reactions. The peptide fragments to be ligated are prepared by conventional solid phase synthesis and used as crude materials in the subsequent steps. An N-terminal His6 unit permits selective immobilization of the full length peptide thioester onto Ni-NTA agarose beads. The C-terminal peptide fragment carries a C-terminal peptide hydrazide and an N-terminal 2-mercapto-2-phenyl-ethyl ligation auxiliary, which serves as a reactivity tag for the full length peptide. As a result, only full length peptides, not truncation products, react in the subsequent on-bead extended NCL. After auxiliary removal the ligation product is liberated into solution upon treatment with mild acid, and is concomitantly captured by an aldehyde-modified resin. This step allows the removal of the most frequently observed by-product in NCL chemistry, i.e. the hydrolysed peptide thioester (which does not contain a C-terminal peptide hydrazide). Finally, the target protein is released with diluted hydrazine or acid. We applied the method in the synthesis of 46 to 126 amino acid long MUC1 proteins comprising 2–6 copies of a 20mer tandem repeat sequence. Only three days were required for the parallel synthesis of 9 MUC1 proteins which were obtained in 8–33% overall yield with 90–98% purity despite the omission of HPLC purification. PMID:28451120

Screening of TiO2 and Au nanoparticles in cosmetics and determination of elemental impurities by multiple techniques (DLS, SP-ICP-MS, ICP-MS and ICP-OES).

PubMed

de la Calle, Inmaculada; Menta, Mathieu; Klein, Marlène; Séby, Fabienne

2017-08-15

Cosmetics are part of the daily life of most of the people. Thus, a complete characterization of the products we applied in our skin is necessary. In this work, an analytical investigation of a wide variety of cosmetics from the point of view of total element content and metallic nanoparticles (NPs) has been performed. Firstly, we analyzed the total element content by ICP-MS and ICP-OES after acid digestion as an assessment of the presence of metal impurities. Prohibited elements in cosmetics, according to the European Commission regulation No 1223/2009, were not detected, and only elements mentioned in the label were found (e.g. Al, Fe, Ti and Si). Secondly, a screening of the presence of NPs has been performed by Dynamic Light Scattering (DLS) and Single Particle Inductively-Coupled Plasma Mass Spectrometry (SP-ICP-MS). Two sample preparation procedures were applied. The first protocol consisted in the preparation of suspensions in 0.1% w/v SDS and the second based on defatting with hexane followed by resuspension in water. DLS was employed as a routine method for a fast analysis of NPs, but this technique showed limitations due to the lack of specificity. SP-ICP-MS analyses were then performed, first as a screening technique to evaluate the presence of TiO 2 and Au NPs in cosmetics suspensions prepared in SDS; and second, when a positive answer was obtained about the presence of NPs from the screening, SP-ICP-MS was used for particle size determination. Results showed that only TiO 2 NPs were present in two sunscreens, one anti-wrinkle day cream, one lip balm protector labeled as 'nano' and in one brand of toothpaste not labeled as 'nano'. Sizes obtained for both sample preparations were compared and ranged from 30 to 120nm in most of the samples. Copyright © 2017 Elsevier B.V. All rights reserved.

Genetics Home Reference: CLN10 disease

MedlinePlus

... Foundation CLIMB: Children Living with Inherited Metabolic Diseases March of Dimes: Neonatal Death The ... Sources for This Page Anderson GW, Goebel HH, Simonati A. Human pathology in NCL. Biochim Biophys Acta. 2013 Nov;1832( ...

A yeast model for the mechanism of the Epstein-Barr virus immune evasion identifies a new therapeutic target to interfere with the virus stealthiness.

PubMed

Lista, María José; Martins, Rodrigo Prado; Angrand, Gaelle; Quillévéré, Alicia; Daskalogianni, Chrysoula; Voisset, Cécile; Teulade-Fichou, Marie-Paule; Fåhraeus, Robin; Blondel, Marc

2017-08-31

The oncogenic Epstein-Barr virus (EBV) evades the immune system but has an Achilles heel: its genome maintenance protein EBNA1. Indeed, EBNA1 is essential for viral genome replication and maintenance but also highly antigenic. Hence, EBV evolved a system in which the glycine-alanine repeat (GAr) of EBNA1 limits the translation of its own mRNA at a minimal level to ensure its essential function thereby, at the same time, minimizing immune recognition. Defining intervention points where to interfere with EBNA1 immune evasion is an important step to trigger an immune response against EBV-carrying cancers. Thanks to a yeast-based assay that recapitulates all the aspects of EBNA1 self-limitation of expression, a recent study by Lista et al. [Nature Communications (2017) 7, 435-444] has uncovered the role of the host cell nucleolin (NCL) in this process via a direct interaction of this protein with G-quadruplexes (G4) formed in GAr-encoding sequence of EBNA1 mRNA. In addition, the G4 ligand PhenDC3 prevents NCL binding on EBNA1 mRNA and reverses GAr-mediated repression of translation and antigen presentation. This shows that the NCL-EBNA1 mRNA interaction is a relevant therapeutic target to unveil EBV-carrying cancers to the immune system and that the yeast model can be successfully used for uncovering drugs and host factors that interfere with EBV stealthiness.

Neuronal ceroid-lipofuscinosis in longhaired Chihuahuas: clinical, pathologic, and MRI findings.

PubMed

Nakamoto, Yuya; Yamato, Osamu; Uchida, Kazuyuki; Nibe, Kazumi; Tamura, Shinji; Ozawa, Tsuyoshi; Ueoka, Naotami; Nukaya, Aya; Yabuki, Akira; Nakaichi, Munekazu

2011-01-01

Neuronal ceroid-lipofuscinosis (NCL) is a rare group of inherited neurodegenerative lysosomal storage diseases characterized histopathologically by the abnormal accumulation of ceroid- or lipofuscin-like lipopigments in neurons and other cells throughout the body. The present article describes the clinical, pathologic, and magnetic resonance imaging (MRI) findings of the NCL in three longhaired Chihuahuas between 16 mo and 24 mo of age. Clinical signs, including visual defects and behavioral abnormalities, started between 16 mo and 18 mo of age. Cranial MRI findings in all the dogs were characterized by diffuse severe dilation of the cerebral sulci, dilated fissures of diencephalons, midbrain, and cerebellum, and lateral ventricular enlargement, suggesting atrophy of the forebrain. As the most unusual feature, diffuse meningeal thickening was observed over the entire cerebrum, which was strongly enhanced on contrast T1-weighted images. The dogs' conditions progressed until they each died subsequent to continued neurologic deterioration between 23 mo and 24 mo of age. Histopathologically, there was severe to moderate neuronal cell loss with diffuse astrogliosis throughout the brain. The remaining neuronal cells showed intracytoplasmic accumulation of pale to slightly yellow lipopigments mimicking ceroid or lipofuscin. The thickened meninges consisted of the proliferation of connective tissues with abundant collagen fibers and mild infiltration of inflammatory cells suggesting neuroimmune hyperactivity. Although the etiology of this neuroimmune hyperactivity is not currently known, MRI findings such as meningeal thickening may be a useful diagnostic marker of this variant form of canine NCL.

Morphometric differences of nasopalatine canal based on 3D classifications: descriptive analysis on CBCT.

PubMed

Fernández-Alonso, A; Suárez-Quintanilla, J A; Rapado-González, O; Suárez-Cunqueiro, María Mercedes

2015-09-01

This descriptive retrospective study analyzed differences among sagittal, coronal and axial NC groups based on the dimensions of nasopalatine canal (NC), buccal bone plate (BBP) and palatal bone plate (PBP) to canal. Measurements were made on 224 CBCTs for NC, BBP and PBP on the three anatomic planes at three levels: level 1, when the incisive foramen is completely closed on the axial plane; level 2, at the midpoint of NC length (NCL) on the sagittal plane; and level 3, at the foramina of Stenson on the sagittal plane. ANOVA tests with post hoc tests were used. The intraclass correlation coefficient and Kappa test were used for evaluating the intraobserver agreement. Regarding coronal classification, these significant differences were found: BBP length (BL)level 1 was lower for the two parallel canals group; PBP length (PL)level 1 was lower for single canal group; and NCL was lower for Y-type canal group. Regarding axial classification, these significant differences were found: LPlevel 1 was lower for 3.1-3 group; PBP width (PW)level 3 was the greatest for 3.1-3; and LPlevel 3 was lower for 1.1. Presurgical evaluation with CBCT in premaxillae region should include analysis on coronal and axial planes and not only on sagittal plane seeing as morphometric differences were found on coronal and axial planes. Following the morphological coronal classification, two parallel canals presented a higher NCL, a higher LP and a lower LV at inferior edge of alveolar ridge.

Stimulus-Response-Outcome Coding in the Pigeon Nidopallium Caudolaterale

PubMed Central

Starosta, Sarah; Güntürkün, Onur; Stüttgen, Maik C.

2013-01-01

A prerequisite for adaptive goal-directed behavior is that animals constantly evaluate action outcomes and relate them to both their antecedent behavior and to stimuli predictive of reward or non-reward. Here, we investigate whether single neurons in the avian nidopallium caudolaterale (NCL), a multimodal associative forebrain structure and a presumed analogue of mammalian prefrontal cortex, represent information useful for goal-directed behavior. We subjected pigeons to a go-nogo task, in which responding to one visual stimulus (S+) was partially reinforced, responding to another stimulus (S–) was punished, and responding to test stimuli from the same physical dimension (spatial frequency) was inconsequential. The birds responded most intensely to S+, and their response rates decreased monotonically as stimuli became progressively dissimilar to S+; thereby, response rates provided a behavioral index of reward expectancy. We found that many NCL neurons' responses were modulated in the stimulus discrimination phase, the outcome phase, or both. A substantial fraction of neurons increased firing for cues predicting non-reward or decreased firing for cues predicting reward. Interestingly, the same neurons also responded when reward was expected but not delivered, and could thus provide a negative reward prediction error or, alternatively, signal negative value. In addition, many cells showed motor-related response modulation. In summary, NCL neurons represent information about the reward value of specific stimuli, instrumental actions as well as action outcomes, and therefore provide signals useful for adaptive behavior in dynamically changing environments. PMID:23437383

Dorsolateral neostriatum contribution to incentive salience: opioid or dopamine stimulation makes one reward cue more motivationally attractive than another.

PubMed

DiFeliceantonio, Alexandra G; Berridge, Kent C

2016-05-01

Pavlovian cues for rewards can become attractive incentives: approached and 'wanted' as the rewards themselves. The motivational attractiveness of a previously learned cue is not fixed, but can be dynamically amplified during re-encounter by simultaneous activation of brain limbic circuitry. Here it was reported that opioid or dopamine microinjections in the dorsolateral quadrant of the neostriatum (DLS) of rats selectively amplify attraction toward a previously learned Pavlovian cue in an individualized fashion, at the expense of a competing cue. In an autoshaping (sign-tracking vs. goal-tracking) paradigm, microinjection of the mu opioid receptor agonist (DAMGO) or dopamine indirect agonist (amphetamine) in the DLS of sign-tracker individuals selectively enhanced their sign-tracking attraction toward the reward-predictive lever cue. By contrast, DAMGO or amphetamine in the DLS of goal-trackers selectively enhanced prepotent attraction toward the reward-proximal cue of sucrose dish. Amphetamine also enhanced goal-tracking in some sign-tracker individuals (if they ever defected to the dish even once). That DLS enhancement of cue attraction was due to stronger motivation, not stronger habits, was suggested by: (i) sign-trackers flexibly followed their cue to a new location when the lever was suddenly moved after DLS DAMGO microinjection; and (ii) DAMGO in the DLS also made sign-trackers work harder on a new instrumental nose-poke response required to earn presentations of their Pavlovian lever cue (instrumental conditioned reinforcement). Altogether, the current results suggest that DLS circuitry can enhance the incentive salience of a Pavlovian reward cue, selectively making that cue a stronger motivational magnet. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Tibial nerve somatosensory evoked potentials in dogs with degenerative lumbosacral stenosis.

PubMed

Meij, Björn P; Suwankong, Niyada; van den Brom, Walter E; Venker-van Haagen, Anjop J; Hazewinkel, Herman A W

2006-02-01

To determine somatosensory evoked potentials (SEPs) in dogs with degenerative lumbosacral stenosis (DLS) and in healthy dogs. Clinical and experimental study. Dogs with DLS (n = 21) and 11 clinically normal dogs, age, and weight matched. Under anesthesia, the tibial nerve was stimulated at the caudolateral aspect of the stifle, and lumbar SEP (LSEP) were recorded percutaneously from S1 to T13 at each interspinous space. Cortical SEP (CSEP) were recorded from the scalp. LSEP were identified as the N1-P1 (latency 3-6 ms) and N2-P2 (latency 7-13 ms) wave complexes in the recordings of dogs with DLS and control dogs. Latency of N1-P1 increased and that of N2-P2 decreased as the active recording electrode was moved cranially from S1 to T13. Compared with controls, latencies were significantly delayed in DLS dogs: .8 ms for N1-P1 and 1.7 ms for the N2-P2 complex. CSEP were not different between groups. Surface needle recording of tibial nerve SEP can be used to monitor somatosensory nerve function of pelvic limbs in dogs. In dogs with DLS, the latency of LSEP, but not of CSEP, is prolonged compared with normal dogs. In dogs with lumbosacral pain from DLS, the cauda equina compression is sufficient to affect LSEP at the lumbar level.

k-neighborhood Decentralization: A Comprehensive Solution to Index the UMLS for Large Scale Knowledge Discovery

PubMed Central

Xiang, Yang; Lu, Kewei; James, Stephen L.; Borlawsky, Tara B.; Huang, Kun; Payne, Philip R.O.

2011-01-01

The Unified Medical Language System (UMLS) is the largest thesaurus in the biomedical informatics domain. Previous works have shown that knowledge constructs comprised of transitively-associated UMLS concepts are effective for discovering potentially novel biomedical hypotheses. However, the extremely large size of the UMLS becomes a major challenge for these applications. To address this problem, we designed a k-neighborhood Decentralization Labeling Scheme (kDLS) for the UMLS, and the corresponding method to effectively evaluate the kDLS indexing results. kDLS provides a comprehensive solution for indexing the UMLS for very efficient large scale knowledge discovery. We demonstrated that it is highly effective to use kDLS paths to prioritize disease-gene relations across the whole genome, with extremely high fold-enrichment values. To our knowledge, this is the first indexing scheme capable of supporting efficient large scale knowledge discovery on the UMLS as a whole. Our expectation is that kDLS will become a vital engine for retrieving information and generating hypotheses from the UMLS for future medical informatics applications. PMID:22154838

New noninvasive index for evaluation of the vascular age of healthy and sick people

NASA Astrophysics Data System (ADS)

Fine, Ilya; Kuznik, Boris I.; Kaminsky, Alexander V.; Shenkman, Louis; Kustovsjya, Evgeniya M.; Maximova, Olga G.

2012-08-01

We conducted a study on 861 healthy and sick subjects and demonstrated that some calculated parameters based on measurement of the dynamic light scattering (DLS) signal from the finger correlate highly with chronological age ranging from 1.5 to 85 years old. Measurements of DLS signals were obtained during both occlusion and nonocclusion of blood flow in the finger. For the nonocclusion case we found that the low-frequency component of the DLS signal significantly correlates with the biological age while the high-frequency component of the DLS signal resembles the arterial pulse-wave and does correlate with age. However, the most prominent correlation between the DLS characteristics and age was noted with the stasis stage measurements. We propose that the observed age-related phenomena are caused by alterations in local blood viscosity and interactions of the endothelial cells with erythrocytes. Further, a new noninvasive index based on the age-related optical characteristics was introduced. This noninvasive index may be used as a research and diagnostic tool to examine the endothelial and thrombolytic properties of the vascular system.

New noninvasive index for evaluation of the vascular age of healthy and sick people.

PubMed

Fine, Ilya; Kuznik, Boris I; Kaminsky, Alexander V; Shenkman, Louis; Kustovsjya, Evgeniya M; Elena, Evgeniya M; Maximova, Olga G

2012-08-01

We conducted a study on 861 healthy and sick subjects and demonstrated that some calculated parameters based on measurement of the dynamic light scattering (DLS) signal from the finger correlate highly with chronological age ranging from 1.5 to 85 years old. Measurements of DLS signals were obtained during both occlusion and nonocclusion of blood flow in the finger. For the nonocclusion case we found that the low-frequency component of the DLS signal significantly correlates with the biological age while the high-frequency component of the DLS signal resembles the arterial pulse-wave and does correlate with age. However, the most prominent correlation between the DLS characteristics and age was noted with the stasis stage measurements. We propose that the observed age-related phenomena are caused by alterations in local blood viscosity and interactions of the endothelial cells with erythrocytes. Further, a new noninvasive index based on the age-related optical characteristics was introduced. This noninvasive index may be used as a research and diagnostic tool to examine the endothelial and thrombolytic properties of the vascular system.

k-Neighborhood decentralization: a comprehensive solution to index the UMLS for large scale knowledge discovery.

PubMed

Xiang, Yang; Lu, Kewei; James, Stephen L; Borlawsky, Tara B; Huang, Kun; Payne, Philip R O

2012-04-01

The Unified Medical Language System (UMLS) is the largest thesaurus in the biomedical informatics domain. Previous works have shown that knowledge constructs comprised of transitively-associated UMLS concepts are effective for discovering potentially novel biomedical hypotheses. However, the extremely large size of the UMLS becomes a major challenge for these applications. To address this problem, we designed a k-neighborhood Decentralization Labeling Scheme (kDLS) for the UMLS, and the corresponding method to effectively evaluate the kDLS indexing results. kDLS provides a comprehensive solution for indexing the UMLS for very efficient large scale knowledge discovery. We demonstrated that it is highly effective to use kDLS paths to prioritize disease-gene relations across the whole genome, with extremely high fold-enrichment values. To our knowledge, this is the first indexing scheme capable of supporting efficient large scale knowledge discovery on the UMLS as a whole. Our expectation is that kDLS will become a vital engine for retrieving information and generating hypotheses from the UMLS for future medical informatics applications. Copyright © 2011 Elsevier Inc. All rights reserved.

The paravertebral muscle and psoas for the maintenance of global spinal alignment in patient with degenerative lumbar scoliosis.

PubMed

Yagi, Mitsuru; Hosogane, Naobumi; Watanabe, Kota; Asazuma, Takashi; Matsumoto, Morio

2016-04-01

Various factors are reported to affect the spinal alignment in degenerative lumbar scoliosis (DLS). Although trunk muscles also appear to affect spinal alignment, the role of the trunk muscles is not yet clear. The aim was to elucidate the role of the multifidus (MF) and psoas (PS) in maintaining global spinal alignment in patients with DLS. This was a multicenter retrospective matched cohort study. Surgically treated 60 paired DLS and lumbar spinal stenosis (LSS) female (120 patients), matched for age and body mass index (BMI; DLS age 68.0±6.8 vs. LSS 67.1±8.9 years; BMI 21.6±3.3 vs. 23.2±3.8 kg/m(2)), were included and were followed for at least 2 years. Spinal alignment, muscle area, and volume were measured from radiographs, magnetic resonance images (MRIs), and whole-body dual-energy X-ray absorptiometry (DXA) scans. Muscle strength was measured by grip power and peak expiratory flow (PEF). As a surrogate of muscle area, we obtained the cross-sectional area (CSA) at the L5-S level from preoperative MRIs. The MF and PS CSAs were significantly smaller in the DLS group than in the LSS group (MF 477.7±192.5 vs. 779.8±248.6 mm(2), p<.01; PS 692.3±201.2 vs. 943.4±272.4 mm(2), p=.002), whereas percentage of difference between the right and left sides was significantly larger in the DLS group (MF 18.4±30.6 vs. 2.4±3.3%, p<.01; PS 14.4±15.8 vs. 2.1±2.2%, p<.01). In the extremities, there were no significant differences in the left- or right-side lean composition and grip strength or PEF tests between the groups. Correlation coefficient tests showed moderate correlations between the MF average CSA (avCSA) and global spinal alignment and spinopelvic alignment (pelvic incidence-lumbar lordosis; R=-0.37, -0.38) in the DLS group. The MF avCSA was correlated with the postoperative progression of kyphosis at the unfused thoracic vertebrae in the DLS group (R=0.34). The CSAs of the MF and PS were significantly smaller in the DLS group. Whole-body DXA showed no significant difference in the lean composition between the groups. There were significant correlations in the DLS patients between the MF CSA and sagittal spinal alignment. These findings suggest the causal relationship between muscles and global spine alignment. Copyright © 2016 Elsevier Inc. All rights reserved.

Complexes of dichloro[2-(dimethylaminomethyl)phenyl-C1,N]gold(III), [Au(damp-C1,N)Cl2], with formylferrocene thiosemicarbazones: synthesis, structure and cytotoxicity.

PubMed

Casas, José S; Castaño, María V; Cifuentes, María C; García-Monteagudo, Juán C; Sánchez, Agustín; Sordo, José; Abram, Ulrich

2004-06-01

Dichloro[2-(dimethylaminomethyl)phenyl- phenyl-C1,N]gold(III), [Au(damp-C1,N)Cl2], reacts with the formylferrocene thiosemicarbazones derived from 4-methyl-, 4-phenyl-, 4-ethyl- and 4,4-dimethyl-3-thiosemicarbazides, HFcTSC, to give complexes of general formula [Au(Hdamp-1C)Cl(FcTSC)]Cl. These complexes were isolated and characterized by elemental analysis, mass spectrometry and IR, 1H NMR and (13)C NMR spectroscopy. In some cases, cyclic voltammetric studies were carried out and these showed that the complexation of gold affects the redox behaviour of the ferrocene unit. The in vitro antitumor activity against the HeLa cell line was also determined for the more soluble complexes. The IC(50) values were found to be higher than that of cisplatin but the maximum antiproliferative activity was similar.

Novel rapid genotyping assays for neuronal ceroid lipofuscinosis in Border Collie dogs and high frequency of the mutant allele in Japan.

PubMed

Mizukami, Keijiro; Chang, Hye-Sook; Yabuki, Akira; Kawamichi, Takuji; Kawahara, Natsuko; Hayashi, Daisuke; Hossain, Mohammad A; Rahman, Mohammad M; Uddin, Mohammad M; Yamato, Osamu

2011-11-01

Neuronal ceroid lipofuscinosis (NCL) constitutes a group of recessively inherited lysosomal storage diseases that primarily affect neuronal cells. Such diseases share certain clinical and pathologic features in human beings and animals. Neuronal ceroid lipofuscinosis in Border Collie dogs was first detected in Australia in the 1980s, and the pathogenic mutation was shown to be a nonsense mutation (c.619C>T) in exon 4 in canine CLN5 gene. In the present study, novel rapid genotyping assays including polymerase chain reaction (PCR)-restriction fragment length polymorphism, PCR primer-induced restriction analysis, mutagenically separated PCR, and real-time PCR with TaqMan minor groove binder probes, were developed. The utility of microchip electrophoresis was also evaluated. Furthermore, a genotyping survey was carried out in a population of Border Collies in Japan using these assays to determine the current allele frequency in Japan, providing information to control and prevent this disease in the next stage. All assays developed in the current study are available to discriminate these genotypes, and microchip electrophoresis showed a timesaving advantage over agarose gel electrophoresis. Of all assays, real-time PCR was the most suitable for large-scale examination because of its high throughput. The genotyping survey demonstrated that the carrier frequency was 8.1%. This finding suggested that the mutant allele frequency of NCL in Border Collies is high enough in Japan that measures to control and prevent the disease would be warranted. The genotyping assays developed in the present study could contribute to the prevention of NCL in Border Collies.

Relative contribution of potential modes of surface dust lead contamination in the homes of boatyard caulkers.

PubMed

Untimanon, Orrapan; Geater, Alan; Chongsuvivatwong, Virasakdi; Saetia, Wiyada; Verkasalo, Pia K

2012-01-01

The aim of this study was to quantify the relative contributions to surface lead contamination of boat-caulkers' houses of three contamination modes, namely "take-home" lead from the caulker, "natural" spatial dispersal from boatyard to household and "redistribution" of accumulated lead-laden dust within the house. Boat-caulkers' houses situated in areas surrounding boat repair yards were recruited. Caulkers' houses that were located close together were divided into location-matched pairs, within which one was randomly assigned to be given a cleaning and designated a CL house, and the other was to be left uncleaned and designated a NCL house. Geographically isolated caulker's houses were randomly assigned to one of the two categories. The nearest non-boatyard worker's house (NB) was additionally recruited for each set. The surface lead loading rate (SLLR), defined as the mass of lead deposited in dust per unit area of surface per unit time, was measured over a period of 3 mo in all houses, and the data were modeled using linear mixed effects regression. Adjusted values of SLLR differed only slightly between CL and NCL houses (0.96 to 1.02 times) but were between 1.65 and 2.03 times higher in CL and NCL houses than in NB houses depending on proximity to the boatyard and between 2.12 and 2.61 times higher in houses within one km of a boatyard than in more distant houses depending on category of house. Newly deposited dust lead likely resulted from the take-home and spatial dispersion modes. The contribution of redistribution is very small.

Spectroscopic parameters, vibrational levels, transition dipole moments and transition probabilities of the 9 low-lying states of the NCl+ cation

NASA Astrophysics Data System (ADS)

Yin, Yuan; Shi, Deheng; Sun, Jinfeng; Zhu, Zunlue

2018-03-01

This work calculates the potential energy curves of 9 Λ-S and 28 Ω states of the NCl+ cation. The technique employed is the complete active space self-consistent field method, which is followed by the internally contracted multireference configuration interaction approach with the Davidson correction. The Λ-S states are X2Π, 12Σ+, 14Π, 14Σ+, 14Σ-, 24Π, 14Δ, 16Σ+, and 16Π, which are yielded from the first two dissociation channels of NCl+ cation. The Ω states are generated from these Λ-S states. The 14Π, 14Δ, 16Σ+, and 16Π states are inverted with the spin-orbit coupling effect included. The 14Σ+, 16Σ+, and 16Π states are very weakly bound, whose well depths are only several-hundred cm- 1. One avoided crossing of PECs occurs between the 12Σ+ and 22Σ+ states. To improve the quality of potential energy curves, core-valence correlation and scalar relativistic corrections are included. The potential energies are extrapolated to the complete basis set limit. The spectroscopic parameters and vibrational levels are calculated. The transition dipole moments are computed. The Franck-Condon factors, Einstein coefficients, and radiative lifetimes of many transitions are determined. The spectroscopic approaches are proposed for observing these states according to the transition probabilities. The spin-orbit coupling effect on the spectroscopic and vibrational properties is evaluated. The spectroscopic parameters, vibrational levels, transition dipole moments, as well as transition probabilities reported in this paper could be considered to be very reliable.

Integration of Multiple Data Sources to Simulate the Dynamics of Land Systems

PubMed Central

Deng, Xiangzheng; Su, Hongbo; Zhan, Jinyan

2008-01-01

In this paper we present and develop a new model, which we have called Dynamics of Land Systems (DLS). The DLS model is capable of integrating multiple data sources to simulate the dynamics of a land system. Three main modules are incorporated in DLS: a spatial regression module, to explore the relationship between land uses and influencing factors, a scenario analysis module of the land uses of a region during the simulation period and a spatial disaggregation module, to allocate land use changes from a regional level to disaggregated grid cells. A case study on Taips County in North China is incorporated in this paper to test the functionality of DLS. The simulation results under the baseline, economic priority and environmental scenarios help to understand the land system dynamics and project near future land-use trajectories of a region, in order to focus management decisions on land uses and land use planning. PMID:27879726

Dynamic lumbopelvic stabilization for treatment of stress urinary incontinence in women: Controlled and randomized clinical trial.

PubMed

de Souza Abreu, Nathalia; de Castro Villas Boas, Bia; Netto, José Murilo Bastos; Figueiredo, André Avarese

2017-11-01

To compare the results of the dynamic lumbopelvic stabilization (DLS) exercises with exercises for the pelvic floor muscles (PFM) in women with stress urinary incontinence. Randomized controlled clinical trial comparing 17 women submitted to the DLS with 16 women submitted to the exercises for the PFM. The evaluated outcomes were incontinence severity, quality of life (QoL), and impression of improvement in three moments. Significance was set at 5%. For socio-demographic and clinical variables, only climacteric was more prevalent in the DLS group (82% vs. 44%, P = 0.02). Soon after the intervention, there was no difference between the groups in relation to the outcomes evaluated. In the evaluation after 90 days, the DLS group presented better values for the severity of the losses (4.1 ± 2.6 vs. 5.7 ± 2.4, P = 0.006, d = 0.64), daytime frequency (4.6 ± 0.4 vs. 6.2 ± 0.6, P < 0.001, d = 2.67), and nighttime frequency (0.4 ± 0.3 vs. 1.4 ± 0.5, P < 0.001, d = 2.50), QoL and impression of improvement (P < 0.001). After treatment, the DLS plus PFM exercise patients had results similar to those performing PFM exercises alone. However, the DLS plus PFM exercises were superior in the outcomes of incontinence severity, QoL, and impression of improvement in the post-90-day evaluation, showing longer lasting effect. © 2017 Wiley Periodicals, Inc.

Quantitative molecular characterization of bovine vitreous and lens with non-invasive dynamic light scattering

NASA Technical Reports Server (NTRS)

Ansari, R. R.; Suh, K. I.; Dunker, S.; Kitaya, N.; Sebag, J.

2001-01-01

The non-invasive technique of dynamic light scattering (DLS) was used to quantitatively characterize vitreous and lens structure on a molecular level by measuring the sizes of the predominant particles and mapping the three-dimensional topographic distribution of these structural macromolecules in three spatial dimensions. The results of DLS measurements in five fresh adult bovine eyes were compared to DLS measurements in model solutions of hyaluronan (HA) and collagen (Coll). In the bovine eyes DLS measurements were obtained from excised samples of gel and liquid vitreous and compared to the model solutions. Measurements in whole vitreous were obtained at multiple points posterior to the lens to generate a three-dimensional 'map' of molecular structure. The macromolecule distribution in bovine lens was similarly characterized.In each bovine vitreous (Bo Vit) specimen, DLS predominantly detected two distinct particles, which differed in diffusion properties and hence size. Comparisons with model vitreous solutions demonstrated that these most likely corresponded to the Coll and HA components of vitreous. Three-dimensional mapping of Bo Vit found heterogeneity throughout the vitreous body, with different particle size distributions for Coll and HA at different loci. In contrast, the three-dimensional distribution of lens macromolecules was more homogeneous. Thus, the non-invasive DLS technique can quantitate the average sizes of vitreous and lens macromolecules and map their three-dimensional distribution. This method to assess quantitatively the macromolecular structure of vitreous and lens should be useful for clinical as well as experimental applications in health and disease. Copyright 2001 Academic Press.

Inhibition of presynaptic calcium transients in cortical inputs to the dorsolateral striatum by metabotropic GABAB and mGlu2/3 receptors

PubMed Central

Kupferschmidt, David A; Lovinger, David M

2015-01-01

Cortical inputs to the dorsolateral striatum (DLS) are dynamically regulated during skill learning and habit formation, and are dysregulated in disorders characterized by impaired action control. Therefore, a mechanistic investigation of the processes regulating corticostriatal transmission is key to understanding DLS-associated circuit function, behaviour and pathology. Presynaptic GABAB and group II metabotropic glutamate (mGlu2/3) receptors exert marked inhibitory control over corticostriatal glutamate release in the DLS, yet the signalling pathways through which they do so are unclear. We developed a novel approach using the genetically encoded calcium (Ca2+) indicator GCaMP6 to assess presynaptic Ca2+ in corticostriatal projections to the DLS. Using simultaneous photometric presynaptic Ca2+ and striatal field potential recordings, we report that relative to P/Q-type Ca2+ channels, N-type channels preferentially contributed to evoked presynaptic Ca2+ influx in motor cortex projections to, and excitatory transmission in, the DLS. Activation of GABAB or mGlu2/3 receptors inhibited both evoked presynaptic Ca2+ transients and striatal field potentials. mGlu2/3 receptor-mediated depression did not require functional N-type Ca2+ channels, but was attenuated by blockade of P/Q-type channels. These findings reveal presynaptic mechanisms of inhibitory modulation of corticostriatal function that probably contribute to the selection and shaping of behavioural repertoires. Key points Plastic changes at cortical inputs to the dorsolateral striatum (DLS) underlie skill learning and habit formation, so characterizing the mechanisms by which these inputs are regulated is important for understanding the neural basis of action control. We developed a novel approach using the genetically encoded calcium (Ca2+) indicator GCaMP6 and brain slice photometry to assess evoked presynaptic Ca2+ transients in cortical inputs to the DLS and study their regulation by GABAB and mGlu2/3 receptors. GABAB and mGlu2/3 receptor activation caused clear reductions in electrical stimulus-evoked presynaptic Ca2+ transients in corticostriatal inputs to the DLS. Functional P/Q-type voltage-gated Ca2+ channels were required for the normal inhibitory action of corticostriatal mGlu2/3 receptors. We provide direct evidence of presynaptic Ca2+ inhibition by G protein-coupled receptors at corticostriatal projections. PMID:25781000

Materials Data on H12W3C4NCl9 (SG:164) by Materials Project

DOE Data Explorer

Kristin Persson

2015-01-27

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

Materials Data on Nb3H12C4NCl9 (SG:164) by Materials Project

DOE Data Explorer

Kristin Persson

2015-01-27

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

NCL-02: Nanomedicine Pharmacokinetics in Rats Evaluated by SITUA | Frederick National Laboratory for Cancer Research

Cancer.gov

The Nanotechnology Characterization Laboratory will evaluate the pharmacokinetics of a nanoparticulate formulation in rats using a novel stable isotope tracer ultrafiltration assay (SITUA) developed at thelaboratory. The SITUA is a method to fr

Materials Data on H12C4NClO4 (SG:18) by Materials Project

DOE Data Explorer

Kristin Persson

2014-11-02

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

Dynamic light scattering: A fast and reliable method to analyze bacterial growth during the lag phase.

PubMed

Vargas, Susana; Millán-Chiu, Blanca E; Arvizu-Medrano, Sofía M; Loske, Achim M; Rodríguez, Rogelio

2017-06-01

A comparison between plate counting (PC) and dynamic light scattering (DLS) is reported. PC is the standard technique to determine bacterial population as a function of time; however, this method has drawbacks, such as the cumbersome preparation and handling of samples, as well as the long time required to obtain results. Alternative methods based on optical density are faster, but do not distinguish viable from non-viable cells. These inconveniences are overcome by using DLS. Two different bacteria strains were considered: Escherichia coli and Staphylococcus aureus. DLS was performed at two different illuminating conditions: continuous and intermittent. By the increment of particle size as a function of time, it was possible to observe cell division and the formation of aggregates containing very few bacteria. The scattered intensity profiles showed the lag phase and the transition to the exponential phase of growth, providing a quantity proportional to viable bacteria concentration. The results revealed a clear and linear correlation in both lag and exponential phase, between the Log 10 (colony-forming units/mL) from PC and the Log 10 of the scattered intensity I s from DLS. These correlations provide a good support to use DLS as an alternative technique to determine bacterial population. Copyright © 2017 Elsevier B.V. All rights reserved.

Sensory Processing in the Dorsolateral Striatum: The Contribution of Thalamostriatal Pathways

PubMed Central

Alloway, Kevin D.; Smith, Jared B.; Mowery, Todd M.; Watson, Glenn D. R.

2017-01-01

The dorsal striatum has two functionally-defined subdivisions: a dorsomedial striatum (DMS) region involved in mediating goal-directed behaviors that require conscious effort, and a dorsolateral striatum (DLS) region involved in the execution of habitual behaviors in a familiar sensory context. Consistent with its presumed role in forming stimulus-response (S-R) associations, neurons in DLS receive massive inputs from sensorimotor cortex and are responsive to both active and passive sensory stimulation. While several studies have established that corticostriatal inputs contribute to the stimulus-induced responses observed in the DLS, there is growing awareness that the thalamus has a significant role in conveying sensory-related information to DLS and other parts of the striatum. The thalamostriatal projections to DLS originate mainly from the caudal intralaminar region, which contains the parafascicular (Pf) nucleus, and from higher-order thalamic nuclei such as the medial part of the posterior (POm) nucleus. Based on recent findings, we hypothesize that the thalamostriatal projections from these two regions exert opposing influences on the expression of behavioral habits. This article reviews the subcortical circuits that regulate the transmission of sensory information through these thalamostriatal projection systems, and describes the evidence that indicates these circuits could be manipulated to ameliorate the symptoms of Parkinson’s disease (PD) and related neurological disorders. PMID:28790899

Enhanced stability of superparamagnetic iron oxide nanoparticles in biological media using a pH adjusted-BSA adsorption protocol

NASA Astrophysics Data System (ADS)

Yu, Si-Ming; Laromaine, Anna; Roig, Anna

2014-07-01

Superparamagnetic iron oxide nanoparticles (SPIONs) are widely used for biological applications due to their unique properties compared to their bulk counterparts, simplified SPIONs stabilization protocols applicable for a wide spectra of biological media remains a challenging issue. In this work, SPIONs with different surface coatings, tetramethylammonium hydroxide-coated SPIONs (T-SPIONs), and citrate-coated SPIONs (C-SPIONs) were synthesized by a facile, rapid and cost effective microwave-assisted method. C-SPIONs show robust stability in biological media of phosphate buffered saline and Roswell Park Memorial Institute Medium, while destabilize in DMEM. T-SPIONs were found to aggregate rapidly and significantly in all tested media. Then, a modified pH adjusted-BSA adsorption protocol and an addition of excess trisodium citrate dihydrate (Na3Cit) were used to enhance their stability in the media. The BSA adsorption protocol showed great efficiency in stabilizing the dispersed state of both SPIONs in the tested media, while the addition of excess Na3Cit showed limited effect, and it was only applicable for C-SPIONs. The formed BSA layer on SPIONs could be imaged by negative staining TEM, and revealed by Cryo-TEM, FTIR, DLS, and the zeta potential measurements. Results indicated that BSA forms a monolayer of a thickness of about 3 ± 1 nm and BSA interacts with C-SPIONs and T-SPIONs through their coating, rather than by replacing them. This synthetic method and stabilization protocol offer a general methodology to obtain SPIONs with a variety of surfactants, stable in different biological media in few minutes.

40 CFR 63.8540 - What parts of my plant does this subpart cover?

Code of Federal Regulations, 2010 CFR

2010-07-01

... retrofitting with a dry lime injection fabric filter (DIFF), dry lime scrubber/fabric filter (DLS/FF), or wet... fired product to meet the relevant standards by retrofitting with a DIFF, DLS/FF, or WS. (g) An affected...

Nanotechnology Laboratory Collaborates with Army to Develop Botulism Vaccine | Frederick National Laboratory for Cancer Research

Cancer.gov

The Nanotechnology Characterization Laboratory (NCL) is collaborating with the Army to develop a candidate vaccine against botulism. Under a collaboration agreement between the National Cancer Institute and the U.S. Army Medical Research Institute of

Materials Data on TaSi2PH18C6(NCl3)2 (SG:14) by Materials Project

DOE Data Explorer

Kristin Persson

2014-11-02

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

Implication of Highly Cytotoxic Natural Killer Cells for Esophageal Squamous Cell Carcinoma Treatment.

PubMed

Lim, Kee Siang; Mimura, Kosaku; Kua, Ley-Fang; Shiraishi, Kensuke; Kono, Koji

2018-04-20

Esophageal squamous cell carcinoma (ESCC) is an aggressive upper gastrointestinal cancer and effective treatments are limited. Previous studies reported that natural killer (NK) cells expanded by coculturing with K562-mb15-41BBL feeder cells, a genetically modified K562 leukemia cell line that expresses membrane-bound interleukin (IL)-15 and 41BBL ligand, were highly proliferative and highly cytotoxic. Here, we investigated the potential of expanded NK cells for ESCC treatment. We analyzed both genetic and surface expression levels of NKG2D ligands (NKG2DLs) in ESCC using publicly available microarray data sets and ESCC cell lines. The cytotoxicity of resting and of IL-2-activated NK cells against ESCC cell lines was compared with that of expanded NK cells. We then also investigated the effect of epithelial mesenchymal transition (EMT) inducers, GSK3β inhibitor and epidermal growth factor, on NKG2DLs expressions. As a result, MICA and MICB were significantly overexpressed in ESCC compared with adjacent normal tissues and surface NKG2DLs were expressed in ESCC cell lines. Expanded NK cells were much potent than IL-2-activated and resting NK cells against ESCC cell lines. Blocking of NKG2D with anti-NKG2D monoclonal antibody dampened expanded NK cell cytotoxicity, suggesting that the NKG2DLs-NKG2D interaction is crucial for NK cells to eliminate ESCC cells. EMT inducers concurrently induced EMT and NKG2DLs expression in ESCC cell lines rendering transitioned cells more sensitive to expanded NK cells. In conclusion, expanded NK cells were highly cytotoxic against NKG2DLs-expressing ESCC cells, particularly the EMT phenotype. These results provide a strong rationale for clinical use of these NK cells in ESCC patients.

Dynamic locking screw improves fixation strength in osteoporotic bone: an in vitro study on an artificial bone model.

PubMed

Pohlemann, Tim; Gueorguiev, Boyko; Agarwal, Yash; Wahl, Dieter; Sprecher, Christoph; Schwieger, Karsten; Lenz, Mark

2015-04-01

The novel dynamic locking screw (DLS) was developed to improve bone healing with locked-plate osteosynthesis by equalising construct stiffness at both cortices. Due to a theoretical damping effect, this modulated stiffness could be beneficial for fracture fixation in osteoporotic bone. Therefore, the mechanical behaviour of the DLS at the screw-bone interface was investigated in an artificial osteoporotic bone model and compared with conventional locking screws (LHS). Osteoporotic surrogate bones were plated with either a DLS or a LHS construct consisting of two screws and cyclically axially loaded (8,500 cycles, amplitude 420 N, increase 2 mN/cycle). Construct stiffness, relative movement, axial screw migration, proximal (P) and distal (D) screw pullout force and loosening at the bone interface were determined and statistically evaluated. DLS constructs exhibited a higher screw pullout force of P 85 N [standard deviation (SD) 21] and D 93 N (SD 12) compared with LHS (P 62 N, SD 28, p = 0.1; D 57 N, SD 25, p < 0.01) and a significantly lower axial migration over cycles compared with LHS (p = 0.01). DLS constructs showed significantly lower axial construct stiffness (403 N/mm, SD 21, p < 0.01) and a significantly higher relative movement (1.1 mm, SD 0.05, p < 0.01) compared with LHS (529 N/mm, SD 27; 0.8 mm, SD 0.04). Based on the model data, the DLS principle might also improve in vivo plate fixation in osteoporotic bone, providing enhanced residual holding strength and reducing screw cutout. The influence of pin-sleeve abutment still needs to be investigated.

Atp13a2-deficient mice exhibit neuronal ceroid lipofuscinosis, limited α-synuclein accumulation and age-dependent sensorimotor deficits

PubMed Central

Schultheis, Patrick J.; Fleming, Sheila M.; Clippinger, Amy K.; Lewis, Jada; Tsunemi, Taiji; Giasson, Benoit; Dickson, Dennis W.; Mazzulli, Joseph R.; Bardgett, Mark E.; Haik, Kristi L.; Ekhator, Osunde; Chava, Anil Kumar; Howard, John; Gannon, Matt; Hoffman, Elizabeth; Chen, Yinhuai; Prasad, Vikram; Linn, Stephen C.; Tamargo, Rafael J.; Westbroek, Wendy; Sidransky, Ellen; Krainc, Dimitri; Shull, Gary E.

2013-01-01

Mutations in ATP13A2 (PARK9), encoding a lysosomal P-type ATPase, are associated with both Kufor–Rakeb syndrome (KRS) and neuronal ceroid lipofuscinosis (NCL). KRS has recently been classified as a rare genetic form of Parkinson's disease (PD), whereas NCL is a lysosomal storage disorder. Although the transport activity of ATP13A2 has not been defined, in vitro studies show that its loss compromises lysosomal function, which in turn is thought to cause neuronal degeneration. To understand the role of ATP13A2 dysfunction in disease, we disrupted its gene in mice. Atp13a2−/− and Atp13a2+/+ mice were tested behaviorally to assess sensorimotor and cognitive function at multiple ages. In the brain, lipofuscin accumulation, α-synuclein aggregation and dopaminergic pathology were measured. Behaviorally, Atp13a2−/− mice displayed late-onset sensorimotor deficits. Accelerated deposition of autofluorescent storage material (lipofuscin) was observed in the cerebellum and in neurons of the hippocampus and the cortex of Atp13a2−/− mice. Immunoblot analysis showed increased insoluble α-synuclein in the hippocampus, but not in the cortex or cerebellum. There was no change in the number of dopaminergic neurons in the substantia nigra or in striatal dopamine levels in aged Atp13a2−/− mice. These results show that the loss of Atp13a2 causes sensorimotor impairments, α-synuclein accumulation as occurs in PD and related synucleinopathies, and accumulation of lipofuscin deposits characteristic of NCL, thus providing the first direct demonstration that null mutations in Atp13a2 can cause pathological features of both diseases in the same organism. PMID:23393156

Chemical synthesis of La1 isolated from the venom of the scorpion Liocheles australasiae and determination of its disulfide bonding pattern.

PubMed

Nagao, Junya; Miyashita, Masahiro; Nakagawa, Yoshiaki; Miyagawa, Hisashi

2015-08-01

La1 is a 73-residue cysteine-rich peptide isolated from the scorpion Liocheles australasiae venom. Although La1 is the most abundant peptide in the venom, its biological function remains unknown. Here, we describe a method for efficient chemical synthesis of La1 using the native chemical ligation (NCL) strategy, in which three peptide components of less than 40 residues were sequentially ligated. The peptide thioester necessary for NCL was synthesized using an aromatic N-acylurea approach with Fmoc-SPPS. After completion of sequential NCL, disulfide bond formation was carried out using a dialysis method, in which the linear peptide dissolved in an acidic solution was dialyzed against a slightly alkaline buffer to obtain correctly folded La1. Next, we determined the disulfide bonding pattern of La1. Enzymatic and chemical digests of La1 without reduction of disulfide bonds were analyzed by liquid chromatography/mass spectrometry (LC/MS), which revealed two of four disulfide bond linkages. The remaining two linkages were assigned based on MS/MS analysis of a peptide fragment containing two disulfide bonds. Consequently, the disulfide bonding pattern of La1 was found to be similar to that of a von Willebrand factor type C (VWC) domain. To our knowledge, this is the first report of the experimental determination of the disulfide bonding pattern of peptides having a single VWC domain as well as their chemical synthesis. La1 synthesized in this study will be useful for investigation of its biological role in the venom. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.

Assembly of a Comprehensive Regulatory Network for the Mammalian Circadian Clock: A Bioinformatics Approach

PubMed Central

Lehmann, Robert; Abreu, Monica; Fuhr, Luise; Herzel, Hanspeter; Leser, Ulf; Relógio, Angela

2015-01-01

By regulating the timing of cellular processes, the circadian clock provides a way to adapt physiology and behaviour to the geophysical time. In mammals, a light-entrainable master clock located in the suprachiasmatic nucleus (SCN) controls peripheral clocks that are present in virtually every body cell. Defective circadian timing is associated with several pathologies such as cancer and metabolic and sleep disorders. To better understand the circadian regulation of cellular processes, we developed a bioinformatics pipeline encompassing the analysis of high-throughput data sets and the exploitation of published knowledge by text-mining. We identified 118 novel potential clock-regulated genes and integrated them into an existing high-quality circadian network, generating the to-date most comprehensive network of circadian regulated genes (NCRG). To validate particular elements in our network, we assessed publicly available ChIP-seq data for BMAL1, REV-ERBα/β and RORα/γ proteins and found strong evidence for circadian regulation of Elavl1, Nme1, Dhx6, Med1 and Rbbp7 all of which are involved in the regulation of tumourigenesis. Furthermore, we identified Ncl and Ddx6, as targets of RORγ and REV-ERBα, β, respectively. Most interestingly, these genes were also reported to be involved in miRNA regulation; in particular, NCL regulates several miRNAs, all involved in cancer aggressiveness. Thus, NCL represents a novel potential link via which the circadian clock, and specifically RORγ, regulates the expression of miRNAs, with particular consequences in breast cancer progression. Our findings bring us one step forward towards a mechanistic understanding of mammalian circadian regulation, and provide further evidence of the influence of circadian deregulation in cancer. PMID:25945798

Vascular endothelial growth factor A (VEGF-A) decreases expression and secretion of pleiotrophin in a VEGF receptor-independent manner.

PubMed

Poimenidi, Evangelia; Theodoropoulou, Christina; Koutsioumpa, Marina; Skondra, Lamprini; Droggiti, Eirini; van den Broek, Marloes; Koolwijk, Pieter; Papadimitriou, Evangelia

2016-05-01

Vascular endothelial growth factor A (VEGF-A) is a key molecule in angiogenesis acting through VEGF receptors (VEGFRs), ανβ3 integrin, receptor protein tyrosine phosphatase beta/zeta (RPTPβ/ζ) and cell surface nucleolin (NCL). Pleiotrophin (PTN) stimulates endothelial cell migration and limits the angiogenic effects of VEGF-A165 to the levels of its own effect, possibly acting as a VEGF-A165 modifier. Since PTN and VEGF-A165 share receptors and actions on endothelial cells, in the present work we studied whether and how VEGF-A165 affects PTN expression or secretion. VEGF-A165 decreased PTN mRNA and protein levels acting at the transcriptional level. Bevacizumab, a selective VEGFR2 tyrosine kinase inhibitor and down-regulation of VEGFR2 expression by siRNA did not affect this decrease, suggesting that it is VEGFR-independent. VEGF-A121 also decreased PTN mRNA and protein levels, suggesting that heparin binding of VEGF-A165 is not involved. Blockage of cell surface NCL, lack of expression or mutation of β3 integrin and down-regulation of RPTPβ/ζ abolished the inhibitory effect of VEGF-A165 on PTN expression and secretion. Down-regulation of endogenous PTN in endothelial cells enhanced VEGF-A165-induced increase in migration and tube formation on matrigel. Collectively, these data suggest that VEGF-A down-regulates PTN expression and secretion through the RPTPβ/ζ-ανβ3-NCL axis to enhance its own effect on cell migration and further highlight the role of RPTPβ/ζ in VEGF-A actions. Copyright © 2016 Elsevier Inc. All rights reserved.

Pathway-Specific Striatal Substrates for Habitual Behavior.

PubMed

O'Hare, Justin K; Ade, Kristen K; Sukharnikova, Tatyana; Van Hooser, Stephen D; Palmeri, Mark L; Yin, Henry H; Calakos, Nicole

2016-02-03

The dorsolateral striatum (DLS) is implicated in habit formation. However, the DLS circuit mechanisms underlying habit remain unclear. A key role for DLS is to transform sensorimotor cortical input into firing of output neurons that project to the mutually antagonistic direct and indirect basal ganglia pathways. Here we examine whether habit alters this input-output function. By imaging cortically evoked firing in large populations of pathway-defined striatal projection neurons (SPNs), we identify features that strongly correlate with habitual behavior on a subject-by-subject basis. Habitual behavior correlated with strengthened DLS output to both pathways as well as a tendency for action-promoting direct pathway SPNs to fire before indirect pathway SPNs. In contrast, habit suppression correlated solely with a weakened direct pathway output. Surprisingly, all effects were broadly distributed in space. Together, these findings indicate that the striatum imposes broad, pathway-specific modulations of incoming activity to render learned motor behaviors habitual. Copyright © 2016 Elsevier Inc. All rights reserved.

A Survey of Complex Object Technologies for Digital Libraries

NASA Technical Reports Server (NTRS)

Nelson, Michael L.; Argue, Brad; Efron, Miles; Denn, Sheila; Pattuelli, Maria Cristina

2001-01-01

Many early web-based digital libraries (DLs) had implicit assumptions reflected in their architecture that the unit of focus in the DL (frequently "reports" or "e-prints") would only be manifested in a single, or at most a few, common file formats such as PDF or PostScript. DLs have now matured to the point where their contents are commonly no longer simple files. Complex objects in DLs have emerged from in response to various requirements, including: simple aggregation of formats and supporting files, bundling additional information to aid digital preservation, creating opaque digital objects for e-commerce applications, and the incorporation of dynamic services with the traditional data files. We examine a representative (but not necessarily exhaustive) number of current and recent historical web-based complex object technologies and projects that are applicable to DLs: Aurora, Buckets, ComMentor, Cryptolopes, Digibox, Document Management Alliance, FEDORA, Kahn-Wilensky Framework Digital Objects, Metadata Encoding & Transmission Standard, Multivalent Documents, Open eBooks, VERS Encapsulated Objects, and the Warwick Framework.

How does sagittal imbalance affect the appropriateness of surgical indications and selection of procedure in the treatment of degenerative scoliosis? Findings from the RAND/UCLA Appropriate Use Criteria study.

PubMed

Daubs, Michael D; Brara, Harsimran S; Raaen, Laura B; Chen, Peggy Guey-Chi; Anderson, Ashaunta T; Asch, Steven M; Nuckols, Teryl K

2018-05-01

Degenerative lumbar scoliosis (DLS) is often associated with sagittal imbalance, which may affect patients' health outcomes before and after surgery. The appropriateness of surgery and preferred operative approaches has not been examined in detail for patients with DLS and sagittal imbalance. The goals of this article were to describe what is currently known about the relationship between sagittal imbalance and health outcomes among patients with DLS and to determine how indications for surgery in patients with DLS differ when sagittal imbalance is present. This study included a literature review and an expert panel using the RAND/University of California at Los Angeles (UCLA) Appropriateness Method. To develop appropriate use criteria for DLS, researchers at the RAND Corporation recently employed the RAND/UCLA Appropriateness Method, which involves a systematic review of the literature and multidisciplinary expert panel process. Experts reviewed a synopsis of published literature and rated the appropriateness of five common operative approaches for 260 different clinical scenarios. In the present work, we updated the literature review and compared panelists' ratings in scenarios where imbalance was present versus absent. This work was funded by the Collaborative Spine Research Foundation, a group of surgical specialty societies and device manufacturers. On the basis of 13 eligible studies that examined sagittal imbalance and outcomes in patients with DLS, imbalance was associated with worse functional status in the absence of surgery and worse symptoms and complications postoperatively. Panelists' ratings demonstrated a consistent pattern across the diverse clinical scenarios. In general, when imbalance was present, surgery was more likely to be appropriate or necessary, including in some situations where surgery would otherwise be inappropriate. For patients with moderate to severe symptoms and imbalance, a deformity correction procedure was usually appropriate and frequently necessary, except in some patients with severe risk factors for complications. Conversely, procedures that did not correct imbalance, when present, were usually inappropriate. Clinical experts agreed that sagittal imbalance is a major factor affecting both when surgery is appropriate and which type of procedure is preferred among patients with DLS. Copyright © 2018 Elsevier Inc. All rights reserved.

High quality draft genome of Nakamurella lactea type strain, a rock actinobacterium, and emended description of Nakamurella lactea

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

Nouioui, Imen; Göker, Markus; Carro, Lorena

Nakamurella lactea DLS-10 T , isolated from rock in Korea, is one of the four type strains of the genus Nakamurella. In this study, we describe the high quality draft genome of N. lactea DLS-10 T and its annotation. A summary of phenotypic data collected from previously published studies was also included. The genome of strain DLS-10 T presents a size of 5.82 Mpb, 5100 protein coding genes, and a C + G content of 68.9%. Based on the genome analysis, emended description of N. lactea in terms of G + C content was also proposed.

High quality draft genome of Nakamurella lactea type strain, a rock actinobacterium, and emended description of Nakamurella lactea

DOE PAGES

Nouioui, Imen; Göker, Markus; Carro, Lorena; ...

2017-01-06

Nakamurella lactea DLS-10 T , isolated from rock in Korea, is one of the four type strains of the genus Nakamurella. In this study, we describe the high quality draft genome of N. lactea DLS-10 T and its annotation. A summary of phenotypic data collected from previously published studies was also included. The genome of strain DLS-10 T presents a size of 5.82 Mpb, 5100 protein coding genes, and a C + G content of 68.9%. Based on the genome analysis, emended description of N. lactea in terms of G + C content was also proposed.

Small nucleoli are a cellular hallmark of longevity

PubMed Central

Tiku, Varnesh; Jain, Chirag; Raz, Yotam; Nakamura, Shuhei; Heestand, Bree; Liu, Wei; Späth, Martin; Suchiman, H. Eka. D.; Müller, Roman-Ulrich; Slagboom, P. Eline; Partridge, Linda; Antebi, Adam

2017-01-01

Animal lifespan is regulated by conserved metabolic signalling pathways and specific transcription factors, but whether these pathways affect common downstream mechanisms remains largely elusive. Here we show that NCL-1/TRIM2/Brat tumour suppressor extends lifespan and limits nucleolar size in the major C. elegans longevity pathways, as part of a convergent mechanism focused on the nucleolus. Long-lived animals representing distinct longevity pathways exhibit small nucleoli, and decreased expression of rRNA, ribosomal proteins, and the nucleolar protein fibrillarin, dependent on NCL-1. Knockdown of fibrillarin also reduces nucleolar size and extends lifespan. Among wildtype C. elegans, individual nucleolar size varies, but is highly predictive for longevity. Long-lived dietary restricted fruit flies and insulin-like-peptide mutants exhibit small nucleoli and fibrillarin expression, as do long-lived dietary restricted and IRS1 knockout mice. Furthermore, human muscle biopsies from individuals who underwent modest dietary restriction coupled with exercise also display small nucleoli. We suggest that small nucleoli are a cellular hallmark of longevity and metabolic health conserved across taxa. PMID:28853436

Small nucleoli are a cellular hallmark of longevity.

PubMed

Tiku, Varnesh; Jain, Chirag; Raz, Yotam; Nakamura, Shuhei; Heestand, Bree; Liu, Wei; Späth, Martin; Suchiman, H Eka D; Müller, Roman-Ulrich; Slagboom, P Eline; Partridge, Linda; Antebi, Adam

2016-08-30

Animal lifespan is regulated by conserved metabolic signalling pathways and specific transcription factors, but whether these pathways affect common downstream mechanisms remains largely elusive. Here we show that NCL-1/TRIM2/Brat tumour suppressor extends lifespan and limits nucleolar size in the major C. elegans longevity pathways, as part of a convergent mechanism focused on the nucleolus. Long-lived animals representing distinct longevity pathways exhibit small nucleoli, and decreased expression of rRNA, ribosomal proteins, and the nucleolar protein fibrillarin, dependent on NCL-1. Knockdown of fibrillarin also reduces nucleolar size and extends lifespan. Among wildtype C. elegans, individual nucleolar size varies, but is highly predictive for longevity. Long-lived dietary restricted fruit flies and insulin-like-peptide mutants exhibit small nucleoli and fibrillarin expression, as do long-lived dietary restricted and IRS1 knockout mice. Furthermore, human muscle biopsies from individuals who underwent modest dietary restriction coupled with exercise also display small nucleoli. We suggest that small nucleoli are a cellular hallmark of longevity and metabolic health conserved across taxa.

Angle-resolved photoelectron spectroscopy of the chloro-substituted methanes

NASA Astrophysics Data System (ADS)

Keller, P. R.; Taylor, J. W.; Carlson, Thomas A.; Grimm, F. A.

1983-09-01

The angular distribution parameter, β, was determined for the valence orbitals (IP ' 21.2 eV) of CCl 4, CHCl 3, CH 2Cl 2, and CH 3Cl in the 10-30 eV photon energy range using dispersed polarized synchrotron radiation. The energy dependence of β in the photoelectron energy range of 2 to 10 eV for the non-bonding chlorine n(Cl) orbitals of these molecules was found to be similar for all n(Cl) orbitals investigated. The energy dependence of β for the σ orbitals in these molecules was similar to that observed previously for other σ orbitals. The experimental CCl 4 results were compared with theoretical CCl 4 results obtained using the Xα multiple scattering formalism. Theory predicts the existence of two strong shape resonances in each of the valence orbitals of CCl 4. The overall agreement between experiment and theory is evaluated along with the experimental evidence concerning the verification of the predicted shape resonances.

An oxazetidine amino acid for chemical protein synthesis by rapid, serine-forming ligations

NASA Astrophysics Data System (ADS)

Pusterla, Ivano; Bode, Jeffrey W.

2015-08-01

Amide-forming ligation reactions allow the chemical synthesis of proteins by the union of unprotected peptide segments, and enable the preparation of protein derivatives not accessible by expression or bioengineering approaches. The native chemical ligation (NCL) of thioesters and N-terminal cysteines is unquestionably the most successful approach, but is not ideal for all synthetic targets. Here we describe the synthesis of an Fmoc-protected oxazetidine amino acid for use in the α-ketoacid-hydroxylamine (KAHA) amide ligation. When incorporated at the N-terminus of a peptide segment, this four-membered cyclic hydroxylamine can be used for rapid serine-forming ligations with peptide α-ketoacids. This ligation operates at low concentration (100 μM-5 mM) and mild temperatures (20-25 °C). The utility of the reaction was demonstrated by the synthesis of S100A4, a 12 kDa calcium-binding protein not easily accessible by NCL or other amide-forming reactions due to its primary sequence and properties.

[Measurement and performance analysis of functional neural network].

PubMed

Li, Shan; Liu, Xinyu; Chen, Yan; Wan, Hong

2018-04-01

The measurement of network is one of the important researches in resolving neuronal population information processing mechanism using complex network theory. For the quantitative measurement problem of functional neural network, the relation between the measure indexes, i.e. the clustering coefficient, the global efficiency, the characteristic path length and the transitivity, and the network topology was analyzed. Then, the spike-based functional neural network was established and the simulation results showed that the measured network could represent the original neural connections among neurons. On the basis of the former work, the coding of functional neural network in nidopallium caudolaterale (NCL) about pigeon's motion behaviors was studied. We found that the NCL functional neural network effectively encoded the motion behaviors of the pigeon, and there were significant differences in four indexes among the left-turning, the forward and the right-turning. Overall, the establishment method of spike-based functional neural network is available and it is an effective tool to parse the brain information processing mechanism.

Forming interdisciplinary expertise: One organization’s journey on the road to translational nanomedicine

PubMed Central

Ku, Sharon

2012-01-01

This paper provides a sociological account of how researchers of different disciplines become experts in translational nanomedicine. Using a case study of the Nanotechnology Characterization Laboratory (NCL) at the National Cancer Institute (NCI), the author argues that the relationship between the different disciplines involved in translational nanomedicine should be understood in the broader socio-political context of the boundary politics between the academy, industry, and government. This study suggests that the process of training the nanobio expert is not simply a process of inculcating skills; it is also a process of institution-building. In the case of the NCL, sustaining the laboratory’s existence at the interface between the university, industry, and government informed how researchers practiced interdisciplinarity and cultivated their interdisciplinary expertise. It required mobilizing institutional resources through administrative/managerial strategies. Viewing the formation of a professional identity as a social process helps clarify the meaning of interdisciplinarity and provides insight in evaluating the performance of interdisciplinary collaboration and the design of nanoscience education. PMID:22517677

Single Body Parts are Processed by Individual Neurons in the Mouse Dorsolateral Striatum

PubMed Central

Coffey, Kevin R.; Nader, Miles; West, Mark O.

2016-01-01

Interest in the dorsolateral striatum (DLS) has generated numerous scientific studies of its neuropathologies, as well as its roles in normal sensorimotor integration and learning. Studies are informed by knowledge of DLS functional organization, the guiding principle being its somatotopic afferent projections from primary somatosensory (S1) and motor (M1) cortices. The potential to connect behaviorally relevant function to detailed structure is elevated by mouse models, which have access to extensive genetic neuroscience tool kits. Remaining to be demonstrated, however, is whether the correspondence between S1/M1 corticostriatal terminal distributions and the physiological properties of DLS neurons demonstrated in rats and non-human primates exists in mice. Given that the terminal distribution of S1/M1 projections to the DLS in mice is similar to that in rats, we studied whether firing rates (FRs) of DLS neurons in awake, behaving mice are related to activity of individual body parts. MSNs exhibited robust, selective increases in FR during movement or somatosensory stimulation of single body parts. Properties of MSNs, including baseline FRs, locations, responsiveness to stimulation, and proportions of responsive neurons were similar to properties observed in rats. Future studies can be informed by the present demonstration that the mouse lateral striatum functions as a somatic sensorimotor sector of the striatum and appears to be a homolog of the primate putamen, as demonstrated in rats (Carelli and West, 1991). PMID:26827625

Effect of the solvent on the size of clay nanoparticles in solution as determined using an ultraviolet-visible (UV-Vis) spectroscopy methodology.

PubMed

Alin, Jonas; Rubino, Maria; Auras, Rafael

2015-06-01

Ultraviolet-visible (UV-Vis) spectroscopy methodology was developed and utilized for the in situ nanoscale measurement of the size of mineral clay agglomerates in various liquid suspensions. The clays studied were organomodified and unmodified montmorillonite clays (I.44p, Cloisite 93a, and PGN). The methodology was compared and validated against dynamic light scattering (DLS) analysis. The method was able to measure clay agglomerates in solvents in situations where DLS analysis was unsuccessful due to the shapes, polydispersity, and high aspect ratios of the clay particles and the complexity of the aggregates, or dispersion medium. The measured clay agglomerates in suspension were found to be in the nanometer range in the more compatible solvents, and their sizes correlated with the Hansen solubility parameter space distance between the clay modifiers and the solvents. Mass detection limits for size determination were in the range from 1 to 9 mg/L. The methodology thus provides simple, rapid, and inexpensive characterization of clays or particles in the nano- or microsize range in low concentrations in various liquid media, including complex mixtures or highly viscous fluids that are difficult to analyze with DLS. In addition, by combining UV-VIS spectroscopy with DLS it was possible to discern flocculation behavior in liquids, which otherwise could result in false size measurements by DLS alone.

The Neuronal Ceroid-Lipofuscinoses

ERIC Educational Resources Information Center

Bennett, Michael J.; Rakheja, Dinesh

2013-01-01

The neuronal ceroid-lipofuscinoses (NCL's, Batten disease) represent a group of severe neurodegenerative diseases, which mostly present in childhood. The phenotypes are similar and include visual loss, seizures, loss of motor and cognitive function, and early death. At autopsy, there is massive neuronal loss with characteristic storage in…

Effect of degassing on the aggregation of carbon nanotubes dispersed in water

NASA Astrophysics Data System (ADS)

Chen, C.-J.; Huang, J.-R.; Hwang, I.-S.; Choi, H. J.; Lai, P.-Y.; Chan, C. K.

2017-10-01

Dynamic light scattering (DLS) along with centrifugation and shaking tests reveal that dissolved gases can significantly affect the aggregation behavior of carbon nanotubes (CNTs) dispersed in water. The CNTs in non-degassed samples form loose, stable networks having the DLS result reminiscent of semidilute polymer solutions, whereas the CNTs in degassed samples aggregate to form Brownian colloids that sediment quickly. Interestingly, the CNTs dispersed in acetone, with or without degassing, also behave like semidilute polymers in DLS experiments. We propose a surface nanobubble-assisted mechanism to explain the observed aggregation behaviors. Our work signifies that dissolved gases may play an important role in determining hydrophobicity and biomolecular functions in aqueous environments.

Characterization of magnetic nanoparticle by dynamic light scattering

PubMed Central

2013-01-01

Here we provide a complete review on the use of dynamic light scattering (DLS) to study the size distribution and colloidal stability of magnetic nanoparticles (MNPs). The mathematical analysis involved in obtaining size information from the correlation function and the calculation of Z-average are introduced. Contributions from various variables, such as surface coating, size differences, and concentration of particles, are elaborated within the context of measurement data. Comparison with other sizing techniques, such as transmission electron microscopy and dark-field microscopy, revealed both the advantages and disadvantages of DLS in measuring the size of magnetic nanoparticles. The self-assembly process of MNP with anisotropic structure can also be monitored effectively by DLS. PMID:24011350

CONTIN XPCS: software for inverse transform analysis of X-ray photon correlation spectroscopy dynamics

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

Andrews, Ross N.; Narayanan, Suresh; Zhang, Fan

X-ray photon correlation spectroscopy (XPCS) and dynamic light scattering (DLS) reveal materials dynamics using coherent scattering, with XPCS permitting the investigation of dynamics in a more diverse array of materials than DLS. Heterogeneous dynamics occur in many material systems. The authors' recent work has shown how classic tools employed in the DLS analysis of heterogeneous dynamics can be extended to XPCS, revealing additional information that conventional Kohlrausch exponential fitting obscures. The present work describes the software implementation of inverse transform analysis of XPCS data. This software, calledCONTIN XPCS, is an extension of traditionalCONTINanalysis and accommodates the various dynamics encountered inmore » equilibrium XPCS measurements.« less

CONTIN XPCS: software for inverse transform analysis of X-ray photon correlation spectroscopy dynamics

DOE PAGES

Andrews, Ross N.; Narayanan, Suresh; Zhang, Fan; ...

2018-02-01

X-ray photon correlation spectroscopy (XPCS) and dynamic light scattering (DLS) reveal materials dynamics using coherent scattering, with XPCS permitting the investigation of dynamics in a more diverse array of materials than DLS. Heterogeneous dynamics occur in many material systems. The authors' recent work has shown how classic tools employed in the DLS analysis of heterogeneous dynamics can be extended to XPCS, revealing additional information that conventional Kohlrausch exponential fitting obscures. The present work describes the software implementation of inverse transform analysis of XPCS data. This software, calledCONTIN XPCS, is an extension of traditionalCONTINanalysis and accommodates the various dynamics encountered inmore » equilibrium XPCS measurements.« less

Solitary waves and double layers in a dusty electronegative plasma.

PubMed

Mamun, A A; Shukla, P K; Eliasson, B

2009-10-01

A dusty electronegative plasma containing Boltzmann electrons, Boltzmann negative ions, cold mobile positive ions, and negatively charged stationary dust has been considered. The basic features of arbitrary amplitude solitary waves (SWs) and double layers (DLs), which have been found to exist in such a dusty electronegative plasma, have been investigated by the pseudopotential method. The small amplitude limit has also been considered in order to study the small amplitude SWs and DLs analytically. It has been shown that under certain conditions, DLs do not exist, which is in good agreement with the experimental observations of Ghim and Hershkowitz [Y. Ghim (Kim) and N. Hershkowitz, Appl. Phys. Lett. 94, 151503 (2009)].

Voluntary Exercise Improves Performance of a Discrimination Task through Effects on the Striatal Dopamine System

ERIC Educational Resources Information Center

Eddy, Meghan C.; Stansfield, Katherine J.; Green, John T.

2014-01-01

We have previously demonstrated that voluntary exercise facilitates discrimination learning in a modified T-maze. There is evidence implicating the dorsolateral striatum (DLS) as the substrate for this task. The present experiments examined whether changes in DLS dopamine receptors might underlie the exercise-associated facilitation. Infusing a…

MSFC Doppler Lidar Science experiments and operations plans for 1981 airborne test flight

NASA Technical Reports Server (NTRS)

Fichtl, G. H.; Bilbro, J. W.; Kaufman, J. W.

1981-01-01

The flight experiment and operations plans for the Doppler Lidar System (DLS) are provided. Application of DLS to the study of severe storms and local weather penomena is addressed. Test plans involve 66 hours of flight time. Plans also include ground based severe storm and local weather data acquisition.

Department of Legal Services

Science.gov Websites

The Department of Legal Services ("DLS") is a dependency of the Secretariat for Legal Affairs of the OAS General Secretariat. www.oas.org/en/sla DLS provides legal advice on: interpretation of Secretariat for Legal Affairs Inter-American Commission on Human Rights Inter-American Court of Human Rights

Protein Analysis by Dynamic Light Scattering: Methods and Techniques for Students

ERIC Educational Resources Information Center

Lorber, Bernard; Fischer, Frederic; Bailly, Marc; Roy, Herve; Kern, Daniel

2012-01-01

Dynamic light scattering (DLS) analyses are routinely used in biology laboratories to detect aggregates in macromolecular solutions, to determine the size of proteins, nucleic acids, and complexes or to monitor the binding of ligands. This article is written for graduate and undergraduate students with access to DLS and for faculty members who…

Analyzing Digital Library Initiatives: 5S Theory Perspective

ERIC Educational Resources Information Center

Isah, Abdulmumin; Mutshewa, Athulang; Serema, Batlang; Kenosi, Lekoko

2015-01-01

This article traces the historical development of Digital Libraries (DLs), examines some DL initiatives in developed and developing countries and uses 5S Theory as a lens for analyzing the focused DLs. The analysis shows that present-day systems, in both developed and developing nations, are essentially content and user centric, with low level…

On the generation of double layers from ion- and electron-acoustic instabilities

NASA Astrophysics Data System (ADS)

Fu, Xiangrong; Cowee, Misa M.; Gary, S. Peter; Winske, Dan

2016-03-01

A plasma double layer (DL) is a nonlinear electrostatic structure that carries a uni-polar electric field parallel to the background magnetic field due to local charge separation. Past studies showed that DLs observed in space plasmas are mostly associated with the ion acoustic instability. Recent Van Allen Probes observations of parallel electric field structures traveling much faster than the ion acoustic speed have motivated a computational study to test the hypothesis that a new type of DLs—electron acoustic DLs—generated from the electron acoustic instability are responsible for these electric fields. Nonlinear particle-in-cell simulations yield negative results, i.e., the hypothetical electron acoustic DLs cannot be formed in a way similar to ion acoustic DLs. Linear theory analysis and the simulations show that the frequencies of electron acoustic waves are too high for ions to respond and maintain charge separation required by DLs. However, our results do show that local density perturbations in a two-electron-component plasma can result in unipolar-like electric field structures that propagate at the electron thermal speed, suggesting another potential explanation for the observations.

NCL-01: Nanomedicine Drug Release Study in Human Plasma Using Stable Isotope Tracer Ultrafiltration Assay (SITUA)  | Frederick National Laboratory for Cancer Research

Cancer.gov

The Nanotechnology Characterization Laboratory will evaluate drug release from a nanoparticulate formulation in vitro in human plasma, using a novel stable isotope tracer ultrafiltration assay (SITUA) developed at the laboratory. The SITUA is a metho

Single body parts are processed by individual neurons in the mouse dorsolateral striatum.

PubMed

Coffey, Kevin R; Nader, Miles; West, Mark O

2016-04-01

Interest in the dorsolateral striatum (DLS) has generated numerous scientific studies of its neuropathologies, as well as its roles in normal sensorimotor integration and learning. Studies are informed by knowledge of DLS functional organization, the guiding principle being its somatotopic afferent projections from primary somatosensory (S1) and motor (M1) cortices. The potential to connect behaviorally relevant function to detailed structure is elevated by mouse models, which have access to extensive genetic neuroscience tool kits. Remaining to be demonstrated, however, is whether the correspondence between S1/M1 corticostriatal terminal distributions and the physiological properties of DLS neurons demonstrated in rats and non-human primates exists in mice. Given that the terminal distribution of S1/M1 projections to the DLS in mice is similar to that in rats, we studied whether firing rates (FRs) of DLS neurons in awake, behaving mice are related to activity of individual body parts. MSNs exhibited robust, selective increases in FR during movement or somatosensory stimulation of single body parts. Properties of MSNs, including baseline FRs, locations, responsiveness to stimulation, and proportions of responsive neurons were similar to properties observed in rats. Future studies can be informed by the present demonstration that the mouse lateral striatum functions as a somatic sensorimotor sector of the striatum and appears to be a homolog of the primate putamen, as demonstrated in rats (Carelli and West, 1991). Copyright © 2016 Elsevier B.V. All rights reserved.

Assessment of the cervical spine denticulate ligament using MRI volumetric sequence: Comparison between 1.5 Tesla and 3.0 Tesla.

PubMed

Seragioli, Rafael; Simao, Marcelo Novelino; Simao, Gustavo Novelino; Herrero, Carlos Fernando P S; Nogueira-Barbosa, Marcello H

2018-03-01

Denticulate ligaments (DLs) are pial extensions on each side of the spinal cord, comprising about 20 to 21 pairs of fibrous structures connecting the dura mater to the spinal cord. These ligaments are significant anatomical landmarks in the surgical approach to intradural structures. To our knowledge, there is no previous study on the detection of DLs using MRI. After IRB approval, we retrospectively evaluated 116 consecutive MRI scans of the cervical spine, using the volumetric sequence 3D COSMIC, 65 and 51 studies with 1.5T and 3.0T respectively. We did not include trauma and tumor cases. Two independent radiologists assessed the detection of cervical spine DLs independently and blinded for each cervical vertebral level. We compared the frequency of detection of these ligaments in 1.5 Tesla and 3.0 Tesla MRI using Fisher exact test considering P<0.05 as significant. We evaluated interobserver agreement with Kappa coefficient. We observed high detection frequency of the cervical spine DLs using both 1.5T (70 to 91%) and 3.0T (68 to 98%). We found no statistically significant difference in the detection frequency of ligaments between the 1.5T and 3.0T MRI in all vertebral levels. Using 3.0T, radiologists identified ligaments better in higher vertebral levels than for lower cervical levels (P=0.0003). Interobserver agreement on the identification of DL was poor both for 1.5T (k=0.3744; CI 95% 0.28-0.46) and 3.0T (k=0.3044; CI 95% 0.18-0.42) MRI. Radiologists identified most of the cervical DLs using volumetric MRI acquisition. Our results suggest 1.5T and 3.0T MRI performed similarly in the detection of DLs. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Shear Bond Strength of Composite and Ceromer Superstructures to Direct Laser Sintered and Ni-Cr-Based Infrastructures Treated with KTP, Nd:YAG, and Er:YAG Lasers: An Experimental Study.

PubMed

Gorler, Oguzhan; Hubbezoglu, Ihsan; Ulgey, Melih; Zan, Recai; Guner, Kubra

2018-04-01

The aim of this study was to examine the shear bond strength (SBS) of ceromer and nanohybrid composite to direct laser sintered (DLS) Cr-Co and Ni-Cr-based metal infrastructures treated with erbium-doped yttrium aluminum garnet (Er:YAG), neodymium-doped yttrium aluminum garnet (Nd:YAG), and potassium titanyl phosphate (KTP) laser modalities in in vitro settings. Experimental specimens had four sets (n = 32) including two DLS infrastructures with ceromer and nanohybrid composite superstructures and two Ni-Cr-based infrastructures with ceromer and nanohybrid composite superstructures. Of each infrastructure set, the specimens randomized into four treatment modalities (n = 8): no treatment (controls) and Er:YAG, Nd:YAG, and KTP lasers. The infrastructures were prepared in the final dimensions of 7 × 3 mm. Ceromer and nanohybrid composite was applied to the infrastructures after their surface treatments according to randomization. The SBS of specimens was measured to test the efficacy of surface treatments. Representative scanning electron microscopy (SEM) images after laser treatments were obtained. Overall, in current experimental settings, Nd:YAG, KTP, and Er:YAG lasers, in order of efficacy, are effective to improve the bonding of ceromer and nanohybrid composite to the DLS and Ni-Cr-based infrastructures (p < 0.05). Nd:YAG laser is more effective in the DLS/ceromer infrastructures (p < 0.05). KTP laser, as second more effective preparation, is more effective in the DLS/ceromer infrastructures (p < 0.05). SEM findings presented moderate accordance with these findings. The results of this study supported the bonding of ceromer and nanohybrid composite superstructures to the DLS and Ni-Cr-based infrastructures suggesting that laser modalities, in order of success, Nd:YAG, KTP, and Er:YAG, are effective to increase bonding of these structures.

Endogenous GLP-1 in lateral septum contributes to stress-induced hypophagia.

PubMed

Terrill, Sarah J; Maske, Calyn B; Williams, Diana L

2018-03-03

Glucagon-like peptide 1 (GLP-1) neurons of the caudal brainstem project to many brain areas, including the lateral septum (LS), which has a known role in stress responses. Previously, we showed that endogenous GLP-1 in the LS plays a physiologic role in the control of feeding under non-stressed conditions, however, central GLP-1 is also involved in behavioral and endocrine responses to stress. Here, we asked whether LS GLP-1 receptors (GLP-1R) contribute to stress-induced hypophagia. Male rats were implanted with bilateral cannulas targeting the dorsal subregion of the LS (dLS). In a within-subjects design, shortly before the onset of the dark phase, rats received dLS injections of saline or the GLP-1R antagonist Exendin (9-39) (Ex9) prior to 30 min restraint stress. Food intake was measured continuously for the next 20 h. The stress-induced hypophagia observed within the first 30 min of dark was not influenced by Ex9 pretreatment, but Ex9 tended to blunt the effect of stress as early as 1 and 2 h into the dark phase. By 4-6 h, there were significant stress X drug interactions, and Ex9 pretreatment blocked the stress-induced suppression of feeding. These effects were mediated entirely through changes in average meal size; stress suppressed meal size while dLS Ex9 attenuated this effect. Using a similar design, we examined the role of dLS GLP-1R in the neuroendocrine response to acute restraint stress. As expected, stress potently increased serum corticosterone, but blockade of dLS GLP-1Rs did not affect this response. Together, these data show that endogenous GLP-1 action in the dLS plays a role in some but not all of the physiologic responses to acute stress. Copyright © 2018 Elsevier Inc. All rights reserved.

Investigation of zinc oxide particles in cosmetic products by means of centrifugal and asymmetrical flow field-flow fractionation.

PubMed

Sogne, Vanessa; Meier, Florian; Klein, Thorsten; Contado, Catia

2017-09-15

The dimensional characterization of insoluble, inorganic particles, such as zinc oxide ZnO, dispersed in cosmetic or pharmaceutical formulations, is of great interest considering the current need of declaring the possible presence of nanomaterials on the label of commercial products. This work compares the separation abilities of Centrifugal- and Asymmetrical Flow Field-Flow Fractionation techniques (CF3 and AF4, respectively), equipped with UV-vis, MALS and DLS detectors, in size sorting ZnO particles, both as pristine powders and after their extraction from cosmetic matrices. ZnO particles, bare and superficially modified with triethoxycaprylyl silane, were used as test materials. To identify the most suitable procedure necessary to isolate the ZnO particles from the cosmetic matrix, two O/W and two W/O emulsions were formulated on purpose. The suspensions, containing the extracted particles ZnO, were separated by both Field-Flow Fractionation (FFF) techniques to establish a common analysis protocol, applicable for the analysis of ZnO particles extracted from three commercial products, sold in Europe for the baby skin care. Key aspects of this study were the selection of an appropriate dispersing agent enabling the particles to stay in stable suspensions (>24h)and the use of multiple detectors (UV-vis, MALS and DLS) coupled on-line with the FFF channels, to determine the particle dimensions without using the retention parameters. Between the two FFF techniques, CF3 revealed to be the most robust one, able to sort all suspensions created in this work. Copyright © 2017 Elsevier B.V. All rights reserved.

Predictors and Course of Daily Living Skills Development in Toddlers with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Green, Shulamite A.; Carter, Alice S.

2014-01-01

Self-sufficiency is central to child and family well-being. This report focuses on predictors of adaptive daily living skills (DLS) development in young children with ASD and whether DLS gains predict decreases in parenting stress. Participants were 162 toddlers with ASD and their parents, assessed at 3 annual timepoints. Hierarchical Linear…

Accurate Size and Size-Distribution Determination of Polystyrene Latex Nanoparticles in Aqueous Medium Using Dynamic Light Scattering and Asymmetrical Flow Field Flow Fractionation with Multi-Angle Light Scattering

PubMed Central

Kato, Haruhisa; Nakamura, Ayako; Takahashi, Kayori; Kinugasa, Shinichi

2012-01-01

Accurate determination of the intensity-average diameter of polystyrene latex (PS-latex) by dynamic light scattering (DLS) was carried out through extrapolation of both the concentration of PS-latex and the observed scattering angle. Intensity-average diameter and size distribution were reliably determined by asymmetric flow field flow fractionation (AFFFF) using multi-angle light scattering (MALS) with consideration of band broadening in AFFFF separation. The intensity-average diameter determined by DLS and AFFFF-MALS agreed well within the estimated uncertainties, although the size distribution of PS-latex determined by DLS was less reliable in comparison with that determined by AFFFF-MALS. PMID:28348293

Exchange Enhancement of the Electron-Phonon Interaction: The Case of Weakly Doped Two-Dimensional Multivalley Semiconductors

NASA Astrophysics Data System (ADS)

Pamuk, Betül; Zoccante, Paolo; Baima, Jacopo; Mauri, Francesco; Calandra, Matteo

2018-04-01

The effect of the exchange interaction on the vibrational properties and on the electron-phonon coupling were investigated in several recent works. In most of the cases, exchange tends to enhance the electron-phonon interaction, although the motivations for such behaviour are not completely understood. Here we consider the class of weakly doped two-dimensional multivalley semiconductors and we demonstrate that a more global picture emerges. In particular we show that in these systems, at low enough doping, even a moderate electron-electron interaction enhances the response to any perturbation inducing a valley polarization. If the valley polarization is due to the electron-phonon coupling, the electron-electron interaction results in an enhancement of the superconducting critical temperature. We demonstrate the applicability of the theory by performing random phase approximation and first principles calculations in transition metal chloronitrides. We find that exchange is responsible for the enhancement of the superconducting critical temperature in LixZrNCl and that much larger Tcs could be obtained in intercalated HfNCl if the synthesis of cleaner samples could remove the Anderson insulating state competing with superconductivity.

General practitioner understanding of abbreviations used in hospital discharge letters.

PubMed

Chemali, Mark; Hibbert, Emily J; Sheen, Adrian

2015-08-03

To determine the incidence of abbreviation use in electronic hospital discharge letters (eDLs) and general practitioner understanding of abbreviations used in eDLsDesign, setting and participants: Retrospective audit of abbreviation use in 200 sequential eDLs was conducted at Nepean Hospital, Sydney, a tertiary referral centre, from 18 December to 31 December 2012. The 15 most commonly used abbreviations and five clinically important abbreviations were identified from the audit. A survey questionnaire using these abbreviations in context was then mailed to 240 GPs in the area covered by the Nepean Blue Mountains Local Health District to determine their understanding of these abbreviations. Number of abbreviations and frequency of their use in eDLs, and GPs' understanding of abbreviations used in the survey. 321 abbreviations were identified in the eDL audit; 48.6% were used only once. Fifty five per cent of GPs (132) responded to the survey. No individual abbreviation was correctly interpreted by all GPs. Six abbreviations were misinterpreted by more than a quarter of GPs. These were SNT (soft non-tender), TTE (transthoracic echocardiogram), EST (exercise stress test), NKDA (no known drug allergies), CTPA (computed tomography pulmonary angiogram), ORIF (open reduction and internal fixation). These abbreviations were interpreted incorrectly by 47.0% (62), 33.3% (44), 33.3% (44) 32.6% (43), 31.1% (41) and 28.0% (37) of GPs, respectively. Abbreviations used in hospital eDLs are not well understood by the GPs who receive them. This has potential to adversely affect patient care in the transition from hospital to community care.

A test bed for investigating and evaluating the use of biometric-encoded driver licenses and their impact on law enforcement

NASA Astrophysics Data System (ADS)

Messner, Richard A.; Hludik, Frank; Crowley, Todd A.; Vidacic, Dragan; Stetson, Barrett; Nadel, Lawrence D.; Nichols, Linda J.; Harris, Carol

2004-08-01

This paper describes the results of a collaborative effort between the University of New Hampshire (UNH) and the Mitretek Systems (MTS) Center for Criminal Justice Technology (CCJT). Mitretek conducted an investigation into the impact of anticipated biometrically encoded driver licenses (DLs) on law enforcement. As part of this activity, Mitretek teamed with UNH to leverage the results of UNH's Project54 and develop a pilot Driver License Interoperability Test Bed to explore both implementation and operational aspects associated with reading and authenticating biometrically encoded DLs in law enforcement scenarios. The test bed enables the exploration of new methods, techniques (both hardware and software), and standards in a structured fashion. Spearheaded by the American Association of Motor Vehicle Administrators (AAMVA) and the International Committee for Information Technology Standards Technical Group M1 (INCITS-M1) initiatives, standards involving both DLs and biometrics, respectively, are evolving at a rapid pace. In order to ensure that the proposed standards will provide for interstate interoperability and proper functionality for the law enforcement community, it is critical to investigate the implementation and deployment issues surrounding biometrically encoded DLs. The test bed described in this paper addresses this and will provide valuable feedback to the standards organizations, the states, and law enforcement officials with respect to implementation and functional issues that are exposed through exploration of actual test systems. The knowledge gained was incorporated into a report prepared by MTS to describe the anticipated impact of biometrically encoded DLs on law enforcement practice.

Sensori-Motor and Daily Living Skills of Preschool Children with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Jasmin, Emmanuelle; Couture, Melanie; McKinley, Patricia; Reid, Greg; Fombonne, Eric; Gisel, Erika

2009-01-01

Sensori-motor development and performance of daily living skills (DLS) remain little explored in children with autism spectrum disorders (ASD). The objective of this study was to determine the impact of sensori-motor skills on the performance of DLS in preschool children with ASD. Thirty-five children, 3-4 years of age, were recruited and assessed…

371. A.J.M. and D.L.S., Delineators April 1934. STATE OF CALIFORNIA; ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

371. A.J.M. and D.L.S., Delineators April 1934. STATE OF CALIFORNIA; DEPARTMENT OF PUBLIC WORKS; SAN FRANCISCO - OAKLAND BAY BRIDGE; SUPERSTRUCTURE - WEST BAY CROSSING; PIER NO. 4; VERTICAL SECTIONS; CONTRACT NO. 2; SUP. DRAWING NO. 17A - San Francisco Oakland Bay Bridge, Spanning San Francisco Bay, San Francisco, San Francisco County, CA

On the generation of double layers from ion- and electron-acoustic instabilities

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

Fu, Xiangrong, E-mail: xrfu@lanl.gov; Cowee, Misa M.; Winske, Dan

2016-03-15

A plasma double layer (DL) is a nonlinear electrostatic structure that carries a uni-polar electric field parallel to the background magnetic field due to local charge separation. Past studies showed that DLs observed in space plasmas are mostly associated with the ion acoustic instability. Recent Van Allen Probes observations of parallel electric field structures traveling much faster than the ion acoustic speed have motivated a computational study to test the hypothesis that a new type of DLs—electron acoustic DLs—generated from the electron acoustic instability are responsible for these electric fields. Nonlinear particle-in-cell simulations yield negative results, i.e., the hypothetical electronmore » acoustic DLs cannot be formed in a way similar to ion acoustic DLs. Linear theory analysis and the simulations show that the frequencies of electron acoustic waves are too high for ions to respond and maintain charge separation required by DLs. However, our results do show that local density perturbations in a two-electron-component plasma can result in unipolar-like electric field structures that propagate at the electron thermal speed, suggesting another potential explanation for the observations.« less

One-step analysis of DNA/chitosan complexes by field-flow fractionation reveals particle size and free chitosan content.

PubMed

Ma, Pei Lian; Buschmann, Michael D; Winnik, Françoise M

2010-03-08

The composition of samples obtained upon complexation of DNA with chitosan was analyzed by asymmetrical flow field flow fractionation (AF4) with online UV-visible, multiangle light scattering (MALS), and dynamic light scattering (DLS) detectors. A chitosan labeled with rhodamine B to facilitate UV-vis detection of the polycation was complexed with DNA under conditions commonly used for transfection (chitosan glucosamine to DNA phosphate molar ratio of 5). AF4 analysis revealed that 73% of the chitosan-rhodamine remained free in the dispersion and that the DNA/chitosan complexes had a broad size distribution ranging from 20 to 160 nm in hydrodynamic radius. The accuracy of the data was assessed by comparison with data from batch-mode DLS and scanning electron microscopy. The AF4 combined with DLS allowed the characterization of small particles that were not detected by conventional batch-mode DLS. The AF4 analysis will prove to be an important tool in the field of gene therapy because it readily provides, in a single measurement, three important physicochemical parameters of the complexes: the amount of unbound polycation, the hydrodynamic size of the complexes, and their size distribution.

Utilizing dynamic light scattering as a process analytical technology for protein folding and aggregation monitoring in vaccine manufacturing.

PubMed

Yu, Zhou; Reid, Jennifer C; Yang, Yan-Ping

2013-12-01

Protein aggregation is a common challenge in the manufacturing of biological products. It is possible to minimize the extent of aggregation through timely measurement and in-depth characterization of aggregation. In this study, we demonstrated the use of dynamic light scattering (DLS) to monitor inclusion body (IB) solubilization, protein refolding, and aggregation near the production line of a recombinant protein-based vaccine candidate. Our results were in good agreement with those measured by size-exclusion chromatography. DLS was also used to characterize the mechanism of aggregation. As DLS is a quick, nonperturbing technology, it can potentially be used as an at-line process analytical technology to ensure complete IB solubilization and aggregate-free refolding. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

Selective depletion of microglial progranulin in mice is not sufficient to cause neuronal ceroid lipofuscinosis or neuroinflammation.

PubMed

Petkau, Terri L; Kosior, Natalia; de Asis, Kathleen; Connolly, Colúm; Leavitt, Blair R

2017-11-17

Progranulin deficiency due to heterozygous null mutations in the GRN gene are a common cause of familial frontotemporal lobar degeneration (FTLD), while homozygous loss-of-function GRN mutations are thought to be a rare cause of neuronal ceroid lipofuscinosis (NCL). Aged progranulin-knockout (Grn-null) mice display highly exaggerated lipofuscinosis, microgliosis, and astrogliosis, as well as mild cell loss in specific brain regions. In the brain, progranulin is predominantly expressed in neurons and microglia, and previously, we demonstrated that neuronal-specific depletion of progranulin does not recapitulate the neuropathological phenotype of Grn-null mice. In this study, we evaluated whether selective depletion of progranulin expression in myeloid-lineage cells, including microglia, causes NCL-like neuropathology or neuroinflammation in mice. We generated mice with progranulin depleted in myeloid-lineage cells by crossing mice homozygous for a floxed progranulin allele to mice expressing Cre recombinase under control of the LyzM promotor (Lyz-cKO). Progranulin expression was reduced by approximately 50-70% in isolated microglia compared to WT levels. Lyz-cKO mice aged to 12 months did not display any increase in lipofuscin deposition, microgliosis, or astrogliosis in the four brain regions examined, though increases were observed for many of these measures in Grn-null animals. To evaluate the functional effect of reduced progranulin expression in isolated microglia, primary cultures were stimulated with controlled standard endotoxin and cytokine release was measured. While Grn-null microglia display a hyper-inflammatory phenotype, Lyz-cKO and WT microglia secreted similar levels of inflammatory cytokines. We conclude that progranulin expression from either microglia or neurons is sufficient to prevent the development of NCL-like neuropathology in mice. Furthermore, microglia that are deficient for progranulin expression but isolated from a progranulin-rich environment have a normal inflammatory profile. Our results suggest that progranulin acts, at least partly, in a non-cell autonomous manner in the brain.

Systematic analysis of protein–detergent complexes applying dynamic light scattering to optimize solutions for crystallization trials

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

Meyer, Arne; Dierks, Karsten; XtalConcepts, Marlowring 19, 22525 Hamburg

Application of in situ dynamic light scattering to solutions of protein–detergent complexes permits characterization of these complexes in samples as small as 2 µl in volume. Detergents are widely used for the isolation and solubilization of membrane proteins to support crystallization and structure determination. Detergents are amphiphilic molecules that form micelles once the characteristic critical micelle concentration (CMC) is achieved and can solubilize membrane proteins by the formation of micelles around them. The results are presented of a study of micelle formation observed by in situ dynamic light-scattering (DLS) analyses performed on selected detergent solutions using a newly designed advancedmore » hardware device. DLS was initially applied in situ to detergent samples with a total volume of approximately 2 µl. When measured with DLS, pure detergents show a monodisperse radial distribution in water at concentrations exceeding the CMC. A series of all-transn-alkyl-β-d-maltopyranosides, from n-hexyl to n-tetradecyl, were used in the investigations. The results obtained verify that the application of DLS in situ is capable of distinguishing differences in the hydrodynamic radii of micelles formed by detergents differing in length by only a single CH{sub 2} group in their aliphatic tails. Subsequently, DLS was applied to investigate the distribution of hydrodynamic radii of membrane proteins and selected water-insoluble proteins in presence of detergent micelles. The results confirm that stable protein–detergent complexes were prepared for (i) bacteriorhodopsin and (ii) FetA in complex with a ligand as examples of transmembrane proteins. A fusion of maltose-binding protein and the Duck hepatitis B virus X protein was added to this investigation as an example of a non-membrane-associated protein with low water solubility. The increased solubility of this protein in the presence of detergent could be monitored, as well as the progress of proteolytic cleavage to separate the fusion partners. This study demonstrates the potential of in situ DLS to optimize solutions of protein–detergent complexes for crystallization applications.« less

Cosmic shear results from the deep lens survey. II. Full cosmological parameter constraints from tomography

DOE PAGES

Jee, M. James; Tyson, J. Anthony; Hilbert, Stefan; ...

2016-06-15

Here, we present a tomographic cosmic shear study from the Deep Lens Survey (DLS), which, providing a limiting magnitudemore » $${r}_{\\mathrm{lim}}\\sim 27$$ ($$5\\sigma $$), is designed as a precursor Large Synoptic Survey Telescope (LSST) survey with an emphasis on depth. Using five tomographic redshift bins, we study their auto- and cross-correlations to constrain cosmological parameters. We use a luminosity-dependent nonlinear model to account for the astrophysical systematics originating from intrinsic alignments of galaxy shapes. We find that the cosmological leverage of the DLS is among the highest among existing $$\\gt 10$$ deg2 cosmic shear surveys. Combining the DLS tomography with the 9 yr results of the Wilkinson Microwave Anisotropy Probe (WMAP9) gives $${{\\rm{\\Omega }}}_{m}={0.293}_{-0.014}^{+0.012}$$, $${\\sigma }_{8}={0.833}_{-0.018}^{+0.011}$$, $${H}_{0}={68.6}_{-1.2}^{+1.4}\\;{\\text{km s}}^{-1}\\;{{\\rm{Mpc}}}^{-1}$$, and $${{\\rm{\\Omega }}}_{b}=0.0475\\pm 0.0012$$ for ΛCDM, reducing the uncertainties of the WMAP9-only constraints by ~50%. When we do not assume flatness for ΛCDM, we obtain the curvature constraint $${{\\rm{\\Omega }}}_{k}=-{0.010}_{-0.015}^{+0.013}$$ from the DLS+WMAP9 combination, which, however, is not well constrained when WMAP9 is used alone. The dark energy equation-of-state parameter w is tightly constrained when baryonic acoustic oscillation (BAO) data are added, yielding $$w=-{1.02}_{-0.09}^{+0.10}$$ with the DLS+WMAP9+BAO joint probe. The addition of supernova constraints further tightens the parameter to $$w=-1.03\\pm 0.03$$. Our joint constraints are fully consistent with the final Planck results and also with the predictions of a ΛCDM universe.« less

Adherence index based on the AHA 2006 diet and lifestyle recommendations is associated with select cardiovascular disease risk factors in older Puerto Ricans.

PubMed

Bhupathiraju, Shilpa N; Lichtenstein, Alice H; Dawson-Hughes, Bess; Tucker, Katherine L

2011-03-01

In 2006, the AHA released diet and lifestyle recommendations (AHA-DLR) for cardiovascular disease (CVD) risk reduction. The effect of adherence to these recommendations on CVD risk is unknown. Our objective was to develop a unique diet and lifestyle score based on the AHA-DLR and to evaluate this score in relation to available CVD risk factors. In a cross-sectional study of Puerto Rican adults aged 45-75 y living in the greater Boston area, information was available for the following variables: diet (semiquantitative FFQ), blood pressure, waist circumference (WC), 10-y risk of coronary heart disease (CHD) (Framingham risk score), and fasting plasma lipids, serum glucose, insulin, and C-reactive protein (CRP) concentrations. We developed a diet and lifestyle score (AHA-DLS) based on the AHA-DLR. The AHA-DLS had both internal consistency and content validity. It was associated with plasma HDL cholesterol (P = 0.001), serum insulin (P = 0.0003), and CRP concentrations (P = 0.02), WC (P < 0.0001), and 10-y risk of CHD score (P = 0.01 in women). The AHA-DLS was inversely associated with serum glucose among those with a BMI < 25 (P = 0.01). Women and men in the highest quartile of the AHA-DLS had lower serum insulin (P-trend = 0.0003) and CRP concentrations (P-trend = 0.002), WC (P-trend = 0.0003), and higher HDL cholesterol (P-trend = 0.008). The AHA-DLS is a useful tool to measure adherence to the AHA-DLR and may be used to examine associations between diet and lifestyle behaviors and CVD risk.

Adherence Index Based on the AHA 2006 Diet and Lifestyle Recommendations Is Associated with Select Cardiovascular Disease Risk Factors in Older Puerto Ricans123

PubMed Central

Bhupathiraju, Shilpa N.; Lichtenstein, Alice H.; Dawson-Hughes, Bess; Tucker, Katherine L.

2011-01-01

In 2006, the AHA released diet and lifestyle recommendations (AHA-DLR) for cardiovascular disease (CVD) risk reduction. The effect of adherence to these recommendations on CVD risk is unknown. Our objective was to develop a unique diet and lifestyle score based on the AHA-DLR and to evaluate this score in relation to available CVD risk factors. In a cross-sectional study of Puerto Rican adults aged 45–75 y living in the greater Boston area, information was available for the following variables: diet (semiquantitative FFQ), blood pressure, waist circumference (WC), 10-y risk of coronary heart disease (CHD) (Framingham risk score), and fasting plasma lipids, serum glucose, insulin, and C-reactive protein (CRP) concentrations. We developed a diet and lifestyle score (AHA-DLS) based on the AHA-DLR. The AHA-DLS had both internal consistency and content validity. It was associated with plasma HDL cholesterol (P = 0.001), serum insulin (P = 0.0003), and CRP concentrations (P = 0.02), WC (P < 0.0001), and 10-y risk of CHD score (P = 0.01 in women). The AHA-DLS was inversely associated with serum glucose among those with a BMI < 25 (P = 0.01). Women and men in the highest quartile of the AHA-DLS had lower serum insulin (P-trend = 0.0003) and CRP concentrations (P-trend = 0.002), WC (P-trend = 0.0003), and higher HDL cholesterol (P-trend = 0.008). The AHA-DLS is a useful tool to measure adherence to the AHA-DLR and may be used to examine associations between diet and lifestyle behaviors and CVD risk. PMID:21270369

Temporal Dissociation of Striatum and Prefrontal Cortex Uncouples Anhedonia and Defense Behaviors Relevant to Depression in 6-OHDA-Lesioned Rats.

PubMed

Matheus, Filipe C; Rial, Daniel; Real, Joana I; Lemos, Cristina; Takahashi, Reinaldo N; Bertoglio, Leandro J; Cunha, Rodrigo A; Prediger, Rui D

2016-08-01

The dorsolateral striatum (DLS) processes motor and non-motor functions and undergoes extensive dopaminergic degeneration in Parkinson's disease (PD). The nigrostriatal dopaminergic degeneration also affects other brain areas including the pre-frontal cortex (PFC), which has been associated with the appearance of anhedonia and depression at pre-motor phases of PD. Using behavioral, neurochemical, and electrophysiological approaches, we investigated the temporal dissociation between the role of the DLS and PFC in the appearance of anhedonia and defense behaviors relevant to depression in rats submitted to bilateral DLS lesions with 6-hydroxydopamine (6-OHDA; 10 μg/hemisphere). 6-OHDA induced partial dopaminergic nigrostriatal damage with no gross motor impairments. Anhedonic-like behaviors were observed in the splash and sucrose consumption tests only 7 days after 6-OHDA lesion. By contrast, defense behaviors relevant to depression evaluated in the forced swimming test and social withdrawal only emerged 21 days after 6-OHDA lesion when anhedonia was no longer present. These temporally dissociated behavioral alterations were coupled to temporal- and structure-dependent alterations in dopaminergic markers such as dopamine D1 and D2 receptors and dopamine transporter, leading to altered dopamine sensitivity in DLS and PFC circuits, evaluated electrophysiologically. These results provide the first demonstration of a dissociated involvement of the DLS and PFC in anhedonic-like and defense behaviors relevant to depression in 6-OHDA-lesioned rats, which was linked with temporal fluctuations in dopaminergic receptor density, leading to altered dopaminergic system sensitivity in these two brain structures. This sheds new light to the duality between depressive and anhedonic symptoms in PD.

Integration of a Finite Element Model with the DAP Bone Remodeling Model to Characterize Bone Response to Skeletal Loading

NASA Technical Reports Server (NTRS)

Werner, Christopher R.; Mulugeta, Lealem; Myers, J. G.; Pennline, J. A.

2015-01-01

NASA's Digital Astronaut Project (DAP) has developed a bone remodeling model that has been validated for predicting volumetric bone mineral density (vBMD) changes of trabecular and cortical bone in the absence of mechanical loading. The model was recently updated to include skeletal loading from exercise and free living activities to maintain healthy bone using a new daily load stimulus (DLS). This new formula was developed based on an extensive review of existing DLS formulas, as discussed in the abstract by Pennline et al. The DLS formula incorporated into the bone remodeling model utilizes strains and stress calculated from finite element model (FEM) of the bone region of interest. The proximal femur was selected for the initial application of the DLS formula, with a specific focus on the femoral neck. METHODS: The FEM was generated from CAD geometry of a femur using de-identified CT data. The femur was meshed using linear tetrahedral elements Figure (1) with higher mesh densities in the femoral neck region, which is the primary region of interest for the initial application of the DLS formula in concert with the DAP bone remodeling model. Nodal loads were applied to the femoral head and the greater trochanter and the base of the femur was held fixed. An L2 norm study was conducted to reduce the length of the femoral shaft without significantly impacting the stresses in the femoral neck. The material properties of the FEM of the proximal femur were separated between cortical and trabecular regions to work with the bone remodeling model. Determining the elements with cortical material properties in the FEM was based off of publicly available CT hip scans [4] that were segmented, cleaned, and overlaid onto the FEM.

Distinct Contributions of Dopamine in the Dorsolateral Striatum and Nucleus Accumbens Shell to the Reinforcing Properties of Cocaine

PubMed Central

Veeneman, Maartje M J; Broekhoven, Mark H; Damsteegt, Ruth; Vanderschuren, Louk J M J

2012-01-01

Dopaminergic neurotransmission in the dorsal and ventral striatum is thought to be involved in distinct aspects of cocaine addiction. Ventral striatal dopamine mediates the acute reinforcing properties of cocaine, whereas dopamine in the dorsolateral striatum (DLS) is thought to become involved in later stages of the addiction process to mediate well-established cue-controlled drug seeking. However, it is unclear whether the DLS also has a role in the reinforcing properties of cocaine itself. Therefore, we systematically investigated the involvement of dopamine in dorsal and ventral striatal regions in cocaine self-administration, using various schedules of reinforcement in animals with limited drug taking experience. Intra-DLS infusion of the dopamine receptor antagonist α-flupenthixol did not affect the acquisition of cocaine self-administration, increased cocaine self-administration under a fixed ratio-1 (FR-1) schedule of reinforcement, caused a rightward and downward shift of the dose–response curve of cocaine under an FR-1 schedule of reinforcement and decreased responding for cocaine under a progressive ratio (PR) schedule of reinforcement. Infusion of α-flupenthixol into the ventral nucleus accumbens (NAcc) shell inhibited the acquisition of cocaine self-administration, reduced responding for the drug under FR-1 and PR schedules of reinforcement, and caused a downward shift of the dose–response curve of cocaine self-administration under an FR-1 schedule of reinforcement. These data show that dopamine in both the DLS and NAcc shell is involved in cocaine reinforcement. We suggest that the DLS and the NAcc shell mediate somewhat distinct facets of the reinforcing properties of cocaine, related to its rewarding and motivational aspects, respectively. PMID:21918505

Analysis of hepatitis C virus RNA dimerization and core-RNA interactions.

PubMed

Ivanyi-Nagy, Roland; Kanevsky, Igor; Gabus, Caroline; Lavergne, Jean-Pierre; Ficheux, Damien; Penin, François; Fossé, Philippe; Darlix, Jean-Luc

2006-01-01

The core protein of hepatitis C virus (HCV) has been shown previously to act as a potent nucleic acid chaperone in vitro, promoting the dimerization of the 3'-untranslated region (3'-UTR) of the HCV genomic RNA, a process probably mediated by a small, highly conserved palindromic RNA motif, named DLS (dimer linkage sequence) [G. Cristofari, R. Ivanyi-Nagy, C. Gabus, S. Boulant, J. P. Lavergne, F. Penin and J. L. Darlix (2004) Nucleic Acids Res., 32, 2623-2631]. To investigate in depth HCV RNA dimerization, we generated a series of point mutations in the DLS region. We find that both the plus-strand 3'-UTR and the complementary minus-strand RNA can dimerize in the presence of core protein, while mutations in the DLS (among them a single point mutation that abolished RNA replication in a HCV subgenomic replicon system) completely abrogate dimerization. Structural probing of plus- and minus-strand RNAs, in their monomeric and dimeric forms, indicate that the DLS is the major if not the sole determinant of UTR RNA dimerization. Furthermore, the N-terminal basic amino acid clusters of core protein were found to be sufficient to induce dimerization, suggesting that they retain full RNA chaperone activity. These findings may have important consequences for understanding the HCV replicative cycle and the genetic variability of the virus.

Concurrent silent strokes impair motor function by limiting behavioral compensation.

PubMed

Faraji, Jamshid; Kurio, Kristyn; Metz, Gerlinde A

2012-08-01

Silent strokes occur more frequently than classic strokes; however, symptoms may go unreported in spite of lasting tissue damage. A silent stroke may indicate elevated susceptibility to recurrent stroke, which may eventually result in apparent and lasting impairments. Here we investigated if multiple silent strokes to the motor system challenge the compensatory capacity of the brain to cumulatively result in permanent functional deficits. Adult male rats with focal ischemia received single focal ischemic mini-lesions in the sensorimotor cortex (SMC) or the dorsolateral striatum (DLS), or multiple lesions affecting both SMC and DLS. The time course and outcome of motor compensation and recovery were determined by quantitative and qualitative assessment of skilled reaching and skilled walking. Rats with SMC or DLS lesion alone did not show behavioral deficits in either task. However, the combination of focal ischemic lesions in SMC and DLS perturbed skilled reaching accuracy and disrupted forelimb placement in the ladder rung walking task. These observations suggest that multiple focal infarcts, each resembling a silent stroke, gradually compromise the plastic capacity of the motor system to cause permanent motor deficits. Moreover, these findings support the notion that cortical and subcortical motor systems cooperate when adopting beneficial compensatory movement strategies. Copyright © 2012 Elsevier Inc. All rights reserved.

An incentive-based distributed mechanism for scheduling divisible loads in tree networks

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

Carroll, T. E.; Grosu, D.

The underlying assumption of Divisible Load Scheduling (DLS) theory is that the pro-cessors composing the network are obedient, i.e., they do not “cheat” the scheduling algorithm. This assumption is unrealistic if the processors are owned by autonomous, self-interested organizations that have no a priori motivation for cooperation and they will manipulate the algorithm if it is beneficial to do so. In this paper, we address this issue by designing a distributed mechanism for scheduling divisible loads in tree net-works, called DLS-T, which provides incentives to processors for reporting their true processing capacity and executing their assigned load at full processingmore » capacity. We prove that the DLS-T mechanism computes the optimal allocation in an ex post Nash equilibrium. Finally, we simulate and study the mechanism under various network structures and processor parameters.« less

Measurement of shear-induced diffusion of red blood cells using dynamic light scattering-optical coherence tomography

NASA Astrophysics Data System (ADS)

Tang, Jianbo; Erdener, Sefik Evren; Li, Baoqiang; Fu, Buyin; Sakadzic, Sava; Carp, Stefan A.; Lee, Jonghwan; Boas, David A.

2018-02-01

Dynamic Light Scattering-Optical Coherence Tomography (DLS-OCT) takes the advantages of using DLS to measure particle flow and diffusion within an OCT resolution-constrained 3D volume, enabling the simultaneous measurements of absolute RBC velocity and diffusion coefficient with high spatial resolution. In this work, we applied DLS-OCT to measure both RBC velocity and the shear-induced diffusion coefficient within penetrating venules of the somatosensory cortex of anesthetized mice. Blood flow laminar profile measurements indicate a blunted laminar flow profile, and the degree of blunting decreases with increasing vessel diameter. The measured shear-induced diffusion coefficient was proportional to the flow shear rate with a magnitude of 0.1 to 0.5 × 10-6 mm2 . These results provide important experimental support for the recent theoretical explanation for why DCS is dominantly sensitive to RBC diffusive motion.

Duodenal and jejunal Dieulafoy’s lesions: optimal management

PubMed Central

Yılmaz, Tonguç Utku; Kozan, Ramazan

2017-01-01

Dieulafoy’s lesions (DLs) are rare and cause gastrointestinal bleeding resulting from erosion of dilated submucosal vessels. The most common location for DL is the stomach, followed by duodenum. There is little information about duodenal and jejunal DLs. Challenges for diagnosis and treatment of Dieulafoy’s lesions include the rare nature of the disease, asymptomatic patients, bleeding symptoms often requiring rapid diagnosis and treatment in symptomatic patients, variability in the diagnosis and treatment methods resulting from different lesion locations, and the risk of re-bleeding. For these reasons, there is no universal consensus about the diagnosis and treatment approach. There are few published case reports and case series recently published. Most duodenal DLs are not evaluated seperately in the studies, which makes it difficult to determine the optimal model. In this study, we summarize the general aspects and recent approaches used to treat duodenal DL. PMID:29158686

Nanotechnology Laboratory Continues Partnership with FDA and National Institute of Standards and Technology | Poster

Cancer.gov

The NCI-funded Nanotechnology Characterization Laboratory (NCL)—a leader in evaluating promising nanomedicines to fight cancer—recently renewed its collaboration with the U.S. Food and Drug Administration (FDA) and the National Institute of Standards and Technology (NIST) to continue its groundbreaking work on characterizing nanomedicines and moving them toward the clinic. In

The CASE Project: Evaluation of Case-Based Approaches to Learning and Teaching in Statistics Service Courses

ERIC Educational Resources Information Center

Fawcett, Lee

2017-01-01

The CASE project (Case-based Approaches to Statistics Education; see www.mas.ncl.ac.uk/~nlf8/innovation) was established to investigate how the use of real-life, discipline-specific case study material in Statistics service courses could improve student engagement, motivation, and confidence. Ultimately, the project aims to promote deep learning…

Experimental study of the solubilities of pyrite in NaCl-bearing aqueous solutions at 250-350°C

NASA Astrophysics Data System (ADS)

Ohmoto, Hiroshi; Hayashi, Ken-Ichiro; Kajisa, Yukari

1994-05-01

A total of sixty-three silica capsule experiments were performed to determine the solubilities of pyrite in NaCl-bearing aqueous solutions (0, 0.1, 0.5, 1, 2, 3, and 4 m) at 250, 300, and 350°C at pressures of vapor/liquid coexistence. The starting materials in the capsules were H2O(1) + FeS2( s) + S ° ( s) ± NaCl ( s). After reaction times up to ~ 60 days, the quenched solutions were analyzed for ΣFe, σH2S, ΣSO42-, and pH; the ΣFe content, ranging 5-1,300 ppm, generally increased with increasing temperature and ΣCl content of solution. The calculated solution compositions at the experimental P-T conditions fall mostly in the following ranges: pH = 2.0 to 3.2, logaH2s = -1.9 to -1.0, logaHSO4- = -3.8 to -2.0, and logaH2( aq) = -7.0 to -5.0. Evaluation of the experimental data suggests that the various redox equilibria between solution and mineral were attained in most of the experimental solutions. The pH, aH2S( aq) , and aH2( aq) of the solutions were controlled by the sulfur hydrolysis reaction (48° + 4 H2O( l) = 3 H2S( aq) + HSO4- + H+) and the sulfide/sulfate reaction ( H2S( aq) + 4 H2O( l) = 4 H2( aq) + H+ + HSO4-). The pyrite solubility is controlled by a general reaction: FeS2( s) + nCl- + 2 H+ + H2( aq) = FeCln2- n + 2 H2S( aq). The equilibrium constants for this reaction, as well as those for association of ferrous chloride complexes ( Fe2+ + nCl- = FeCln2- n), were obtained at 250, 300, and 350°C; they were used also to compute the equilibrium constants for the reactions controlling the solubilities of pyrrhotite, magnetite, and hematite: FeS( s) + 2 H+ + nCl- = FeCln2- n + H2S( aq); Fe3O4( s) + 6 H+ + 3 nCl- + H2( aq) = 3 FeCln2- n + H2O( aq); Fe2O3( s) + 4 H+ + 2 nCl- + H2( aq) = 2 FeCln2- n + 3 H2O( aq). Our experimental data suggest that the dominant Fe-Cl complex is FeCl + in solutions of ΣCl ≤ 0.5 m at 250°C and ΣCl ≤ 0.1 m at 300 and 350°C; FeCl 20 is dominant in solutions of the higher ΣCl contents at each temperature. The association constants for FeCl + and FeCl 2 estimated from this study are in good agreement with those estimated recently by HEINRICH and SEWARD (1990), DING and SEYFRIED (1992), Fein et al. (1992), and Palmer and Hyde (1992). Our solubility constants for pyrite are in good agreement with those obtained by CRERAR et al. (1978) and WOOD et al. (1987) for 3 m ΣCl solution at 350°C, but are 0.5-2 orders of magnitude higher than those obtained by them at lower temperatures and/or at lower ΣCl values. Our data suggest that natural hydrothermal fluids that are in equilibrium with pyrite, the most abundant sulfide mineral in the upper crust, are able to transport sufficient amounts (> 10 -m) of both Fe and H 2S to produce pyrite-rich ore deposits at temperatures above 250°C, and possibly at lower temperatures. The solubility of pyrite (and of other Fe-bearing minerals) is affected very little by a change of temperature, provided the pH, aH2( aq), aH2S( aq), and ΣCl values remain constant.

Parent Perceptions and Observations of Their Children with Autism Age 14-to-26 Concerning Generalization of Daily Living Skills at Home and in the Community

ERIC Educational Resources Information Center

Crosby, Patrick H.

2009-01-01

The purpose of this sequential mixed methods study was to determine if students with autism from 19-to-26 years of age who receive instruction in Daily Living Skills (DLS) class sustain, improve, or decline in their ability to generalize DLS at home and in the community. Research regarding how well students with autism from 19-to-26 years of age…

Analysis of hepatitis C virus RNA dimerization and core–RNA interactions

PubMed Central

Ivanyi-Nagy, Roland; Kanevsky, Igor; Gabus, Caroline; Lavergne, Jean-Pierre; Ficheux, Damien; Penin, François; Fossé, Philippe; Darlix, Jean-Luc

2006-01-01

The core protein of hepatitis C virus (HCV) has been shown previously to act as a potent nucleic acid chaperone in vitro, promoting the dimerization of the 3′-untranslated region (3′-UTR) of the HCV genomic RNA, a process probably mediated by a small, highly conserved palindromic RNA motif, named DLS (dimer linkage sequence) [G. Cristofari, R. Ivanyi-Nagy, C. Gabus, S. Boulant, J. P. Lavergne, F. Penin and J. L. Darlix (2004) Nucleic Acids Res., 32, 2623–2631]. To investigate in depth HCV RNA dimerization, we generated a series of point mutations in the DLS region. We find that both the plus-strand 3′-UTR and the complementary minus-strand RNA can dimerize in the presence of core protein, while mutations in the DLS (among them a single point mutation that abolished RNA replication in a HCV subgenomic replicon system) completely abrogate dimerization. Structural probing of plus- and minus-strand RNAs, in their monomeric and dimeric forms, indicate that the DLS is the major if not the sole determinant of UTR RNA dimerization. Furthermore, the N-terminal basic amino acid clusters of core protein were found to be sufficient to induce dimerization, suggesting that they retain full RNA chaperone activity. These findings may have important consequences for understanding the HCV replicative cycle and the genetic variability of the virus. PMID:16707664

Characterization of Gd loaded chitosan-TPP nanohydrogels by a multi-technique approach combining dynamic light scattering (DLS), asymetrical flow-field-flow-fractionation (AF4) and atomic force microscopy (AFM) and design of positive contrast agents for molecular resonance imaging (MRI)

NASA Astrophysics Data System (ADS)

Rigaux, G.; Gheran, C. V.; Callewaert, M.; Cadiou, C.; Voicu, S. N.; Dinischiotu, A.; Andry, M. C.; Vander Elst, L.; Laurent, S.; Muller, R. N.; Berquand, A.; Molinari, M.; Huclier-Markai, S.; Chuburu, F.

2017-02-01

Chitosan CS—tripolyphosphate TPP/hyaluronic acid HA nanohydrogels loaded with gadolinium chelates (GdDOTA ⊂ CS-TPP/HA NGs) synthesized by ionic gelation were designed for lymph node (LN) MRI. In order to be efficiently drained to LNs, nanogels (NGs) needed to exhibit a diameter ϕ < 100 nm. For that, formulation parameters were tuned, using (i) CS of two different molecular weights (51 and 37 kDa) and (ii) variable CS/TPP ratio (2 < CS/TPP < 8). Characterization of NG size distribution by dynamic light scattering (DLS) and asymetrical flow-field-flow-fractionation (AF4) showed discrepancies since DLS diameters were consistently above 200 nm while AF4 showed individual nano-objects with ϕ < 100 nm. Such a difference could be correlated to the presence of aggregates inherent to ionic gelation. This point was clarified by atomic force microscopy (AFM) in liquid mode which highlighted the main presence of individual nano-objects in nanosuspensions. Thus, combination of DLS, AF4 and AFM provided a more precise characterization of GdDOTA ⊂ CS-TPP/HA nanohydrogels which, in turn, allowed to select formulations leading to NGs of suitable mean sizes showing good MRI efficiency and negligible toxicity.

Evidence for the involvement of extinction-associated inhibitory learning in the forced swimming test.

PubMed

Campus, P; Colelli, V; Orsini, C; Sarra, D; Cabib, S

2015-02-01

The forced swimming test (FST) remains one of the most used tools for screening antidepressants in rodent models. Nonetheless, the nature of immobility, its main behavioral measure, is still a matter of debate. The present study took advantage of our recent finding that mice of the inbred DBA/2J strain require a functioning left dorsolateral striatum (DLS) to consolidate long-term memory of FST to test whether immobility is the outcome of stress-related learning. Infusion of the GABA-A agonist muscimol in the left DLS immediately after a single experience of FST prevented and infusion in the left or the right amygdala impaired recall of the acquired levels of immobility in a probe test performed 24h later. Post-training left DLS infusion of muscimol, at a dose capable of preventing retention of FST-induced immobility, did not influence 24h retention of inhibitory avoidance training or of the escape response acquired in a water T-maze. However, this same treatment prevented 24h retention of the extinction training of the consolidated escape response. These results indicate that a left DLS-centered memory system selectively mediates memory consolidation of FST and of escape extinction and support the hypothesis that immobility is the result of extinction-like inhibitory learning involving all available escape responses due to the inescapable/unavoidable nature of FST experience. Copyright © 2014 Elsevier B.V. All rights reserved.

Impact of asymmetrical flow field-flow fractionation on protein aggregates stability.

PubMed

Bria, Carmen R M; Williams, S Kim Ratanathanawongs

2016-09-23

The impact of asymmetrical flow field-flow fractionation (AF4) on protein aggregate species is investigated with the aid of multiangle light scattering (MALS) and dynamic light scattering (DLS). The experimental parameters probed in this study include aggregate stability in different carrier liquids, shear stress (related to sample injection), sample concentration (during AF4 focusing), and sample dilution (during separation). Two anti-streptavidin (anti-SA) IgG1 samples composed of low and high molar mass (M) aggregates are subjected to different AF4 conditions. Aggregates suspended and separated in phosphate buffer are observed to dissociate almost entirely to monomer. However, aggregates in citric acid buffer are partially stable with dissociation to 25% and 5% monomer for the low and high M samples, respectively. These results demonstrate that different carrier liquids change the aggregate stability and low M aggregates can behave differently than their larger counterparts. Increasing the duration of the AF4 focusing step showed no significant changes in the percent monomer, percent aggregates, or the average Ms in either sample. Syringe-induced shear related to sample injection resulted in an increase in hydrodynamic diameter (dh) as measured by batch mode DLS. Finally, calculations showed that dilution during AF4 separation is significantly lower than in size exclusion chromatography with dilution occurring mainly at the AF4 channel outlet and not during the separation. This has important ramifications when analyzing aggregates that rapidly dissociate (<∼2s) upon dilution as the size calculated by AF4 theory may be more accurate than that measured by online DLS. Experimentally, the dhs determined by online DLS generally agreed with AF4 theory except for the more well retained larger aggregates for which DLS showed smaller sizes. These results highlight the importance of using AF4 retention theory to understand the impacts of dilution on analytes. Copyright © 2016 Elsevier B.V. All rights reserved.

Visual Performance of Contact Lens-Corrected Ametropic Aviators with the M-43 Protective Mask

DTIC Science & Technology

1990-05-01

the HDU consists of a miniature cathode ray tube (CRT) located at the end of an optical relay tube attached to the side of the aviator’s helmet...14.6 =1441 Corneal thickness (mm) CL group_ Premask_ Postmask NCL group_ Premask Postmask (Subject O[_D OSj 1C D OS [Subject OID 0S_ _D OS 0001 .506

Long-Cycling Aqueous Organic Redox Flow Battery (AORFB) toward Sustainable and Safe Energy Storage.

PubMed

Hu, Bo; DeBruler, Camden; Rhodes, Zayn; Liu, T Leo

2017-01-25

Redox flow batteries (RFBs) are a viable technology to store renewable energy in the form of electricity that can be supplied to electricity grids. However, widespread implementation of traditional RFBs, such as vanadium and Zn-Br 2 RFBs, is limited due to a number of challenges related to materials, including low abundance and high costs of redox-active metals, expensive separators, active material crossover, and corrosive and hazardous electrolytes. To address these challenges, we demonstrate a neutral aqueous organic redox flow battery (AORFB) technology utilizing a newly designed cathode electrolyte containing a highly water-soluble ferrocene molecule. Specifically, water-soluble (ferrocenylmethyl)trimethylammonium chloride (FcNCl, 4.0 M in H 2 O, 107.2 Ah/L, and 3.0 M in 2.0 NaCl, 80.4 Ah/L) and N 1 -ferrocenylmethyl-N 1 ,N 1 ,N 2 ,N 2 ,N 2 -pentamethylpropane-1,2-diaminium dibromide, (FcN 2 Br 2 , 3.1 M in H 2 O, 83.1 Ah/L, and 2.0 M in 2.0 M NaCl, 53.5 Ah/L) were synthesized through structural decoration of hydrophobic ferrocene with synergetic hydrophilic functionalities including an ammonium cation group and a halide anion. When paired with methyl viologen (MV) as an anolyte, resulting FcNCl/MV and FcN 2 Br 2 /MV AORFBs were operated in noncorrosive neutral NaCl supporting electrolytes using a low-cost anion-exchange membrane. These ferrocene/MV AORFBs are characterized as having high theoretical energy density (45.5 Wh/L) and excellent cycling performance from 40 to 100 mA/cm 2 . Notably, the FcNCl/MV AORFBs (demonstrated at 7.0 and 9.9 Wh/L) exhibited unprecedented long cycling performance, 700 cycles at 60 mA/cm 2 with 99.99% capacity retention per cycle, and delivered power density up to 125 mW/cm 2 . These AORFBs are built from earth-abundant elements and are environmentally benign, thus representing a promising choice for sustainable and safe energy storage.

Cosmological parameter constraints with the Deep Lens Survey using galaxy-shear correlations and galaxy clustering properties

NASA Astrophysics Data System (ADS)

Yoon, Mijin; Jee, Myungkook James; Tyson, Tony

2018-01-01

The Deep Lens Survey (DLS), a precursor to the Large Synoptic Survey Telescope (LSST), is a 20 sq. deg survey carried out with NOAO’s Blanco and Mayall telescopes. The strength of the survey lies in its depth reaching down to ~27th mag in BVRz bands. This enables a broad redshift baseline study and allows us to investigate cosmological evolution of the large-scale structure. In this poster, we present the first cosmological analysis from the DLS using galaxy-shear correlations and galaxy clustering signals. Our DLS shear calibration accuracy has been validated through the most recent public weak-lensing data challenge. Photometric redshift systematic errors are tested by performing lens-source flip tests. Instead of real-space correlations, we reconstruct band-limited power spectra for cosmological parameter constraints. Our analysis puts a tight constraint on the matter density and the power spectrum normalization parameters. Our results are highly consistent with our previous cosmic shear analysis and also with the Planck CMB results.

Characterization of nanoparticles of lidocaine in w/o microemulsions using small-angle neutron scattering and dynamic light scattering

NASA Astrophysics Data System (ADS)

Shukla, A.; Kiselev, M. A.; Hoell, A.; Neubert, R. H. H.

2004-08-01

Microemulsions (MEs) are of special interest because a variety of Reactants can be introduced into the nanometer-sized aqueous domains, leading to materials with controlled size and shape [1,2]. In the past few years, significant research has been conducted in the reverse ME-mediated synthesis of organic nanoparticles [3,4]. In this study, a w/o ME medium was employed for the synthesis of lidocaine by direct precipitation in w/o microemulsion systems: water/isopropylpalmitat/Tween80/Span80. The particle size as well as the location of nanoparticles in the ME droplet were characterized by means of dynamic light scattering (DLS) and small angle neutron scattering (SANS). It is observed that lidocaine precipitated in the aqueous cores because of its insolubility in water. Hydrodynamic radius and gyration radius of microemulsion droplets were estimated as ~15 nm and ~4.50 nm from DLS and SANS respectively. Furthermore, different size parameters obtained by DLS and SANS experiments were compared

Inverse Transformation: Unleashing Spatially Heterogeneous Dynamics with an Alternative Approach to XPCS Data Analysis.

PubMed

Andrews, Ross N; Narayanan, Suresh; Zhang, Fan; Kuzmenko, Ivan; Ilavsky, Jan

2018-02-01

X-ray photon correlation spectroscopy (XPCS), an extension of dynamic light scattering (DLS) in the X-ray regime, detects temporal intensity fluctuations of coherent speckles and provides scattering vector-dependent sample dynamics at length scales smaller than DLS. The penetrating power of X-rays enables probing dynamics in a broad array of materials with XPCS, including polymers, glasses and metal alloys, where attempts to describe the dynamics with a simple exponential fit usually fails. In these cases, the prevailing XPCS data analysis approach employs stretched or compressed exponential decay functions (Kohlrausch functions), which implicitly assume homogeneous dynamics. In this paper, we propose an alternative analysis scheme based upon inverse Laplace or Gaussian transformation for elucidating heterogeneous distributions of dynamic time scales in XPCS, an approach analogous to the CONTIN algorithm widely accepted in the analysis of DLS from polydisperse and multimodal systems. Using XPCS data measured from colloidal gels, we demonstrate the inverse transform approach reveals hidden multimodal dynamics in materials, unleashing the full potential of XPCS.

Inverse Transformation: Unleashing Spatially Heterogeneous Dynamics with an Alternative Approach to XPCS Data Analysis

PubMed Central

Andrews, Ross N.; Narayanan, Suresh; Zhang, Fan; Kuzmenko, Ivan; Ilavsky, Jan

2018-01-01

X-ray photon correlation spectroscopy (XPCS), an extension of dynamic light scattering (DLS) in the X-ray regime, detects temporal intensity fluctuations of coherent speckles and provides scattering vector-dependent sample dynamics at length scales smaller than DLS. The penetrating power of X-rays enables probing dynamics in a broad array of materials with XPCS, including polymers, glasses and metal alloys, where attempts to describe the dynamics with a simple exponential fit usually fails. In these cases, the prevailing XPCS data analysis approach employs stretched or compressed exponential decay functions (Kohlrausch functions), which implicitly assume homogeneous dynamics. In this paper, we propose an alternative analysis scheme based upon inverse Laplace or Gaussian transformation for elucidating heterogeneous distributions of dynamic time scales in XPCS, an approach analogous to the CONTIN algorithm widely accepted in the analysis of DLS from polydisperse and multimodal systems. Using XPCS data measured from colloidal gels, we demonstrate the inverse transform approach reveals hidden multimodal dynamics in materials, unleashing the full potential of XPCS. PMID:29875506

Orbitofrontal and striatal circuits dynamically encode the shift between goal-directed and habitual actions

PubMed Central

Gremel, Christina M.; Costa, Rui M.

2014-01-01

Shifting between goal-directed and habitual actions allows for efficient and flexible decision-making. Here we demonstrate a novel, within-subject instrumental lever-pressing paradigm where mice shift between goal-directed and habitual actions. We identify a role for orbitofrontal cortex (OFC) in actions following outcome-revaluation, and confirm that dorsal medial (DMS) and lateral striatum (DLS) mediate different action strategies. In-vivo simultaneous recordings of OFC, DMS, and DLS neuronal ensembles during shifting reveal that the same neurons display different activity depending on whether presses are goal-directed or habitual, with DMS and OFC becoming more—and DLS less-engaged during goal-directed actions. Importantly, the magnitude of neural activity changes in OFC following changes in outcome value positively correlates with the level of goal-directed behavior. Chemogenetic inhibition of OFC disruptsgoal-directed actions, while optogenetic activation of OFC specifically increases goal-directed pressing. They also reveal a role for OFC in action revaluation, which has implications for understanding compulsive behavior. PMID:23921250

Practical technique to quantify small, dense low-density lipoprotein cholesterol using dynamic light scattering

NASA Astrophysics Data System (ADS)

Trirongjitmoah, Suchin; Iinaga, Kazuya; Sakurai, Toshihiro; Chiba, Hitoshi; Sriyudthsak, Mana; Shimizu, Koichi

2016-04-01

Quantification of small, dense low-density lipoprotein (sdLDL) cholesterol is clinically significant. We propose a practical technique to estimate the amount of sdLDL cholesterol using dynamic light scattering (DLS). An analytical solution in a closed form has newly been obtained to estimate the weight fraction of one species of scatterers in the DLS measurement of two species of scatterers. Using this solution, we can quantify the sdLDL cholesterol amount from the amounts of the low-density lipoprotein cholesterol and the high-density lipoprotein (HDL) cholesterol, which are commonly obtained through clinical tests. The accuracy of the proposed technique was confirmed experimentally using latex spheres with known size distributions. The applicability of the proposed technique was examined using samples of human blood serum. The possibility of estimating the sdLDL amount using the HDL data was demonstrated. These results suggest that the quantitative estimation of sdLDL amounts using DLS is feasible for point-of-care testing in clinical practice.

Multiphase Flow Modeling of Slag Entrainment During Ladle Change-Over Operation

NASA Astrophysics Data System (ADS)

Morales, Rodolfo D.; Garcia-Hernandez, Saul; Barreto, Jose de Jesus; Ceballos-Huerta, Ariana; Calderon-Ramos, Ismael; Gutierrez, Enif

2016-08-01

Steel transfer from the ladle to a single-strand tundish using a conventional ladle shroud (CLS), and a dissipative ladle shroud (DLS) is studied during the transient period of ladle change-over operation. Fluid velocities and fluid flow turbulence statistics during this unsteady operation were recorded by an ultrasound velocimetry probe in a 1/3 scale water-oil-air analog model (to emulate steel-slag-air system). Reynolds stress model and volume of fluid model allow the tracking of water-oil, water-air, and oil-air interfaces during this operation. Velocity measurements indicate a very high turbulence with the formation of a water-air bubbles-oil emulsion. Flow turbulence and the intensity of the emulsification decrease considerably due to an efficient dissipation of the turbulent kinetic energy employing the DLS instead of the CLS. The modeling results indicate that DLS is widely recommended to substitute flow control devices to improve the fluid dynamics of liquid steel during this transient operation.

Alteration of synaptic plasticity in rat dorsal striatum induced by chronic ethanol intake and withdrawal via ERK pathway.

PubMed

Cui, Sheng-zhong; Wang, Shen-jun; Li, Jing; Xie, Gui-qin; Zhou, Rong; Chen, Ling; Yuan, Xiao-ru

2011-02-01

The dorsal striatum has been proposed to contribute to the formation of drug-seeking behaviors, leading to excessive and compulsive drug usage, such as addiction. The current study aimed to investigate the involvement of extracellular signal-regulated kinase (ERK) pathway in the modification of striatal synaptic plasticity. Ethanol was administered to rats in drinking water at concentration of 6% (v/v) for 30 days. Rats were sacrificed on day 10, 20, or 30 during ethanol intake or on withdrawal day 1, 3, or 7 following 30-d ethanol intake. The striata were removed either for electrophysiological recording or for protein immuno-blot analysis. Extracellular recording technique was used to record population spikes (PS) induced by high-frequency stimulation (HFS) in the dorsolateral striatum (DLS). Corticostriatal long-term depression (LTD) was determined to be dependent upon ERK signaling. Chronic ethanol intake (CEI) attenuated ERK phosphorylation and LTD induction, whereas withdrawal for one day (W1D) potentiated ERK phosphorylation and LTD induction. These results showed that the impact of chronic ethanol intake and withdrawal on corticostriatal synaptic plasticity was associated with ethanol's effect on ERK phosphorylation. In particular, pharmacological inhibition of ERK hyper-phosphorylation by U0126 prevented LTD induction in the DLS and attenuated ethanol withdrawal syndrome as well. In rat DLS, chronic ethanol intake and withdrawal altered LTD induction via ERK signaling pathway. Ethanol withdrawal syndrome is mediated, at least partly, by ERK hyper-phosphorylation in the DLS.

Transarticular facet screw stabilization and dorsal laminectomy in 26 dogs with degenerative lumbosacral stenosis with instability.

PubMed

Hankin, Elyshia J; Jerram, Richard M; Walker, Alexander M; King, Michael D; Warman, Christopher G A

2012-07-01

To describe outcome after transarticular facet screw stabilization and dorsal laminectomy for treatment of dynamic degenerative lumbosacral stenosis (DLS) in 26 dogs. Retrospective case series. Dogs (n = 26) with dynamic DLS. Medical records (2004-2009) of dogs treated with transarticular facet screw stabilization and dorsal laminectomy were reviewed. Dogs (n = 26) were available for immediate postoperative follow-up, 21 dogs at 6 weeks, and 15 at greater than 6 months. Dogs were evaluated by radiographic assessment and owner questionnaire. Lumbosacral (LS) intervertebral disc (IVD) spaces were measured on pre and postoperative 6-week and 6-month radiographs. In 23 dogs, improvement in clinical signs occurred within 7 days of surgery. Overall postsurgical complication rate directly related to the surgical procedure was 15.4%. LS IVD space measurements taken immediately postoperatively, at 6 weeks, and ≥ 6 months were all significantly increased compared with preoperative measurements. All working dogs (4) returned to full work within 14 months. Most owners (85%) reported their dog was ambulating normally at 6 months with no perceptible lameness during normal activity. All owners perceived their dog's ability to walk, run, and jump after surgery to be improved. Transarticular facet screw stabilization and dorsal laminectomy maintains distraction of the LS IVD space for medium-to-large breed dogs with dynamic DLS with a high degree of owner satisfaction, and is comparable to other reported surgical techniques for DLS. © Copyright 2012 by The American College of Veterinary Surgeons.

Brain oxytocin in social fear conditioning and its extinction: involvement of the lateral septum.

PubMed

Zoicas, Iulia; Slattery, David A; Neumann, Inga D

2014-12-01

Central oxytocin (OXT) has anxiolytic and pro-social properties both in humans and rodents, and has been proposed as a therapeutic option for anxiety and social dysfunctions. Here, we utilized a mouse model of social fear conditioning (SFC) to study the effects of OXT on social fear, and to determine whether SFC causes alterations in central OXT receptor (OXTR) binding and local OXT release. Central infusion of OXT, but not arginine vasopressin, prior to social fear extinction training completely abolished social fear expression in an OXTR-mediated fashion without affecting general anxiety or locomotion. SFC caused increased OXTR binding in the dorso-lateral septum (DLS), central amygdala, dentate gyrus, and cornu ammunis 1, which normalized after social fear extinction, suggesting that these areas form part of a brain network involved in the development and neural support of social fear. Microdialysis revealed that the increase in OXT release observed in unconditioned mice within the DLS during social fear extinction training was attenuated in conditioned mice. Consequently, increasing the availability of local OXT by infusion of OXT into the DLS reversed social fear. Thus, alterations in the brain OXT system, including altered OXTR binding and OXT release within the DLS, play an important role in SFC and social fear extinction. Thus, we suggest that the OXT system is adversely affected in disorders associated with social fear, such as social anxiety disorder and reinstalling an appropriate balance of the OXT system may alleviate some of the symptoms.

Native N-glycopeptide thioester synthesis through N→S acyl transfer

PubMed Central

Premdjee, Bhavesh; Adams, Anna L.; Macmillan, Derek

2011-01-01

Peptide thioesters are important tools for the total synthesis of proteins using native chemical ligation (NCL). Preparation of glycopeptide thioesters, that enable the assembly of homogeneously glycosylated proteins, is complicated by the perceived fragile nature of the sugar moiety. Herein, we demonstrate the compatibility of thioester formation via N→S acyl transfer with native N-glycopeptides and report observations that will aid in their preparation. PMID:21676613

Data are from Mars, Tools are from Venus

NASA Technical Reports Server (NTRS)

Lee, H. Joe

2017-01-01

Although during the data production phase, the data producers will usually ensure the products to be easily used by the specific power users the products serve. However, most data products are also posted for general public to use. It is not straightforward for data producers to anticipate what tools that these general end-data users are likely to use. In this talk, we will try to help fill in the gap by going over various tools related to Earth Science and how they work with the existing NASA HDF (Hierarchical Data Format) data products and the reasons why some products cannot be visualized or analyzed by existing tools. One goal is for to give insights for data producers on how to make their data product more interoperable. On the other hand, we also provide some hints for end users on how to make tools work with existing HDF data products. (tool category list: check the comments) HDF-EOS tools: HDFView HDF-EOS Plugin, HEG, h4tonccf, hdf-eos2 dumper, NCL, MATLAB, IDL, etc.net; CDF-Java tools: Panoply, IDV, toosUI, NcML, etc.net; CDF-C tools: ArcGIS Desktop, GrADS, NCL, NCO, etc.; GDAL tools: ArcGIS Desktop, QGIS, Google Earth, etc.; CSV tools: ArcGIS Online, MS Excel, Tableau, etc.

In-situ precipitation of ultra-stable nano-magnetite slurry

NASA Astrophysics Data System (ADS)

Ramimoghadam, Donya; Bagheri, Samira; Hamid, Sharifah Bee Abd

2015-04-01

In this contribution, we prepared water-based magnetic fluids of iron oxide nanoparticles using an in-situ precipitation method. The effect of dodecanoic acid addition as a surfactant on the physico-chemical and magnetic properties of iron oxide nanoparticles was investigated as well. The quantity of the surfactant was varied between 3 and 5 g. Raman spectroscopy and X-ray diffraction (XRD) were utilized to confirm the presence of spinel phase magnetites (Fe3O4). Dynamic light scattering (DLS) and transmission electron microscopy (TEM) were used to characterize the resulting magnetic nanoparticles' size and morphology. The results showed polydispersed hexagonal nanoparticles (average diameter of ca. 70 nm) as a result of the protocol. Moreover, the pH-dependent stability of the samples confirms that magnetite nanofluids were highly stable in the wide range of pH, from 4-12. The optimal amount of dodecanoic acid to produce ultra-stable nano-magnetite slurry with the highest saturation magnetization of 8.6 emu g-1 was determined to be 4.5 g.

Bis-demethoxy curcumin analog nanoparticles: synthesis, characterization, and anticancer activity in vitro.

PubMed

Francis, Arul Prakash; Murthy, Prakhya Balakishna; Devas, Thiyagarajan

2014-07-01

We have optimized a protocol for the preparation of bisdemethoxy curcumin analog nanoparticles (BDMCA-NP) by the solvent assisted process. The structural similarities between bulk and nano BDMCA were determined by Co-TLC, NMR and F-TIR. This shows that our synthesis protocol enhanced the dispersibility and reduce the size of BDMCA without altering the integrity of functional moieties and structure, which is crucial for anticancer and antioxidant activities. The morphology and size of BDMCA-NP as determined by SEM, HRTEM and DLS was found to be around 80 nm. BDMCA-NP treated breast cancer cell lines (MCF 7) showed cell death as characterized by MTT assay. Flow cytometric analysis of BDMCA-NP treated MCF 7 cell lines showed an increase of cell count in G2/M phase indicates the cell cycle arrest. Western blot analysis revealed the presence of caspase 3, caspase 9, cleaved fragments of PARP and Bax proteins in the BDMCA-NP treated MCF 7 cell lines, but not in untreated cell lines. To recap, we have prepared BDMCA-NP by solvent assisted process, which exerted anticancer activity against breast cancer cells, which may be due to (i) enhanced dispersibility and surface: volume ratio, (ii) apoptosis (iii) mitochondrial pathway induced cell death, (iv) G2/M phase cell cycle arrest and (v) disassembly of mitotic spindle of the cancer cells. Thus, nano BDMCA can be used as a potent anticancer agent.

Minimally invasive decompression surgery for lumbar spinal stenosis with degenerative scoliosis: Predictive factors of radiographic and clinical outcomes.

PubMed

Minamide, Akihito; Yoshida, Munehito; Iwahashi, Hiroki; Simpson, Andrew K; Yamada, Hiroshi; Hashizume, Hiroshi; Nakagawa, Yukihiro; Iwasaki, Hiroshi; Tsutsui, Shunji; Kagotani, Ryohei; Sonekatsu, Mayumi; Sasaki, Takahide; Shinto, Kazunori; Deguchi, Tsuyoshi

2017-05-01

There is ongoing controversy regarding the most appropriate surgical treatment for lumbar spinal stenosis (LSS) with concurrent degenerative lumbar scoliosis (DLS): decompression alone, decompression with limited spinal fusion, or long spinal fusion for deformity correction. The coexistence of degenerative stenosis and deformity is a common scenario; Nonetheless, selecting the appropriate surgical intervention requires thorough understanding of the patients clinical symptomatology as well as radiographic parameters. Minimally invasive (MIS) decompression surgery was performed for LSS patients with DLS. The aims of this study were (1) to investigate the clinical outcomes of MIS decompression surgery in LSS patients with DLS, and (2) to identify the predictive factors for both radiographic and clinical outcomes after MIS surgery. 438 consecutive patients were enrolled in this study. Inclusion criteria was evidence of LSS and DLS with coronal curvature measuring greater than 10°. The Japanese Orthopaedic Association (JOA) score, JOA recovery rate, low back pain (LBP), and radiographic features were evaluated preoperatively and at over 2 years postoperatively. Of the 438 patients, 122 were included in final analysis, with a mean follow-up of 2.4 years. The JOA recovery rate was 47.6%. LBP was significantly improved at final follow-up. Cobb angle was maintained for 2 years postoperatively (p = 0.159). Clinical outcomes in foraminal stenosis patients were significantly related to sex, preoperative high Cobb angle and progression of scoliosis (p = 0.008). In the severe scoliosis patients, the JOA recovery was 44%, and was significantly depended on progression of scoliosis (Cobb angle: preoperation 29.6°, 2-years follow-up 36.9°) and mismatch between the pelvic incidence (PI) and the lumbar lordosis (LL) (preoperative PI-LL 35.5 ± 21.2°) (p = 0.028). This study investigated clinical outcomes of MIS decompression surgery in LSS patients with DLS. The predictive risk factors of clinical outcomes were severe scoliosis, foramina stenosis, progressive scoliosis and large mismatch of PI-LL. Copyright © 2016 The Japanese Orthopaedic Association. All rights reserved.

Schedule-induced polydipsia is associated with increased spine density in dorsolateral striatum neurons.

PubMed

Íbias, J; Soria-Molinillo, E; Kastanauskaite, A; Orgaz, C; DeFelipe, J; Pellón, R; Miguéns, M

2015-08-06

Schedule-induced polydipsia (SIP) is an adjunctive behavior in which rats exhibit excessive drinking as a consequence of intermittent feeding, and it has been proposed as a candidate model to study the development of compulsive and repetitive behavior. Although several brain structures are involved in compulsive behavior, it has been suggested that alterations in fronto-striatal circuits may underlie compulsive spectrum disorders. In the present work, we examined whether SIP would induce modifications in dorsolateral striatum (DLS) and anterior prefrontal cortex (aPFC) neurons. Specifically, the effects of 20 sessions of SIP were determined in the dendrites of DLS medium spiny neurons and in the basal dendritic arbors of layer V pyramidal cells in the aPFC. The structure, size and branching complexity in aPFC neurons were also studied. Results showed that SIP resulted in an increase in dendritic spine density in DLS neurons. Moreover, dendritic spine density was highly correlated with the level of drinking in animals subjected to SIP. By contrast, we observed no differences either in dendritic spine density or in the morphological structure of the dendrites of the aPFC in SIP rats compared to their control counterparts. We hypothesize that SIP-induced structural plasticity in DLS neurons could be related to inflexible response in compulsive behavior. The findings of this study could provide new insights into the involvement of particular cell populations of the dorsolateral striatum and anterior prefrontal cortex regions in compulsive spectrum disorders. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Angle Dependent Optics of Plasmonic Core-Shell Nanoparticles

DTIC Science & Technology

2018-02-21

RESEARCH Final Report 02/21/2018 DISTRIBUTION A: Distribution approved for public release. AF Office Of Scientific Research (AFOSR)/ IOA Arlington...Virginia 22203 Air Force Research Laboratory Air Force Materiel Command   a. REPORT Unclassified   b. ABSTRACT Unclassified   c. THIS PAGE Unclassified...EDUCATION AND RESEARCH 900, NCL Innovation Park, Dr Homi Bhabha Road, Pashan PUNE, 411008 IN 8.  PERFORMING ORGANIZATION      REPORT NUMBER 9

Family Structure, Psychosocial Factors, and Cardiovascular Risk Factors in the NHLBI CARDIA Study

DTIC Science & Technology

2013-11-21

Sciences In partial fulfillment of the requirements for the degree of Master of Science 2013 UNH’ORMIED SlERVlCES UNIVERSHY OF THE HEAL TH scrnNClES...IF. lEDW ARD HEBERT SCHOOL OF MEDKCJNE GRADUATE PROGRAMS IN nm lBiOMEDICAL SCIENCES AND PUBUC HEAL TH Ph.D. Degrees lnterdisci pl inary...Emerging Infectious Diseases -Molecular & Cell Biology -Neuroscience Departmental -Clinical Psychology -Environmental Health Sciences -Medical

Inverse transformation: unleashing spatially heterogeneous dynamics with an alternative approach to XPCS data analysis

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

Andrews, Ross N.; Narayanan, Suresh; Zhang, Fan

X-ray photon correlation spectroscopy (XPCS), an extension of dynamic light scattering (DLS) in the X-ray regime, detects temporal intensity fluctuations of coherent speckles and provides scattering-vector-dependent sample dynamics at length scales smaller than DLS. The penetrating power of X-rays enables XPCS to probe the dynamics in a broad array of materials, including polymers, glasses and metal alloys, where attempts to describe the dynamics with a simple exponential fit usually fail. In these cases, the prevailing XPCS data analysis approach employs stretched or compressed exponential decay functions (Kohlrausch functions), which implicitly assume homogeneous dynamics. This paper proposes an alternative analysis schememore » based upon inverse Laplace or Gaussian transformation for elucidating heterogeneous distributions of dynamic time scales in XPCS, an approach analogous to the CONTIN algorithm widely accepted in the analysis of DLS from polydisperse and multimodal systems. In conclusion, using XPCS data measured from colloidal gels, it is demonstrated that the inverse transform approach reveals hidden multimodal dynamics in materials, unleashing the full potential of XPCS.« less

Note: Evaluation of slurry particle size analyzers for chemical mechanical planarization process

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

Jang, Sunjae; Kulkarni, Atul; Qin, Hongyi

In the chemical mechanical planarization (CMP) process, slurry particle size is important because large particles can cause defects. Hence, selection of an appropriate particle measuring system is necessary in the CMP process. In this study, a scanning mobility particle sizer (SMPS) and dynamic light scattering (DLS) were compared for particle size distribution (PSD) measurements. In addition, the actual particle size and shape were confirmed by transmission electron microscope (TEM) results. SMPS classifies the particle size according to the electrical mobility, and measures the particle concentration (single particle measurement). On the other hand, the DLS measures the particle size distribution bymore » analyzing scattered light from multiple particles (multiple particle measurement). For the slurry particles selected for evaluation, it is observed that SMPS shows bi-modal particle sizes 30 nm and 80 nm, which closely matches with the TEM measurements, whereas DLS shows only single mode distribution in the range of 90 nm to 100 nm and showing incapability of measuring small particles. Hence, SMPS can be a better choice for the evaluation of CMP slurry particle size and concentration measurements.« less

PARTITIONING OF PERFLUOROOCTANOATE INTO PHOSPHATIDYLCHOLINE BILAYERS IS CHAIN LENGTH-INDEPENDENT

PubMed Central

Xie, Wei; Bothun, Geoffrey D.; Lehmler, Hans-Joachim

2010-01-01

The chain length dependence of the interaction of PFOA, a persistent environmental contaminant, with dimyristoyl- (DMPC), dipalmitoyl- (DPPC) and distearoylphosphatidylcholine (DSPC) was investigated using steady-state fluorescence anisotropy spectroscopy, differential scanning calorimetry (DSC) and dynamic light scattering (DLS). PFOA caused a linear depression of the main phase transition temperature Tm while increasing the width of the phase transition of all three phosphatidylcholines. Although PFOA’s effect on the on Tm and the transition width decreased in the order DMPC > DPPC > DSPC, its relative effect on the phase behavior was largely independent of the phosphatidylcholine. PFOA caused swelling of DMPC but not DPPC and DSPC liposomes at 37°C in the DLS experiments, which suggests that PFOA partitions more readily into bilayers in the fluid phase. These findings suggest that PFOA’s effect on the phase behavior of phosphatidylcholines depends on the cooperativity and state (i.e., gel versus liquid phase) of the membrane. DLS experiments are also consistent with partial liposome solubilization at PFOA/lipid molar ratios > 1, which suggests the formation of mixed PFOA-lipid micelles. PMID:20096277

A Smoluchowski model of crystallization dynamics of small colloidal clusters

NASA Astrophysics Data System (ADS)

Beltran-Villegas, Daniel J.; Sehgal, Ray M.; Maroudas, Dimitrios; Ford, David M.; Bevan, Michael A.

2011-10-01

We investigate the dynamics of colloidal crystallization in a 32-particle system at a fixed value of interparticle depletion attraction that produces coexisting fluid and solid phases. Free energy landscapes (FELs) and diffusivity landscapes (DLs) are obtained as coefficients of 1D Smoluchowski equations using as order parameters either the radius of gyration or the average crystallinity. FELs and DLs are estimated by fitting the Smoluchowski equations to Brownian dynamics (BD) simulations using either linear fits to locally initiated trajectories or global fits to unbiased trajectories using Bayesian inference. The resulting FELs are compared to Monte Carlo Umbrella Sampling results. The accuracy of the FELs and DLs for modeling colloidal crystallization dynamics is evaluated by comparing mean first-passage times from BD simulations with analytical predictions using the FEL and DL models. While the 1D models accurately capture dynamics near the free energy minimum fluid and crystal configurations, predictions near the transition region are not quantitatively accurate. A preliminary investigation of ensemble averaged 2D order parameter trajectories suggests that 2D models are required to capture crystallization dynamics in the transition region.

Microgravity Diode Laser Spectroscopy Measurements in a Reacting Vortex Ring

NASA Technical Reports Server (NTRS)

Chen, Shin-Juh; Dahm, Werner J. A.; Silver, Joel A.; Piltch, Nancy D.

2001-01-01

The technique of Diode Laser Spectroscopy (DLS) with wavelength modulation is utilized to measure the concentration of methane in reacting vortex rings under microgravity conditions. From the measured concentration of methane, other major species such as water, carbon dioxide, nitrogen, and oxygen can be easily computed under the assumption of equilibrium chemistry with the method of Interactive Temperature with Assumed Chemistry (ITAC). The conserved scalar approach in modelling the coupling between fluid dynamics and combustion is utilized to represent the unknown variables in terms of the mixture fraction and scalar dissipation rate in conjunction with ITAC. Post-processing of the DLS measurements and the method of ITAC used in computing the species concentration are discussed. From the flame luminosity results, the increase in ring circulation appears to increase the fuel consumption rate inside the reacting vortex ring and the flame height for cases with similar fuel volumes. Preliminary results and application of ITAC show some potential capabilities of ITAC in DLS. The measured concentration of methane, and computed concentrations of water and carbon dioxide agree well with available results from numerical simulations.

Inverse transformation: unleashing spatially heterogeneous dynamics with an alternative approach to XPCS data analysis

DOE PAGES

Andrews, Ross N.; Narayanan, Suresh; Zhang, Fan; ...

2018-02-01

X-ray photon correlation spectroscopy (XPCS), an extension of dynamic light scattering (DLS) in the X-ray regime, detects temporal intensity fluctuations of coherent speckles and provides scattering-vector-dependent sample dynamics at length scales smaller than DLS. The penetrating power of X-rays enables XPCS to probe the dynamics in a broad array of materials, including polymers, glasses and metal alloys, where attempts to describe the dynamics with a simple exponential fit usually fail. In these cases, the prevailing XPCS data analysis approach employs stretched or compressed exponential decay functions (Kohlrausch functions), which implicitly assume homogeneous dynamics. This paper proposes an alternative analysis schememore » based upon inverse Laplace or Gaussian transformation for elucidating heterogeneous distributions of dynamic time scales in XPCS, an approach analogous to the CONTIN algorithm widely accepted in the analysis of DLS from polydisperse and multimodal systems. In conclusion, using XPCS data measured from colloidal gels, it is demonstrated that the inverse transform approach reveals hidden multimodal dynamics in materials, unleashing the full potential of XPCS.« less

A New Clinical Instrument for The Early Detection of Cataract Using Dynamic Light Scattering and Corneal Topography

NASA Technical Reports Server (NTRS)

Ansari, Rafat R.; Datiles, Manuel B., III; King, James F.

2000-01-01

A growing cataract can be detected at the molecular level using the technique of dynamic light scattering (DLS). However, the success of this method in clinical use depends upon the precise control of the scattering volume inside a patient's eye and especially during patient's repeat visits. This is important because the scattering volume (cross-over region between the scattered fight and incident light) inside the eye in a high-quality DLS set-up is very small (few microns in dimension). This precise control holds the key for success in the longitudinal studies of cataract and during anti-cataract drug screening. We have circumvented these problems by fabricating a new DLS fiber optic probe with a working distance of 40 mm and by mounting it inside a cone of a corneal analyzer. This analyzer is frequently used in mapping the corneal topography during PRK (photorefractive keratectomy) and LASIK (laser in situ keratomileusis) procedures in shaping of the cornea to correct myopia. This new instrument and some preliminary clinical tests on one of us (RRA) showing the data reproducibility are described.

New clinical instrument for the early detection of cataract using dynamic light scattering and corneal topography

NASA Astrophysics Data System (ADS)

Ansari, Rafat R.; Datiles, Manuel B., III; King, James F.

2000-06-01

A growing cataract can be detected at the molecular level using the technique of dynamic light scattering (DLS). However, the success of this method in clinical use depends upon the precise control of the scattering volume inside a patient's eye and especially during patient's repeat visits. This is important because the scattering volume (cross-over region between the scattered light and incident light) inside the eye in a high-quality DLS set-up is very small (few microns in dimension). This precise control holds the key for success in the longitudinal studies of cataract and during anti-cataract drug screening. We have circumvented these problems by fabricating a new DLS fiber optic probe with a working distance of 40 mm and by mounting it inside a cone of a corneal analyzer. This analyzer is frequently used in mapping the corneal topography during PRK (photorefractive keratectomy) and LASIK (laser in situ keratomileusis) procedures in shaping of the cornea to correct myopia. This new instrument and some preliminary clinical tests on one of us (RRA) showing the data reproducibility are described.

Highly sensitive and selective dynamic light-scattering assay for TNT detection using p-ATP attached gold nanoparticle.

PubMed

Dasary, Samuel S R; Senapati, Dulal; Singh, Anant Kumar; Anjaneyulu, Yerramilli; Yu, Hongtao; Ray, Paresh Chandra

2010-12-01

TNT is one of the most commonly used nitro aromatic explosives for landmines of military and terrorist activities. As a result, there is an urgent need for rapid and reliable methods for the detection of trace amount of TNT for screenings in airport, analysis of forensic samples, and environmental analysis. Driven by the need to detect trace amounts of TNT from environmental samples, this article demonstrates a label-free, highly selective, and ultrasensitive para-aminothiophenol (p-ATP) modified gold nanoparticle based dynamic light scattering (DLS) probe for TNT recognition in 100 pico molar (pM) level from ethanol:acetonitile mixture solution. Because of the formation of strong π-donor-acceptor interaction between TNT and p-ATP, para-aminothiophenol attached gold nanoparticles undergo aggregation in the presence of TNT, which changes the DLS intensity tremendously. A detailed mechanism for significant DLS intensity change has been discussed. Our experimental results show that TNT can be detected quickly and accurately without any dye tagging in 100 pM level with excellent discrimination against other nitro compounds.

A novel method of testing the shear strength of thick honeycomb composites

NASA Technical Reports Server (NTRS)

Hodge, A. J.; Nettles, A. T.

1991-01-01

Sandwich composites of aluminum and glass/phenolic honeycomb core were tested for shear strength before and after impact damage. The assessment of shear strength was performed in two ways; by four point bend testing of sandwich beams and by a novel double lap shear (DLS) test. This testing technique was developed so smaller specimens could be used, thus making the use of common lab scale fabrication and testing possible. The two techniques yielded similar data. The DLS test gave slightly lower shear strength values of the two methods but were closer to the supplier's values for shear strength.

Application of dynamic light scattering for studying the evolution of micro- and nano-droplets

NASA Astrophysics Data System (ADS)

Derkachov, G.; Jakubczyk, D.; Kolwas, K.; Shopa, Y.; Woźniak, M.; Wojciechowski, T.

2018-01-01

The dynamic light scattering (DLS) technique was used for studying the processes of aggregation of spherical SiO2 particles in various diethylene glycol (DEG) suspensions. The suspensions were studied in a cuvette, in a millimeter-sized droplet and in a micrometer-sized droplet. For the first time DLS signals for droplets of picolitre volume, levitated in an electrodynamic quadrupole trap, were obtained. It is shown that the correlation analysis of light scattered from a micro-droplet allows monitoring the changes of its internal structure, as well as its motions: trap-constricted Brownian motions and random rotations.

CONTIN XPCS: Software for Inverse Transform Analysis of X-Ray Photon Correlation Spectroscopy Dynamics

PubMed Central

Narayanan, Suresh; Zhang, Fan; Kuzmenko, Ivan; Ilavsky, Jan

2018-01-01

X-ray photon correlation spectroscopy (XPCS) and dynamic light scattering (DLS) both reveal dynamics using coherent scattering, but X-rays permit investigating of dynamics in a much more diverse array of materials. Heterogeneous dynamics occur in many such materials, and we showed how classic tools employed in analysis of heterogeneous DLS dynamics extend to XPCS, revealing additional information that conventional Kohlrausch exponential fitting obscures. This work presents the software implementation of inverse transform analysis of XPCS data called CONTIN XPCS, an extension of traditional CONTIN that accommodates dynamics encountered in equilibrium XPCS measurements. PMID:29875507

CONTIN XPCS: Software for Inverse Transform Analysis of X-Ray Photon Correlation Spectroscopy Dynamics.

PubMed

Andrews, Ross N; Narayanan, Suresh; Zhang, Fan; Kuzmenko, Ivan; Ilavsky, Jan

2018-02-01

X-ray photon correlation spectroscopy (XPCS) and dynamic light scattering (DLS) both reveal dynamics using coherent scattering, but X-rays permit investigating of dynamics in a much more diverse array of materials. Heterogeneous dynamics occur in many such materials, and we showed how classic tools employed in analysis of heterogeneous DLS dynamics extend to XPCS, revealing additional information that conventional Kohlrausch exponential fitting obscures. This work presents the software implementation of inverse transform analysis of XPCS data called CONTIN XPCS, an extension of traditional CONTIN that accommodates dynamics encountered in equilibrium XPCS measurements.

Effects of UV 254 irradiation on residual chlorine and DBPs in chlorination of model organic-N precursors in swimming pools.

PubMed

Weng, ShihChi; Li, Jing; Blatchley, Ernest R

2012-05-15

Ultraviolet (UV) irradiation is commonly applied as a secondary disinfection process in chlorinated pools. UV-based systems have been reported to yield improvements in swimming pool water and air chemistry, but to date these observations have been largely anecdotal. The objectives of this investigation were to evaluate the effects of UV irradiation on chlorination of important organic-N precursors in swimming pools. Creatinine, L-arginine, L-histidine, glycine, and urea, which comprise the majority of the organic-N in human sweat and urine, were selected as precursors for use in conducting batch experiments to examine the time-course behavior of several DBPs and residual chlorine, with and without UV(254) irradiation. In addition, water samples from two natatoria were subjected to monochromatic UV irradiation at wavelengths of 222 nm and 254 nm to evaluate changes of liquid-phase chemistry. UV(254) irradiation promoted formation and/or decay of several chlorinated N-DBPs and also increased the rate of free chlorine consumption. UV exposure resulted in loss of inorganic chloramines (e.g., NCl(3)) from solution. Dichloromethylamine (CH(3)NCl(2)) formation from creatinine was promoted by UV exposure, when free chlorine was present in solution; however, when free chlorine was depleted, CH(3)NCl(2) photodecay was observed. Dichloroacetonitrile (CNCHCl(2)) formation (from L-histidine and L-arginine) was promoted by UV(254) irradiation, as long as free chlorine was present in solution. Likewise, UV exposure was observed to amplify cyanogen chloride (CNCl) formation from chlorination of L-histidine, L-arginine, and glycine, up to the point of free chlorine depletion. The results from experiments involving UV irradiation of chlorinated swimming pool water were qualitatively consistent with the results of model experiments involving UV/chlorination of precursors in terms of the behavior of residual chlorine and DBPs measured in this study. The results indicate that UV(254) irradiation promotes several reactions that are involved in the formation and/or destruction of chlorinated N-DBPs in pool settings. Enhancement of DBP formation was consistent with a mechanism whereby a rate-limiting step in DBP formation was promoted by UV exposure. Promotion of these reactions also resulted in increases of free chlorine consumption rates. Copyright © 2012 Elsevier Ltd. All rights reserved.

Advanced Computational Techniques in Regional Wave Studies

DTIC Science & Technology

1990-01-03

UiNCL.ASSIriEDIUNLIMITED C SAME AS RPT. C DTIC USERS CUNCLASSIFIED ; a 𔃾AM OF RE.;PONSIBL- E INOIVIDIJAL 22D. TELEPHCNE NUMBER 22c. OFFICE SYMBOL...this system is right We define the components of the time dependent force handed). Then, e ,, e ., and e , are the unit vectors moment tensor as towards...are constants representing the components of the 1 , ,( ,, - second order seismic moment tensor M, usually termed , M,- "(x,/,,t ,( E ,’ the moment tensor

The National Nanotechnology Initiative: Research and Development Leading to a Revolution in Technology and Industry. Supplement to the President’s FY 2008 Budget

DTIC Science & Technology

2007-07-31

nanoscale materials for cancer diagnostics, imaging agents, and therapeutics. Recently NCL has extended its work to in vivo models and testing by...THE NATIONAL NANOTECHNOLOGY INITIATIVE Research and Development Leading to a Revolution in Technology and Industry Supplement to the President’s FY...clear national goals for Federal science and technology investments in areas ranging from nanotechnology and health research to improving

Cln6 mutants associated with neuronal ceroid lipofuscinosis are degraded in a proteasome-dependent manner.

PubMed

Oresic, Kristina; Mueller, Britta; Tortorella, Domenico

2009-06-01

NCLs (neuronal ceroid lipofuscinoses), a group of inherited neurodegenerative lysosomal storage diseases that predominantly affect children, are the result of autosomal recessive mutations within one of the nine cln genes. The wild-type cln gene products are composed of membrane and soluble proteins that localize to the lysosome or the ER (endoplasmic reticulum). However, the destiny of the Cln variants has not been fully characterized. To explore a possible link between ER quality control and processing of Cln mutants, we investigated the fate of two NCL-related Cln6 mutants found in patient samples (Cln6(G123D) and Cln6(M241T)) in neuronal-derived human cells. The point mutations are predicted to be in the putative transmembrane domains and most probably generate misfolded membrane proteins that are subjected to ER quality control. Consistent with this paradigm, both mutants underwent rapid proteasome-mediated degradation and complexed with components of the ER extraction apparatus, Derlin-1 and p97. In addition, knockdown of SEL1L [sel-1 suppressor of lin-12-like (Caenorhabditis elegans)], a member of an E3 ubiquitin ligase complex involved in ER protein extraction, rescued significant amounts of Cln6(G123D) and Cln6(M241T) polypeptides. The results implicate ER quality control in the instability of the Cln variants that probably contributes to the development of NCL.

GM2 Gangliosidosis in Shiba Inu Dogs with an In-Frame Deletion in HEXB.

PubMed

Kolicheski, A; Johnson, G S; Villani, N A; O'Brien, D P; Mhlanga-Mutangadura, T; Wenger, D A; Mikoloski, K; Eagleson, J S; Taylor, J F; Schnabel, R D; Katz, M L

2017-09-01

Consistent with a tentative diagnosis of neuronal ceroid lipofuscinosis (NCL), autofluorescent cytoplasmic storage bodies were found in neurons from the brains of 2 related Shiba Inu dogs with a young-adult onset, progressive neurodegenerative disease. Unexpectedly, no potentially causal NCL-related variants were identified in a whole-genome sequence generated with DNA from 1 of the affected dogs. Instead, the whole-genome sequence contained a homozygous 3 base pair (bp) deletion in a coding region of HEXB. The other affected dog also was homozygous for this 3-bp deletion. Mutations in the human HEXB ortholog cause Sandhoff disease, a type of GM2 gangliosidosis. Thin-layer chromatography confirmed that GM2 ganglioside had accumulated in an affected Shiba Inu brain. Enzymatic analysis confirmed that the GM2 gangliosidosis resulted from a deficiency in the HEXB encoded protein and not from a deficiency in products from HEXA or GM2A, which are known alternative causes of GM2 gangliosidosis. We conclude that the homozygous 3-bp deletion in HEXB is the likely cause of the Shiba Inu neurodegenerative disease and that whole-genome sequencing can lead to the early identification of potentially disease-causing DNA variants thereby refocusing subsequent diagnostic analyses toward confirming or refuting candidate variant causality. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Synthesis, crystal structure and electrical properties of (C5H13NCl)2 SnCl6

NASA Astrophysics Data System (ADS)

Rgaieg, R.; Karoui, K.; Zouari, R.

2017-10-01

In this work, a novel compound Bis(2-chloropropyl-N,N-dimethyl-1-ammonium) hexachloridostannate(IV) was synthesized and characterized by; single X-ray diffraction, Hirshfeld surface analysis, differential scanning calorimetric and dielectric measurement. The crystal structure refinement at room temperature reveled that this later belongs to the monoclinic compound with P21/n space group with the following unit cell parameters a = 7.2894(7) Å, b = 12.9351(12) Å, c = 12.2302(13) Å and β = 93.423 (6) °. The structure consists of isolated (SnCl6)2- octahedral anions connected together into layers via hydrogen bonds N-H….Cl between the chlorine atoms of the anions and the hydrogen atoms of the NH groups of the [C5H13NCl]+ cations. Hirschfeld surface analysis has been performed to gain insight into the behavior of these interactions. The differential scanning calorimetry spectrum discloses phase transitions at 367 and 376.7 K. The electrical properties of this compound have been measured in the temperature range 300-420 K and the frequency range 209 Hz-5 MHz. The Cole-Cole (Z‧ versus Z″) plots are well fitted to an equivalent circuit model. The transition phase observed in the calorimetric study is confirmed by the change as function of temperature of electrical parameter such as the conductivity of grain (σg) and the σdc.

Sensitivity Enhancement in Si Nanophotonic Waveguides Used for Refractive Index Sensing

PubMed Central

Shi, Yaocheng; Ma, Ke; Dai, Daoxin

2016-01-01

A comparative study is given for the sensitivity of several typical Si nanophotonic waveguides, including SOI (silicon-on-insulator) nanowires, nanoslot waveguides, suspended Si nanowires, and nanofibers. The cases for gas sensing (ncl ~ 1.0) and liquid sensing (ncl ~ 1.33) are considered. When using SOI nanowires (with a SiO2 buffer layer), the sensitivity for liquid sensing (S ~ 0.55) is higher than that for gas sensing (S ~ 0.35) due to lower asymmetry in the vertical direction. By using SOI nanoslot waveguides, suspended Si nanowires, and Si nanofibers, one could achieve a higher sensitivity compared to sensing with a free-space beam (S = 1.0). The sensitivity for gas sensing is higher than that for liquid sensing due to the higher index-contrast. The waveguide sensitivity of an optimized suspended Si nanowire for gas sensing is as high as 1.5, which is much higher than that of a SOI nanoslot waveguide. Furthermore, the optimal design has very large tolerance to the core width variation due to the fabrication error (∆w ~ ±50 nm). In contrast, a Si nanofiber could also give a very high sensitivity (e.g., ~1.43) while the fabrication tolerance is very small (i.e., ∆w < ±5 nm). The comparative study shows that suspended Si nanowire is a good choice to achieve ultra-high waveguide sensitivity. PMID:26950132

Homozygous PPT1 Splice Donor Mutation in a Cane Corso Dog With Neuronal Ceroid Lipofuscinosis.

PubMed

Kolicheski, A; Barnes Heller, H L; Arnold, S; Schnabel, R D; Taylor, J F; Knox, C A; Mhlanga-Mutangadura, T; O'Brien, D P; Johnson, G S; Dreyfus, J; Katz, M L

2017-01-01

A 10-month-old spayed female Cane Corso dog was evaluated after a 2-month history of progressive blindness, ataxia, and lethargy. Neurologic examination abnormalities indicated a multifocal lesion with primarily cerebral and cerebellar signs. Clinical worsening resulted in humane euthanasia. On necropsy, there was marked astrogliosis throughout white matter tracts of the cerebrum, most prominently in the corpus callosum. In the cerebral cortex and midbrain, most neurons contained large amounts of autofluorescent storage material in the perinuclear area of the cells. Cerebellar storage material was present in the Purkinje cells, granular cell layer, and perinuclear regions of neurons in the deep nuclei. Neuronal ceroid lipofuscinosis (NCL) was diagnosed. Whole genome sequencing identified a PPT1c.124 + 1G>A splice donor mutation. This nonreference assembly allele was homozygous in the affected dog, has not previously been reported in dbSNP, and was absent from the whole genome sequences of 45 control dogs and 31 unaffected Cane Corsos. Our findings indicate a novel mutation causing the CLN1 form of NCL in a previously unreported dog breed. A canine model for CLN1 disease could provide an opportunity for therapeutic advancement, benefiting both humans and dogs with this disorder. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Model annotation for synthetic biology: automating model to nucleotide sequence conversion

PubMed Central

Misirli, Goksel; Hallinan, Jennifer S.; Yu, Tommy; Lawson, James R.; Wimalaratne, Sarala M.; Cooling, Michael T.; Wipat, Anil

2011-01-01

Motivation: The need for the automated computational design of genetic circuits is becoming increasingly apparent with the advent of ever more complex and ambitious synthetic biology projects. Currently, most circuits are designed through the assembly of models of individual parts such as promoters, ribosome binding sites and coding sequences. These low level models are combined to produce a dynamic model of a larger device that exhibits a desired behaviour. The larger model then acts as a blueprint for physical implementation at the DNA level. However, the conversion of models of complex genetic circuits into DNA sequences is a non-trivial undertaking due to the complexity of mapping the model parts to their physical manifestation. Automating this process is further hampered by the lack of computationally tractable information in most models. Results: We describe a method for automatically generating DNA sequences from dynamic models implemented in CellML and Systems Biology Markup Language (SBML). We also identify the metadata needed to annotate models to facilitate automated conversion, and propose and demonstrate a method for the markup of these models using RDF. Our algorithm has been implemented in a software tool called MoSeC. Availability: The software is available from the authors' web site http://research.ncl.ac.uk/synthetic_biology/downloads.html. Contact: anil.wipat@ncl.ac.uk Supplementary information: Supplementary data are available at Bioinformatics online. PMID:21296753

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

Hart, Y.M.; Andermann, E.; Mitchison, H.M.

The neuronal ceroid lipofuscinoses (NCL) are a group of related lysosomal storage diseases classified according to the age of onset, clinical syndrome, and pathology. The clinical syndromes include myoclonus, visual failure, progressive dementia, ataxia and generalized tonic clonic seizures in varying combinations depending on the age of onset and pathology. The mode of inheritance is autosomal recessive in most cases, except for several families with the adult form (Kufs` disease) which have autosomal dominant inheritance. Linkage for the infantile (Halatia-Santavuori) form (CLN1), characterized ultrastructurally by lysosomal granular osmiophilic deposits (GROD), has been demonstrated with markers on chromosome lp, while themore » gene for the typical juvenile (Spielmeyer-Vogt) form (CLN3), characterized by fingerprint-profile inclusions, has been linked to chromosome 16p. The gene locations of the late infantile (Jansky-Bielschowsky) and adult (Kufs` disease) forms are unknown, although it has recently been shown that the late infantile form does not link to chromosome 16p. We describe three siblings, including a pair of monozygotic twins, with juvenile onset NCL with GROD in whom linkage to the CLN3 region of chromsome 16p has been excluded. This would suggest that there is genetic heterogeneity not only among the different clinical syndromes, but also among identical clinical syndromes with different ultrastructural characteristics. Preliminary studies of linkage to chromosome 1p employing the microsatellite marker HY-TM1 have been uninformative. Further studies with other chromosome 1 markers are underway.« less

Detection of tripeptidyl peptidase I activity in living cells by fluorogenic substrates.

PubMed

Steinfeld, Robert; Fuhrmann, Jens C; Gärtner, Jutta

2006-09-01

Tripeptidyl peptidase I (TPP-I) is a lysosomal peptidase with unclear physiological function. TPP-I deficiency is associated with late-infantile neuronal ceroid lipofuscinosis (NCL), a fatal neurodegenerative disease of childhood that is characterized by loss of neurons and photoreceptor cells. We have developed two novel fluorogenic substrates, [Ala-Ala-Phe]2-rhodamine 110 and [Arg-Nle-Nle]2-rhodamine 110, that are cleaved by TPP-I in living cells. Fluorescence of liberated rhodamine 110 was detected by flow cytometry and was dependent on the level of TPP-I expression. Rhodamine-related fluorescence could be suppressed by preincubation with a specific inhibitor of TPP-I. When investigated by fluorescent confocal microscopy, rhodamine signals colocalized with lysosomal markers. Thus, cleavage of these rhodamide-derived substrates is a marker for mature enzymatically active TPP-I. In addition, TPP-I-induced cleavage of [Ala-Ala-Phe]2-rhodamine 110 could be visualized in primary neurons. We conclude that [Ala-Ala-Phe]2-rhodamine 110 and [Arg-Nle-Nle]2-rhodamine 110 are specific substrates for determining TPP-I activity and intracellular localization in living cells. Further, these substrates could be a valuable tool for studying the neuronal pathology underlying classical late-infantile NCL. This article contains online supplemental material at http://www.jhc.org. Please visit this article online to view these materials.

Sensitivity Enhancement in Si Nanophotonic Waveguides Used for Refractive Index Sensing.

PubMed

Shi, Yaocheng; Ma, Ke; Dai, Daoxin

2016-03-03

A comparative study is given for the sensitivity of several typical Si nanophotonic waveguides, including SOI (silicon-on-insulator) nanowires, nanoslot waveguides, suspended Si nanowires, and nanofibers. The cases for gas sensing (ncl ~ 1.0) and liquid sensing (ncl ~ 1.33) are considered. When using SOI nanowires (with a SiO₂ buffer layer), the sensitivity for liquid sensing (S ~ 0.55) is higher than that for gas sensing (S ~ 0.35) due to lower asymmetry in the vertical direction. By using SOI nanoslot waveguides, suspended Si nanowires, and Si nanofibers, one could achieve a higher sensitivity compared to sensing with a free-space beam (S = 1.0). The sensitivity for gas sensing is higher than that for liquid sensing due to the higher index-contrast. The waveguide sensitivity of an optimized suspended Si nanowire for gas sensing is as high as 1.5, which is much higher than that of a SOI nanoslot waveguide. Furthermore, the optimal design has very large tolerance to the core width variation due to the fabrication error (∆w ~ ±50 nm). In contrast, a Si nanofiber could also give a very high sensitivity (e.g., ~1.43) while the fabrication tolerance is very small (i.e., ∆w < ±5 nm). The comparative study shows that suspended Si nanowire is a good choice to achieve ultra-high waveguide sensitivity.

The effect of two gases forming supercritical fluids (Xe and CO 2) on the spectral characteristics and analytical capabilities of microwave induced plasmas

NASA Astrophysics Data System (ADS)

Montes-Bayón, M.; Camuña-Aguilar, F.; Pereiro, R.; Sánchez-Uria, J. E.; Sanz-Medel, A.

1996-06-01

A comparative study of the effect of CO 2 and Xe added along with the plasma gas to He and Ar microwave induced plasmas (MIPs), simulating possible conditions to be used when a MIP is employed as specific detector for supercritical fluid chromatography (SFC), has been carried out. The proportions of CO 2 and Xe to the plasma gas investigated are comparable to the typical percentages used for SFC-MIP couplings. The study has been performed with two different MIP systems: an atmospheric pressure discharge held in a Beenakker cavity TM 010 and a reduced pressure surfatron-MIP. The influence of CO 2 and Xe addition on the spectrochemical properties of the discharge has been studied by using the atomic emission of mercury and some typical non-metals (chlorine, carbon and sulfur) at different wavelengths (atomic and ionic lines). Results showed that ion line emission intensities are always reduced more significantly than atom line emissions by both dopant gases on study, whatever the pressure. In general terms, however, the effect of adding Xe is less severe, both for atom and ion lines, than that of CO 2; in most cases the detection limits (DLs) observed are better for Xe than for CO 2 as dopant gas. In fact, the DLs obtained for the selected lines of mercury measured were practically unaltered by the addition of 0.2% Xe to atmospheric pressure Ar or He MIPs. CO 2 addition (0.2%) produced about 1.5 times worsening of the observed DLs for mercury. For non-metal analyses better DLs were also obtained, in general terms, with Xe than with CO 2 as dopant gas.

Dynamic Light Scattering of Diabetic Vitreopathy

NASA Technical Reports Server (NTRS)

Sebag, J.; Ansari, Rafat R.; Dunker, Stephan; Suh, Kwang I.

1999-01-01

Diabetes induces pathology throughout the body via nonenzymatic glycation of proteins. Vitreous, which is replete with type 11 collagen, undergoes significant changes in diabetes. The resultant diabetic vitreopathy plays an important role in diabetic retinopathy. Detecting these molecular changes could provide insight into diabetic eye disease as well as molecular effects elsewhere in the body. Human eyes were obtained at autopsy and studied in the fresh, unfixed state. Sclera, choroid, and retina were dissected off the vitreous for dark-field slit microscopy and dynamic light scattering (DLS). For the former, the entire vitreous was exposed. For the latter, only a window at the equator was dissected in some specimens, and the anterior segment was removed leaving the posterior lens capsule intact in others. DLS was performed to determine particle sizes at multiple sites 0.5 mm apart, spanning the globe at the equator (window dissections) and along the antero-posterior axis. Dark-field slit microscopy in diabetic subjects detected findings typical of age-related vitreous degeneration, but at much younger ages than nondiabetic controls. Noninvasive DLS measurements found a greater heterogeneity and larger particle sizes in vitreous of subjects with diabetes as compared to age-matched controls. DLS can detect and quantify the early molecular effects that cause vitreous collagen fibrils to cross-link and aggregate. This could provide valuable insight into ocular and systemic effects of hyperglycemia, because the molecular changes in diabetic vitreopathy could serve as an index of such effects throughout the body. In addition to the diagnostic implications, this methodology could provide a rapid, reproducible way to monitor the response to therapy with novel agents intended to prevent the complications of diabetes on a molecular level.

Formation and stability of nanoemulsions with mixed ionic-nonionic surfactants.

PubMed

Wang, Lijuan; Tabor, Rico; Eastoe, Julian; Li, Xuefeng; Heenan, Richard K; Dong, Jinfeng

2009-11-14

A simple, low-energy two-step dilution process has been applied with binary mixtures of ionic-nonionic surfactants to prepare nanoemulsions. The systems consist of water/DDAB-C(12)E(5)/decane. Nanoemulsions were obtained by dilution of concentrates located in bicontinuous microemulsion or lamellar liquid crystal phase regions. The nanoemulsions generated were investigated both by contrast-variation small-angle neutron scattering (SANS) and dynamic light scattering (DLS). The SANS profiles show that C(12)E(5) nanodroplets suffer essentially no structural change on incorporation of the cationic DDAB surfactant, except for increased electrostatic repulsive interactions. Interestingly, SANS indicated that the preferred droplet sizes were hardly affected by the surfactant mixture composition (up to a DDAB molar ratio (m(DDAB)/(m(DDAB) + m(C(12)E(5))) of 0.40) and droplet volume fraction, phi, between 0.006 and 0.120. No notable changes in the structure or radius of nanoemulsion droplets were observed by SANS over the test period of 1 d, although the droplet number intensity decreased significantly in systems stabilized by C(12)E(5) only. However, the DLS sizing shows a marked increase with time, with higher droplet volume fractions giving rise to the largest changes. The discrepancy between apparent nanoemulsion droplet size determined by DLS and SANS data can be attributed to long-range droplet interactions occurring outside of the SANS sensitivity range. The combined SANS and DLS results suggest flocculation is the main mechanism of instability for these nanoemulsions. The flocculation rate is shown to be significantly retarded by addition of the charged DDAB, which may be due to enhanced electrostatic repulsive forces between droplets, leading to improved stability of the nanoemulsions.

Basolateral amygdalar D2 receptor activation is required for the companions-exerted suppressive effect on the cocaine conditioning.

PubMed

Tzeng, Wen-Yu; Cherng, Chian-Fang G; Yu, Lung; Wang, Ching-Yi

2017-01-01

The presence of companions renders decreases in cocaine-stimulated dopamine release in the nucleus accumbens and cocaine-induced conditioned place preference (CPP) magnitude. Limbic systems are widely believed to underlie the modulation of accumbal dopamine release and cocaine conditioning. Thus, this study aimed to assess whether intact basolateral nucleus of amygdala (BLA), dorsal hippocampus (DH), and dorsolateral striatum (DLS) is required for the companions-exerted suppressive effect on the cocaine-induced CPP. Three cage mates, serving as companions, were arranged to house with the experimental mice in the cocaine conditioning compartment throughout the cocaine conditioning sessions. Approximately 1week before the conditioning procedure, intracranial ibotenic acid infusions were done in an attempt to cause excitotoxic lesions targeting bilateral BLA, DH and DLS. Albeit their BLA, DH, and DLS lesions, the lesioned mice exhibited comparable cocaine-induced CPP magnitudes compared to the intact and sham lesion controls. Bilateral BLA, but not DH or DLS, lesions abolished the companions-exerted suppressive effect on the cocaine-induced CPP. Intact mice receiving intra-BLA infusion of raclopride, a selective D2 antagonist, 30min prior to the cocaine conditioning did not exhibit the companions-exerted suppressive effect on the cocaine-induced CPP. Intra-BLA infusion of Sch23390, a selective D1 antagonist, did not affect the companions-exerted suppressive effect on the CPP. These results, taken together, prompt us to conclude that the intactness of BLA is required for the companions-exerted suppressive effect on the cocaine-induced CPP. Importantly, activation of D2 receptor in the BLA is required for such suppressive effect on the CPP. Copyright © 2016 Elsevier Inc. All rights reserved.

Decreased synaptic plasticity in the medial prefrontal cortex underlies short-term memory deficits in 6-OHDA-lesioned rats.

PubMed

Matheus, Filipe C; Rial, Daniel; Real, Joana I; Lemos, Cristina; Ben, Juliana; Guaita, Gisele O; Pita, Inês R; Sequeira, Ana C; Pereira, Frederico C; Walz, Roger; Takahashi, Reinaldo N; Bertoglio, Leandro J; Da Cunha, Cláudio; Cunha, Rodrigo A; Prediger, Rui D

2016-03-15

Parkinson's disease (PD) is characterized by motor dysfunction associated with dopaminergic degeneration in the dorsolateral striatum (DLS). However, motor symptoms in PD are often preceded by short-term memory deficits, which have been argued to involve deregulation of medial prefrontal cortex (mPFC). We now used a 6-hydroxydopamine (6-OHDA) rat PD model to explore if alterations of synaptic plasticity in DLS and mPFC underlie short-term memory impairments in PD prodrome. The bilateral injection of 6-OHDA (20μg/hemisphere) in the DLS caused a marked loss of dopaminergic neurons in the substantia nigra (>80%) and decreased monoamine levels in the striatum and PFC, accompanied by motor deficits evaluated after 21 days in the open field and accelerated rotarod. A lower dose of 6-OHDA (10μg/hemisphere) only induced a partial degeneration (about 60%) of dopaminergic neurons in the substantia nigra with no gross motor impairments, thus mimicking an early premotor stage of PD. Notably, 6-OHDA (10μg)-lesioned rats displayed decreased monoamine levels in the PFC as well as short-term memory deficits evaluated in the novel object discrimination and in the modified Y-maze tasks; this was accompanied by a selective decrease in the amplitude of long-term potentiation in the mPFC, but not in DLS, without changes of synaptic transmission in either brain regions. These results indicate that the short-term memory dysfunction predating the motor alterations in the 6-OHDA model of PD is associated with selective changes of information processing in PFC circuits, typified by persistent changes of synaptic plasticity. Copyright © 2015 Elsevier B.V. All rights reserved.

A study of the dimer formation of Rous sarcoma virus RNA and of its effect on viral protein synthesis in vitro.

PubMed

Bieth, E; Gabus, C; Darlix, J L

1990-01-11

The genetic material of all retroviruses examined so far is an RNA dimer where two identical RNA subunits are joined at their 5' ends by a structure named dimer linkage structure (DLS). Since the precise location and structure of the DLS as well as the mechanism and role(s) of RNA dimerization remain unclear, we analysed the dimerization process of Rous sarcoma virus (RSV) RNA. For this purpose we set up an in vitro model for RSV RNA dimerization. Using this model RSV RNA was shown to form dimeric molecules and this dimerization process was greatly activated by nucleocapsid protein (NCp12) of RSV. Furthermore, RSV RNA dimerization was performed in the presence of complementary 5'32P-DNA oligomers in order to probe the monomer and dimer forms of RSV RNA. Data indicated that the DLS of RSV RNA probably maps between positions 544-564 from the 5' end. In an attempt to define sequences needed for the dimerization of RSV RNA, deletion mutageneses were generated in the 5' 600 nt. The results showed that the dimer promoting sequences probably are located within positions 208-270 and 400-600 from the 5' end and hence possibly encompassing the cis-acting elements needed for the specific encapsidation of RSV genomic RNA. Also it is reported that synthesis of the polyprotein precursor Pr76gag is inhibited upon dimerization of RSV RNA. These results suggest that dimerization and encapsidation of genome length RSV RNA might be linked in the course of virion formation since they appear to be under the control of the same cis elements, E and DLS, and the trans-acting factor nucleocapsid protein NCp12.

A study of the dimer formation of Rous sarcoma virus RNA and of its effect on viral protein synthesis in vitro.

PubMed Central

Bieth, E; Gabus, C; Darlix, J L

1990-01-01

The genetic material of all retroviruses examined so far is an RNA dimer where two identical RNA subunits are joined at their 5' ends by a structure named dimer linkage structure (DLS). Since the precise location and structure of the DLS as well as the mechanism and role(s) of RNA dimerization remain unclear, we analysed the dimerization process of Rous sarcoma virus (RSV) RNA. For this purpose we set up an in vitro model for RSV RNA dimerization. Using this model RSV RNA was shown to form dimeric molecules and this dimerization process was greatly activated by nucleocapsid protein (NCp12) of RSV. Furthermore, RSV RNA dimerization was performed in the presence of complementary 5'32P-DNA oligomers in order to probe the monomer and dimer forms of RSV RNA. Data indicated that the DLS of RSV RNA probably maps between positions 544-564 from the 5' end. In an attempt to define sequences needed for the dimerization of RSV RNA, deletion mutageneses were generated in the 5' 600 nt. The results showed that the dimer promoting sequences probably are located within positions 208-270 and 400-600 from the 5' end and hence possibly encompassing the cis-acting elements needed for the specific encapsidation of RSV genomic RNA. Also it is reported that synthesis of the polyprotein precursor Pr76gag is inhibited upon dimerization of RSV RNA. These results suggest that dimerization and encapsidation of genome length RSV RNA might be linked in the course of virion formation since they appear to be under the control of the same cis elements, E and DLS, and the trans-acting factor nucleocapsid protein NCp12. Images PMID:2155394

Frit inlet field-flow fractionation techniques for the characterization of polyion complex self-assemblies.

PubMed

Till, Ugo; Gaucher, Mireille; Amouroux, Baptiste; Gineste, Stéphane; Lonetti, Barbara; Marty, Jean-Daniel; Mingotaud, Christophe; Bria, Carmen R M; Williams, S Kim Ratanathanawongs; Violleau, Frédéric; Mingotaud, Anne-Françoise

2017-01-20

Polymer self-assemblies joining oppositely charged chains, known as polyion complexes (PICs), have been formed using poly(ethyleneoxide - b - acrylic acid)/poly(l-lysine), poly(ethyleneoxide-b-acrylic acid)/dendrigraft poly(l-lysine) and poly[(3-acrylamidopropyl) trimethylammonium chloride - b - N - isopropyl acrylamide]/poly(acrylic acid). The self-assemblies have been first characterized in batch by Dynamic Light Scattering. In a second step, their analysis by Flow Field-Flow Fractionation techniques (FlFFF) was examined. They were shown to be very sensitive to shearing, especially during the focus step of the fractionation, and this led to an incompatibility with asymmetrical FlFFF. On the other hand, Frit Inlet FlFFF proved to be very efficient to observe them, either in its symmetrical (FI-FlFFF) or asymmetrical version (FI-AsFlFFF). Conditions of elution were found to optimize the sample recovery in pure water. Spherical self-assemblies were detected, with a size range between 70-400nm depending on the polymers. Compared to batch DLS, FI-AsFlFFF clearly showed the presence of several populations in some cases. The influence of salt on poly(ethyleneoxide-b-acrylic acid) (PEO-PAA) 6000-3000/dendrigraft poly(l-lysine) (DGL 3) was also assessed in parallel in batch DLS and FI-AsFlFFF. Batch DLS revealed a first process of swelling of the self-assembly for low concentrations up to 0.8M followed by the dissociation. FI-AsFlFFF furthermore indicated a possible ejection of DGL3 from the PIC assembly for concentrations as low as 0.2M, which could not be observed in batch DLS. Copyright © 2016 Elsevier B.V. All rights reserved.

Inhibiting PKMζ reveals dorsal lateral and dorsal medial striatum store the different memories needed to support adaptive behavior.

PubMed

Pauli, Wolfgang M; Clark, Alexandra D; Guenther, Heidi J; O'Reilly, Randall C; Rudy, Jerry W

2012-06-20

Evidence suggests that two regions of the striatum contribute differential support to instrumental response selection. The dorsomedial striatum (DMS) is thought to support expectancy-mediated actions, and the dorsolateral striatum (DLS) is thought to support habits. Currently it is unclear whether these regions store task-relevant information or just coordinate the learning and retention of these solutions by other brain regions. To address this issue, we developed a two-lever concurrent variable-interval reinforcement operant conditioning task and used it to assess the trained rat's sensitivity to contingency shifts. Consistent with the view that these two regions make different contributions to actions and habits, injecting the NMDA antagonist DL-AP5 into the DMS just prior to the shift impaired the rat's performance but enhanced performance when injected into the DLS. To determine if these regions support memory content, we first trained rats on a biased concurrent schedule (Lever 1: VI 40" and Lever 2: VI 10"). With the intent of "erasing" the memory content stored in striatum, after this training we inhibited the putative memory-maintenance protein kinase C isozyme protein kinase Mζ (PKMζ). Infusing zeta inhibitory peptide (ZIP) into the DLS enhanced the rat's ability to adapt to the contingency shift 2 d later, whereas injecting it into the DMS had the opposite effect. Infusing GluR2(3Y) into the DMS 1 h before ZIP infusions prevented ZIP from impairing the rat's sensitivity to the contingency shift. These results support the hypothesis that the DMS stores information needed to support actions and the DLS stores information needed to support habits.

Incorrect dosimetric leaf separation in IMRT and VMAT treatment planning: Clinical impact and correlation with pretreatment quality assurance.

PubMed

Sjölin, Maria; Edmund, Jens Morgenthaler

2016-07-01

Dynamic treatment planning algorithms use a dosimetric leaf separation (DLS) parameter to model the multi-leaf collimator (MLC) characteristics. Here, we quantify the dosimetric impact of an incorrect DLS parameter and investigate whether common pretreatment quality assurance (QA) methods can detect this effect. 16 treatment plans with intensity modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT) technique for multiple treatment sites were calculated with a correct and incorrect setting of the DLS, corresponding to a MLC gap difference of 0.5mm. Pretreatment verification QA was performed with a bi-planar diode array phantom and the electronic portal imaging device (EPID). Measurements were compared to the correct and incorrect planned doses using gamma evaluation with both global (G) and local (L) normalization. Correlation, specificity and sensitivity between the dose volume histogram (DVH) points for the planning target volume (PTV) and the gamma passing rates were calculated. The change in PTV and organs at risk DVH parameters were 0.4-4.1%. Good correlation (>0.83) between the PTVmean dose deviation and measured gamma passing rates was observed. Optimal gamma settings with 3%L/3mm (per beam and composite plan) and 3%G/2mm (composite plan) for the diode array phantom and 2%G/2mm (composite plan) for the EPID system were found. Global normalization and per beam ROC analysis of the diode array phantom showed an area under the curve <0.6. A DLS error can worsen pretreatment QA using gamma analysis with reasonable credibility for the composite plan. A low detectability was demonstrated for a 3%G/3mm per beam gamma setting. Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Length scale dependence of the dynamic properties of hyaluronic acid solutions in the presence of salt.

PubMed

Horkay, Ferenc; Falus, Peter; Hecht, Anne-Marie; Geissler, Erik

2010-12-02

In solutions of the charged semirigid biopolymer hyaluronic acid in salt-free conditions, the diffusion coefficient D(NSE) measured at high transfer momentum q by neutron spin echo is more than an order of magnitude smaller than that determined by dynamic light scattering, D(DLS). This behavior contrasts with neutral polymer solutions. With increasing salt content, D(DLS) approaches D(NSE), which is independent of ionic strength. Contrary to theoretical expectation, the ion-polymer coupling, which dominates the low q dynamics of polyelectrolyte solutions, already breaks down at distance scales greater than the Debye-Hückel length.

Integrated instrument for dynamic light scattering and natural fluorescence measurements

NASA Astrophysics Data System (ADS)

Rovati, Luigi; Pollonini, Luca; Ansari, Rafat R.

2001-06-01

Over the past two decades, great efforts have been made in ophthalmology to use optical techniques based on dynamic light scattering and tissue natural fluorescence for early (at molecular level) diagnosis of ocular pathologies. In our previous studies, the relationship between the corneal AF and DLS decay widths of ocular tissues were established by performing measurements on diabetes mellitus patients. In those studies, corneal AF mean intensities were significantly correlated with DLS decay width measurements for each diabetic retinopathy grade in the vitreous and in the cornea. This suggested that the quality of the diagnosis could be significantly improved by properly combining these two powerful techniques into a single instrument. Our approach is based on modifying a commercial scanning ocular fluorometer (Fluorotron Master, Ocumetrics Inc., CA, USA) to include both techniques in the same scanning unit. This configuration provides both DLS and AF real time measurements from the same ocular volume: they can be located in each section of the optical axis of the eye from the cornea to the retina. In this paper, the optical setup of the new system is described and preliminary in-vitro and in-vivo measurements are presented.

Buckets: Smart Objects for Digital Libraries

NASA Technical Reports Server (NTRS)

Nelson, Michael L.

2001-01-01

Current discussion of digital libraries (DLs) is often dominated by the merits of the respective storage, search and retrieval functionality of archives, repositories, search engines, search interfaces and database systems. While these technologies are necessary for information management, the information content is more important than the systems used for its storage and retrieval. Digital information should have the same long-term survivability prospects as traditional hardcopy information and should be protected to the extent possible from evolving search engine technologies and vendor vagaries in database management systems. Information content and information retrieval systems should progress on independent paths and make limited assumptions about the status or capabilities of the other. Digital information can achieve independence from archives and DL systems through the use of buckets. Buckets are an aggregative, intelligent construct for publishing in DLs. Buckets allow the decoupling of information content from information storage and retrieval. Buckets exist within the Smart Objects and Dumb Archives model for DLs in that many of the functionalities and responsibilities traditionally associated with archives are pushed down (making the archives dumber) into the buckets (making them smarter). Some of the responsibilities imbued to buckets are the enforcement of their terms and conditions, and maintenance and display of their contents.

A simple and rapid creatinine sensing via DLS selectivity, using calix[4]arene thiol functionalized gold nanoparticles.

PubMed

Sutariya, Pinkesh G; Pandya, Alok; Lodha, Anand; Menon, Shobhana K

2016-01-15

A new, simple, ultra-sensitive and selective approach has been reported for the "on spot" colorimetric detection of creatinine based on calix[4]arene functionalized gold nanoparticles (AuNPs) with excellent discrimination in the presence of other biomolecules. The lower detection limit of the method is 2.16nM. The gold nanoparticles and p-tert-butylcalix[4]arene were synthesized by microwave assisted method. Specifically, in our study, we used dynamic light scattering (DLS) which is a powerful method for the determination of small changes in particle size, improved selectivity and sensitivity of the creatinine detection system over colorimetric method. The nanoassembly is characterized by Transmission electron microscopy (TEM), DLS, UV-vis and ESI-MS spectroscopy, which demonstrates the binding affinity due its ability of hydrogen bonding and electrostatic interaction between -NH group of creatinine and pSDSC4. It exhibits fast response time (<60s) to creatinine and has long shelf-life (>5 weeks). The developed pSDSC4-AuNPs based creatinine biosensor will be established as simple, reliable and accurate tool for the determination of creatinine in human urine samples. Copyright © 2015 Elsevier B.V. All rights reserved.

SPORT: An Algorithm for Divisible Load Scheduling with Result Collection on Heterogeneous Systems

NASA Astrophysics Data System (ADS)

Ghatpande, Abhay; Nakazato, Hidenori; Beaumont, Olivier; Watanabe, Hiroshi

Divisible Load Theory (DLT) is an established mathematical framework to study Divisible Load Scheduling (DLS). However, traditional DLT does not address the scheduling of results back to source (i. e., result collection), nor does it comprehensively deal with system heterogeneity. In this paper, the DLSRCHETS (DLS with Result Collection on HET-erogeneous Systems) problem is addressed. The few papers to date that have dealt with DLSRCHETS, proposed simplistic LIFO (Last In, First Out) and FIFO (First In, First Out) type of schedules as solutions to DLSRCHETS. In this paper, a new polynomial time heuristic algorithm, SPORT (System Parameters based Optimized Result Transfer), is proposed as a solution to the DLSRCHETS problem. With the help of simulations, it is proved that the performance of SPORT is significantly better than existing algorithms. The other major contributions of this paper include, for the first time ever, (a) the derivation of the condition to identify the presence of idle time in a FIFO schedule for two processors, (b) the identification of the limiting condition for the optimality of FIFO and LIFO schedules for two processors, and (c) the introduction of the concept of equivalent processor in DLS for heterogeneous systems with result collection.

Interference from Proteins and Surfactants on Particle Size Distributions Measured by Nanoparticle Tracking Analysis (NTA).

PubMed

Bai, Kelvin; Barnett, Gregory V; Kar, Sambit R; Das, Tapan K

2017-04-01

Characterization of submicron protein particles continues to be challenging despite active developments in the field. NTA is a submicron particle enumeration technique, which optically tracks the light scattering signal from suspended particles undergoing Brownian motion. The submicron particle size range NTA can monitor in common protein formulations is not well established. We conducted a comprehensive investigation with several protein formulations along with corresponding placebos using NTA to determine submicron particle size distributions and shed light on potential non-particle origin of size distribution in the range of approximately 50-300 nm. NTA and DLS are performed on polystyrene size standards as well as protein and placebo formulations. Protein formulations filtered through a 20 nm filter, with and without polysorbate-80, show NTA particle counts. As such, particle counts above 20 nm are not expected in these solutions. Several other systems including positive and negative controls were studied using NTA and DLS. These apparent particles measured by NTA are not observed in DLS measurements and may not correspond to real particles. The intent of this article is to raise awareness about the need to interpret particle counts and size distribution from NTA with caution.

Dynamic light scattering as an efficient tool to study glyconanoparticle-lectin interactions.

PubMed

Wang, Xin; Ramström, Olof; Yan, Mingdi

2011-10-21

Glyconanomaterials, an emerging class of bio-functional nanomaterials, have shown promise in detecting, imaging and targeting proteins, bacteria, and cells. In this article, we report that dynamic light scattering (DLS) can be used as an efficient tool to study glyconanoparticle (GNP)--lectin interactions. Silica and Au nanoparticles (NPs) conjugated with D-mannose (Man) and D-galactose (Gal) were treated with the lectins Concanavalin A (Con A) and Ricinus communis agglutinin (RCA(120)), and the hydrodynamic volumes of the resulting aggregates were measured by DLS. The results showed that the particle size grew with increasing lectin concentration. The limit of detection (LOD) was determined to be 2.9 nM for Con A with Man-conjugated and 6.6 nM for RCA(120) with Gal-conjugated silica NPs (35 nm), respectively. The binding affinity was also determined by DLS and the results showed 3-4 orders of magnitude higher affinity of GNPs than the free ligands with lectins. The assay sensitivity and affinity were particle size dependent and decreased with increasing particle diameter. Because the method relies on the particle size growth, it is therefore general and can be applied to nanomaterials of different compositions.

Age effects on discrimination of timing in auditory sequences

NASA Astrophysics Data System (ADS)

Fitzgibbons, Peter J.; Gordon-Salant, Sandra

2004-08-01

The experiments examined age-related changes in temporal sensitivity to increments in the interonset intervals (IOI) of components in tonal sequences. Discrimination was examined using reference sequences consisting of five 50-ms tones separated by silent intervals; tone frequencies were either fixed at 4 kHz or varied within a 2-4-kHz range to produce spectrally complex patterns. The tonal IOIs within the reference sequences were either equal (200 or 600 ms) or varied individually with an average value of 200 or 600 ms to produce temporally complex patterns. The difference limen (DL) for increments of IOI was measured. Comparison sequences featured either equal increments in all tonal IOIs or increments in a single target IOI, with the sequential location of the target changing randomly across trials. Four groups of younger and older adults with and without sensorineural hearing loss participated. Results indicated that DLs for uniform changes of sequence rate were smaller than DLs for single target intervals, with the largest DLs observed for single targets embedded within temporally complex sequences. Older listeners performed more poorly than younger listeners in all conditions, but the largest age-related differences were observed for temporally complex stimulus conditions. No systematic effects of hearing loss were observed.

Protection against UV and X-ray cataracts using dynamic light scattering

NASA Technical Reports Server (NTRS)

Giblin, Frank J.

2005-01-01

Static and dynamic light scattering (SLS and DLS) analysis was used to investigate the aggregation of lens proteins in a hyperbaric oxygen (HBO)/guinea pig in vivo model for nuclear cataract. Nuclear cataract, an opacity which occurs in the center of the lens, is a major type of human maturity-onset cataract for which the cause is not well-understood. HBO is commonly used in major hospitals for treating complications such as poor wound healing due to impaired blood circulation. It is known that treatment of human patients with HBO for extended periods of time can produce nuclear cataract. Guinea pigs, initially 18 months old, were treated with HBO (2.5 atm of 100% O2 for 2.5 hr) 3x per week for 7 months to increase tie level of lens nuclear light scattering. Age-matched animals were used for controls. The eyes of the animals were analyzed in vivo using an integrated static and DLS fiber optic probe in collaboration with the NASA group. DLS in vivo was used to measure the size of lens proteins at 50 different locations across the optical axis of the guinea pig lens.

The effect of bridge exercise accompanied by the abdominal drawing-in maneuver on an unstable support surface on the lumbar stability of normal adults.

PubMed

Gong, Wontae

2015-01-01

[Purpose] The present study sought to investigate the influence on static and dynamic lumbar stability of bridge exercise accompanied by an abdominal drawing-in maneuver (ADIM) performed on an uneven support surface. [Subjects] A total of 30 participants were divided into an experimental group (15 participants) and a control group (15 participants). [Methods] The experimental group performed bridge exercise on an unstable surface, whereas the control group performed bridge exercise on a stable surface. The respective bridge exercises were performed for 30 minutes, 3 times per week, for 6 weeks. The static lumbar stability (SLS) and dynamic lumbar stability (DLS) of both the experimental group and the control group were measured using a pressure biofeedback unit. [Results] In the comparison of the initial and final results of the experimental and control groups, only the SLS and DLS of the experimental group were found to be statistically significant. [Conclusion] The results of the present study show that when using bridge exercise to improve SLS and DLS, performing the bridge exercise accompanied by ADIM on an uneven surface is more effective than performing the exercise on a stable surface.

The Deep Lens Survey : Real--time Optical Transient and Moving Object Detection

NASA Astrophysics Data System (ADS)

Becker, Andy; Wittman, David; Stubbs, Chris; Dell'Antonio, Ian; Loomba, Dinesh; Schommer, Robert; Tyson, J. Anthony; Margoniner, Vera; DLS Collaboration

2001-12-01

We report on the real-time optical transient program of the Deep Lens Survey (DLS). Meeting the DLS core science weak-lensing objective requires repeated visits to the same part of the sky, 20 visits for 63 sub-fields in 4 filters, on a 4-m telescope. These data are reduced in real-time, and differenced against each other on all available timescales. Our observing strategy is optimized to allow sensitivity to transients on several minute, one day, one month, and one year timescales. The depth of the survey allows us to detect and classify both moving and stationary transients down to ~ 25th magnitude, a relatively unconstrained region of astronomical variability space. All transients and moving objects, including asteroids, Kuiper belt (or trans-Neptunian) objects, variable stars, supernovae, 'unknown' bursts with no apparent host, orphan gamma-ray burst afterglows, as well as airplanes, are posted on the web in real-time for use by the community. We emphasize our sensitivity to detect and respond in real-time to orphan afterglows of gamma-ray bursts, and present one candidate orphan in the field of Abell 1836. See http://dls.bell-labs.com/transients.html.

Altered movement patterns and muscular activity during single and double leg squats in individuals with anterior cruciate ligament injury.

PubMed

Trulsson, Anna; Miller, Michael; Hansson, Gert-Åke; Gummesson, Christina; Garwicz, Martin

2015-02-13

Individuals with Anterior Cruciate Ligament (ACL) injury often show altered movement patterns, suggested to be partly due to impaired sensorimotor control. Here, we therefore aimed to assess muscular activity during movements often used in ACL-rehabilitation and to characterize associations between deviations in muscular activity and specific altered movement patterns, using and further exploring the previously developed Test for substitution Patterns (TSP). Sixteen participants (10 women) with unilateral ACL rupture performed Single and Double Leg Squats (SLS; DLS). Altered movement patterns were scored according to TSP, and Surface Electromyography (SEMG) was recorded bilaterally in six hip, thigh and shank muscles. To quantify deviations in muscular activity, SEMG ratios were calculated between homonymous muscles on injured and non-injured sides, and between antagonistic muscles on the same side. Correlations between deviations of injured/non-injured side SEMG ratios and specific altered movement patterns were calculated. Injured/non-injured ratios were low at transition from knee flexion to extension in quadriceps in SLS, and in quadriceps and hamstrings in DLS. On injured side, the quadriceps/hamstrings ratio prior to the beginning of DLS and end of DLS and SLS, and tibialis/gastrocnemius ratio at end of DLS were lower than on non-injured side. Correlations were found between specific altered movement patterns and deviating muscular activity at transition from knee flexion to extension in SLS, indicating that the more deviating the muscular activity on injured side, the more pronounced the altered movement pattern. "Knee medial to supporting foot" correlated to lower injured/non-injured ratios in gluteus medius (rs = -0.73, p = 0.001), "lateral displacement of hip-pelvis-region" to lower injured/non-injured ratios in quadriceps (rs = -0.54, p = 0.03) and "displacement of trunk" to higher injured/non-injured ratios in gluteus medius (rs = 0.62, p = 0.01). Deviations in muscular activity between injured and non-injured sides and between antagonistic muscular activity within injured as compared to non-injured sides indicated specific alterations in sensorimotor control of the lower limb in individuals with ACL rupture. Also, correlations between deviating muscular activity and specific altered movement patterns were suggested as indications of altered sensorimotor control. We therefore advocate that quantitative assessments of altered movement patterns should be considered in ACL-rehabilitation.

A New Methodology for Modeling National Command Level Decisionmaking in War Games and Simulations.

DTIC Science & Technology

1986-07-01

Conclusions about Utility and Development Options, The Rand Corporation, R-2945-DNA, March 1983. Drucker , Peter F., Management : Tasks, Responsibilities...looks to the worst case can readily find himself paralyzed. Of course, it is also true ’The effort to affect an opponent’s image of oneself is part of...how to manage forces on a continuing basis. So long as the broad features of the NCL-specified plan continue to appear valid, it is the military com

The Magnetopause Boundary Layer

DTIC Science & Technology

1990-06-29

y.CL4 SSFICATION o UNCLASSIFIED/UNLIMITED 0 SAME AS RPT DTIC USERS i ncl assi le ,a NAME OF RE,ONSIBLE iNDIVIDUAL 22b T;LEPHONE (include Ar-a Cod...where A is the latitude of the foot of the field line in the cosity (finite vIand particle acceleration (finite K ionosphere and L is the radial...processes and inertial . k:; le 1 .410) range spectra have not been analyzed. To the extent that both S= llK. ) ’L. " + -- ". 1201 inertial ranges are a

Antimicrobial Cellulose: Preparation and Application of 5-Methyl-5-Aminomethylhydantoin

DTIC Science & Technology

2006-08-01

they release active chlorine to microbes relatively more rapidly and kill the pathogens in the shortest time. Amide N-Cl bonds being relatively more...for 5~35 min. A 1% Clorox solution was used for chlorination without pH adjustment. bCoating solution: 5 % AH in distilled water. cCoating solution...0.37% 0.75 % 0.94 % 0.80 % 0.80 % aThe cloth samples were cured at 1450C for 35 min and then chlorinated with 1% Clorox 12 without pH adjustment

The Effect of Acid Deposition on Potentially Sensitive Soil-Plant Systems at Vandenberg AFB, California.

DTIC Science & Technology

1988-04-30

and reproductive tissues 23 of cucumber (Cucumis sativus L.). New Phytol. 105, 139-147. 0! 8. KEELEY J. E. (1987) Role of fire in seed germination of...foliage due to acid application in cucumbers (Cucumis sativus L.) while Lee et. al. (1981) found a stimulation in the stems and leaves of sweet corn...natural additions of NCl from the reaction between sea salt and air pollutants, may be enhanced by bo further burdens of HC inputs such as those

Interactions and release of two palmitoyl peptides from phytantriol cubosomes.

PubMed

Akhlaghi, Seyedeh Parinaz; Loh, Watson

2017-08-01

Phytantriol cubosomes loaded with two palmitoyl peptides (Palpepcubes), namely GHKcube and GQPRcube, were prepared using an ultrasonication protocol. The Palpepcubes dimensions were characterized by dynamic light scattering (DLS) and cryo-transmission electron microscopy (cryo-TEM). Small-angle X-ray scattering (SAXS) analyses revealed that the bicontinuous cubic structure remained even at palmitoyl peptide contents as high as 5wt.%, with an increase in the cell parameter from approximately 6.5 to 7.2nm. Isothermal titration calorimetry (ITC) was used to elucidate the interactions between the blank cubosomes and the palmitoyl peptides, revealing an exothermic process of interaction. Moreover, the in vitro release of the palmitoyl peptides from the Palpepcubes was studied using a dialysis method coupled with liquid chromatography-mass spectrometry (LC/MS) technique, in which a sustained release of up to a few days was observed. Finally, the stability of the aqueous solutions of the palmitoyl peptides and the Palpepcubes kept at room temperature and at low temperature (4°C) was studied by LC/MS method, indicating that incorporation into cubosomes increases the peptide stability significantly. Copyright © 2017 Elsevier B.V. All rights reserved.

Size distribution of extracellular vesicles by optical correlation techniques.

PubMed

Montis, Costanza; Zendrini, Andrea; Valle, Francesco; Busatto, Sara; Paolini, Lucia; Radeghieri, Annalisa; Salvatore, Annalisa; Berti, Debora; Bergese, Paolo

2017-10-01

Understanding the colloidal properties of extracellular vesicles (EVs) is key to advance fundamental knowledge in this field and to develop effective EV-based diagnostics, therapeutics and devices. Determination of size distribution and of colloidal stability of purified EVs resuspended in buffered media is a complex and challenging issue - because of the wide range of EV diameters (from 30 to 2000nm), concentrations of interest and membrane properties, and the possible presence of co-isolated contaminants with similar size and densities, such as protein aggregates and fat globules - which is still waiting to be fully addressed. We report here a fully detailed protocol for accurate and robust determination of the size distribution and stability of EV samples which leverages a dedicated combination of Fluorescence Correlation Spectroscopy (FCS) and Dynamic Light Scattering (DLS). The theoretical background, critical experimental steps and data analysis procedures are thoroughly presented and finally illustrated through the representative case study of EV formulations obtained from culture media of B16 melanoma cells, a murine tumor cell line used as a model for human skin cancers. Copyright © 2017 Elsevier B.V. All rights reserved.

Flocculation and aggregation in a microgravity environment (FAME)

NASA Technical Reports Server (NTRS)

Ansari, Rafat R.; Dhadwal, Harbans S.; Suh, Kwang I.

1994-01-01

An experiment to study flocculation phenomena in the constrained microgravity environment of a space shuttle or space station is described. The small size and light weight experiment easily fits in a Spacelab Glovebox. Using an integrated fiber optic dynamic light scattering (DLS) system we obtain high precision particle size measurements from dispersions of colloidal particles within seconds, needs no onboard optical alignment, no index matching fluid, and offers sample mixing and shear melting capabilities to study aggregation (flocculation and coagulation) phenomena under both quiescent and controlled agitation conditions. The experimental system can easily be adapted for other microgravity experiments requiring the use of DLS. Preliminary results of ground-based study are reported.

Zeta-potential and particle size studies of silver sulphide nanoparticles

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

Sharma, Vikash, E-mail: vikash@csr.res.in; Tarachand,; Ganesan, V.

Silver sulfide (Ag{sub 2}S) nanoparticles (NPs) were prepared successfully for the first time using diethylene glycol (DEG) as a surfactant. X-ray diffraction (XRD) data revealed single phase nature of the compound and energy-dispersive X-ray (EDX) confirmed its nominal composition. Their sizes were 43 nm from XRD, 50 nm from atomic force microscopy (AFM) and 19 nm & 213 nm from dynamic light scattering (DLS); their differences have been discussed. Autotitration study of zeta potential of these NPs in deionized water by DLS at different pH values confirmed an isoelectric point at pH = 5.14 and their very unstable nature in deionized water.

Effect of interparticle interactions on size determination of zirconia and silica based systems – A comparison of SAXS, DLS, BET, XRD and TEM

PubMed Central

Pabisch, Silvia; Feichtenschlager, Bernhard; Kickelbick, Guido; Peterlik, Herwig

2012-01-01

The aim of this work is a systematic comparison of size characterisation methods for two completely different model systems of oxide nanoparticles, i.e. amorphous spherical silica and anisotropic facet-shaped crystalline zirconia. Size and/or size distribution were determined in a wide range from 5 to 70 nm using small-angle X-ray scattering (SAXS), dynamic light scattering (DLS), nitrogen sorption (BET), X-ray diffraction (XRD) and transmission electron microscopy (TEM). A nearly perfect coincidence was observed only for SAXS and TEM for both types of particles. For zirconia nanoparticles considerable differences between different measurement methods were observed. PMID:22347721

Myeloperoxidase-hydrogen peroxide-chloride antimicrobial system: effect of exogenous amines on antibacterial action against Escherichia coli.

PubMed

Thomas, E L

1979-07-01

Exogenous ammonium ions (NH(4) (+)) and amine compounds had a profound influence on the antibacterial activity of the myeloperoxidase-hydrogen peroxide-chloride system against Escherichia coli. The rate of killing increased in the presence of NH(4) (+) and certain guanidino compounds and decreased in the presence of alpha-amino acids, polylysine, taurine, or tris (hydroxymethyl) aminomethane. Myeloperoxidase catalyzed the oxidation of chloride to hypochlorous acid, which reacted either with bacterial amine or amide components or both or with the exogenous compounds to yield chloramine or chloramide derivatives or both. These nitrogen-chlorine derivatives could oxidize bacterial components. Killing was correlated with oxidation of bacterial components. The rate of oxidation of bacterial sulfhydryls increased in the presence of the compounds that increased the rate of killing and decreased in the presence of the other compounds. The reaction of HOCl with NH(4) (+) yielded monochloramine (NH(2)Cl), which could be extracted into organic solvents. The N-Cl derivatives of bacterial components or of polylysine, taurine, or tris(hydroxymethyl)aminomethane could not be extracted. The effect of NH(4) (+) on killing is attributed to the ability of NH(2)Cl to penetrate the hydrophobic cell membrane and thus to oxidize intracellular components. Polylysine, taurine, and tris(hydroxymethyl)aminomethane formed high-molecular-weight, charged, or polar N-Cl derivatives that would be unable to penetrate the cell membrane. These results suggest an important role for leukocyte amine components in myeloperoxidase-catalyzed antimicrobial activity in vivo.

Improving the mining soil quality for a vegetation cover after addition of sewage sludges: inorganic ions and low-molecular-weight organic acids in the soil solution.

PubMed

Peña, Aránzazu; Mingorance, Mª Dolores; Guzmán-Carrizosa, Ignacio; Fernández-Espinosa, Antonio J

2015-03-01

We assessed the effects of applying stabilized sewage sludge (SSL) and composted sewage sludge (CLV), at 5 and 10% to an acid mining soil. Limed soil (NCL) amended or not with SSL and CLV was incubated for 47 days. We studied the cations and organic and inorganic anions in the soil solution by means of ion chromatography. Liming led to big increases in Ca(2+) and SO4(2-) and to significant decreases in K(+), Mg(2+), NH4(+) and NO3(-). Addition of both organic amendments increased some cations (NH4(+), K(+), Mg(2+), Na(+)) and anions (Cl(-), NO3(-) only with CLV and PO4(3-) only with SSL) and provided a greater amount of low-molecular-weight organic acids (LMWOAs) (SSL more than CLV). Incubation led to decreases in all cations, particularly remarkable for Ca(2+) and Mg(2+) in SSL-10. A decrease in NH4(+) was associated with variations in NO2(-) and NO3(-) resulting from nitrification reactions. During incubation the LMWOAs content tended to decrease similarly to the cations, especially in SSL-10. Chemometric tools revealed a clear discrimination between SSL, CLV and NCL. Furthermore, treatment effects depended upon dose, mainly in SSL. Amendment nature and dose affect the quality of a mining soil and improve conditions for plant establishment. Copyright © 2014 Elsevier Ltd. All rights reserved.

A study of the aggregation of cyclodextrins: Determination of the critical aggregation concentration, size of aggregates and thermodynamics using isodesmic and K2-K models.

PubMed

Do, Thao Thi; Van Hooghten, Rob; Van den Mooter, Guy

2017-04-15

The aggregation of three different cyclodextrins (CDs): 2-hydroxypropyl-β-cyclodextrin (HP-β-CD), 2-hydroxypropyl-γ-cyclodextrin (HP-γ-CD) and sulfobutylether-β-cyclodextrin (SBE-β-CD) was studied. The critical aggregation concentration (cac) of these three CDs is quite similar and is situated at ca. 2% (m/v). There was only a small difference in the cac values determined by DLS and 1 H NMR. DLS measurements revealed that CDs in solution have three size populations wherein one of them is that of a single CD molecule. The size of aggregates determined by TEM appears to be similar to the size of the aggregates in the second size distribution determined by DLS. Isodesmic and K 2 -K self-assembly models were used for studying the aggregation process of HP-β-CD, HP-γ-CD and SBE-β-CD. The results showed that the aggregation process of these CDs is a cooperative one, where the first step of aggregation is less favorable than the next steps. The determined thermodynamic parameters showed that the aggregation process of all three CDs is spontaneous and exothermic and it is driven by an increase of the entropy of the environment. Copyright © 2017 Elsevier B.V. All rights reserved.

Clinical Detection of Pre-Cataractous Lens Protein Changes using Dynamic Light Scattering

PubMed Central

Datiles, Manuel B.; Ansari, Rafat R.; Suh, Kwang I.; Vitale, Susan; Reed, George F.; Zigler, J. Samuel; Ferris., Frederick L.

2008-01-01

Purpose To use Dynamic Light Scattering (DLS) to clinically assess early pre-cataractous lens protein changes. Methods We performed a cross sectional study in 380 eyes of 235 subjects aged 7–86 years with AREDS clinical lens nuclear grades ranging from 0–3.8. A DLS device was used to assess α-crystallin, a molecular chaperone protein shown to bind other damaged lens proteins, preventing their aggregation. The outcome measure was the α-crystallin index (ACI), a measure of unbound α-crystallin in each lens. The association of ACI with increasing nuclear opacity and aging was determined. Results There was a significant decrease in ACI associated with increasing grades of lens nuclear opacity (p<0.0001). There are significant losses of α-crystallin even in clinically clear lenses associated with aging (p<0.0001). The standard error of measurement was 3%. Conclusions DLS clinically detects loss of α-crystallin proteins even in clinically clear lenses. ACI measurements may be useful in identifying patients at high risk for developing cataract, and as an outcome variable in clinical lens studies. Clinical Relevance Our studies suggest that the ACI may be a useful measure of the protective α-crystallin molecular chaperone reserve present in a lens, analogous to creatinine clearance in estimating renal function reserve. PMID:19064850

Core-shell structure of Miglyol/poly(D,L-lactide)/Poloxamer nanocapsules studied by small-angle neutron scattering.

PubMed

Rübe, Andrea; Hause, Gerd; Mäder, Karsten; Kohlbrecher, Joachim

2005-10-03

The contrast variation technique in small angle neutron scattering (SANS) was used to investigate the inner structure of nanocapsules on the example of poly(D,L-lactide) (PLA) nanocapsules. The determination of the PLA and Poloxamer shell thickness was the focus of this study. Highest sensitivity on the inner structure of the nanocapsules was obtained when the scattering length density of the solvent was varied between the one of the Miglyol core and the PLA shell. According to the fit data the PLA shell thickness was 9.8 nm. The z-averaged radius determined by SANS experiments correlated well with dynamic light scattering (DLS) results, although DLS values were systematically slightly higher than the ones measured by SANS. This could be explained by taking into account the influence of Poloxamer attached to the nanocapsules surface. For a refined fit model with a second shell consisting of Poloxamer, SANS values and DLS values fitted well with each other. The characterization method presented here is significant because detailed insights into the nanocapsule and the Poloxamer shell were gained for the first time. This method could be used to develop strategies for the optimization of the shell properties concerning controlled release and to study changes in the shell structure during degradation processes.

Quantitative characterization of nanoparticle agglomeration within biological media

NASA Astrophysics Data System (ADS)

Hondow, Nicole; Brydson, Rik; Wang, Peiyi; Holton, Mark D.; Brown, M. Rowan; Rees, Paul; Summers, Huw D.; Brown, Andy

2012-07-01

Quantitative analysis of nanoparticle dispersion state within biological media is essential to understanding cellular uptake and the roles of diffusion, sedimentation, and endocytosis in determining nanoparticle dose. The dispersion of polymer-coated CdTe/ZnS quantum dots in water and cell growth medium with and without fetal bovine serum was analyzed by transmission electron microscopy (TEM) and dynamic light scattering (DLS) techniques. Characterization by TEM of samples prepared by plunge freezing the blotted solutions into liquid ethane was sensitive to the dispersion state of the quantum dots and enabled measurement of agglomerate size distributions even in the presence of serum proteins where DLS failed. In addition, TEM showed a reduced packing fraction of quantum dots per agglomerate when dispersed in biological media and serum compared to just water, highlighting the effect of interactions between the media, serum proteins, and the quantum dots. The identification of a heterogeneous distribution of quantum dots and quantum dot agglomerates in cell growth medium and serum by TEM will enable correlation with the previously reported optical metrology of in vitro cellular uptake of this quantum dot dispersion. In this paper, we present a comparative study of TEM and DLS and show that plunge-freeze TEM provides a robust assessment of nanoparticle agglomeration state.

The effects of real and illusory glides on pure-tone frequency discrimination.

PubMed

Lyzenga, J; Carlyon, R P; Moore, B C J

2004-07-01

Experiment 1 measured pure-tone frequency difference limens (DLs) at 1 and 4 kHz. The stimuli had two steady-state portions, which differed in frequency for the target. These portions were separated by a middle section of varying length, which consisted of a silent gap, a frequency glide, or a noise burst (conditions: gap, glide, and noise, respectively). The noise burst created an illusion of the tone continuing through the gap. In the first condition, the stimuli had an overall duration of 500 ms. In the second condition, stimuli had a fixed 50-ms middle section, and the overall duration was varied. DLs were lower for the glide than for the gap condition, consistent with the idea that the auditory system contains a mechanism specific for the detection of dynamic changes. DLs were generally lower for the noise than for the gap condition, suggesting that this mechanism extracts information from an illusory glide. In a second experiment, pure-tone frequency direction-discrimination thresholds were measured using similar stimuli as for the first experiment. For this task, the type of the middle section hardly affected the thresholds, suggesting that the frequency-change detection mechanism does not facilitate the identification of the direction of frequency changes.

Rate discrimination at low pulse rates in normal-hearing and cochlear implant listeners: Influence of intracochlear stimulation site.

PubMed

Stahl, Pierre; Macherey, Olivier; Meunier, Sabine; Roman, Stéphane

2016-04-01

Temporal pitch perception in cochlear implantees remains weaker than in normal hearing listeners and is usually limited to rates below about 300 pulses per second (pps). Recent studies have suggested that stimulating the apical part of the cochlea may improve the temporal coding of pitch by cochlear implants (CIs), compared to stimulating other sites. The present study focuses on rate discrimination at low pulse rates (ranging from 20 to 104 pps). Two experiments measured and compared pulse rate difference limens (DLs) at four fundamental frequencies (ranging from 20 to 104 Hz) in both CI and normal-hearing (NH) listeners. Experiment 1 measured DLs in users of the (Med-El CI, Innsbruck, Austria) device for two electrodes (one apical and one basal). In experiment 2, DLs for NH listeners were compared for unresolved harmonic complex tones filtered in two frequency regions (lower cut-off frequencies of 1200 and 3600 Hz, respectively) and for different bandwidths. Pulse rate discrimination performance was significantly better when stimulation was provided by the apical electrode in CI users and by the lower-frequency tone complexes in NH listeners. This set of data appears consistent with better temporal coding when stimulation originates from apical regions of the cochlea.

cis elements and trans-acting factors involved in dimer formation of murine leukemia virus RNA.

PubMed

Prats, A C; Roy, C; Wang, P A; Erard, M; Housset, V; Gabus, C; Paoletti, C; Darlix, J L

1990-02-01

The genetic material of all retroviruses examined so far consists of two identical RNA molecules joined at their 5' ends by the dimer linkage structure (DLS). Since the precise location of the DLS as well as the mechanism and role(s) of RNA dimerization remain unclear, we analyzed the dimerization process of Moloney murine leukemia virus (MoMuLV) genomic RNA. For this purpose we derived an in vitro model for RNA dimerization. By using this model, murine leukemia virus RNA was shown to form dimeric molecules. Deletion mutagenesis in the 620-nucleotide leader of MoMuLV RNA showed that the dimer promoting sequences are located within the encapsidation element Psi between positions 215 and 420. Furthermore, hybridization assays in which DNA oligomers were used to probe monomer and dimer forms of MoMuLV RNA indicated that the DLS probably maps between positions 280 and 330 from the RNA 5' end. Also, retroviral nucleocapsid protein was shown to catalyze dimerization of MoMuLV RNA and to be tightly bound to genomic dimer RNA in virions. These results suggest that MoMuLV RNA dimerization and encapsidation are probably controlled by the same cis element, Psi, and trans-acting factor, nucleocapsid protein, and thus might be linked during virion formation.

cis elements and trans-acting factors involved in dimer formation of murine leukemia virus RNA.

PubMed Central

Prats, A C; Roy, C; Wang, P A; Erard, M; Housset, V; Gabus, C; Paoletti, C; Darlix, J L

1990-01-01

The genetic material of all retroviruses examined so far consists of two identical RNA molecules joined at their 5' ends by the dimer linkage structure (DLS). Since the precise location of the DLS as well as the mechanism and role(s) of RNA dimerization remain unclear, we analyzed the dimerization process of Moloney murine leukemia virus (MoMuLV) genomic RNA. For this purpose we derived an in vitro model for RNA dimerization. By using this model, murine leukemia virus RNA was shown to form dimeric molecules. Deletion mutagenesis in the 620-nucleotide leader of MoMuLV RNA showed that the dimer promoting sequences are located within the encapsidation element Psi between positions 215 and 420. Furthermore, hybridization assays in which DNA oligomers were used to probe monomer and dimer forms of MoMuLV RNA indicated that the DLS probably maps between positions 280 and 330 from the RNA 5' end. Also, retroviral nucleocapsid protein was shown to catalyze dimerization of MoMuLV RNA and to be tightly bound to genomic dimer RNA in virions. These results suggest that MoMuLV RNA dimerization and encapsidation are probably controlled by the same cis element, Psi, and trans-acting factor, nucleocapsid protein, and thus might be linked during virion formation. Images PMID:2153242

Primary chromatic aberration elimination via optimization work with genetic algorithm

NASA Astrophysics Data System (ADS)

Wu, Bo-Wen; Liu, Tung-Kuan; Fang, Yi-Chin; Chou, Jyh-Horng; Tsai, Hsien-Lin; Chang, En-Hao

2008-09-01

Chromatic Aberration plays a part in modern optical systems, especially in digitalized and smart optical systems. Much effort has been devoted to eliminating specific chromatic aberration in order to match the demand for advanced digitalized optical products. Basically, the elimination of axial chromatic and lateral color aberration of an optical lens and system depends on the selection of optical glass. According to reports from glass companies all over the world, the number of various newly developed optical glasses in the market exceeds three hundred. However, due to the complexity of a practical optical system, optical designers have so far had difficulty in finding the right solution to eliminate small axial and lateral chromatic aberration except by the Damped Least Squares (DLS) method, which is limited in so far as the DLS method has not yet managed to find a better optical system configuration. In the present research, genetic algorithms are used to replace traditional DLS so as to eliminate axial and lateral chromatic, by combining the theories of geometric optics in Tessar type lenses and a technique involving Binary/Real Encoding, Multiple Dynamic Crossover and Random Gene Mutation to find a much better configuration for optical glasses. By implementing the algorithms outlined in this paper, satisfactory results can be achieved in eliminating axial and lateral color aberration.

Melt-Pool Temperature and Size Measurement During Direct Laser Sintering

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

List, III, Frederick Alyious; Dinwiddie, Ralph Barton; Carver, Keith

2017-08-01

Additive manufacturing has demonstrated the ability to fabricate complex geometries and components not possible with conventional casting and machining. In many cases, industry has demonstrated the ability to fabricate complex geometries with improved efficiency and performance. However, qualification and certification of processes is challenging, leaving companies to focus on certification of material though design allowable based approaches. This significantly reduces the business case for additive manufacturing. Therefore, real time monitoring of the melt pool can be used to detect the development of flaws, such as porosity or un-sintered powder and aid in the certification process. Characteristics of the melt poolmore » in the Direct Laser Sintering (DLS) process is also of great interest to modelers who are developing simulation models needed to improve and perfect the DLS process. Such models could provide a means to rapidly develop the optimum processing parameters for new alloy powders and optimize processing parameters for specific part geometries. Stratonics’ ThermaViz system will be integrated with the Renishaw DLS system in order to demonstrate its ability to measure melt pool size, shape and temperature. These results will be compared with data from an existing IR camera to determine the best approach for the determination of these critical parameters.« less

Impairment of endocannabinoids activity in the dorsolateral striatum delays extinction of behavior in a procedural memory task in rats.

PubMed

Rueda-Orozco, Pavel E; Montes-Rodriguez, Corinne J; Soria-Gomez, Edgar; Méndez-Díaz, Mónica; Prospéro-García, Oscar

2008-07-01

The dorsolateral striatum (DLS) has been implicated in the learning of habits and procedural memories. Extinction of this kind of memories has been poorly studied. The DLS expresses high levels of the cannabinergic receptor one (CB1), and, lately, it has been suggested that the activation of CB1 in this structure is indispensable for long-term depression (LTD) development. We performed experiments in a T-maze and evaluated the effects of intrastriatal and intrahipocampal administration of the CB1 antagonist AM251 on extinction and on c-Fos expression. We also administered anandamide to evaluate if an artificial increase of endocannabinoids facilitates extinction. Our results indicate clearly a dose-response blockade of extinction induced by AM251 injected into the striatum but a facilitation of extinction when administered into the hippocampus. Anandamide did not induce any observable changes. AM251 effects were accompanied by an increase in c-Fos immunoreactivity in the DLS and its decrease in the hippocampal region, suggesting that the activation of CB1 in the striatum is necessary for the extinction of procedural memories. These findings could be important in some neurological conditions, such as obsessive-compulsive disorder in which striatal activity seems to be abnormal.

Sizing of colloidal particle and protein molecules in a hanging fluid drop

NASA Technical Reports Server (NTRS)

Ansari, Rafat R.; Suh, Kwang I.

1995-01-01

We report non-invasive particle size measurements of polystyrene latex colloidal particles and bovine serum albumin (BSA) protein molecules suspended in tiny hanging fluid drops of 30 micro-Liter volume using a newly designed fiber optic probe. The probe is based upon the principles of the technique of dynamic light scattering (DLS). The motivation for this work comes from growing protein crystals in outer space. Protein crystals have been grown previously in hanging drops in microgravity experiments on-board the space shuttle orbiter. However, obtaining quantitative information on nucleation and growth of the protein crystals in real time has always been a desired goal, but hitherto not achieved. Several protein researchers have shown interest in using DLS to monitor crystal growth process in a droplet, but elaborate instrumentation and optical alignment problems have made in-situ applications difficult. We demonstrate that such an experiment is now possible. Our system offers fast (5 seconds) determination of particle size, utilize safe levels of very low laser power (less than or equal to 0.2 mW), a small scattering volume (approximately 2 x 10(exp -5) cu mm) and high spatial coherence (Beta) values. This is a major step forward when compared to currently available DLS systems.

Adherence to the 2006 American Heart Association Diet and Lifestyle Recommendations for cardiovascular disease risk reduction is associated with bone health in older Puerto Ricans123

PubMed Central

Bhupathiraju, Shilpa N; Lichtenstein, Alice H; Dawson-Hughes, Bess; Hannan, Marian T

2013-01-01

Background: Cardiovascular disease (CVD) and osteoporosis are 2 major public health problems that share common pathophysiological mechanisms. It is possible that strategies to reduce CVD risk may also benefit bone health. Objective: We tested the hypothesis that adherence to the 2006 American Heart Association Diet and Lifestyle Recommendations (AHA-DLR) is associated with bone health. Design: We previously developed a unique diet and lifestyle score (American Heart Association Diet and Lifestyle Score; AHA-DLS) to assess adherence to the AHA-DLR. In a cross-sectional study of 933 Puerto Ricans aged 47–79 y, we modified the AHA-DLS to test associations with bone health. Bone mineral density (BMD) at the femoral neck, trochanter, total hip, and lumbar spine (L2–L4) was measured by using dual-energy X-ray absorptiometry. Results: For every 5-unit increase in the modified AHA-DLS, BMD at the femoral neck, trochanter, total hip, and lumbar spine (L2–L4) was associated with a 0.005–0.008-g/cm2 (P < 0.05) higher value. No component of the AHA-DLR alone was responsible for the observed positive associations. For every 5-unit increase in the modified AHA-DLS, the odds for osteoporosis or osteopenia at the trochanter, total hip, and lumbar spine (L2–L4) were lower by 14% (OR: 0.86; 95% CI: 0.79, 0.92), 17% (OR: 0.83; 95% CI: 0.76, 0.92), and 9% (OR: 0.91; 95% CI: 0.84, 0.99), respectively. Conclusions: Dietary guidelines for CVD risk reduction may also benefit bone health in this Hispanic cohort. Synchronizing dietary guidelines for these 2 common diseases may provide a simplified public health message. This trial was registered at clinicaltrials.gov as NCT01231958. PMID:24047918

Current-free double layers: A review

NASA Astrophysics Data System (ADS)

Singh, Nagendra

2011-12-01

During the last decade, there has been an upsurge in the research on current-free DLs (CFDLs). Research includes theory, laboratory measurements, and various applications of CFDLs ranging from plasma thrusters to acceleration of charged particles in space and astrophysical plasmas. The purpose of this review is to present a unified understanding of the basic plasma processes, which lead to the formation of CFDLs. The review starts with the discussion on early research on electric fields and double layers (DLs) and ion acceleration in planar plasma expansion. The review continues with the formation of DLs and rarefaction shocks (RFS) in expanding plasma with two electron populations with different temperatures. The basic theory mitigating the formation of a CFDL by two-electron temperature population is reviewed; we refer to such CFDLs as double layers structures formation by two-temperature electron populations (TET-CFDLs). Application of TET-CFDLS to ion acceleration in laboratory and space plasmas was discussed including the formation of stationary steady-state DLs. A quite different type of CFDLs forms in a helicon plasma device (HPD), in which plasma abruptly expands from a narrow plasma source tube into a wide diffusion tube with abruptly diverging magnetic fields. The formation mechanism of the CFDL in HPD, referred here as current free double layer structure in helicon plasma device (HPD-CFDL), and its applications are reviewed. The formation of a TET-CFDL is due to the self-consistent separation of the two electron populations parallel to the ambient magnetic field. In contrast, a HPD-CFDL forms due to self-consistent separation of electrons and ion perpendicular to the abruptly diverging magnetic field in conjunction with the conducting wall of the expansion chamber in the HPD. One-dimensional theoretical models of CFDLs based on steady-state solution of Vlasov-Poisson system of equations are briefly discussed. Applications of CFDLs ranging from helicon double-layer thrusters (HDLTs) to the accelerations of ions in space and astrophysical plasmas are summarized.

Protein size resolution in human eye lenses by dynamic light scattering after in vivo measurements: first analysis of a clinical validation

NASA Astrophysics Data System (ADS)

Dierks, Karsten; Dieckmann, Matthias; Niederstrasser, Dirk; Schwartz, R.; Wegener, Alfred R.

1995-01-01

Laser light source powers of our instrument LEPOSIAR are minimized so that dynamic light scattering (DLS) measurements can be conducted with lowest intensity levels on human eye lenses (3.2 mW/cm2) within measurement times of 3 to 5 seconds. We describe an extension of DLS and an eye lens characterization along the optical axis (OA), revealing the molecular size ranges together with distributions found in lens regions parallel to the OA. The microstructures of various lens regions are separated by the analyzed radius distributions reflecting the visco-elastic properties of the eye lens. Detailed analysis and applied statistical categorization of results are described. The data obtained by DLS allow for an objective interpretation of opacity occurrences on molecular size range which are related to refraction anomalies. Apart from changes in color and fluorescence properties, the refractive anomalies can be assumed as the origin of the cataract. The bimodal radius distributions are characterized as a function of patient ages varying from 9 to 85 years. Our clinical study on 42 subjects proves a size decrease of the monomeric fraction with age, whereby their relative frequency of occurrence decreases. The larger polymeric radius fractions which are detected in lenses of all subjects increase with their age. An increase of protein polymer size is likely to be linked to the decrease of the (gamma) -crystallin fraction in old eye lens nuclei. Our preliminary analysis of clinical results is corresponding to the chemical gradients parallel to the OA of the lenses which are reported by O. Hockwin after examination on extracted eye lenses. The normalization of the lens densitometric data derived after Scheimpflug- photography against the protein size fraction analysis by DLS is performed. As a comparison mean between both techniques on identical eye lenses, an absorption corrected densitometry is conducted for the first time.

Effects of cardiac glycosides on sodium pump expression and function in LLC-PK1 and MDCK cells.

PubMed

Liu, Jiang; Periyasamy, Sankaridrug M; Gunning, William; Fedorova, Olga V; Bagrov, Alexei Y; Malhotra, Deepak; Xie, Zijian; Shapiro, Joseph I

2002-12-01

The decreases in proximal tubule sodium reabsorption seen with chronic renal failure and volume expansion have been ascribed to circulating digitalis-like substances (DLS). However, the circulating concentrations of DLS do not acutely inhibit the sodium pump to a degree consistent with the observed changes in proximal tubule sodium reabsorption. We examined how cell lines that simulated proximal (LLC-PK1) and distal tubule (MDCK) cells responded to acute (30 min) and long-term (up to 12 hours) Na+,K+-ATPase inhibition with DLS. In LLC-PK1, but not MDCK cells, low concentrations of ouabain decreased 86Rb uptake profoundly in a time and dose dependent manner. In LLC-PK1 cells grown to confluence, transcellular 22Na flux was markedly reduced in concert with the decreases in 86Rb uptake. Similar findings were observed with marinobufagenin (MBG) and deproteinated extract of serum derived from patients with chronic renal failure. However, inhibition of the Na+,K+-ATPase with low extracellular potassium concentrations did not produce any of these effects. Western and Northern blots detected no change in alpha1 Na+,K+-ATPase protein and message RNA, respectively, in LLC-PK1 cells treated with ouabain for 12 hours. However, the decrease in enzymatic activity of Na+,K+-ATPase of these cells was comparable to observed decreases in 86Rb uptake. Differential centrifugation as well as biotinylation experiments demonstrated a shift of the Na+,K+-ATPase from the plasmalemma with prolonged ouabain treatment. The results show that binding of cardiac glycosides by proximal (but not distal) tubular cells results in internalization of Na+,K+-ATPase with the net effect to amplify inhibition of the Na+,K+-ATPase. As the circulating concentrations of DLS increase with chronic renal failure and volume expansion, we suggest that this phenomenon explains some of the decreased sodium reabsorption by the proximal tubule seen in these conditions.

New Programs Utilizing Light Scattering and Flow Imaging Techniques for Macromolecular Crystal Growth and Fluid Dynamics Studies

NASA Technical Reports Server (NTRS)

2003-01-01

Dr. Phil Segre, a physicist by training, is a recent addition to the Biotech group, SD46, having joined NASA in August of 2000. Over the past two years he has been developing a laboratory for the study of macromolecular and protein crystal growth. The main apparatus for this work is a Dynamic Light Scattering apparatus, DLS, which is capable of making highly precise measurements of size distributions of both protein solutions and protein crystals. With Drs. Chernov and Thomas (USRA), he has begun a collaboration studying the affects of protein impurities on protein crystal growth and subsequent crystal quality. One of the hypotheses behind the differences between Earth and space grown protein crystals is that the absorption of harmful impurities is reduced in space due to the absence of convective flows. Using DLS measurements we are examining crystal growth with varying amounts of impurities and testing whether there is a strong physical basis behind this hypothesis. With Dr. Joe Ng of UAH he has been collaborating on a project to examine the folding/unfolding dynamics of large RNA complexes. A detailed understanding of this process is necessary for the handling of RNA in biotech applications, and the DLS instrument gives details and results beyond that of other instruments. With Prof. Jim McClymer of the University of Maine (summer faculty visitor to NASA in 2001, 2002), we have been studying the crystallization process in model colloidal suspensions whose behavior in some cases can mimic that of much smaller protein solutions. An understanding of the self-assembly of colloids is the first step in the process of engineering novel materials for photonic and light switching applications. Finally, he has begun an investigation into the physics of particle sedimentation. In addition to the DLS instrument he also has an instrument (called PIV) that can measure flow fields of fluids. The applications are to the dynamics of protein crystal motions both on earth and in low-gravity.

Effect of patient position on the lordosis and scoliosis of patients with degenerative lumbar scoliosis

PubMed Central

Fei, Han; Li, Wei-shi; Sun, Zhuo-ran; Jiang, Shuai; Chen, Zhong-qiang

2017-01-01

Abstract This study aimed to analyze the effect of patient positions on the lordosis and scoliosis of patients with degenerative lumbar scoliosis (DLS). Seventy-seven patients with DLS were retrospectively analyzed. We measured lordosis and Cobb's angle on preoperative upright x-rays and magnetic resonance imagings in supine position. The lordosis and scoliosis of surgical segments in intraoperative prone position were measured on intraoperative radiographs of 20 patients to compare with that in standing position. Paired t tests were performed to investigate the parameters of the sample. From standing to supine position the whole lordosis increased (29.2 ± 15.7 degree vs. 34.9 ± 11.2 degree), and the whole scoliosis decreased (24.3 ± 11.8 degree vs. 19.0 ± 10.5 degree); 53 of 77 (68.8%) cases had increased lordosis, and 67 of 77 (87%) cases had decreased scoliosis. The lordosis of surgical segments in standing position had no difference with that in intraoprerative prone position. But in changing from supine/standing position to intraoprerative prone position, the scoliosis of surgical segments decreased (14.7 ± 9.4 degree vs. 11.4 ± 7.0 degree; 19.0 ± 11.8 degree vs. 11.4 ± 7.0 degree, respectively), and 18 of 20 (90%) cases had decreased scoliosis in intraoperative prone position than that in standing position. Compared with standing position in DLS patients, supine position increased lordosis and reduced scoliosis, and intraoperative prone position reduced scoliosis significantly. When evaluating the severity of DLS and making preoperative surgical plans, lumbar lordosis in supine position should also be evaluated in addition to upright x-ray, and the effects of different positions should be taken into consideration to reduce deviation. PMID:28796046

Effect of patient position on the lordosis and scoliosis of patients with degenerative lumbar scoliosis.

PubMed

Fei, Han; Li, Wei-Shi; Sun, Zhuo-Ran; Jiang, Shuai; Chen, Zhong-Qiang

2017-08-01

This study aimed to analyze the effect of patient positions on the lordosis and scoliosis of patients with degenerative lumbar scoliosis (DLS).Seventy-seven patients with DLS were retrospectively analyzed. We measured lordosis and Cobb's angle on preoperative upright x-rays and magnetic resonance imagings in supine position. The lordosis and scoliosis of surgical segments in intraoperative prone position were measured on intraoperative radiographs of 20 patients to compare with that in standing position. Paired t tests were performed to investigate the parameters of the sample.From standing to supine position the whole lordosis increased (29.2 ± 15.7 degree vs. 34.9 ± 11.2 degree), and the whole scoliosis decreased (24.3 ± 11.8 degree vs. 19.0 ± 10.5 degree); 53 of 77 (68.8%) cases had increased lordosis, and 67 of 77 (87%) cases had decreased scoliosis. The lordosis of surgical segments in standing position had no difference with that in intraoprerative prone position. But in changing from supine/standing position to intraoprerative prone position, the scoliosis of surgical segments decreased (14.7 ± 9.4 degree vs. 11.4 ± 7.0 degree; 19.0 ± 11.8 degree vs. 11.4 ± 7.0 degree, respectively), and 18 of 20 (90%) cases had decreased scoliosis in intraoperative prone position than that in standing position.Compared with standing position in DLS patients, supine position increased lordosis and reduced scoliosis, and intraoperative prone position reduced scoliosis significantly. When evaluating the severity of DLS and making preoperative surgical plans, lumbar lordosis in supine position should also be evaluated in addition to upright x-ray, and the effects of different positions should be taken into consideration to reduce deviation.

The Substitution of IVD (Ion Vapor Deposition) Aluminum for Cadmium

DTIC Science & Technology

1989-08-01

environment, it can finu its A in( the water suHpl o- fooo chain. Also, with electroplated cadmium processing, tnere are auditional nazaros associated win...no , - r e CUr r in ( polut io n- r elIt e costs. Tne po IIut ion controlI costs for all caG;iul n processing , nclIUd ino, clpitl treatm’ient , col...H T P, H VacuumCadmium None T. O. H T. P. H Key T - Toxic materials 0 - OSHA standards imposed P - Polution control required H - Hazardous waste

Development of Fracture Mechanics Maps for Composite Materials. Volume 2.

DTIC Science & Technology

1985-12-01

AD-A169 663 DEP 1/3UR OIOST l uNCL~ss~~n HUCI S I B M 11 1*2 AF,:P,.-TR-?5,-4150 DEVELOPMENT OF FRACTURE MECHANICS MAPS FOR COMPOSITE MATERIALS Dr. H...coIo. Development of N/A N/A N/A N/A Fracture Mechanics Maps for Composite Materials 12. PERSONAL AUTHORISI Editor (Dr. H. W. Bergmann) 13. TYPE OF...GROUP SUB GR. Fiber Reinforced Composites , Dynamic Test, Thermal Cycling, 1I1 04 Quality Control, Static Test, Stress Concentrations 01 03 19

A Thermally Activated Solid State Reaction Process for Fabricating Ohmic Contacts to Semiconducting Diamond

DTIC Science & Technology

1990-09-01

due to Ken Regan. Dr. Howard Rast, Dr. Carl Zeisse, Maureen O * Brien , Dr. Don Mullin, Richard Nguyen, Paul Thibado. Dr. Charlesý Kewett, and Dr. Alan...Standard form 298 (FRONT) 1!NCL-ASSIFIED 21a. NAME OF RESPONS’OLL NOWVfOUAý J. R. Zeidler 69)55" 1 - I~ C( 7 ci) NMH 7540-01 .2$ O -8600 SIA,~afre tO~m...boron nitride could extend the operating temperature of devices to temperatures in excess of 1000*C. TABLE I. Selected properties of semiconductors

Studies of the Electric Field Distribution in Biological Bodies - Experimental Dosimetry at Radiofrequencies

DTIC Science & Technology

1985-12-05

tissues The latter is :0 0 STRI96T:ON, AVAILAS LITY OF ABSTRACT ~ 21 ABSTRACT SECURITY CLASSFICATION " -~I’NCL.ASS F E ,-UN ITEO 0 SAME AS ROT 0 DTIC...measurements were performed at three frequencies, 160, 350 and 915 MHz, for two polarizations ( E and H) and at one frequency (350 MHz) for three ( E ,H & k...direction of wave propagation, and much higher SARs than the whole body average are produced in the nack for the E polarization at 160 and 350 MHz

Combinatorial Strategies and High Throughput Screening in Drug Discovery Targeted to the Channel of Botulinum Neurotoxin

DTIC Science & Technology

2006-09-01

block the HC channel. memantine NH2 amantadine H2N quinacrine NH O N lidocaine NH O N QX-222 S N Cl chlorpromazine N NCl O HN N Our objective was to...M2 protein2 and its derivative, memantine , which blocks the NMDA receptor channel3, and is approved by the FDA for the treatment of dementia...intracellular processing of BoNTs by collapsing the pH gradient across endosomes6,7. Chlorpromazine, quinacrine and memantine , in addition, cross the blood

Power law relation between particle concentrations and their sizes in the blood plasma

NASA Astrophysics Data System (ADS)

Kirichenko, M. N.; Chaikov, L. L.; Zaritskii, A. R.

2016-08-01

This work is devoted to the investigation of sizes and concentrations of particles in blood plasma by dynamic light scattering (DLS). Blood plasma contains many different proteins and their aggregates, microparticles and vesicles. Their sizes, concentrations and shapes can give information about donor's health. Our DLS study of blood plasma reveals unexpected dependence: with increasing of the particle sizes r (from 1 nm up to 1 μm), their concentrations decrease as r-4 (almost by 12 orders). We found also that such dependence was repeated for model solution of fibrinogen and thrombin with power coefficient is -3,6. We believe that this relation is a fundamental law of nature that shows interaction of proteins (and other substances) in biological liquids.

Quasi-Elastic Light Scattering in Ophthalmology

NASA Astrophysics Data System (ADS)

Ansari, Rafat R.

The eye is not just a "window to the soul"; it can also be a "window to the human body." The eye is built like a camera. Light which travels from the cornea to the retina traverses through tissues that are representative of nearly every tissue type and fluid type in the human body. Therefore, it is possible to diagnose ocular and systemic diseases through the eye. Quasi-elastic light scattering (QELS) also known as dynamic light scattering (DLS) is a laboratory technique routinely used in the characterization of macromolecular dispersions. QELS instrumentation has now become more compact, sensitive, flexible, and easy to use. These developments have made QELS/DLS an important tool in ophthalmic research where disease can be detected early and noninvasively before the clinical symptoms appear.

Intracellular Proteolysis of Progranulin Generates Stable, Lysosomal Granulins that Are Haploinsufficient in Patients with Frontotemporal Dementia Caused by GRN Mutations

PubMed Central

Taylor, Georgia; Deng, Qiudong

2017-01-01

Homozygous or heterozygous mutations in the GRN gene, encoding progranulin (PGRN), cause neuronal ceroid lipofuscinosis (NCL) or frontotemporal dementia (FTD), respectively. NCL and FTD are characterized by lysosome dysfunction and neurodegeneration, indicating PGRN is important for lysosome homeostasis in the brain. PGRN is trafficked to the lysosome where its functional role is unknown. PGRN can be cleaved into seven 6-kDa proteins called granulins (GRNs); however, little is known about how GRNs are produced or if levels of GRNs are altered in FTD-GRN mutation carriers. Here, we report the identification and characterization of antibodies that reliably detect several human GRNs by immunoblot and immunocytochemistry. Using these tools, we find that endogenous GRNs are present within multiple cell lines and are constitutively produced. Further, extracellular PGRN is endocytosed and rapidly processed into stable GRNs within lysosomes. Processing of PGRN into GRNs is conserved between humans and mice and is modulated by sortilin expression and mediated by cysteine proteases (i.e. cathpesin L). Induced lysosome dysfunction caused by alkalizing agents or increased expression of transmembrane protein 106B (TMEM106B) inhibit processing of PGRN into GRNs. Finally, we find that multiple GRNs are haploinsufficient in primary fibroblasts and cortical brain tissue from FTD-GRN patients. Taken together, our findings raise the interesting possibility that GRNs carry out critical lysosomal functions and that loss of GRNs should be explored as an initiating factor in lysosomal dysfunction and neurodegeneration caused by GRN mutations. PMID:28828399

Effect of E-waste Recycling on Urinary Metabolites of Organophosphate Flame Retardants and Plasticizers and Their Association with Oxidative Stress.

PubMed

Lu, Shao-You; Li, Yan-Xi; Zhang, Tao; Cai, Dan; Ruan, Ju-Jun; Huang, Ming-Zhi; Wang, Lei; Zhang, Jian-Qing; Qiu, Rong-Liang

2017-02-21

In this study, three chlorinated (Cl-mOPs) and five nonchlorinated (NCl-mOPs) organophosphate metabolites were determined in urine samples collected from participants living in an electronic waste (e-waste) dismantling area (n = 175) and two reference areas (rural, n = 29 and urban, n = 17) in southern China. Bis(2-chloroethyl) phosphate [BCEP, geometric mean (GM): 0.72 ng/mL] was the most abundant Cl-mOP, and diphenyl phosphate (DPHP, 0.55 ng/mL) was the most abundant NCl-mOP. The GM concentrations of mOPs in the e-waste dismantling sites were higher than those in the rural control site. These differences were significant for BCEP (p < 0.05) and DPHP (p < 0.01). Results suggested that e-waste dismantling activities contributed to human exposure to OPs. In the e-waste sites, the urinary concentrations of bis(2-chloro-isopropyl) phosphate (r = 0.484, p < 0.01), BCEP (r = 0.504, p < 0.01), dibutyl phosphate (r = 0.214, p < 0.05), and DPHP (r = 0.440, p < 0.01) were significantly increased as the concentration of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of DNA oxidative stress, increased. Our results also suggested that human exposure to OPs might be correlated with DNA oxidative stress for residents in e-waste dismantling areas. To our knowledge, this study is the first to report the urinary levels of mOPs in China and examine the association between OP exposure and 8-OHdG in humans.

RNA helicase A is not required for RISC activity.

PubMed

Liang, Xue-Hai; Crooke, Stanley T

2013-10-01

It has been shown that siRNAs can compete with each other or with endogenous miRNAs for RISC components. This competition may complicate the interpretations of phenotypes observed through siRNA-mediated knockdown of genes, especially those genes implicated in the RISC pathway. In this study, we re-examined the function of RNA helicase A (RHA), which has been previously proposed to function in RISC loading based on siRNA-mediated knockdown studies. Here we show that reduced RISC activity or loading of siRNAs was observed only in cells depleted of RHA using siRNA, but not using RNaseH-dependent antisense oligonucleotides (ASOs), suggesting that the impaired RISC function stems from the competition between pre-existing and newly transfected siRNAs, but not from reduction of the RHA protein. This view is further supported by the findings that cells depleted of a control protein, NCL1, using siRNA, but not ASO, exhibited similar defects on the loading and activity of a subsequently transfected siRNA. Transfection of RHA or NCL1 siRNAs, but not ASOs, reduced the levels of endogenous miRNAs, suggesting a competition mechanism. As a positive control, we showed that reduction of MOV10 by either siRNA or ASO decreased siRNA activity, confirming its role in RISC function. Together, our results indicate that RHA is not required for RISC activity or loading, and suggest that proper controls are required when using siRNAs to functionalize genes to avoid competition effects. © 2013. Published by Elsevier B.V. All rights reserved.

Aquifer-scale controls on the distribution of nitrate and ammonium in ground water near La Pine, Oregon, USA

USGS Publications Warehouse

Hinkle, S.R.; Böhlke, J.K.; Duff, J.H.; Morgan, D.S.; Weick, R.J.

2007-01-01

Geochemical and isotopic tools were applied at aquifer, transect, and subtransect scales to provide a framework for understanding sources, transport, and fate of dissolved inorganic N in a sandy aquifer near La Pine, Oregon. NO3 is a common contaminant in shallow ground water in this area, whereas high concentrations of NH4-N (up to 39 mg/L) are present in deep ground water. N concentrations, N/Cl ratios, tracer-based apparent ground-water ages, N isotope data, and hydraulic gradients indicate that septic tank effluent is the primary source of NO3. N isotope data, N/Cl and N/C relations, 3H data, and hydraulic considerations point to a natural, sedimentary organic matter source for the high concentrations of NH4, and are inconsistent with an origin as septic tank N. Low recharge rates and flow velocities have largely restricted anthropogenic NO3 to isolated plumes within several meters of the water table. A variety of geochemical and isotopic data indicate that denitrification also affects NO3 gradients in the aquifer. Ground water in the La Pine aquifer evolves from oxic to increasingly reduced conditions. Suboxic conditions are achieved after about 15-30 y of transport below the water table. NO3 is denitrified near the oxic/suboxic boundary. Denitrification in the La Pine aquifer is characterized well at the aquifer scale with a redox boundary approach that inherently captures spatial variability in the distribution of electron donors. ?? 2006 Elsevier B.V. All rights reserved.

Different molecular mechanisms involved in spontaneous and oxidative stress-induced mitochondrial fragmentation in tripeptidyl peptidase-1 (TPP-1)-deficient fibroblasts

PubMed Central

Van Beersel, Guillaume; Tihon, Eliane; Demine, Stéphane; Hamer, Isabelle; Jadot, Michel; Arnould, Thierry

2012-01-01

NCLs (neuronal ceroid lipofuscinoses) form a group of eight inherited autosomal recessive diseases characterized by the intralysosomal accumulation of autofluorescent pigments, called ceroids. Recent data suggest that the pathogenesis of NCL is associated with the appearance of fragmented mitochondria with altered functions. However, even if an impairement in the autophagic pathway has often been evoked, the molecular mechanisms leading to mitochondrial fragmentation in response to a lysosomal dysfunction are still poorly understood. In this study, we show that fibroblasts that are deficient for the TPP-1 (tripeptidyl peptidase-1), a lysosomal hydrolase encoded by the gene mutated in the LINCL (late infantile NCL, CLN2 form) also exhibit a fragmented mitochondrial network. This morphological alteration is accompanied by an increase in the expression of the protein BNIP3 (Bcl2/adenovirus E1B 19 kDa interacting protein 3) as well as a decrease in the abundance of mitofusins 1 and 2, two proteins involved in mitochondrial fusion. Using RNAi (RNA interference) and quantitative analysis of the mitochondrial morphology, we show that the inhibition of BNIP3 expression does not result in an increase in the reticulation of the mitochondrial population in LINCL cells. However, this protein seems to play a key role in cell response to mitochondrial oxidative stress as it sensitizes mitochondria to antimycin A-induced fragmentation. To our knowledge, our results bring the first evidence of a mechanism that links TPP-1 deficiency and oxidative stress-induced changes in mitochondrial morphology. PMID:23249249

Gold nanoparticle-based simple colorimetric and ultrasensitive dynamic light scattering assay for the selective detection of Pb(II) from paints, plastics, and water samples.

PubMed

Beqa, Lule; Singh, Anant Kumar; Khan, Sadia Afrin; Senapati, Dulal; Arumugam, Sri Ranjini; Ray, Paresh Chandra

2011-03-01

Pb (II) is a common water pollutant with high toxicity. According to the CDC, about 310,000 U.S. children of ages 1-5 have high levels of lead in their blood that it is due to the exposure to lead from plastic toys and other products. As a result, the development of ultrasensitive assays for the real-time detection of Pb(II) from plastic toys and paints is very important for water controlling, clinical toxicology and industrial processes. Driven by the need to detect trace amounts of Pb(II) from water samples, we report a label-free, highly selective and ultra sensitive glutathione modified gold nanoparticle based dynamic light scattering (DLS) probe for Pb(II) recognition in 100 ppt level from aqueous solution with excellent discrimination against other heavy metals. The sensitivity of our assay to detect Pb(II) level in water is almost 2 orders of magnitude higher than the EPA standard limit. We have also demonstrated that our DLS assay is capable of measuring the amount of Pb(II) in paint, plastic toys, and water from MS river. A possible mechanism and operating principles of our DLS assay have been discussed. Ultimately, this nanotechnology driven assay could have enormous potential applications in rapid, on-site monitoring of Pb(II) from day-to-day sample.

Targeted ablation of cholinergic interneurons in the dorsolateral striatum produces behavioral manifestations of Tourette syndrome

PubMed Central

Xu, Meiyu; Kobets, Andrew; Du, Jung-Chieh; Lennington, Jessica; Li, Lina; Banasr, Mounira; Duman, Ronald S.; Vaccarino, Flora M.; DiLeone, Ralph J.; Pittenger, Christopher

2015-01-01

Gilles de la Tourette syndrome (TS) is characterized by tics, which are transiently worsened by stress, acute administration of dopaminergic drugs, and by subtle deficits in motor coordination and sensorimotor gating. It represents the most severe end of a spectrum of tic disorders that, in aggregate, affect ∼5% of the population. Available treatments are frequently inadequate, and the pathophysiology is poorly understood. Postmortem studies have revealed a reduction in specific striatal interneurons, including the large cholinergic interneurons, in severe disease. We tested the hypothesis that this deficit is sufficient to produce aspects of the phenomenology of TS, using a strategy for targeted, specific cell ablation in mice. We achieved ∼50% ablation of the cholinergic interneurons of the striatum, recapitulating the deficit observed in patients postmortem, without any effect on GABAergic markers or on parvalbumin-expressing fast-spiking interneurons. Interneuron ablation in the dorsolateral striatum (DLS), corresponding roughly to the human putamen, led to tic-like stereotypies after either acute stress or d-amphetamine challenge; ablation in the dorsomedial striatum, in contrast, did not. DLS interneuron ablation also led to a deficit in coordination on the rotorod, but not to any abnormalities in prepulse inhibition, a measure of sensorimotor gating. These results support the causal sufficiency of cholinergic interneuron deficits in the DLS to produce some, but not all, of the characteristic symptoms of TS. PMID:25561540

Vasopressin facilitates excitatory transmission in slices of the rat dorso-lateral septum.

PubMed

Van den Hooff, P; Urban, I J

1990-01-01

The effect of vasopressin on neurons of the rat dorso-lateral septum (DLS) was studied in brain slices with intracellular microelectrodes. Two out of 13 neurons showed a small depolarization, spontaneous activity, and increased input resistances following a 15 min exposure to 10(-6) to 10(-8) M vasopressin (VP). These membrane effects disappeared completely within 3-5 min after the application. The remaining DLS neurons treated with these vasopressin concentrations showed an increase in glutamate-mediated excitatory postsynaptic potentials (EPSPs), evoked by stimulation of the fimbria fibers. As little as 10(-12) MVP increased these EPSPs markedly in nearly 80% of the cells studied. This increase in most of the cells disappeared within 15 min after the application period, whereas the increase in EPSPs induced by 10(-10) M VP outlasted the peptide application period for more than 30 min. Neither the blockade of GABA-ergic synaptic inhibition nor the pre-treatment of the neurons with d(CH2)5-Tyr(Me)-arginine vasopressin or 2-amino-5-phosphonovaleric acid (2-APV), antagonists for the V1 type of vasopressin receptor and NMDA receptors, respectively, interfered with the EPSPs potentiating effect of the peptide. It is concluded that a type of vasopressin receptor other then the V1 type is involved in the long-lasting potentiation of the primarily non-NMDA receptor mediated transmission in DLS neurons.

Going skin deep: A direct comparison of penetration potential of lipid-based nanovesicles on the isolated perfused human skin flap model.

PubMed

Ternullo, Selenia; de Weerd, Louis; Holsæter, Ann Mari; Flaten, Gøril Eide; Škalko-Basnet, Nataša

2017-12-01

Phospholipid-based nanocarriers are attractive drug carriers for improved local skin therapy. In the present study, the recently developed isolated perfused human skin flap (IPHSF) model was used to directly compare the skin penetration enhancing potential of the three commonly used nanocarriers, namely conventional liposomes (CLs), deformable liposomes (DLs) and solid lipid nanoparticles (SLNs). Two fluorescent markers, calcein (hydrophilic) or rhodamine (lipophilic), were incorporated individually in the three nanosystems. The nanocarrier size ranged between 200 and 300nm; the surface charge and entrapment efficiency for both markers were dependent on the lipid composition and the employed surfactant. Both carrier-associated markers could not penetrate the full thickness human skin, confirming their suitability for dermal drug delivery. CLs exhibited higher retention of both markers on the skin surface compared to DLs and SLNs, indicating a depo formation. DLs and SLNs enabled the deeper penetration of the two markers into the skin layers. In vitro and ex vivo skin penetration studies performed on the cellophane membrane and full thickness pig/human skin, respectively, confirmed the findings. In conclusion, efficient dermal drug delivery can be achieved by optimization of a lipid nanocarrier on the suitable skin-mimicking model to assure system's accumulation in the targeted skin layer. Copyright © 2017 Elsevier B.V. All rights reserved.

Preparation and pharmaceutical characterization of amorphous cefdinir using spray-drying and SAS-process.

PubMed

Park, Junsung; Park, Hee Jun; Cho, Wonkyung; Cha, Kwang-Ho; Kang, Young-Shin; Hwang, Sung-Joo

2010-08-30

The aim of this study was to investigate the effects of micronization and amorphorization of cefdinir on solubility and dissolution rate. The amorphous samples were prepared by spray-drying (SD) and supercritical anti-solvent (SAS) process, respectively and their amorphous natures were confirmed by DSC, PXRD and FT-IR. Thermal gravimetric analysis was performed by TGA. SEM was used to investigate the morphology of particles and the processed particle had a spherical shape, while the unprocessed crystalline particle had a needle-like shape. The mean particle size and specific surface area were measured by dynamic light scattering (DLS) and BET, respectively. The DLS result showed that the SAS-processed particle was the smallest, followed by SD and the unprocessed cefdinir. The BET result was the same as DLS result in that the SAS-processed particle had the largest surface area. Therefore, the processed cefdinir, especially the SAS-processed particle, appeared to have enhanced apparent solubility, improved intrinsic dissolution rate and better drug release when compared with SD-processed and unprocessed crystalline cefdinir due not only to its amorphous nature, but also its reduced particle size. Conclusions were that the solubility and dissolution rate of crystalline cefdinir could be improved by physically modifying the particles using SD and SAS-process. Furthermore, SAS-process was a powerful methodology for improving the solubility and dissolution rate of cefdinir. Copyright 2010 Elsevier B.V. All rights reserved.

Histidinemia and Infantile Autism

ERIC Educational Resources Information Center

Kotsopoulos, S.; Kutty, K. M.

1979-01-01

The article presents a case history of a boy with both infantile autism and histidenia (an inborn error of amino acid metabolism), and discusses the possible relationship between the two conditions. (DLS)

Functionalisation of Detonation Nanodiamond for Monodispersed, Soluble DNA-Nanodiamond Conjugates Using Mixed Silane Bead-Assisted Sonication Disintegration

DOE PAGES

Edgington, Robert; Spillane, Katelyn M.; Papageorgiou, George; ...

2018-01-15

Here, nanodiamonds have many attractive properties that make them suitable for a range of biological applications, but their practical use has been limited because nanodiamond conjugates tend to aggregate in solution during or after functionalisation. Here we demonstrate the production of DNA-detonation nanodiamond (DNA-DND) conjugates with high dispersion and solubility using an ultrasonic, mixed-silanization chemistry protocol based on the in situ Bead-Assisted Sonication Disintegration (BASD) silanization method. We use two silanes to achieve these properties: (1) 3-(trihydroxysilyl)propyl methylphosphonate (THPMP); a negatively charged silane that imparts high zeta potential and solubility in solution; and (2) (3-aminopropyl)triethoxysilane (APTES); a commonly used functionalmore » silane that contributes an amino group for subsequent bioconjugation. We target these amino groups for covalent conjugation to thiolated, single-stranded DNA oligomers using the heterobifunctional crosslinker sulfosuccinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate (Sulfo-SMCC). The resulting DNA-DND conjugates are the smallest reported to date, as determined by Dynamic Light Scattering (DLS) and Atomic Force Microscopy (AFM). The functionalisation method we describe is versatile and can be used to produce a wide variety of soluble DND-biomolecule conjugates.« less

Functionalisation of Detonation Nanodiamond for Monodispersed, Soluble DNA-Nanodiamond Conjugates Using Mixed Silane Bead-Assisted Sonication Disintegration.

PubMed

Edgington, Robert; Spillane, Katelyn M; Papageorgiou, George; Wray, William; Ishiwata, Hitoshi; Labarca, Mariana; Leal-Ortiz, Sergio; Reid, Gordon; Webb, Martin; Foord, John; Melosh, Nicholas; Schaefer, Andreas T

2018-01-15

Nanodiamonds have many attractive properties that make them suitable for a range of biological applications, but their practical use has been limited because nanodiamond conjugates tend to aggregate in solution during or after functionalisation. Here we demonstrate the production of DNA-detonation nanodiamond (DNA-DND) conjugates with high dispersion and solubility using an ultrasonic, mixed-silanization chemistry protocol based on the in situ Bead-Assisted Sonication Disintegration (BASD) silanization method. We use two silanes to achieve these properties: (1) 3-(trihydroxysilyl)propyl methylphosphonate (THPMP); a negatively charged silane that imparts high zeta potential and solubility in solution; and (2) (3-aminopropyl)triethoxysilane (APTES); a commonly used functional silane that contributes an amino group for subsequent bioconjugation. We target these amino groups for covalent conjugation to thiolated, single-stranded DNA oligomers using the heterobifunctional crosslinker sulfosuccinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate (Sulfo-SMCC). The resulting DNA-DND conjugates are the smallest reported to date, as determined by Dynamic Light Scattering (DLS) and Atomic Force Microscopy (AFM). The functionalisation method we describe is versatile and can be used to produce a wide variety of soluble DND-biomolecule conjugates.

Functionalisation of Detonation Nanodiamond for Monodispersed, Soluble DNA-Nanodiamond Conjugates Using Mixed Silane Bead-Assisted Sonication Disintegration

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

Edgington, Robert; Spillane, Katelyn M.; Papageorgiou, George

Here, nanodiamonds have many attractive properties that make them suitable for a range of biological applications, but their practical use has been limited because nanodiamond conjugates tend to aggregate in solution during or after functionalisation. Here we demonstrate the production of DNA-detonation nanodiamond (DNA-DND) conjugates with high dispersion and solubility using an ultrasonic, mixed-silanization chemistry protocol based on the in situ Bead-Assisted Sonication Disintegration (BASD) silanization method. We use two silanes to achieve these properties: (1) 3-(trihydroxysilyl)propyl methylphosphonate (THPMP); a negatively charged silane that imparts high zeta potential and solubility in solution; and (2) (3-aminopropyl)triethoxysilane (APTES); a commonly used functionalmore » silane that contributes an amino group for subsequent bioconjugation. We target these amino groups for covalent conjugation to thiolated, single-stranded DNA oligomers using the heterobifunctional crosslinker sulfosuccinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate (Sulfo-SMCC). The resulting DNA-DND conjugates are the smallest reported to date, as determined by Dynamic Light Scattering (DLS) and Atomic Force Microscopy (AFM). The functionalisation method we describe is versatile and can be used to produce a wide variety of soluble DND-biomolecule conjugates.« less

A response strategy predicts acquisition of schedule-induced polydipsia in rats.

PubMed

Gregory, James Gardner; Hawken, Emily R; Banasikowski, Tomek J; Dumont, Eric C; Beninger, Richard J

2015-08-03

Schedule-induced polydipsia (SIP) is excessive, non-regulatory drinking. We aimed to identify phenotypic learning traits representative of neural circuitry that underlies SIP and hypothesized that rats that are response-learners will be more susceptible in developing compulsive water drinking. Using the Y-maze, the rats were characterized as either place- or response-learners. They were exposed to the SIP protocol for a period of 21days. Subsequent histological staining for FosB/ΔFosB examined neuronal activation associated with SIP in several brain regions. The rats with a preference for a response-learning strategy were more likely to develop SIP than the rats using a place-learning strategy. Furthermore amphetamine sensitization, observed to increase SIP, also shifted learning strategy to a response-learning strategy. No differences were observed in FosB/ΔFosB expression between SIP and non-SIP rats in the dorsolateral striatum (DLS) and CA1 region of the hippocampus. However, SIP rats had greater FosB/ΔFosB expression in prefrontal cortex regions. The rats that develop SIP have a preference for response-learning strategies and increased neuronal activation in frontal cortical regions associated with habit formation and compulsion. Copyright © 2015 Elsevier Inc. All rights reserved.

Magnetic high throughput screening system for the development of nano-sized molecularly imprinted polymers for controlled delivery of curcumin.

PubMed

Piletska, Elena V; Abd, Bashar H; Krakowiak, Agata S; Parmar, Anitha; Pink, Demi L; Wall, Katie S; Wharton, Luke; Moczko, Ewa; Whitcombe, Michael J; Karim, Kal; Piletsky, Sergey A

2015-05-07

Curcumin is a versatile anti-inflammatory and anti-cancer agent known for its low bioavailability, which could be improved by developing materials capable of binding and releasing drug in a controlled fashion. The present study describes the preparation of magnetic nano-sized Molecularly Imprinted Polymers (nanoMIPs) for the controlled delivery of curcumin and their high throughput characterisation using microtitre plates modified with magnetic inserts. NanoMIPs were synthesised using functional monomers chosen with the aid of molecular modelling. The rate of release of curcumin from five polymers was studied under aqueous conditions and was found to correlate well with the binding energies obtained computationally. The presence of specific monomers was shown to be significant in ensuring effective binding of curcumin and to the rate of release obtained. Characterisation of the polymer particles was carried out using dynamic light scattering (DLS) technique and scanning electron microscopy (SEM) in order to establish the relationship between irradiation time and particle size. The protocols optimised during this study could be used as a blueprint for the development of nanoMIPs capable of the controlled release of potentially any compound of interest.

Teaching Typing by Transcription.

ERIC Educational Resources Information Center

Janson, Eleanor L.

1978-01-01

In addition to discussing the program for teaching typewriting to blind students using the auditory mode, the article presents a sample lesson in print, along with typing rates achieved by earlier classes. (DLS)

One Community Responds.

ERIC Educational Resources Information Center

Crossland, Cathy L.; Hasselbring, Ted S.

1979-01-01

The article describes Life Experiences, Inc., an organization in Cary, North Carolina, that operates and maintains facilities and programs for handicapped adults and assists them to function as productive citizens of the community. (DLS)

Job Attitudes of AFSC (Air Force Systems Command) Acquisition Project Managers.

DTIC Science & Technology

1986-04-01

for performance (3rd ed.). Homewood, IL: Irwin. Ajzen , 1. & Fishbein , M . (1977). Attitude-behavior relations: A theoretical analysis and review of...factors that may be influencing job attitudes. I X. Chapter One I NTRODUCTION Today, about 2000 Air Force members manage the acquisit ion of bi1lions of...ison.i .ncl I (’ate" Nt ro’ p 2ject ranager s and cther AFSC o tI c rs ha N.e s ie m a r - a t t ,.des, IL t their att itudes ai e lower compai ed to

Insight into the SEA amide thioester equilibrium. Application to the synthesis of thioesters at neutral pH.

PubMed

Pira, S L; El Mahdi, O; Raibaut, L; Drobecq, H; Dheur, J; Boll, E; Melnyk, O

2016-07-26

The bis(2-sulfanylethyl)amide (SEA) N,S-acyl shift thioester surrogate has found a variety of useful applications in the field of protein total synthesis. Here we present novel insights into the SEA amide/thioester equilibrium in water which is an essential step in any reaction involving the thioester surrogate properties of the SEA group. We also show that the SEA amide thioester equilibrium can be efficiently displaced at neutral pH for accessing peptide alkylthioesters, i.e. the key components of the native chemical ligation (NCL) reaction.

Antitubercular cassane furanoditerpenoids from the roots of Caesalpinia pulcherrima.

PubMed

Promsawan, Netnapa; Kittakoop, Prasat; Boonphong, Surat; Nongkunsarn, Pakawan

2003-08-01

Activity-guided fractionation of a root extract of Caesalpinia pulcherrima led to the isolation of two cassane-furanoditerpenoids, 6 beta-benzoyl-7 beta-hydroxyvouacapen-5 alpha-ol (1) and 6 beta-cinnamoyl-7beta-hydroxyvouacapen-5 alpha-ol (2). Compound 2 showed strong antitubercular activity with a minimum inhibitory concentration (MIC) of 6.25 microg/mL, whereas the benzoyl analogue (1) was less active (MIC 25 microg/mL). Both compounds expressed moderate cytotoxic activity towards KB (human oral carcinonoid cancer), BC (human breast cancer) and NCl-H187 (small cell lung cancer) cell lines.

Tunneling STM/STS and break-junction spectroscopy of the layered nitro-chloride superconductors MNCl (M = Ti, Hf, Zr)

NASA Astrophysics Data System (ADS)

Ekino, Toshikazu; Sugimoto, Akira; Gabovich, Alexander M.; Zheng, Zhanfeng; Zhang, Shuai; Yamanaka, Shoji

2014-05-01

The layered superconductors β-MNCl with the critical temperatures Tc = 14 K (M = Zr) - 25 K (M = Hf) were investigated by means of scanning-tunneling microscopy/spectroscopy and break-junction tunneling spectroscopy. The STM/STS was used to investigate the surface electronic structures in nanometer length scale, while the BJTS was employed to precisely determine the gap characteristics. Both techniques consistently clarified the unusually large size of the superconducting gap. Wide gap distributions with large-scale maximum gap values were also revealed in α-KyTiNCl with a different crystal structure.

Hazard Assessment Computer System HACS/UIM Users’ Operation Manual. Volume I.

DTIC Science & Technology

1981-09-01

941999-A U NCL A SSI7IED USCG-D-75-AL R_1 3 ~hhE~ I EEmhh.EEohmhE 2 I 1.I25 1.fl4 L MICROCOP RtfSCLUTItN IEST HTAK ’I’l ONAL BURLAU OF STANDARDS-1963...to assist in obtaining the compound recognition code used to refer- ence data for a particular chemical, a separate set of indices have been produced...and are given in a separate report. These indices enable a user of HACS to obtain a compound recognition code for a chemical given either the compound

Can Infants Use the Sonicguide? Two Years Experience of Project VIEW!

ERIC Educational Resources Information Center

Ferrell, Kay Alicyn

1980-01-01

Preliminary results indicated that the binaural sensory aid is useful within a regular program of developmental intervention, but that positive effects cannot be attributed to the device alone. (Author/DLS)

Environmental decontamination

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

Cristy, G.A.; Jernigan, H.C.

1981-02-01

The record of the proceedings of the workshop on environmental decontamination contains twenty-seven presentations. Emphasis is placed upon soil and surface decontamination, the decommissioning of nuclear facilities, and assessments of instrumentation and equipment used in decontamination. (DLS)

Compressive and rarefactive double layers in non-uniform plasma with q-nonextensive distributed electrons

NASA Astrophysics Data System (ADS)

Shan, S. Ali; Saleem, H.

2018-05-01

Electrostatic solitary waves and double layers (DLs) formed by the coupled ion acoustic (IA) and drift waves have been investigated in non-uniform plasma using q-nonextensive distribution function for the electrons and assuming ions to be cold Ti< Te. It is found that both compressive and rarefactive nonlinear structures (solitary waves and DLs) are possible in such a system. The steeper gradients are supportive for compressive solitary (and double layers) and destructive for rarefactive ones. The q-nonextensivity parameter q and the magnitudes of gradient scale lengths of density and temperature have significant effects on the amplitude of the double layers (and double layers) as well as on the speed of these structures. This theoretical model is general which has been applied here to the F-region ionosphere for illustration.

Woofer-tweeter adaptive optics scanning laser ophthalmoscopic imaging based on Lagrange-multiplier damped least-squares algorithm.

PubMed

Zou, Weiyao; Qi, Xiaofeng; Burns, Stephen A

2011-07-01

We implemented a Lagrange-multiplier (LM)-based damped least-squares (DLS) control algorithm in a woofer-tweeter dual deformable-mirror (DM) adaptive optics scanning laser ophthalmoscope (AOSLO). The algorithm uses data from a single Shack-Hartmann wavefront sensor to simultaneously correct large-amplitude low-order aberrations by a woofer DM and small-amplitude higher-order aberrations by a tweeter DM. We measured the in vivo performance of high resolution retinal imaging with the dual DM AOSLO. We compared the simultaneous LM-based DLS dual DM controller with both single DM controller, and a successive dual DM controller. We evaluated performance using both wavefront (RMS) and image quality metrics including brightness and power spectrum. The simultaneous LM-based dual DM AO can consistently provide near diffraction-limited in vivo routine imaging of human retina.

Successful correction of D-lactic acid neurotoxicity (drunken lamb syndrome) by bolus administration of oral sodium bicarbonate.

PubMed

Angell, J W; Jones, G L; Voigt, K; Grove-White, D H

2013-08-31

Drunken lamb syndrome (DLS) has recently been described as lamb D-lactic acidosis syndrome (LDLAS). In 2012, 18 lambs aged between 7 days and 28 days with LDLAS were identified. Biochemically, each lamb had a metabolic acidosis characterised by D-lactic acidosis and exhibited clinical signs including: not hyperthermic, no evidence of dehydration, demonstrating an ataxic gait tending to recumbency (DLS) and possibly somnolence. These lambs received 50 mmol of sodium bicarbonate as an 8.4 per cent solution given orally, together with parenteral long-acting amoxicillin. All 18 cases made a full clinical recovery. This study demonstrates a novel effective treatment for a disease that is usually fatal, and also demonstrates a strong correlation between venous plasma bicarbonate concentrations and venous plasma D-lactate concentrations (R(2)=0.49).

A Method for Identifying Small-Molecule Aggregators Using Photonic Crystal Biosensor Microplates

PubMed Central

Chan, Leo L.; Lidstone, Erich A.; Finch, Kristin E.; Heeres, James T.; Hergenrother, Paul J.; Cunningham, Brian T.

2010-01-01

Small molecules identified through high-throughput screens are an essential element in pharmaceutical discovery programs. It is now recognized that a substantial fraction of small molecules exhibit aggregating behavior leading to false positive results in many screening assays, typically due to nonspecific attachment to target proteins. Therefore, the ability to efficiently identify compounds within a screening library that aggregate can streamline the screening process by eliminating unsuitable molecules from further consideration. In this work, we show that photonic crystal (PC) optical biosensor microplate technology can be used to identify and quantify small-molecule aggregation. A group of aggregators and nonaggregators were tested using the PC technology, and measurements were compared with those gathered by three alternative methods: dynamic light scattering (DLS), an α-chymotrypsin colorimetric assay, and scanning electron microscopy (SEM). The PC biosensor measurements of aggregation were confirmed by visual observation using SEM, and were in general agreement with the α-chymotrypsin assay. DLS measurements, in contrast, demonstrated inconsistent readings for many compounds that are found to form aggregates in shapes, very different from the classical spherical particles assumed in DLS modeling. As a label-free detection method, the PC biosensor aggregation assay is simple to implement and provides a quantitative direct measurement of the mass density of material adsorbed to the transducer surface, whereas the microplate-based sensor format enables compatibility with high-throughput automated liquid-handling methods used in pharmaceutical screening. PMID:20930952

Unveiling the development of intracranial injury using dynamic brain EIT: an evaluation of current reconstruction algorithms.

PubMed

Li, Haoting; Chen, Rongqing; Xu, Canhua; Liu, Benyuan; Tang, Mengxing; Yang, Lin; Dong, Xiuzhen; Fu, Feng

2017-08-21

Dynamic brain electrical impedance tomography (EIT) is a promising technique for continuously monitoring the development of cerebral injury. While there are many reconstruction algorithms available for brain EIT, there is still a lack of study to compare their performance in the context of dynamic brain monitoring. To address this problem, we develop a framework for evaluating different current algorithms with their ability to correctly identify small intracranial conductivity changes. Firstly, a simulation 3D head phantom with realistic layered structure and impedance distribution is developed. Next several reconstructing algorithms, such as back projection (BP), damped least-square (DLS), Bayesian, split Bregman (SB) and GREIT are introduced. We investigate their temporal response, noise performance, location and shape error with respect to different noise levels on the simulation phantom. The results show that the SB algorithm demonstrates superior performance in reducing image error. To further improve the location accuracy, we optimize SB by incorporating the brain structure-based conductivity distribution priors, in which differences of the conductivities between different brain tissues and the inhomogeneous conductivity distribution of the skull are considered. We compare this novel algorithm (called SB-IBCD) with SB and DLS using anatomically correct head shaped phantoms with spatial varying skull conductivity. Main results and Significance: The results showed that SB-IBCD is the most effective in unveiling small intracranial conductivity changes, where it can reduce the image error by an average of 30.0% compared to DLS.

Abundance of Cysteine Endopeptidase Dionain in Digestive Fluid of Venus Flytrap (Dionaea muscipula Ellis) Is Regulated by Different Stimuli from Prey through Jasmonates

PubMed Central

Libiaková, Michaela; Floková, Kristýna; Novák, Ondřej; Slováková, L'udmila; Pavlovič, Andrej

2014-01-01

The trap of the carnivorous plant Venus flytrap (Dionaea muscipula) catches prey by very rapid closure of its modified leaves. After the rapid closure secures the prey, repeated mechanical stimulation of trigger hairs by struggling prey and the generation of action potentials (APs) result in secretion of digestive fluid. Once the prey's movement stops, the secretion is maintained by chemical stimuli released from digested prey. We investigated the effect of mechanical and chemical stimulation (NH4Cl, KH2PO4, further N(Cl) and P(K) stimulation) on enzyme activities in digestive fluid. Activities of β-D-glucosidases and N-acetyl-β-D-glucosaminidases were not detected. Acid phosphatase activity was higher in N(Cl) stimulated traps while proteolytic activity was higher in both chemically induced traps in comparison to mechanical stimulation. This is in accordance with higher abundance of recently described enzyme cysteine endopeptidase dionain in digestive fluid of chemically induced traps. Mechanical stimulation induced high levels of cis-12-oxophytodienoic acid (cis-OPDA) but jasmonic acid (JA) and its isoleucine conjugate (JA-Ile) accumulated to higher level after chemical stimulation. The concentration of indole-3-acetic acid (IAA), salicylic acid (SA) and abscisic acid (ABA) did not change significantly. The external application of JA bypassed the mechanical and chemical stimulation and induced a high abundance of dionain and proteolytic activity in digestive fluid. These results document the role of jasmonates in regulation of proteolytic activity in response to different stimuli from captured prey. The double trigger mechanism in protein digestion is proposed. PMID:25153528

Characterization of gene encoding amylopullulanase from plant-originated lactic acid bacterium, Lactobacillus plantarum L137.

PubMed

Kim, Jong-Hyun; Sunako, Michihiro; Ono, Hisayo; Murooka, Yoshikatsu; Fukusaki, Eiichiro; Yamashita, Mitsuo

2008-11-01

A starch-hydrolyzing lactic acid bacterium, Lactobacillus plantarum L137, was isolated from traditional fermented food made from fish and rice in the Philippines. A gene (apuA) encoding an amylolytic enzyme from Lactobacillus plantarum L137 was cloned, and its nucleotide sequence was determined. The apuA gene consisted of an open reading frame of 6171 bp encoding a protein of 2056 amino acids, the molecular mass of which was calculated to be 215,625 Da. The catalytic domains of amylase and pullulanase were located in the same region within the middle of the N-terminal region. The deduced amino acid sequence revealed four highly conserved regions that are common among amylolytic enzymes. In the N-terminal region, a six-amino-acid sequence (Asp-Ala/Thr-Ala-Asn-Ser-Thr) is repeated 39 times, and a three-amino-acid sequence (Gln-Pro-Thr) is repeated 50 times in the C-terminal region. The apuA gene was subcloned in L. plantarum NCL21, which is a plasmid-cured derivative of the wild-type L137 strain and has no amylopullulanase activity, and the gene was overexpressed under the control of its own promoter. The ApuA enzyme from this recombinant L. plantarum NCL21 harboring apuA gene was purified. The enzyme has both alpha-amylase and pullulanase activities. The N-terminal sequence of the purified enzyme showed that the signal peptide was cleaved at Ala(36) and the molecular mass of the mature extracellular enzyme is 211,537 Da. The major reaction products from soluble starch were maltotriose (G3) and maltotetraose (G4). Only maltotriose (G3) was produced from pullulan. From these results, we concluded that ApuA is an amylolytic enzyme belonging to the amylopullulanase family.

Functional activity of L-carnitine transporters in human airway epithelial cells.

PubMed

Ingoglia, Filippo; Visigalli, Rossana; Rotoli, Bianca Maria; Barilli, Amelia; Riccardi, Benedetta; Puccini, Paola; Dall'Asta, Valeria

2016-02-01

Carnitine plays a physiologically important role in the β-oxidation of fatty acids, facilitating the transport of long-chain fatty acids across the inner mitochondrial membrane. Distribution of carnitine within the body tissues is mainly performed by novel organic cation transporter (OCTN) family, including the isoforms OCTN1 (SLC22A4) and OCTN2 (SLC22A5) expressed in human. We performed here a characterization of carnitine transport in human airway epithelial cells A549, Calu-3, NCl-H441, and BEAS-2B, by means of an integrated approach combining data of mRNA/protein expression with the kinetic and inhibition analyses of L-[(3)H]carnitine transport. Carnitine uptake was strictly Na(+)-dependent in all cell models. In A549 and BEAS-2B cells, carnitine uptake was mediated by one high-affinity component (Km<2 μM) identifiable with OCTN2. In both these cell models, indeed, carnitine uptake was maximally inhibited by betaine and strongly reduced by SLC22A5/OCTN2 silencing. Conversely, Calu-3 and NCl-H441 exhibited both a high (Km~20 μM) and a low affinity (Km>1 mM) transport component. While the high affinity component is identifiable with OCTN2, the low affinity uptake is mediated by ATB(0,+), a Na(+), and Cl(-)-coupled transport system for neutral and cationic amino acids, as demonstrated by the inhibition by leucine and arginine, as well as by SLC6A14/ATB(0,+) silencing. The presence of this transporter leads to a massive accumulation of carnitine inside the cells and may be of peculiar relevance in pathologic conditions of carnitine deficiency, such as those associated to OCTN2 defects. Copyright © 2015 Elsevier B.V. All rights reserved.

Trehalose upregulates progranulin expression in human and mouse models of GRN haploinsufficiency: a novel therapeutic lead to treat frontotemporal dementia.

PubMed

Holler, Christopher J; Taylor, Georgia; McEachin, Zachary T; Deng, Qiudong; Watkins, William J; Hudson, Kathryn; Easley, Charles A; Hu, William T; Hales, Chadwick M; Rossoll, Wilfried; Bassell, Gary J; Kukar, Thomas

2016-06-24

Progranulin (PGRN) is a secreted growth factor important for neuronal survival and may do so, in part, by regulating lysosome homeostasis. Mutations in the PGRN gene (GRN) are a common cause of frontotemporal lobar degeneration (FTLD) and lead to disease through PGRN haploinsufficiency. Additionally, complete loss of PGRN in humans leads to neuronal ceroid lipofuscinosis (NCL), a lysosomal storage disease. Importantly, Grn-/- mouse models recapitulate pathogenic lysosomal features of NCL. Further, GRN variants that decrease PGRN expression increase the risk of developing Alzheimer's disease (AD) and Parkinson's disease (PD). Together these findings demonstrate that insufficient PGRN predisposes neurons to degeneration. Therefore, compounds that increase PGRN levels are potential therapeutics for multiple neurodegenerative diseases. Here, we performed a cell-based screen of a library of known autophagy-lysosome modulators and identified multiple novel activators of a human GRN promoter reporter including several common mTOR inhibitors and an mTOR-independent activator of autophagy, trehalose. Secondary cellular screens identified trehalose, a natural disaccharide, as the most promising lead compound because it increased endogenous PGRN in all cell lines tested and has multiple reported neuroprotective properties. Trehalose dose-dependently increased GRN mRNA as well as intracellular and secreted PGRN in both mouse and human cell lines and this effect was independent of the transcription factor EB (TFEB). Moreover, trehalose rescued PGRN deficiency in human fibroblasts and neurons derived from induced pluripotent stem cells (iPSCs) generated from GRN mutation carriers. Finally, oral administration of trehalose to Grn haploinsufficient mice significantly increased PGRN expression in the brain. This work reports several novel autophagy-lysosome modulators that enhance PGRN expression and identifies trehalose as a promising therapeutic for raising PGRN levels to treat multiple neurodegenerative diseases.

Prevalence of Clostridium difficile infection in hospitalized patients with diarrhoea: Results of a Polish multicenter, prospective, biannual point-prevalence study.

PubMed

Pituch, Hanna; Obuch-Woszczatyński, Piotr; Lachowicz, Dominika; Kuthan, Robert; Dzierżanowska-Fangrat, Katarzyna; Mikucka, Agnieszka; Jermakow, Katarzyna; Pituch-Zdanowska, Aleksandra; Davies, Kerrie

2018-04-13

We aimed to measure the underdiagnosis of Clostridium difficile infection across Poland and the distribution of PCR-ribotypes of C. difficile. Twenty seven Polish healthcare facilities (HCFs) participated in this prospective study. Each HCF systematically sent all diarrhoeal stools received from inpatients at their laboratories on two days (one in January 2013 and one in July 2013), independently of CDI test request, to the National Coordinating Laboratory (NCL) for standardized testing of CDI. Positive samples (using two-stage algorithm), had CDI, confirmed by qPCR and toxigenic culture. C. difficile isolates were characterized by PCR-ribotyping. Hospitals were questioned about their methods and testing policy for CDI during the study period: September 2011 to August 2013. During the study period, participating hospitals reported a mean of 33.2 tests for CDI per 10 000 patient-days and a mean of 8.4 cases of CDI per 10 000 patient-days. The overall prevalence of positive CDI patients at NCL was 16.5%. Due to absence of clinical suspicion, 19.1% of these patients were not diagnosed by the local diagnostic laboratory. We identified 23 different PCR-ribotypes among 87C. difficile strains isolated from patients. PCR-ribotype 027 (48%) was the most prevalent. The incidence of CDI in Poland in study period was very high. It should be noted however, that there is a lack of clinical suspicion and underestimation of the need to perform diagnostic tests for CDI in hospitalized patients. This will have an impact on the reported epidemiological status of CDI in Poland. Copyright © 2018 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.

Cervical Microbiome and Cytokine Profile at Various Stages of Cervical Cancer: A Pilot Study

PubMed Central

Bahena-Román, Margarita; Téllez-Sosa, Juan; Martínez-Barnetche, Jesús; Cortina-Ceballos, Bernardo; López-Estrada, Guillermina; Delgado-Romero, Karina; Burguete-García, Ana I.; Cantú, David; García-Carrancá, Alejandro; Madrid-Marina, Vicente

2016-01-01

Cervical cancer (CC) is caused by high-risk human papillomavirus persistence due to the immunosuppressive tumor microenvironment mediated by cytokines. Vaginal microbiota determines the presence of certain cytokines locally. We assessed the association between cervical microbiota diversity and the histopathological diagnosis of each stage of CC, and we evaluated mRNA cervical expression levels of IL-4, IL-6, IL-10, TGF-β1, TNF-α and IFN-γ across the histopathological diagnosis and specific bacterial clusters. We determined the cervical microbiota by high throughput sequencing of 16S rDNA amplicons and classified it in community state types (CST). Mean difference analyses between alpha-diversity and histopathological diagnosis were carried out, as well as a β-diversity analysis within the histological diagnosis. Cervical cytokine mRNA expression was analyzed across the CSTs and the histopathological diagnoses. We found a significant difference in microbiota's diversity in NCL-HPV negative women vs those with squamous intraepithelial lesions (SIL) and CC(p = 0.006, p = 0.036).When β-diversity was evaluated, the CC samples showed the highest variation within groups (p<0.0006) and the largest distance compared to NCL-HPV negative ones (p<0.00001). The predominant bacteria in women with normal cytology were L. crispatus and L. iners, whereas for SIL, it was Sneathia spp. and for CC, Fusobacterium spp. We found higher median cervical levels of IL-4 and TGF-β1 mRNA in the CST dominated by Fusobacterium spp. These results suggest that the cervical microbiota may be implicated in cervical cancer pathology. Further cohort studies are needed to validate these findings. PMID:27115350

Proteomic Profiling in the Brain of CLN1 Disease Model Reveals Affected Functional Modules.

PubMed

Tikka, Saara; Monogioudi, Evanthia; Gotsopoulos, Athanasios; Soliymani, Rabah; Pezzini, Francesco; Scifo, Enzo; Uusi-Rauva, Kristiina; Tyynelä, Jaana; Baumann, Marc; Jalanko, Anu; Simonati, Alessandro; Lalowski, Maciej

2016-03-01

Neuronal ceroid lipofuscinoses (NCL) are the most commonly inherited progressive encephalopathies of childhood. Pathologically, they are characterized by endolysosomal storage with different ultrastructural features and biochemical compositions. The molecular mechanisms causing progressive neurodegeneration and common molecular pathways linking expression of different NCL genes are largely unknown. We analyzed proteome alterations in the brains of a mouse model of human infantile CLN1 disease-palmitoyl-protein thioesterase 1 (Ppt1) gene knockout and its wild-type age-matched counterpart at different stages: pre-symptomatic, symptomatic and advanced. For this purpose, we utilized a combination of laser capture microdissection-based quantitative liquid chromatography tandem mass spectrometry (MS) and matrix-assisted laser desorption/ionization time-of-flight MS imaging to quantify/visualize the changes in protein expression in disease-affected brain thalamus and cerebral cortex tissue slices, respectively. Proteomic profiling of the pre-symptomatic stage thalamus revealed alterations mostly in metabolic processes and inhibition of various neuronal functions, i.e., neuritogenesis. Down-regulation in dynamics associated with growth of plasma projections and cellular protrusions was further corroborated by findings from RNA sequencing of CLN1 patients' fibroblasts. Changes detected at the symptomatic stage included: mitochondrial functions, synaptic vesicle transport, myelin proteome and signaling cascades, such as RhoA signaling. Considerable dysregulation of processes related to mitochondrial cell death, RhoA/Huntington's disease signaling and myelin sheath breakdown were observed at the advanced stage of the disease. The identified changes in protein levels were further substantiated by bioinformatics and network approaches, immunohistochemistry on brain tissues and literature knowledge, thus identifying various functional modules affected in the CLN1 childhood encephalopathy.

Chlorination pattern effect on thermodynamic parameters and environmental degradability for C₁₀-SCCPs: Quantum chemical calculation based on virtual combinational library.

PubMed

Sun, Yuzhen; Pan, Wenxiao; Lin, Yuan; Fu, Jianjie; Zhang, Aiqian

2016-01-01

Short-chain chlorinated paraffins (SCCPs) are still controversial candidates for inclusion in the Stockholm Convention. The inherent mixture nature of SCCPs makes it rather difficult to explore their environmental behaviors. A virtual molecule library of 42,720 C10-SCCP congeners covering the full structure spectrum was constructed. We explored the structural effects on the thermodynamic parameters and environmental degradability of C10-SCCPs through semi-empirical quantum chemical calculations. The thermodynamic properties were acquired using the AM1 method, and frontier molecular orbital analysis was carried out to obtain the E(HOMO), E(LUMO) and E(LUMO)-E(HOMO) for degradability exploration at the same level. The influence of the chlorination degree (N(Cl)) on the relative stability and environmental degradation was elucidated. A novel structural descriptor, μ, was proposed to measure the dispersion of the chlorine atoms within a molecule. There were significant correlations between thermodynamic values and N(Cl), while the reported N(Cl)-dependent pollution profile of C10-SCCPs in environmental samples was basically consistent with the predicted order of formation stability of C10-SCCP congeners. In addition, isomers with large μ showed higher relative stability than those with small μ. This could be further verified by the relationship between μ and the reactivity of nucleophilic substitution and OH attack respectively. The C10-SCCP congeners with less Cl substitution and lower dispersion degree are susceptible to environmental degradation via nucleophilic substitution and hydroxyl radical attack, while direct photolysis of C10-SCCP congeners cannot readily occur due to the large E(LUMO)-E(HOMO) values. The chlorination effect and the conclusions were further checked with appropriate density functional theory (DFT) calculations. Copyright © 2015. Published by Elsevier B.V.

High-throughput Identification of DNA-Encoded IgG Ligands that Distinguish Active and Latent Mycobacterium Tuberculosis Infections

PubMed Central

Ndungu, John Maina; Suponitsky-Kroyter, Irena; Cavett, Valerie J.; McEnaney, Patrick J.; MacConnell, Andrew B.; Doran, Todd. M.; Ronacher, Katharina; Stanley, Kim; Utset, Ofelia; Walzl, Gerhard; Paegel, Brian M.; Kodadek, Thomas

2017-01-01

The circulating antibody repertoire encodes a patient's health status and pathogen exposure history, but identifying antibodies with diagnostic potential usually requires knowledge of the antigen(s). We previously circumvented this problem by screening libraries of bead-displayed small molecules against case and control serum samples to discover “epitope surrogates” (ligands of IgGs enriched in the case sample). Here, we describe an improved version of this technology that employs DNA-encoded libraries and high-throughput FACS-based screening to discover epitope surrogates that differentiate noninfectious/latent (LTB) patients from infectious/active TB (ATB) patients, which is imperative for proper treatment selection and antibiotic stewardship. Normal control/LTB (10 patients each, NCL) and ATB (10 patients) serum pools were screened against a library (5 × 106 beads, 448k unique compounds) using fluorescent anti-human IgG to label hit compound beads for FACS. Deep sequencing decoded all hit structures and each hit's occurrence frequencies. ATB hits were pruned of NCL hits and prioritized for resynthesis based on occurrence and homology. Several structurally homologous families were identified and 16/21 resynthesized representative hits validated as selective ligands of ATB serum IgGs (p < 0.005). The native secreted TB protein Ag85B (though not the E. coli recombinant form) competed with one of the validated ligands for binding to antibodies, suggesting that it mimics a native Ag85B epitope. The use of DNA-encoded libraries and FACS-based screening in epitope surrogate discovery reveals thousands of potential hit structures. Distilling this list down to several consensus chemical structures yielded a diagnostic panel for ATB composed of thermally stable and economically produced small molecule ligands in place of protein antigens. PMID:27957856

A tailored mouse model of CLN2 disease: A nonsense mutant for testing personalized therapies

PubMed Central

Geraets, Ryan D.; Beraldi, Rosanna; Weimer, Jill M.; Pearce, David A.

2017-01-01

The Neuronal Ceroid Lipofuscinoses (NCLs), also known as Batten disease, result from mutations in over a dozen genes. Although, adults are susceptible, the NCLs are frequently classified as pediatric neurodegenerative diseases due to their greater pediatric prevalence. Initial clinical presentation usually consists of either seizures or retinopathy but develops to encompass both in conjunction with declining motor and cognitive function. The NCLs result in premature death due to the absence of curative therapies. Nevertheless, preclinical and clinical trials exist for various therapies. However, the genotypes of NCL animal models determine which therapeutic approaches can be assessed. Mutations of the CLN2 gene encoding a soluble lysosomal enzyme, tripeptidyl peptidase 1 (TPP1), cause late infantile NCL/CLN2 disease. The genotype of the original mouse model of CLN2 disease, Cln2-/-, excludes mutation guided therapies like antisense oligonucleotides and nonsense suppression. Therefore, the purpose of this study was to develop a model of CLN2 disease that allows for the assessment of all therapeutic approaches. Nonsense mutations in CLN2 disease are frequent, the most common being CLN2R208X. Thus, we created a mouse model that carries a mutation equivalent to the human p.R208X mutation. Molecular assessment of Cln2R207X/R207X tissues determined significant reduction in Cln2 transcript abundance and TPP1 enzyme activity. This reduction leads to the development of neurological impairment (e.g. tremors) and neuropathology (e.g. astrocytosis). Collectively, these assessments indicate that the Cln2R207X/R207X mouse is a valid CLN2 disease model which can be used for the preclinical evaluation of all therapeutic approaches including mutation guided therapies. PMID:28464005

Hyperkinesis and Chemotherapy.

ERIC Educational Resources Information Center

Calhoun, George

1979-01-01

The article discusses several criticisms of the use of drugs in the treatment of hyperactivity, and suggests some nondrug procedures for parents and teachers to use in the home and classroom to minimize and control a child's hyperactive behavior. (DLS)

Career Development Programs in Residential Schools for the Deaf: A Survey

ERIC Educational Resources Information Center

Twyman, Lee H.; Ouellette, Sue E.

1978-01-01

Sixty-four residential schools for the deaf were surveyed regarding ten aspects of career education programs, including objectives, details of program implementation, program content, special needs, environmental factors, and occupational choices. (DLS)

Span of Apprehension in Learning Disabled Boys.

ERIC Educational Resources Information Center

McIntyre, Curtis W.; And Others

1978-01-01

The span of apprehension (a measure of the amount of information processed simultaneously from a brief visual display) was studied in two experiments involving 40 normal and learning disabled boys (ages 6-11 years). (Author/DLS)

Setting Goals and Objectives for LD Children-Process and Problems

ERIC Educational Resources Information Center

Gallistel, Elizabeth R.

1978-01-01

Discussed are problems and procedures in setting goals and objectives for learning disabled children in the implementation of Individualized Education Programs required by the Education for All Handicapped Children Act. (Author/ DLS)

The Political Values of Mentally Retarded Citizens.

ERIC Educational Resources Information Center

Green, Barbara B.; Klein, Nancy K.

1980-01-01

The findings indicated that the retarded are affected by the process of political socialization much like their nonretarded peers. In forming a ranking of goal-values, age and socioeconomic status outweighed differences in cognitive ability. (Author/DLS)

The Tragic Story of Two Highly Gifted, Genius-Level Boys.

ERIC Educational Resources Information Center

Bergman, Jerry

1979-01-01

The article discusses the celebrated case of Nathan Leopold and Richard Loeb, two highly gifted boys who were convicted of a murder that the author states was caused in large part by their giftedness. (DLS)

Dynamic light scattering for the characterization and counting of extracellular vesicles: a powerful noninvasive tool

NASA Astrophysics Data System (ADS)

Palmieri, Valentina; Lucchetti, Donatella; Gatto, Ilaria; Maiorana, Alessandro; Marcantoni, Margherita; Maulucci, Giuseppe; Papi, Massimiliano; Pola, Roberto; De Spirito, Marco; Sgambato, Alessandro

2014-09-01

Extracellular vesicles (EVs) are cell-to-cell shuttles that have recently drawn interest both as drug delivery platforms and disease biomarkers. Despite the increasingly recognized relevance of these vesicles, their detection, and characterization still have several technical drawbacks. In this paper, we accurately assess the size distribution and concentration of EVs by using a high-throughput non-perturbative technique such as Dynamic Light Scattering (DLS). The vesicle radii distribution, as further confirmed by Atomic Force Microscopy experiments, ranges from 10 to 80 nm and appears very asymmetric towards larger radii with a main peak at roughly 30 nm. By combining DLS and Bradford assay, we also demonstrate the feasibility of recovering the concentration and its distribution of proteins contained inside vesicles. The sensitivity of our approach allows to detect protein concentrations as low as 0.01 mg/ml.

Trimetallic oxide nanocomposites of transition metals titanium and vanadium by sol-gel technique: synthesis, characterization and electronic properties

NASA Astrophysics Data System (ADS)

Kumar, Amit; Mishra, Neeraj Kumar; Sachan, Komal; Ali, Md Asif; Soaham Gupta, Sachchidanand; Singh, Rajeev

2018-04-01

Novel titanium and vanadium based trimetallic oxide nanocomposites (TMONCs) have been synthesized using metal salts of titanium-vanadium along with three others metals viz. tin, aluminium and zinc as precursors by the sol-gel method. Aqueous ammonia and hydrazine hydrate were used as the reducing agents. The preparations of nanocomposites were monitored by observing the visual changes during each step of synthesis. The synthesized TMONCs were characterized using UV–vis, SEM, EDX, TEM and DLS. Band gap of the synthesized TMONCs ranges from 3–4.5 eV determined using tauc plot. FTIR study revealed the molecular stretching and bending peaks of corresponding M–O/M–O–M bonds thus confirming their formation. Molecular composition and particle size were determined using EDX and DLS respectively. Molecular shape, size and surface morphology have been examined by SEM and TEM.

Antibacterial, anticancer and antioxidant potential of silver nanoparticles engineered using Trigonella foenum-graecum seed extract.

PubMed

Goyal, Shivangi; Gupta, Nidhi; Kumar, Ajeet; Chatterjee, Sreemoyee; Nimesh, Surendra

2018-06-01

In this study, the authors report a simple and eco-friendly method for the synthesis of silver nanoparticles (AgNPs) using Trigonella foenum-graecum (TFG) seed extract. They explored several parameters dictating the biosynthesis of TFG-AgNPs such as reaction time, temperature, concentration of AgNO 3 , and TFG extract amount. Physicochemical characterisation of TFG-AgNPs was done on dynamic light scattering (DLS), field emission electron microscopy, energy dispersive X-ray spectroscopy, X-ray diffraction and Fourier transform infrared spectroscopy. The size determination studies using DLS revealed of TFG-AgNPs size between 95 and 110 nm. The antibacterial activity was studied against Escherichia coli, Proteus vulgaris, Pseudomonas aeruginosa and Staphylococcus aureus . The biosynthesised TFG-AgNPs showed remarkable anticancer efficacy against skin cancer cell line, A431 and also exhibited significant antioxidant efficacy.

Trichoderma koningii assisted biogenic synthesis of silver nanoparticles and evaluation of their antibacterial activity

NASA Astrophysics Data System (ADS)

Tripathi, R. M.; Gupta, Rohit Kumar; Shrivastav, Archana; Singh, M. P.; Shrivastav, B. R.; Singh, Priti

2013-09-01

The present study demonstrates the biosynthesis of silver nanoparticles using Trichoderma koningii and evaluation of their antibacterial activity. Trichoderma koningii secretes proteins and enzymes that act as reducing and capping agent. The biosynthesized silver nanoparticles (AgNPs) were characterized by UV-Vis spectroscopy, dynamic light scattering (DLS), transmission electron microscopy (TEM) and x-ray diffraction (XRD). UV-Vis spectra showed absorbance peak at 413 nm corresponding to the surface plasmon resonance of silver nanoparticles. DLS was used to find out the size distribution profile. The size and morphology of the AgNPs was determined by TEM, which shows the formation of spherical nanoparticles in the size range of 8-24 nm. X-ray diffraction showed intense peaks corresponding to the crystalline silver. The antibacterial activity of biosynthesized AgNPs was evaluated by growth curve and inhibition zone and it was found that the AgNPs show potential effective antibacterial activity.

Fluorescent carbon and graphene oxide nanoparticles synthesized by the laser ablation in liquid

NASA Astrophysics Data System (ADS)

Małolepszy, A.; Błonski, S.; Chrzanowska-Giżyńska, J.; Wojasiński, M.; Płocinski, T.; Stobinski, L.; Szymanski, Z.

2018-04-01

The results of synthesis of the fluorescent carbon dots (CDots) from graphite target and reduced graphene oxide (rGO) nanoparticles performed by the nanosecond laser ablation in polyethylene glycol 200 (PEG200) are shown. Two-step laser irradiation (first graphite target, next achieved suspension) revealed a very effective production of CDots. However, the ablation in PEG appeared to be effective with 1064 nm laser pulse in contrast to the ablation with 355 nm laser pulse. In the case of rGO nanoparticles similar laser irradiation procedure was less efficient. In both cases, received nanoparticles exhibited strong, broadband photoluminescence with a maximum dependent on the excitation wavelength. The size distribution for obtained CDots was evaluated using the DLS technique and HRTEM images. The results from both methods show quite good agreement in nanoparticle size estimation although the DLS method slightly overestimates nanoparticle's diameter.

Observation of dynamic equilibrium cluster phase in nanoparticle-polymer system

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

Kumar, Sugam, E-mail: sugam@barc.gov.in; Mehan, S.; Aswal, V. K.

2016-05-23

Small-angle neutron scattering (SANS) and dynamic light scattering (DLS) have been used to investigate the existence of a cluster phase in a nanoparticle-polymer system. The nanoparticle-polymer system shows an interesting reentrant phase behavior where the charge stabilized silica nanoparticles undergo particle clustering and back to individual nanoparticles as a function of polymer concentration. This kind of phase behavior is believed to be directed by opposing attractive and repulsive interactions present in the system. The phase behavior shows two narrow regions of polymer concentration immediately before and after the two-phase formation indicating the possibility of the existence of some equilibrium clusters.more » DLS results show a much higher size of particles than individuals in these two regions which remains unchanged even after dilution. The SANS data show the evolution of attraction with increased volume fraction of the particles supporting the dynamic nature of these clusters.« less

Physicochemical properties of micelles of poly(styrene-b-[3-(methacryloylamino)propyl]trimethylammonium chloride-b-ethylene oxide) in aqueous solutions.

PubMed

Liu, Jingjing; Liu, Dian; Yokoyama, Yuuichi; Yusa, Shin-Ichi; Nakashima, Kenichi

2009-01-20

Polymeric micelles from a new triblock copolymer, polystyrene-block-poly[(3-(methacryloylamino)propyl)trimethylammonium chloride]-block-poly(ethylene oxide) (PS-b-PMAPTAC-b-PEO), were prepared in aqueous solutions and characterized by various techniques including dynamic light scattering (DLS), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and fluorescence spectroscopy. The micelle consists of a PS core, PMAPTAC shell, and PEO corona. It was revealed by SEM and DLS measurements that the micelles have a spherical structure with a hydrodynamic diameter about 75 nm. The addition of tungstate to the micellar solution caused a morphological change in the micelles from extended to shrunken spheres, which can be attributed to the fact that electrostatic repulsion among the cationic PMAPTAC blocks is canceled by the negative charge of the bound tungstate ions. Effective incorporation of tungstate ions into the micelles were confirmed by TEM and zeta-potential measurements.

Antimicrobial activity of silver nanoparticles impregnated wound dressing

NASA Astrophysics Data System (ADS)

Shinde, V. V.; Jadhav, P. R.; Patil, P. S.

2013-06-01

In this work, silver nanoparticles were synthesized by simple wet chemical reduction method. The silver nitrate was reduced by Sodium borohydride used as reducing agent and Poly (vinyl pyrrolidone) (PVP) as stabilizing agent. The formation of silver nanoparticles was evaluated by UV-visible spectroscope and transmission electron microscope (TEM). Absorption spectrum consist two plasmon peaks at 410 and 668 nm revels the formation of anisotropic nanoparticles confirmed by TEM. The formation of silver nanoparticles was also evidenced by dynamic light scattering (DLS) study. DLS showed polydisperse silver nanoparticles with hydrodynamic size 32 nm. Protecting mechanism of PVP was manifested by FT-Raman study. Silver nanoparticles were impregnated into wound dressing by sonochemical method. The Kirby-Bauer disc diffusion methods were used for antimicrobial susceptibility testing. The antimicrobial activity of the samples has been tested against gram-negative bacterium Escherichia coli and gram-positive bacterium Staphylococcus aureus.

Populations of striatal medium spiny neurons encode vibrotactile frequency in rats: modulation by slow wave oscillations

PubMed Central

Hawking, Thomas G.

2013-01-01

Dorsolateral striatum (DLS) is implicated in tactile perception and receives strong projections from somatosensory cortex. However, the sensory representations encoded by striatal projection neurons are not well understood. Here we characterized the contribution of DLS to the encoding of vibrotactile information in rats by assessing striatal responses to precise frequency stimuli delivered to a single vibrissa. We applied stimuli in a frequency range (45–90 Hz) that evokes discriminable percepts and carries most of the power of vibrissa vibration elicited by a range of complex fine textures. Both medium spiny neurons and evoked potentials showed tactile responses that were modulated by slow wave oscillations. Furthermore, medium spiny neuron population responses represented stimulus frequency on par with previously reported behavioral benchmarks. Our results suggest that striatum encodes frequency information of vibrotactile stimuli which is dynamically modulated by ongoing brain state. PMID:23114217

Multifractal detrended fluctuation analysis of intensity time series of photons scattered by tracer particles within a polymeric gel

NASA Astrophysics Data System (ADS)

Telesca, Luciano; Haro-Pérez, Catalina; Moreno-Torres, L. Rebeca; Ramirez-Rojas, Alejandro

2018-01-01

Some properties of spatial confinement of tracer colloidal particles within polyacrylamide dispersions are studied by means of the well-known dynamic light scattering (DLS) technique. DLS allows obtaining sequences of elapsed times of scattered photons. In this work, the aqueous polyacrylamide dispersion has no crosslinking and the volume fraction occupied by the tracer particles is 0.02 %. Our experimental setup provides two sequences of photons scattered by the same scattering volume that corresponds to two simultaneous experiments (Channel A and Channel B). By integration of these sequences, the intensity time series are obtained. We find that both channels are antipersistent with Hurst exponent, H ∼0.43 and 0.36, respectively. The antipersistence of the intensity time series indicates a subdiffusive dynamics of the tracers in the polymeric network, which is in agreement with the time dependence of the tracer's mean square displacement.

Thermoelectric properties of CuS/Ag{sub 2}S nanocomposites synthesed by modified polyol method

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

Tarachand,, E-mail: tarachand@csr.res.in; Sharma, Vikash; Ganesan, V.

This is the report on successful synthesis of Ag doped CuS nanostructures by modified polyol method. The resulting samples were characterized by powder X-ray diffraction (XRD), energy dispersive X-ray (EDX), atomic force microscopy (AFM) and dynamic light scattering (DLS). Particle size of pure CuS nanoparticles (NPs) was 17 nm, 38 nm and 97 nm as determined from Scherrer formula, AFM and DLS, respectively. Introduction of Ag led to formation of CuS/Ag{sub 2}S composites. A transition at 55 K in thermopower is ascribed to structural transformation from hexagonal to orthorhombic structure. Further, their thermoelectric properties exhibit remarkable change owing to Agmore » doping in CuS nanostructures. The power factor improves with increasing Ag content. They reveal that CuS/Ag{sub 2}S nanocomposites are some of the potential candidates for generation of thermoelectricity in future.« less

Dynamic laser speckle technique as an alternative tool to determine hygroscopic capacity and specific surface area of microporous zeolites

NASA Astrophysics Data System (ADS)

Mojica-Sepulveda, Ruth Dary; Mendoza-Herrera, Luís Joaquín; Grumel, Eduardo; Soria, Delia Beatriz; Cabello, Carmen Inés; Trivi, Marcelo

2018-07-01

Adsorption phenomena have several technological applications such as desiccants, catalysts, and separation of gases. Their uses depend on the textural properties of the solid adsorbent and the type of the adsorbed liquid or gas. Therefore, it is important to determine these properties. The most common measurement methods are physicochemical based on adsorption of N2 to determine the surface area and the distribution of pores size. However these techniques present certain limitations for microporous materials. In this paper we propose the use of the Dynamic Laser Speckle (DLS) technique to measure the hygroscopic capacity of a microporous natural zeolite and their modified forms. This new approach based on the adsorption of water by solids allows determine their specific surface area (S). To test the DLS results, we compared the obtained S values to those calculated by different conventional isotherms using the N2 adsorption-desorption method.

U. S. Naval Forces, Vietnam Monthly Historical Supplement for April 1966

DTIC Science & Technology

1966-05-27

direction *: DTIC SELECTEB^ JAN 2 4 «66 11 < OPV o2 . K JL,.(.:’.IPI?> • UNCLASSIFIED ■f r’ Best Available Copy - ’ DHCtÄS«^ ’ \\ mf, i...8217 ■ • UNCUSSIQED • • i ■ « , •■.•••«• •• ÜNClÄSSIflED ■** . • H? [^O r>it*fx’ KVliVL 1966 PAGfi KAVFOJY ytstabliahment of U.S. K &TaX Force...for K /.CVj and Coraander U.S. tlaval Forces« PhlUpplnos vao navy area coordina* tion authority» CoranAndlng Qenoral III VAT*» »any function» enco

A Fiber Optic Probe for Monitoring Protein Aggregation, Nucleation, and Crystallization

NASA Technical Reports Server (NTRS)

Ansari, Rafat R.; Suh, Kwang I.; Arabshahi, Alireza; Wilson, William W.; Bray, Terry L.; DeLucas, Lawrence J.

1996-01-01

Protein crystals are experimentally grown in hanging drops in microgravity experiments on-board the Space Shuttle orbiter. The technique of dynamic light scattering (DLS) can be used to monitor crystal growth process in hanging droplets (approx. 30 (L)) in microgravity experiments, but elaborate instrumentation and optical alignment problems have made in-situ applications difficult. In this paper we demonstrate that such experiments are now feasible. We apply a newly developed fiber optic probe to various earth and space (micro- gravity) bound protein crystallization system configurations to test its capability. These include conventional batch (cuvette or capillary) systems, hanging drop method in a six-pack hanging drop vapor diffusion apparatus (HDVDA), a modified HDVDA for temperature- induced nucleation and aggregation studies, and a newly envisioned dynamically controlled vapor diffusion system (DCVDS) configuration. Our compact system exploits the principles of DLS and offers a fast (within a few seconds) means of quantitatively and non-invasively monitoring the various growth stages of protein crystallization. In addition to DLS capability, the probe can also be used for performing single-angle static light scattering measurements. It utilizes extremely low levels of laser power (approx. few (W)) without a need of having any optical alignment and vibration isolation. The compact probe is also equipped with a miniaturized microscope for visualization of macroscopic protein crystals. This new optical diagnostic system opens up enormous opportunity for exploring new ways to grow good quality crystals suitable for x-ray crystallographic analysis and may help develop a concrete scientific basis for understanding the process of crystallization.

Power of a Labrador Retriever-Greyhound pedigree for linkage analysis of hip dysplasia and osteoarthritis.

PubMed

Todhunter, Rory J; Casella, George; Bliss, Stuart P; Lust, George; Williams, Alma Jo; Hamilton, Samuel; Dykes, Nathan L; Yeager, Amy E; Gilbert, Robert O; Burton-Wurster, Nancy I; Mellersh, Cathryn C; Acland, Gregory M

2003-04-01

To estimate the number of dogs required to find linkage to heritable traits of hip dysplasia in dogs from an experimental pedigree. 147 Labrador Retrievers, Greyhounds, and their crossbreed offspring. Labrador Retrievers with hip dysplasia were crossed with unaffected Greyhounds. Age at detection of femoral capital ossification, distraction index (DI), hip joint dorsolateral subluxation (DLS) score, and hip joint osteoarthritis (OA) were recorded. Power to find linkage of a single marker to a quantitative trait locus (QTL) controlling 100% of the variation in a dysplastic trait in the backcross dogs was determined. For the DI at the observed effect size, recombination fraction of 0.05, and heterozygosity of 0.75, 35 dogs in the backcross of the F1 to the Greyhound generation would yield linkage at a power of 0.8. For the DLS score, 35 dogs in the backcross to the Labrador Retriever generation would be required for linkage at the same power. For OSS, 45 dogs in the backcross to the founding Labrador Retrievers would yield linkage at the same power. Fewer dogs were projected to be necessary to find linkage to hip OA. Testing for linkage to the DLS at 4 loci simultaneously, each controlling 25% of the phenotypic variation, yielded an overall power of 0.7 CONCLUSIONS AND CLINICAL SIGNIFICANCE: Based on this conservative single-marker estimate, this pedigree has the requisite power to find microsatellites linked to susceptibility loci for hip dysplasia and hip OA by breeding a reasonable number of backcross dogs.

Conformations of gelatin in trivalent chromium salt solutions: Viscosity and dynamic light scattering study

NASA Astrophysics Data System (ADS)

Qiao, Congde; Zhang, Jianlong; Kong, Aiqun

2017-02-01

An investigation of the influences of pH, salt type, and salt concentration on the conformations of gelatin molecules in trivalent chromium salt solutions was performed by viscosity and dynamic light scattering (DLS) techniques. It was found that the viscosity behaviors as polyelectrolytes or polyampholytes depended on the charge distribution on the gelatin chains, which can be tuned by the value of pH of the gelatin solution. The intrinsic viscosity of gelatin in basic chromium sulfate aqueous solution at pH = 2.0 first decreased and then increased with increasing Cr(OH)SO4 concentration, while a monotonic decrease of the intrinsic viscosity of gelatin was observed in CrCl3 solution. However, the intrinsic viscosity of gelatin at pH = 5.0 was found to be increased first and then decreased with an increase in salt concentration in Cr(OH)SO4 solution, as well as in CrCl3 solution. We suggested that the observed viscosity behavior of gelatin in trivalent chromium salt solutions was attributed to the comprehensive effects of shielding, overcharging, and crosslinking (complexation) caused by the introduction of the different counterions. In addition, the average hydrodynamic radius ( R h ) of gelatin molecules in various salt solutions was determined by DLS. It was found that the change trend of R h with salt concentration was the same as the change of intrinsic viscosity. Based on the results of the viscosity and DLS, a possible mechanism for the conformational transition of gelatin chains with external conditions including pH, salt concentration, and salt type is proposed.

Description of Particle Size, Distribution, and Behavior of Talc Preparations Commercially Available Within the United States.

PubMed

Gilbert, Christopher R; Furman, Benjamin R; Feller-Kopman, David J; Haouzi, Philippe

2018-01-01

Widespread use of talc pleurodesis remains controversial for many providers concerned by adverse events such as respiratory failure, which are sometimes fatal. Particle talc size has been implicated in these adverse effects, mainly on the basis of animal studies utilizing large amounts of talc or in observational studies performed on different continents with different talc preparations and doses. Our aim was to determine the particle size and distribution of only the commercially available US-talc preparations and whether the fluid content can affect this distribution. Commercially available US talc was evaluated under scanning electron microscopy and dynamic light scattering (DLS). Distribution of talc particle size was obtained in saline and various protein-based solutions. Talc particle size by DLS was performed with commercially available Sterile Talc Powder and Sclerosol Intrapleural Aerosol. Sterile Talc Powder demonstrated a median diameter of 26.57 μm with a range of particle sizes from 0.399 μm to 100.237 μm. Sclerosol demonstrated a median diameter of 24.49 μm with a range of particle sizes from 0.224 μm to 100.237 μm. The exposure of talc to a protein rich environment (bovine serum albumin and human pleural fluid) led to the development of measureable, new, larger aggregated particle (>100 μm). Currently available US talc seems to have size characteristics similar to previous described "graded" talc preparations. The exposure of talc to a protein rich environment seems to modify the overall distribution of talc particle size when examined by DLS.

X-Ray Temperatures, Luminosities, and Masses from XMM-Newton Follow-up of the First Shear-selected Galaxy Cluster Sample

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

Deshpande, Amruta J.; Hughes, John P.; Wittman, David, E-mail: amrejd@physics.rutgers.edu, E-mail: jph@physics.rutgers.edu, E-mail: dwittman@physics.ucdavis.edu

We continue the study of the first sample of shear-selected clusters from the initial 8.6 square degrees of the Deep Lens Survey (DLS); a sample with well-defined selection criteria corresponding to the highest ranked shear peaks in the survey area. We aim to characterize the weak lensing selection by examining the sample’s X-ray properties. There are multiple X-ray clusters associated with nearly all the shear peaks: 14 X-ray clusters corresponding to seven DLS shear peaks. An additional three X-ray clusters cannot be definitively associated with shear peaks, mainly due to large positional offsets between the X-ray centroid and the shearmore » peak. Here we report on the XMM-Newton properties of the 17 X-ray clusters. The X-ray clusters display a wide range of luminosities and temperatures; the L {sub X} − T {sub X} relation we determine for the shear-associated X-ray clusters is consistent with X-ray cluster samples selected without regard to dynamical state, while it is inconsistent with self-similarity. For a subset of the sample, we measure X-ray masses using temperature as a proxy, and compare to weak lensing masses determined by the DLS team. The resulting mass comparison is consistent with equality. The X-ray and weak lensing masses show considerable intrinsic scatter (∼48%), which is consistent with X-ray selected samples when their X-ray and weak lensing masses are independently determined.« less

Effects of long-term wearing of high-heeled shoes on the control of the body's center of mass motion in relation to the center of pressure during walking.

PubMed

Chien, Hui-Lien; Lu, Tung-Wu; Liu, Ming-Wei

2014-04-01

High-heeled shoes are associated with instability and falling, leading to injuries such as fracture and ankle sprain. This study investigated the effects of habitual wearing of high-heeled shoes on the body's center of mass (COM) motion relative to the center of pressure (COP) during gait. Fifteen female experienced wearers and 15 matched controls walked with high-heeled shoes (7.3cm) while kinematic and ground reaction force data were measured and used to calculate temporal-distance parameters, joint moments, COM-COP inclination angles (IA) and the rate of IA changes (RCIA). Compared with inexperienced wearers, experienced subjects showed significantly reduced frontal IA with increased ankle pronator moments during single-limb support (p<0.05). During double-limb support (DLS), they showed significantly increased magnitudes of the frontal RCIA at toe-off and contralateral heel-strike, and reduced DLS time (p<0.05) but unaltered mean RCIA over DLS. In the sagittal plane experienced wearers showed significantly increased mean RCIA (p<0.05) and significant differences in the RCIA at toe-off and contralateral heel-strike (p<0.05). Significantly increased hip flexor moments and knee extensor moments at toe-off (p<0.05) were needed for forward motion of the trailing limb. The current results identified the change in the balance control in females after long-term use of high-heeled shoes, providing a basis for future design of strategies to minimize the risk of falling during high-heeled gait. Copyright © 2014 Elsevier B.V. All rights reserved.

Hippocampus NMDA receptors selectively mediate latent extinction of place learning.

PubMed

Goodman, Jarid; Gabriele, Amanda; Packard, Mark G

2016-09-01

Extinction of maze learning may be achieved with or without the animal performing the previously acquired response. In typical "response extinction," animals are given the opportunity to make the previously acquired approach response toward the goal location of the maze without reinforcement. In "latent extinction," animals are not given the opportunity to make the previously acquired response and instead are confined to the previous goal location without reinforcement. Previous evidence indicates that the effectiveness of these protocols may depend on the type of memory being extinguished. Thus, one aim of the present study was to further examine the effectiveness of response and latent extinction protocols across dorsolateral striatum (DLS)-dependent response learning and hippocampus-dependent place learning tasks. In addition, previous neural inactivation experiments indicate a selective role for the hippocampus in latent extinction, but have not investigated the precise neurotransmitter mechanisms involved. Thus, the present study also examined whether latent extinction of place learning might depend on NMDA receptor activity in the hippocampus. In experiment 1, adult male Long-Evans rats were trained in a response learning task in a water plus-maze, in which animals were reinforced to make a consistent body-turn response to reach an invisible escape platform. Results indicated that response extinction, but not latent extinction, was effective at extinguishing memory in the response learning task. In experiment 2, rats were trained in a place learning task, in which animals were reinforced to approach a consistent spatial location containing the hidden escape platform. In experiment 2, animals also received intra-hippocampal infusions of the NMDA receptor antagonist 2-amino-5-phosphopentanoic acid (AP5; 5.0 or 7.5 ug/0.5 µg) or saline vehicle immediately before response or latent extinction training. Results indicated that both extinction protocols were effective at extinguishing memory in the place learning task. In addition, intra-hippocampal AP5 (7.5 µg) impaired latent extinction, but not response extinction, suggesting that hippocampal NMDA receptors are selectively involved in latent extinction. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Uses of the Sonicguide as a Concept Development Device.

ERIC Educational Resources Information Center

Vopata, Alvin E.

1978-01-01

The article discusses the Sonicguide, and electronic mobility device for the blind, and makes some suggestions for its introduction to young children and for its use as an aid in the development of spatial concepts. (Author/DLS)

The Effects of Treatment upon the Relationship between Vocational Interest and Vocational Ability of the Educable Mentally Retarded Adolescent.

ERIC Educational Resources Information Center

Stodden, Robert A.; Lazar, Alfred L.

1979-01-01

Findings suggested that the prevocational exploratory experience was statistically effective in contributing to a positive change in the relationship between Ss' vocational interests and ability. (Author/DLS)

Davidoff-Dyke-Masson Syndrome Presenting as Childhood Schizophrenia.

ERIC Educational Resources Information Center

White, James H.; Rust, John B.

1979-01-01

The article presents a case history of a child displaying symptoms of schizophrenia, seizures, and retardation without neurological abnormalities, which were eventually diagnosed as being due to Davidoff-Dyke-Masson syndrome, a condition involving gross anatomical brain pathology. (DLS)

Plasma Levels of Folates, Riboflavin, Vitamin B6, and Ascorbate in Severely Disturbed Children.

ERIC Educational Resources Information Center

Sankar, D. V. Siva

1979-01-01

The plasma levels of folic acid, ascorbic acid, pyridoxine, and riboflavin were studied in 125 severely emotionally disturbed children (ages 5-16 years) to determine whether they had overt vitamin deficiencies. (Author/DLS)

Asian and Pacific American Exceptional Children. A Conversation.

ERIC Educational Resources Information Center

Decano, Pio

1979-01-01

Presented in the format of an imaginary dialogue between seven educators of Asian and Pacific American (APA) backgrounds, the article addresses some issues and concerns in the training of special education personnel to work with APA handicapped children. (DLS)

The Families of Handicapped Children: Context for Disability.

ERIC Educational Resources Information Center

Murphy, Albert T.

1979-01-01

The article discusses the family of the hearing impaired child as the context for his or her disability, exploring such aspects as the father's role, the role of siblings, and the relationship between mental health and hearing impairment. (DLS)

Reducing Adolescent Obesity through a School Health Program.

ERIC Educational Resources Information Center

Botvin, G. J.; And Others

1979-01-01

A 10-session weight reduction program that included behavior modification, nutrition education, and exercise management was found to be effective in reducing weight. (Author/DLS) Journal Availability: C. V. Mosby Company, 11830 Westline Industrial Dr., St. Louis, MO 63141

Imaginary Figures of Early Childhood: Santa Claus, Easter Bunny, and the Tooth Fairy.

ERIC Educational Resources Information Center

Prentice, Norman M.; And Others

1978-01-01

The developmental progression of belief in three major imaginary figures of early childhood was examined in 20 White, Christian children (ages four to eight years) by means of interviews and parental questionnaires. (Author/DLS)

Double layers in expanding plasmas and their relevance to the auroral plasma processes

NASA Astrophysics Data System (ADS)

Singh, Nagendra; Khazanov, George

2003-04-01

When a dense plasma consisting of a cold and a sufficiently warm electron population expands, a rarefaction shock forms [, 1978]. In the expansion of the polar wind in the magnetosphere, it has been previously shown that when a sufficiently warm electron population also exists, in addition to the usual cold ionospheric one, a discontinuity forms in the electrostatic potential distribution along the magnetic field lines [, 1984]. Despite the lack of spatial resolution and the assumption of quasi-neutrality in the polar wind models, such discontinuities have been called double layers (DLs). Recently similar discontinuities have been invoked to partly explain the auroral acceleration of electrons and ions in the upward current region [, 2000]. By means of one-dimensional Vlasov simulations of expanding plasmas, for the first time we make here the connection between (1) the rarefaction shocks, (2) the discontinuities in the potential distributions, and (3) DLs. We show that when plasmas expand from opposite directions into a deep density cavity with a potential drop across it and when the plasma on the high-potential side contains hot and cold electron populations, the temporal evolution of the potential and the plasma distribution generates evolving multiple double layers with an extended density cavity between them. One of the DLs is the rarefaction-shock (RFS) and it forms by the reflections of the cold electrons coming from the high-potential side; it supports a part of the potential drop approximately determined by the hot electron temperature. The other DLs evolve from charge separations arising either from reflection of ions coming from the low-potential side or stemming from plasma instabilities; they support the rest of the potential drop. The instabilities forming these additional double layers involve electron-ion (e-i) Buneman or ion-ion (i-i) two-stream interactions. The electron-electron two-stream interactions on the high-potential side of the RFS generate electron-acoustic waves, which evolve into electron phase-space holes. The ion population originating from the low-potential side and trapped by the RFS is energized by the e-i and i-i instabilities and it eventually precipitates into the high-potential plasma along with an electron beam. Applications of these findings to the auroral plasma physics are discussed.

Double Layers in Expanding Plasmas and Their Relevance to the Auroral Plasma Processes

NASA Technical Reports Server (NTRS)

Singh, Nagendra; Khazanov, George

2003-01-01

When a dense plasma consisting of a cold and a sufficiently warm electron population expands, a rarefaction shock forms [Bezzerides et al., 1978]. In the expansion of the polar wind in the magnetosphere, it has been previously shown that when a sufficiently warm electron population also exists, in addition to the usual cold ionospheric one, a discontinuity forms in the electrostatic potential distribution along the magnetic field lines [Barakat and Schunk, 1984]. Despite the lack of spatial resolution and the assumption of quasi-neutrality in the polar wind models, such discontinuities have been called double layers (DLs). Recently similar discontinuities have been invoked to partly explain the auroral acceleration of electrons and ions in the upward current region [Ergun et al., 2000]. By means of one-dimensional Vlasov simulations of expanding plasmas, for the first time we make here the connection between (1) the rarefaction shocks, (2) the discontinuities in the potential distributions, and (3) DLs. We show that when plasmas expand from opposite directions into a deep density cavity with a potential drop across it and when the plasma on the high-potential side contains hot and cold electron populations, the temporal evolution of the potential and the plasma distribution generates evolving multiple double layers with an ,extended density cavity between them. One of the DLs is the rarefaction-shock (RFS) and it forms by the reflections of the cold electrons coming from the high-potential side; it supports a part of the potential drop approximately determined by the hot electron temperature. The other DLs evolve from charge separations arising either from reflection of ions coming from the low-potential side or stemming from plasma instabilities; they support the rest of the potential drop. The instabilities forming these additional double layers involve electron-ion (e-i) Buneman or ion-ion (i-i) two-stream interactions. The electron-electron two-stream interactions on the high-potential side of the RFS generate electron-acoustic waves, which evolve into electron phase-space holes. The ion population originating from the low-potential side and trapped by the RFS is energized by the e-i and i-i instabilities and it eventually precipitates into the high-potential plasma along with an electron beam. Applications of these findings to the auroral plasma physics are discussed.

Outer Membrane Vesicles from Neisseria Meningitidis (Proteossome) Used for Nanostructured Zika Virus Vaccine Production.

PubMed

Martins, Paula; Machado, Daisy; Theizen, Thais Holtz; Guarnieri, João Paulo Oliveira; Bernardes, Bruno Gaia; Gomide, Gabriel Piccirillo; Corat, Marcus Alexandre Finzi; Abbehausen, Camilla; Módena, José Luiz Proença; Melo, Carlos Fernando Odir Rodrigues; Morishita, Karen Noda; Catharino, Rodrigo Ramos; Arns, Clarice Weis; Lancellotti, Marcelo

2018-05-29

The increase of Zika virus (ZIKV) infections in Brazil in the last two years leaves a prophylactic measures on alert for this new and emerging pathogen. Concerning of our positive experience, we developed a new prototype using Neisseria meningitidis outer membrane vesicles (OMV) on ZIKV cell growth in a fusion of OMV in the envelope of virus particles. The fusion of nanoparticles resulting from outer membrane vesicles of N. meningitidis with infected C6/36 cells line were analyzed by Nano tracking analysis (NTA), zeta potential, differential light scattering (DLS), scan and scanning transmission eletronic microscopy (SEM and STEM) and high resolution mass spectometry (HRMS) for nanostructure characterization. Also, the vaccination effects were viewed by immune response in mice protocols immunization (ELISA and inflammatory chemokines) confirmed by Zika virus soroneutralization test. The results of immunizations in mice showed that antibody production had a titer greater than 1:160 as compared to unvaccinated mice. The immune response of the adjuvant and non-adjuvant formulation activated the cellular immune response TH1 and TH2. In addition, the serum neutralization was able to prevent infection of virus particles in the glial tumor cell model (M059J). This research shows efficient strategies without recombinant technology or DNA vaccines.

Incestuous Rape: A Cause for Hysterical Seizures in Four Adolescent Girls.

ERIC Educational Resources Information Center

Gross, Meir

1979-01-01

The etiology of such hysteroepilepsy is explored. It is suggested that, for all girls presented to the clinician with symptoms of hysterical seizures, a detailed history should be taken to explore for the possibility of incest. (Author/DLS)

Labeling, Attention and Perception, A Developmental Study.

ERIC Educational Resources Information Center

Sagi, Abraham

1979-01-01

Findings of this Israeli study suggest that perception is affected by lables, learning, and selective attention; that these effects are determined developmentally; and that as age increases, the effects of verbal cues diminish, while the effects of perceptual cues increase. (Author/DLS)

The Lighthouse Project.

ERIC Educational Resources Information Center

LeRose, Barbara; And Others

1979-01-01

The project is based on a general systems approach. Developmental stage theory is employed as a starting point, and the developmental "minitasks" which act as stair risers from one developmental level to another are carried through with the use of Bloom's cognitive taxonomy. (Author/DLS)

Growth, Hypothalamic Function, and Brain Ventricle Size in Mentally Retarded Subjects

ERIC Educational Resources Information Center

Leisti, S.; Iianainen, M.

1978-01-01

To determine whether moderate enlargement of the third brain ventricle or the temporal horns of the lateral ventricles was associated with hypothalamic dysfunction, 15 mentally retarded Ss (ages 12-25 years) with such characteristics were studies. (DLS)

Diet Control in the Management of Behavior Disorders.

ERIC Educational Resources Information Center

Knapczyk, Dennis R.

1979-01-01

The article describes three major types of diet-related conditions which lead to behavior disorders in school-age children--hypoglycemia, vitamin/mineral deficiencies, and allergies to food and food additives--and discusses diet control in the management of such conditions. (DLS)

Voice Therapy: A Need for Research.

ERIC Educational Resources Information Center

Reed, Charles G.

1980-01-01

Conceptual and methodological guidelines for voice therapy research are presented, and suggestions are offered for selecting experimental designs. Divergent terminology, philosophy, and issues of voice therapy are examined to serve as an overview and as a basis for research direction. (Author/DLS)

Knowledge and Epidemiology of Child Abuse: A Critical Review of Concepts.

ERIC Educational Resources Information Center

Newberger, Eli H.; Daniel, Jessica H.

1976-01-01

Insight Publishing Company, Inc., 150 E. 58th Street, New York, New York 10022. The article discusses concepts underlying present knowledge of child abuse, focusing on the magnitude of the problem and the meaning of present data and practice. (DLS)

Story Retelling Used with Average and Learning Disabled Readers as a Measure of Reading Comprehension.

ERIC Educational Resources Information Center

Hansen, Cheryl L.

1978-01-01

A method for quantifying story retells, called proposition analysis, was used to study the reading comprehension performances of 34 learning disabled and normal fifth and sixth graders. Journal availability: see EC 112 927. (DLS) 927

Is There a Child with Epilepsy in the Classroom?

ERIC Educational Resources Information Center

Zakariasen, Hazel

1979-01-01

The condition is defined, and some of its manifestations are outlined, including petit mal epilepsy, psychomotor epilepsy, and grand mal epilepsy. Constructive ways to deal with epileptic students are suggested, including specific ways to handle a seizure, should one occur. (DLS)

Complementary Travel Aids for Blind Persons: The Sonicguide Used with a Dog Guide.

ERIC Educational Resources Information Center

Jocobson, William

1979-01-01

The article discusses the use of the Sonicguide (a binaural sensory mobility aid) in conjunction with a guide dog, and reports on a study of one blind student who was trained to use both techniques together. (Author/DLS)

Learning Disabilities Research: Defining Populations.

ERIC Educational Resources Information Center

Lovitt, Thomas C.; Jenkins, Joseph R.

1979-01-01

The article emphasizes the need for a uniform format for defining the populations selected for research, particularly with learning disabled individuals. The population descriptions from three studies dealing with some aspect of reading are presented and scrutinized in terms of the four categories. (Author/DLS)

Research and Educational Implications of Some Recent Conceptualizations in Learning Disabilities.

ERIC Educational Resources Information Center

Wong, Bernice

1979-01-01

The three theories considered are H. S. Adelman's interactional model of learning disabilities, A. O. Ross' theory of developmental lag in selective attention, and J. K. Torgesen's conceptualization of the learning disabled child as an inactive learner. (Author/DLS)

X-Ray Temperatures, Luminosities, and Masses from XMM-Newton Follow-upof the First Shear-selected Galaxy Cluster Sample

NASA Astrophysics Data System (ADS)

Deshpande, Amruta J.; Hughes, John P.; Wittman, David

2017-04-01

We continue the study of the first sample of shear-selected clusters from the initial 8.6 square degrees of the Deep Lens Survey (DLS); a sample with well-defined selection criteria corresponding to the highest ranked shear peaks in the survey area. We aim to characterize the weak lensing selection by examining the sample’s X-ray properties. There are multiple X-ray clusters associated with nearly all the shear peaks: 14 X-ray clusters corresponding to seven DLS shear peaks. An additional three X-ray clusters cannot be definitively associated with shear peaks, mainly due to large positional offsets between the X-ray centroid and the shear peak. Here we report on the XMM-Newton properties of the 17 X-ray clusters. The X-ray clusters display a wide range of luminosities and temperatures; the L X -T X relation we determine for the shear-associated X-ray clusters is consistent with X-ray cluster samples selected without regard to dynamical state, while it is inconsistent with self-similarity. For a subset of the sample, we measure X-ray masses using temperature as a proxy, and compare to weak lensing masses determined by the DLS team. The resulting mass comparison is consistent with equality. The X-ray and weak lensing masses show considerable intrinsic scatter (˜48%), which is consistent with X-ray selected samples when their X-ray and weak lensing masses are independently determined. Some of the data presented herein were obtained at the W.M. Keck Observatory, which is operated as a scientific partnership among the California Institute of Technology, the University of California, and the National Aeronautics and Space Administration. The Observatory was made possible by the generous financial support of the W. M. Keck Foundation.

Determination of size and mass-and number-based concentration of biogenic SeNPs synthesized by lactic acid bacteria by using a multimethod approach.

PubMed

Moreno-Martin, Gustavo; Pescuma, Micaela; Pérez-Corona, Teresa; Mozzi, Fernanda; Madrid, Yolanda

2017-11-01

Selenium nanoparticles (SeNPs) were synthesized by a green technology using lactic acid bacteria (LAB, Lactobacillus acidophilus, L. delbrueckii subsp. bulgaricus and L. reuteri). The exposure of aqueous sodium selenite to LAB led to the synthesis of SeNPs. Characterization of SeNPs by transmission electron microscopy with energy dispersive X-ray spectrum (EDXS) analysis revealed the presence of stable, predominantly monodispersed and spherical SeNPs of an average size of 146 ± 71 nm. Additionally, SeNPs hydrodynamic size was determined by dispersive light scattering (DLS) and nanoparticle tracking analysis (NTA). For this purpose, a methodology based on the use of surfactants in basic medium was developed for isolating SeNPs from the bacterial pellet. The hydrodynamic size values provided by DLS and NTA were 258 ± 4 and 187 ± 56 nm, respectively. NTA measurements of number-based concentration reported values of (4.67±0.30)x10 9 SeNPs mL -1 with a relative standard deviation lower than 5% (n = 3). The quantitative results obtained by NTA were supported by theoretical calculations. Asymmetrical flow field flow fractionation (AF 4 ) on line coupled to the inductively couple plasma mass spectrometry (ICP-MS) and off-line coupled to DLS was further employed to characterize biogenic SeNPs. The distribution of the particle size for the Se-containing peak provide an average size of (247 ± 14) nm. The data obtained by independent techniques were in good agreement and the developed methodology could be implemented for characterizing NPs in complex matrices such as biogenic nanoparticles embedded inside microbial material. Copyright © 2017. Published by Elsevier B.V.

Monitoring the Stability of Perfluorocarbon Nanoemulsions by Cryo-TEM Image Analysis and Dynamic Light Scattering

PubMed Central

Grapentin, Christoph; Barnert, Sabine; Schubert, Rolf

2015-01-01

Perfluorocarbon nanoemulsions (PFC-NE) are disperse systems consisting of nanoscale liquid perfluorocarbon droplets stabilized by an emulsifier, usually phospholipids. Perfluorocarbons are chemically inert and non-toxic substances that are exhaled after in vivo administration. The manufacture of PFC-NE can be done in large scales by means of high pressure homogenization or microfluidization. Originally investigated as oxygen carriers for cases of severe blood loss, their application nowadays is more focused on using them as marker agents in 19F Magnetic Resonance Imaging (19F MRI). 19F is scarce in organisms and thus PFC-NE are a promising tool for highly specific and non-invasive imaging of inflammation via 19F MRI. Neutrophils, monocytes and macrophages phagocytize PFC-NE and subsequently migrate to inflamed tissues. This technique has proven feasibility in numerous disease models in mice, rabbits and mini pigs. The translation to clinical trials in human needs the development of a stable nanoemulsion whose droplet size is well characterized over a long storage time. Usually dynamic light scattering (DLS) is applied as the standard method for determining particle sizes in the nanometer range. Our study uses a second method, analysis of transmission electron microscopy images of cryo-fixed samples (Cryo-TEM), to evaluate stability of PFC-NE in comparison to DLS. Four nanoemulsions of different composition are observed for one year. The results indicate that DLS alone cannot reveal the changes in particle size, but can even mislead to a positive estimation of stability. The combination with Cryo-TEM images gives more insight in the particulate evolution, both techniques supporting one another. The study is one further step in the development of analytical tools for the evaluation of a clinically applicable perfluorooctylbromide nanoemulsion. PMID:26098661

A Comparative Study of the Influence of Sugars Sucrose, Trehalose, and Maltose on the Hydration and Diffusion of DMPC Lipid Bilayer at Complete Hydration: Investigation of Structural and Spectroscopic Aspect of Lipid-Sugar Interaction.

PubMed

Roy, Arpita; Dutta, Rupam; Kundu, Niloy; Banik, Debasis; Sarkar, Nilmoni

2016-05-24

It is well-known that sugars protect membrane structures against fusion and leakage. Here, we have investigated the interaction between different sugars (sucrose, trehalose, and maltose) and phospholipid membrane of 1,2-dimyristoyl-sn-glycero-3-phoshpocholine (DMPC) using dynamic light scattering (DLS), transmission electron microscopy (TEM), and other various spectroscopic techniques. DLS measurement reveals that the addition of sugar molecule results a significant increase of the average diameter of DMPC membrane. We have also noticed that in the presence of different sugars the rotational relaxation and solvation time of coumarin 480 (C480) and coumarin 153 (C153) surrounding DMPC membrane increases, suggesting a marked reduction of the hydration behavior at the surface of phospholipid membrane. In addition, we have also investigated the effect of sugar molecules on the lateral mobility of phospholipids. Interestingly, the relative increase in rotational, solvation and lateral diffusion is more prominent for C480 than that of C153 because of their different location in lipid bilayer. It is because of preferential location of comparatively hydrophilic probe C480 in the interfacial region of the lipid bilayer. Sugars intercalate with the phospholipid headgroup through hydrogen bonding and replace smaller sized water molecules from the membrane surface. Therefore, overall, we have monitored a comparative analysis regarding the interaction of different sugar molecules (sucrose, trehalose, and maltose) with the DMPC membrane through DLS, TEM, solvation dynamics, time-resolved anisotropy, and fluorescence correlation spectroscopy (FCS) measurements to explore the structural and spectroscopic aspect of lipid-sugar interaction.

Targeting dopa-sensitive and dopa-resistant gait dysfunction in Parkinson's disease: selective responses to internal and external cues.

PubMed

Rochester, Lynn; Baker, Katherine; Nieuwboer, Alice; Burn, David

2011-02-15

Independence of certain gait characteristics from dopamine replacement therapies highlights its complex pathophysiology in Parkinson's disease (PD). We explored the effect of two different cue strategies on gait characteristics in relation to their response to dopaminergic medications. Fifty people with PD (age 69.22 ± 6.6 years) were studied. Participants walked with and without cues presented in a randomized order. Cue strategies were: (1) internal cue (attention to increase step length) and (2) external cue (auditory cue with instruction to take large step to the beat). Testing was carried out two times at home (on and off medication). Gait was measured using a Stride Analyzer (B&L Engineering). Gait outcomes were walking speed, stride length, step frequency, and coefficient of variation (CV) of stride time and double limb support duration (DLS). Walking speed, stride length, and stride time CV improved on dopaminergic medications, whereas step frequency and DLS CV did not. Internal and external cues increased stride time and walking speed (on and off dopaminergic medications). Only the external cue significantly improved stride time CV and DLS CV, whereas the internal cue had no effect (on and off dopaminergic medications). Internal and external cues selectively modify gait characteristics in relation to the type of gait disturbance and its dopa-responsiveness. Although internal (attention) and external cues target dopaminergic gait dysfunction (stride length), only external cues target stride to stride fluctuations in gait. Despite an overlap with dopaminergic pathways, external cues may effectively address nondopaminergic gait dysfunction and potentially increase mobility and reduce gait instability and falls. Copyright © 2010 Movement Disorder Society.

A novel vesicular carrier, transethosome, for enhanced skin delivery of voriconazole: characterization and in vitro/in vivo evaluation.

PubMed

Song, Chung Kil; Balakrishnan, Prabagar; Shim, Chang-Koo; Chung, Suk-Jae; Chong, Saeho; Kim, Dae-Duk

2012-04-01

This study describes a novel carrier, transethosome, for enhanced skin delivery of voriconazole. Transethosomes (TELs) are composed of phospholipid, ethanol, water and edge activator (surfactants) or permeation enhancer (oleic acid). Characterization of the TELs was based on results from recovery, particle size, transmission electron microscopy (TEM), zeta potential and elasticity studies. In addition, skin permeation profile was obtained using static vertical diffusion Franz cells and hairless mouse skin treated with TELs containing 0.3% (w/w) voriconazole, and compared with those of ethosomes (ELs), deformable liposomes (DLs), conventional liposomes (CLs) and control (polyethylene glycol, PG) solutions. The recovery of the studied vesicles was above 90% in all vesicles, as all of them contained ethanol (7-30%). There was no significant difference in the particles size of all vesicles. The TEM study revealed that the TELs were in irregular spherical shape, implying higher fluidity due to perturbed lipid bilayer compared to that of other vesicles which were of spherical shape. The zeta potential of vesicles containing sodium taurocholate or oleic acid showed higher negative value compared to other vesicles. The elasticities of ELs and TELs were much higher than that of CLs and DLs. Moreover, TELs dramatically enhanced the skin permeation of voriconazole compared to the control and other vesicles (p<0.05). Moreover, the TELs enhanced both in vitro and in vivo skin deposition of voriconazole in the dermis/epidermis region compared to DLs, CLs and control. Therefore, based on the current study, the novel carrier TELs could serve as an effective dermal delivery for voriconazole. Copyright © 2011 Elsevier B.V. All rights reserved.

Imaging electrical conductivity, permeability, and/or permittivity contrasts using the Born Scattering Inversion (BSI)

NASA Astrophysics Data System (ADS)

Darrh, A.; Downs, C. M.; Poppeliers, C.

2017-12-01

Born Scattering Inversion (BSI) of electromagnetic (EM) data is a geophysical imaging methodology for mapping weak conductivity, permeability, and/or permittivity contrasts in the subsurface. The high computational cost of full waveform inversion is reduced by adopting the First Born Approximation for scattered EM fields. This linearizes the inverse problem in terms of Born scattering amplitudes for a set of effective EM body sources within a 3D imaging volume. Estimation of scatterer amplitudes is subsequently achieved by solving the normal equations. Our present BSI numerical experiments entail Fourier transforming real-valued synthetic EM data to the frequency-domain, and minimizing the L2 residual between complex-valued observed and predicted data. We are testing the ability of BSI to resolve simple scattering models. For our initial experiments, synthetic data are acquired by three-component (3C) electric field receivers distributed on a plane above a single point electric dipole within a homogeneous and isotropic wholespace. To suppress artifacts, candidate Born scatterer locations are confined to a volume beneath the receiver array. Also, we explore two different numerical linear algebra algorithms for solving the normal equations: Damped Least Squares (DLS), and Non-Negative Least Squares (NNLS). Results from NNLS accurately recover the source location only for a large dense 3C receiver array, but fail when the array is decimated, or is restricted to horizontal component data. Using all receiver stations and all components per station, NNLS results are relatively insensitive to a sub-sampled frequency spectrum, suggesting that coarse frequency-domain sampling may be adequate for good target resolution. Results from DLS are insensitive to diminishing array density, but contain spatially oscillatory structure. DLS-generated images are consistently centered at the known point source location, despite an abundance of surrounding structure.

Wurtsmith AFB, Michigan. Revised Uniform Summary of Surface Weather Observations. Parts A-F.

DTIC Science & Technology

1987-06-12

UNIFORM SUMMARY OF ASURFACE WEATHER OBSERVATIONS WURTSMITH AFB MI MSC 726395 N 44 27 W 0 8 3 24 ELEV 634 FT KOSC PARTS A - F HOURS SUMMARIZED 0000...SNOaFA[ USAFETAC FWCM SJPMAPY Of DAY [ATA AIR AFATHtr 5!RVICE/MAC STATION NUMSLR: 726395 STAT1O N NAmE : wURTSMITH Arb MI PI 0 IOU Or Pt COPD : ,j-7...1 1 1 F U),,%! WVAI limb, : r UC ’,1iL (L7’AI7,LOGY PRANC*tH Pt.FP NIA’ - FPR(’U,7NCY OF OCCURr-NCL OF SUPFACE WINO UIRECrIPN V(R.SUS gIE . 7 Ajj L1

Mechanically interlocked gold and silver nanoparticles using metallosupramolecular catenane chemistry.

PubMed

Otter, Carl A; Patty, Philipus J; Williams, Martin A K; Waterland, Mark R; Telfer, Shane G

2011-03-01

We have employed the toolbox of metallosupramolecular chemistry to mechanically interlock gold and silver nanoparticles. A specifically designed PEGthiol-functionalized bis(phenanthroline)copper(I) complex acts to 'catenate' the nanoparticles. The interlocked assemblies were characterised by three complementary techniques: DLS, SERS and TEM.

The Burn-Out Syndrome.

ERIC Educational Resources Information Center

Sullivan, Ruth Christ

1979-01-01

An article is presented on the "burn-out" of parents, particularly those of autistic children (i.e., the exhaustion of their psychological and/or physical resources as a result of long and intense caring for their children), along with the comments and responses of five parents and professionals. (DLS)

Metallated DNA Aptamers for Prostate Cancer Treatment. Revision

DTIC Science & Technology

2013-10-01

determined using Matlab software. Dynamic light scattering (DLS) was performed under ambient conditions using a Malvern Zetasizer nano series ZEN-1600... entangling porphyrins as suitable vessels for light-induced energy and electron transfer. J Mater Chem 2008;18:802-5. 57. Meenakshisundaram G, Eteshola

Development from Grades V through XI of Children's Ability to Make Correct Causal Inferences.

ERIC Educational Resources Information Center

Chen, Benjamin; Tuddenham, Read D.

1979-01-01

Unless sensitized to avoid them, Ss (regardless of grade) tended to draw overly sweeping inferences, perhaps because of a need for closure. Older Ss, however, were more successful at suspending judgment when no definite conclusion was justified. (Author/DLS)

Response-Contingent Taste-Aversion in Treating Chronic Ruminative Vomiting of Institutionalised Profoundly Retarded Children.

ERIC Educational Resources Information Center

Marholin, D., II; And Others

1980-01-01

Two case studies are presented illustrating how the treatment program eliminated rumination with effects maintained 1 to 9 months following treatment, and how substantial weight gain was also demonstrated with one S who had previously lost weight. (Author/DLS)

Self-Modification Technique for the Control of Eating Behavior for the Visually Handicapped.

ERIC Educational Resources Information Center

Snoy, Mary T.; van Benten, Letitia

1978-01-01

A ten-week study was done of four visually handicapped overweight adolescents (ages 15-19 years) in a residential school to evaluate the efficacy of an operant conditioning technique designed to promote weight loss by altering eating habits. (Author/DLS)

Sheep or Goats? Learning Disabilities and Educational Services for Children with Special Needs: A Canadian Perspective

ERIC Educational Resources Information Center

Kendall, David

1977-01-01

Presented at the First National Conference on Learning Disabilities in Ottawa, Canada in October, 1977, the article discusses learning disabilities and their appropriate special educational services in Canada, focusing on the processes of categorization and labeling. (DLS)

A Very Special Teacher.

ERIC Educational Resources Information Center

Matchan, Don

1979-01-01

The article presents a profile of a teacher of educationally handicapped children at Taft Elementary School in Redwood City, California. Focus is on her concern for proper nutrition (including additive free food) and good eating habits, and how she teaches this to the students and their parents. (DLS)

3-Dimensional Colloidal Crystals From Hollow Spheres

NASA Astrophysics Data System (ADS)

Zhang, Jian; Work, William J.; Sanyal, Subrata; Lin, Keng-Hui; Yodh, A. G.

2000-03-01

We have succeeded in synthesizing submicron-sized, hollow PMMA spheres and self-assembling them into colloidal crystalline structures using the depletion force. The resulting structures can be used as templates to make high refractive-index contrast, porous, inorganic structures without the need to use calcination or chemical-etching. With the method of emulsion polymerization, we managed to coat a thin PMMA shell around a swellable P(MMA/MAA/EGDMA) core. After neutralization and heating above the glass transition temperature of PMMA, we obtained water-swollen hydrogel particles encapsulated in PMMA shells. These composite particles become hollow spheres after drying. We characterized the particles with both transmission electron microscopy (TEM) and dynamic light scattering (DLS). The TEM results confirmed that each sphere has a hollow core. The DLS results showed that our hollow spheres are submicron-sized, with a swelling ratio of at least 25%, and with a polydispersity less than 5%. We anticipate using this method in the near-future to encapsulate ferrofluid emulsion droplets and liquid crystal droplets.

Using magnetic nanoparticles to probe protein damage in ferritin caused by freeze concentration

NASA Astrophysics Data System (ADS)

Chagas, E. F.; Correia Carreira, S.; Schwarzacher, W.

2015-11-01

We demonstrate a method for monitoring the damage caused to a protein during freeze-thawing in the presence of glycerol, a cryo-protectant. For this work we synthesized magnetite nanoparticles doped with 2.5% cobalt inside the protein ferritin (CMF), dissolved them in different concentration glycerol solutions and measured their magnetization after freezing in a high applied field (5 T). As the temperature was raised, a step-like decrease in the sample magnetization was observed, corresponding to the onset of Brownian relaxation as the viscosity of the freeze-concentrated glycerol solution decreased. The position of the step reveals changes to the protein hydrodynamic radius that we attribute to protein unfolding, while its height depends on how much protein is trapped by ice during freeze concentration. Changes to the protein hydrodynamic radius are confirmed by dynamic light scattering (DLS) measurements, but unlike DLS, the magnetic measurements can provide hydrodynamic data while the solution remains mainly frozen.

Photo-triggered release in polyamide nanosized capsules

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

Marturano, V.; Ambrogi, V.; Cerruti, P.

2014-05-15

In this work, nanosized capsules based on a lightly cross-linked polyamide containing azobenzene moieties in the main chain were synthesized by miniemulsion interfacial polymerization. The obtained nanocapsules were loaded either with toluene or with the fluorescent probe coumarin-6 as a core. Diameters of the nanocapsules were in the 100-900 nm range, depending on the selected emulsion conditions. The morphology and shape of the samples were observed by TEM and SEM while the emulsion droplets and nanocapsules size was measured by DLS. Under continuous UV irradiation the polymer underwent E-Z photoisomerization allowing the release of the encapsulated material. Variation in diametermore » of the nanocapsules with the time of UV irradiation was detected through DLS analysis. 10-30% growth was observed, depending on the sample. The kinetics of release of coumarin-6 was followed by spectrofluorimetry in ethanol. In absence of irradiation, the fluorescence intensity appeared to be constant over time, while it increased when the sample was irradiated with 360 nm UV light.« less

Quantification of nanoparticle concentration in colloidal suspensions by a non-destructive optical method

NASA Astrophysics Data System (ADS)

Clement, Sandhya; Gardner, Brint; Razali, Wan Aizuddin W.; Coleman, Victoria A.; Jämting, Åsa K.; Catchpoole, Heather J.; Goldys, Ewa M.; Herrmann, Jan; Zvyagin, Andrei

2017-11-01

The estimation of nanoparticle number concentration in colloidal suspensions is a prerequisite in many procedures, and in particular in multi-stage, low-yield reactions. Here, we describe a rapid, non-destructive method based on optical extinction and dynamic light scattering (DLS), which combines measurements using common bench-top instrumentation with a numerical algorithm to calculate the particle size distribution (PSD) and concentration. These quantities were derived from Mie theory applied to measurements of the optical extinction spectrum of homogeneous, non-absorbing nanoparticles, and the relative PSD of a colloidal suspension. The work presents an approach to account for PSDs achieved by DLS which, due to the underlying model, may not be representative of the true sample PSD. The presented approach estimates the absolute particle number concentration of samples with mono-, bi-modal and broad size distributions with <50% precision. This provides a convenient and practical solution for number concentration estimation required during many applications of colloidal nanomaterials.

Golgi study of medium spiny neurons from dorsolateral striatum of the turtle Trachemys scripta elegans.

PubMed

González, Carolina; Mendoza, Janeth; Avila-Costa, María Rosa; Arias, Juan M; Barral, Jaime

2013-11-27

Comparative anatomy has shown similarities between reptilian and mammalian basal ganglia. Here the morphological characteristics of the medium spiny neurons (MSN) in the dorsolateral striatum (DLS) of the turtle are described after staining them with the Golgi technique. The soma of MSN in DLS showed three main forms: spherical, ovoid, and fusiform. The number of primary dendritic branches (3-4 den-drites/cell) was less than observed in mammals. The MSN axon originates mainly from the soma, and randomly it emerges at the beginning of the primary dendrite. The main differences between turtle and mammalian MSN were detected on dendritic spines. Short, thin, bifurcated and fungiform types of den-dritic spines were observed in the turtle's MSN, according to their shape. In most of the analyzed spines,it was found that its length considerably exceeded that reported in mammals, with dendritic spines upto 8 μm in length. These differences could play an important role in the modulation of motor networks preserved along the vertebrate evolution.

A Fiber Optic Probe for the Detection of Cataracts

NASA Technical Reports Server (NTRS)

Ansari, Rafat R.; Dhadwal, Harbans S.

1993-01-01

A compact fiber optic probe developed for on-orbit science experiments was used to detect the onset of cataracts, a capability that could eliminate physicians' guesswork and result in new drugs to 'dissolve' or slow down the cataract formation before surgery is necessary. The probe is based upon dynamic light scattering (DLS) principles. It has no moving parts, no apertures, and requires no optical alignment. It is flexible and easy to use. Results are presented for excised but intact human eye lenses. In a clinical setting, the device can be easily incorporated into a slit-lamp apparatus (ophthalmoscope) for complete eye diagnostics. In this set-up, the integrated fiber optic probe, the size of a pencil, delivers a low power cone of laser light into the eye of a patient and guides the light which is backscattered by the protein molecules of the lens through a receiving optical fiber to a photo detector. The non-invasive DLS measurements provide rapid determination of protein crystalline size and its size distribution in the eye lens.

Microgravity Diode Laser Spectroscopy Measurements in a Reacting Vortex Ring

NASA Technical Reports Server (NTRS)

Chen, Shin-Juh; Dahm, Werner J. A.; Silver, Joel A.; Piltch, Nancy D.; VanderWal, R. (Technical Monitor)

2001-01-01

The technique of Diode Laser Spectroscopy (DLS) with wavelength modulation is utilized to measure the concentration of methane in reacting vortex rings under microgravity conditions. From the measured concentration of methane, other major species such as water, carbon dioxide, nitrogen, and oxygen can be easily computed under the assumption of equilibrium chemistry with an iterative method called ITAC (Iterative Temperature with Assumed Chemistry). The conserved scalar approach in modelling the coupling between fluid dynamics and combustion is utilized to represent the unknown variables in terms of the mixture fraction and scalar dissipation rate in conjunction with ITAC. Post-processing of the DLS and the method used to compute the species concentration are discussed. From the flame luminosity results, ring circulation appears to increase the fuel consumption rate inside the reacting vortex ring and the flame height for cases with similar fuel volumes but different ring circulations. The concentrations of methane, water, and carbon dioxide agree well with available results from numerical simulations.

Striatal fast-spiking interneurons selectively modulate circuit output and are required for habitual behavior

PubMed Central

O'Hare, Justin K; Li, Haofang; Kim, Namsoo; Gaidis, Erin; Ade, Kristen; Beck, Jeff; Yin, Henry

2017-01-01

Habit formation is a behavioral adaptation that automates routine actions. Habitual behavior correlates with broad reconfigurations of dorsolateral striatal (DLS) circuit properties that increase gain and shift pathway timing. The mechanism(s) for these circuit adaptations are unknown and could be responsible for habitual behavior. Here we find that a single class of interneuron, fast-spiking interneurons (FSIs), modulates all of these habit-predictive properties. Consistent with a role in habits, FSIs are more excitable in habitual mice compared to goal-directed and acute chemogenetic inhibition of FSIs in DLS prevents the expression of habitual lever pressing. In vivo recordings further reveal a previously unappreciated selective modulation of SPNs based on their firing patterns; FSIs inhibit most SPNs but paradoxically promote the activity of a subset displaying high fractions of gamma-frequency spiking. These results establish a microcircuit mechanism for habits and provide a new example of how interneurons mediate experience-dependent behavior. PMID:28871960

Experimental investigation of current free double layers in helicon plasmas

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

Sahu, B. B.; Tarey, R. D.; Ganguli, A.

2014-02-15

The paper presents investigations of current free double layer (CFDL) that forms in helicon plasmas. In contrast to the other work reporting on the same subject, in the present investigations the double layer (DL) forms in a mirror-like magnetic field topology. The RF compensated Langmuir probe measurements show multiple DLs, which are in connection with, the abrupt fall of densities along with potential drop of about 24 V and 18 V. The DLs strengths (e ΔV{sub p})/(k T{sub e}) are about 9.5 and 6, and the corresponding widths are about 6 and 5 D lengths. The potential drop is nearly equal tomore » the thermal anisotropies between the two plasma regions forming the DL, which is present in the plateau region of mirror, unlike the earlier studies on the DL formation in the region of strong gradients in the magnetic field. Also, it presents a qualitative discussion on the mechanism of DL formation.« less

Application of a novel new multispectral nanoparticle tracking technique

NASA Astrophysics Data System (ADS)

McElfresh, Cameron; Harrington, Tyler; Vecchio, Kenneth S.

2018-06-01

Fast, reliable, and accurate particle size analysis techniques must meet the demands of evolving industrial and academic research in areas of functionalized nanoparticle synthesis, advanced materials development, and other nanoscale enabled technologies. In this study a new multispectral particle tracking analysis (m-PTA) technique enabled by the ViewSizer™ 3000 (MANTA Instruments, USA) was evaluated using solutions of monomodal and multimodal gold and polystyrene latex nanoparticles, as well as a spark eroded polydisperse 316L stainless steel nanopowder, and large (non-Brownian) borosilicate particles. It was found that m-PTA performed comparably to the DLS in evaluation of monomodal particle size distributions. When measuring bimodal, trimodal and polydisperse solutions, the m-PTA technique overwhelmingly outperformed traditional dynamic light scattering (DLS) in both peak detection and relative particle concentration analysis. It was also observed that the m-PTA technique is less susceptible to large particle overexpression errors. The ViewSizer™ 3000 was also found to be successful in accurately evaluating sizes and concentrations of monomodal and bimodal sinking borosilicate particles.

The chaperone-like activity of the hepatitis C virus IRES and CRE elements regulates genome dimerization.

PubMed

Romero-López, Cristina; Barroso-delJesus, Alicia; Berzal-Herranz, Alfredo

2017-02-24

The RNA genome of the hepatitis C virus (HCV) establishes a network of long-distance RNA-RNA interactions that direct the progression of the infective cycle. This work shows that the dimerization of the viral genome, which is initiated at the dimer linkage sequence (DLS) within the 3'UTR, is promoted by the CRE region, while the IRES is a negative regulatory partner. Using differential 2'-acylation probing (SHAPE-dif) and molecular interference (HMX) technologies, the CRE activity was found to mainly lie in the critical 5BSL3.2 domain, while the IRES-mediated effect is dependent upon conserved residues within the essential structural elements JIIIabc, JIIIef and PK2. These findings support the idea that, along with the DLS motif, the IRES and CRE are needed to control HCV genome dimerization. They also provide evidences of a novel function for these elements as chaperone-like partners that fine-tune the architecture of distant RNA domains within the HCV genome.

Target Nanoparticles for Therapy - SANS and DLS of Drug Carrier Liposomes and Polymer Nanoparticles

NASA Astrophysics Data System (ADS)

Nawroth, T.; Johnson, R.; Krebs, L.; Khoshakhlagh, P.; Langguth, P.; Hellmann, N.; Goerigk, G.; Boesecke, P.; Bravin, A.; Le Duc, G.; Szekely, N.; Schweins, R.

2016-09-01

T arget Nano-Pharmaceutics shall improve therapy and diagnosis of severe diseases, e.g. cancer, by individual targeting of drug-loaded nano-pharmaceuticals towards cancer cells, and drug uptake receptors in other diseases. Specific ligands, proteins or cofactors, which are recognized by the diseased cells or cells of food and drug uptake, are bound to the nanoparticle surface, and thus capable of directing the drug carriers. The strategy has two branches: a) for parenteral cancer medicine a ligand set (2-5 different, surface-linked) are selected according to the biopsy analysis of the patient tissue e.g. from tumor.; b) in the oral drug delivery part the drug transport is enforced by excipients/ detergents in combination with targeting materials for cellular receptors resulting in an induced drug uptake. Both targeting nanomaterials are characterized by a combination of SANS + DLS and SAXS or ASAXS in a feedback process during development by synthesis, nanoparticle assembly and formulation.

Stabilizing Off-pathway Oligomers by Polyphenol Nanoassemblies for IAPP Aggregation Inhibition

NASA Astrophysics Data System (ADS)

Nedumpully-Govindan, Praveen; Kakinen, Aleksandr; Pilkington, Emily H.; Davis, Thomas P.; Chun Ke, Pu; Ding, Feng

2016-01-01

Experimental studies have shown that many naturally occurring polyphenols have inhibitory effect on the aggregation of several proteins. Here, we use discrete molecular dynamics (DMD) simulations and high-throughput dynamic light scattering (DLS) experiments to study the anti-aggregation effects of two polyphenols, curcumin and resveratrol, on the aggregation of islet amyloid polypeptide (IAPP or amylin). Our DMD simulations suggest that the aggregation inhibition is caused by stabilization of small molecular weight IAPP off-pathway oligomers by the polyphenols. Our analysis indicates that IAPP-polyphenol hydrogen bonds and π-π stacking combined with hydrophobic interactions are responsible for the stabilization of oligomers. The presence of small oligomers is confirmed with DLS measurements in which nanometer-sized oligomers are found to be stable for up to 7.5 hours, the time frame within which IAPP aggregates in the absence of polyphenols. Our study offers a general anti-aggregation mechanism for polyphenols, and further provides a computational framework for the future design of anti-amyloid aggregation therapeutics.

The chaperone-like activity of the hepatitis C virus IRES and CRE elements regulates genome dimerization

PubMed Central

Romero-López, Cristina; Barroso-delJesus, Alicia; Berzal-Herranz, Alfredo

2017-01-01

The RNA genome of the hepatitis C virus (HCV) establishes a network of long-distance RNA-RNA interactions that direct the progression of the infective cycle. This work shows that the dimerization of the viral genome, which is initiated at the dimer linkage sequence (DLS) within the 3′UTR, is promoted by the CRE region, while the IRES is a negative regulatory partner. Using differential 2′-acylation probing (SHAPE-dif) and molecular interference (HMX) technologies, the CRE activity was found to mainly lie in the critical 5BSL3.2 domain, while the IRES-mediated effect is dependent upon conserved residues within the essential structural elements JIIIabc, JIIIef and PK2. These findings support the idea that, along with the DLS motif, the IRES and CRE are needed to control HCV genome dimerization. They also provide evidences of a novel function for these elements as chaperone-like partners that fine-tune the architecture of distant RNA domains within the HCV genome. PMID:28233845

The Effect of Treatment on Mental and Psychomotor Development of Marasmic Infants According to Age of Admission.

ERIC Educational Resources Information Center

Celedon, J. M.; And Others

1980-01-01

The mental and psychomotor development of 35 severely malnourished infants in Chile were examined during nutritional and psychological treatment. There was a significant difference between younger and older infants in their response to the treatment. (Author/DLS)

Managing to Lead: Reframing School Leadership and Management

ERIC Educational Resources Information Center

Spillane, James P.

2009-01-01

By concentrating on the formal school organization, researchers can miss the informal relationships that are fundamental to leadership. Distributed Leadership Studies (DLS) provides a framework for examining school leadership and management that considers the interactions of leaders, followers, and aspects of the context. The framework involves…

Synthesis and characterization of metal oxide-polyaniline emeraldine salt based nanocomposite

NASA Astrophysics Data System (ADS)

Kumar, K. Siva; Kavitha, B.; Prabakar, K.; Srinivasu, D.; Srinivas, Ch.; Narsimlu, N.

2013-02-01

This paper describes the synthesis of TiO2 (core)/Polyaniline (shell) core-shell structured nanocomposites and characterization of the synthesized material. The morphological characterization is performed with XRD, SEM, DLS and SANS. Spectroscopic characterization is performed with FTIR, UV/Visible and ESR techniques.

Characterization of nanomaterial test solutions for terrestrial plant dose-response studies: A comparative study of DLS and SAXS

EPA Science Inventory

Industrial applications of nanomaterials have expanded at an increasing rate in recent years, accompanied by the need for comprehensive toxicological assessments to establish environmental health and safety standards. Relatively few studies have examined the effects of nanoparti...

"Irreconcilable Differences" between Parent and Child: A Case Report of Interactional Pathology.

ERIC Educational Resources Information Center

Tooley, Kay M.

1978-01-01

The article presents two illustrative case reports of an unusual type of child abuse: parents who use their child as a representative of their own unacceptable impulses, thereby perceiving the youngster as evil and seeking experts to confirm their mistaken opinions. (Author/DLS)

Extinction, emission, and scattering spectroscopy of 5-50 nm citrate-coated gold nanoparticles: An argument for curvature effects on aggregation

NASA Astrophysics Data System (ADS)

Esfahani, Milad Rabbani; Pallem, Vasanta L.; Stretz, Holly A.; Wells, Martha J. M.

2017-03-01

The interaction of macromolecules with gold nanoparticles (GNPs) is of interest in the emerging field of biomedical and environmental detection devices. However, the physicochemical properties, including spectra, of GNPs in aqueous solution in the absence of metal-macromolecular interactions must first be considered before their activity in biological and environmental systems can be understood. The specific objective of this research was to experimentally illuminate the role of nanoparticle core size on the spectral (simultaneous consideration of extinction, emission, and scattering) versus aggregation behaviors of citrate-coated GNPs (CT-GNPs). It is difficult to find in the literature systematic simultaneous presentation of scattering, emission, and extinction spectra, including the UV range, and thus the present work will aid those who would use such particles for spectroscopic related separations or sensors. The spectroscopic behavior of CT-GNPs with different core sizes (5, 10, 30, and 50 nm) was studied in ultra-pure water at pH 6.0-6.5 employing UV-visible extinction, excitation-emission matrix (EEM), resonance Rayleigh scattering, and dynamic light scattering (DLS) spectroscopies. The CT-GNP-5 and CT-GNP-10 samples aggregated, absorbed light, and emitted light. In contrast, the CT-GNP-30 and CT-GNP-50 samples did not aggregate and did not emit light, but scattered light intensely. Multimodal peaks were observed in the intensity-based DLS spectra of CT-GNP-5 and CT-GNP-10 samples. Monomodal peaks in the volume-based DLS spectra overestimated particle diameters by 60% and 30% for the CT-GNP-5 and CT-GNP-10 samples, respectively, but underestimated diameters by 10% and 4% for the CT-GNP-30 and CT-GNP-50 samples. The volume-based DLS spectra indicated that dimer and trimer aggregates contributed most to the overall volume of particles in the 5- and 10-nm CT-GNPs, whereas the CT-GNP-30 and CT-GNP-50 samples did not aggregate. Here, we discuss the potential influence that differences in preparation, ionic strength, zeta potential, and conformation of adsorbed citrate anions (due to surface curvature of corona) may exert on the aggregation and spectral observations in these data. In particular, the severe surface curvature of the 5- and 10-nm GNP corona may affect the efficiency of the di-/tribasic citrate compatiblizer molecule to shield the core from interactions with light and from GNP-GNP homoaggregation.

Functional characterization of the organic cation transporters (OCTs) in human airway pulmonary epithelial cells.

PubMed

Ingoglia, Filippo; Visigalli, Rossana; Rotoli, Bianca Maria; Barilli, Amelia; Riccardi, Benedetta; Puccini, Paola; Dall'Asta, Valeria

2015-07-01

Organic cation transporters (OCT1-3) mediate the transport of organic cations including inhaled drugs across the cell membrane, although their role in lung epithelium hasn't been well understood yet. We address here the expression and functional activity of OCT1-3 in human airway epithelial cells A549, Calu-3 and NCl-H441. Kinetic and inhibition analyses, employing [(3)H]1-methyl-4-phenylpyridinium (MPP+) as substrate, and the compounds quinidine, prostaglandine E2 (PGE2) and corticosterone as preferential inhibitors of OCT1, OCT2, and OCT3, respectively, have been performed. A549 cells present a robust MPP+ uptake mediated by one high-affinity component (Km~50μM) which is identifiable with OCT3. Corticosterone, indeed, completely inhibits MPP+ transport, while quinidine and PGE2 are inactive and SLC22A3/OCT3 silencing with siRNA markedly lowers MPP+ uptake. Conversely, Calu-3 exhibits both a high (Km<20μM) and a low affinity (Km>0.6mM) transport components, referable to OCT3 and OCT1, respectively, as demonstrated by the inhibition analysis performed at proper substrate concentrations and confirmed by the use of specific siRNA. These transporters are active also when cells are grown under air-liquid interface (ALI) conditions. Only a very modest saturable MPP+ uptake is measurable in NCl-H441 cells and the inhibitory effect of quinidine points to OCT1 as the subtype functionally involved in this model. Finally, the characterization of MPP+ transport in human bronchial BEAS-2B cells suggests that OCT1 and OCT3 are operative. These findings could help to identify in vitro models to be employed for studies concerning the specific involvement of each transporter in drug transportation. Copyright © 2015 Elsevier B.V. All rights reserved.

N leaching to groundwater from dairy production involving grazing over the winter on a clay-loam soil.

PubMed

Necpalova, M; Fenton, O; Casey, I; Humphreys, J

2012-08-15

This study investigated concentrations of various N species in shallow groundwater (<2.2m below ground level) and N losses from dairy production involving grazing over the winter period on a clay loam soil with a high natural attenuation capacity in southern Ireland (52°51'N, 08°21'W) over a 2-year period. A dense network of shallow groundwater piezometers was installed to determine groundwater flow direction and N spatial and temporal variation. Estimated vertical travel times through the unsaturated zone (<0.5 yr, time lag) allowed the correlation of management with groundwater N within a short space of time. There was a two way interaction of the system and sampling date (P<0.05) on concentrations of DON, oxidised N and NO(3)(-)-N. In contrast, concentrations of NH(4)(+)-N and NO(2)(-)-N were unaffected by the dairy system. Grazing over the winter had no effect on N losses to groundwater. Mean concentrations of DON, NH(4)(+)-N, NO(2)(-)-N and NO(3)(-)-N were 2.16, 0.35, 0.01 and 0.37 mg L(-1) respectively. Soil attenuation processes such as denitrification and DNRA resulted in increased NH(4)(+)-N levels. For this reason, DON and NH(4)(+)-N represented the highest proportion of N losses from the site. Some of the spatial and temporal variation of N concentrations was explained by correlations with selected chemical and hydro-topographical parameters (NO(3)(-)-N/Cl(-) ratio, distance of the sampling point from the closest receptor, watertable depth, depth of sampling piezometer, DOC concentration). A high explanatory power of NO(3)(-)-N/Cl(-) ratio and the distance of the sampling point from the closest receptor indicated the influence of point sources and groundwater-surface water interactions. Copyright © 2012 Elsevier B.V. All rights reserved.

Mucin gene expression in human urothelium and in intestinal segments transposed into the urinary tract.

PubMed

N'Dow, J; Pearson, J P; Bennett, M K; Neal, D E; Robson, C N

2000-10-01

The repertoire of mucin (MUC) gene expression in the normal human urothelium is poorly defined and the alterations in MUC gene expression following transposition of intestinal segments into the urinary tract has not previously been studied. The aims of this study were to define MUC gene expression in the normal human urothelium; and in transposed intestinal segments. Non-isotopic in-situ hybridization was carried out using eight digoxigenin labeled oligonucleotide mucin gene probes (MUC 1 - 7). Immunohistochemistry using NCL-MUC1 and NCL-MUC2 monoclonal antibodies was performed on sections of paraffin-embedded tissues. Twenty-seven patients were investigated (normal human urothelium, n = 6; transposed ileal segments, n = 14 and normal ileal controls, n = 7). MUC1 and MUC4 were the predominant mucin genes expressed in the normal urothelium with MUC3 being expressed in a third of cases studied; MUC2, 5AC, 5B, 6 and 7 were not expressed. Despite the morphological changes seen in transposed ileal segments, MUC2 and MUC3 continued to be expressed in these segments albeit in a disorganised fashion. Both MUC1 and MUC4 were up-regulated in transposed ileal segments, genes expressed by the normal human urothelium. All eight mucin genes were expressed in an area of pyloric-type metaplasia found in one transposed ileal segment. In patients with clam enterocystoplasty there was evidence of increasing up-regulation of MUC2, 3, 4 and 5AC expression in the urothelium toward the anastomotic site. Transposition of ileal segments into the urinary tract results in up-regulation of MUC1 and MUC4, the predominant MUC genes expressed in the human bladder. The clinical implication of the up-regulation of some MUC genes toward the anastomotic site in patients with an enteroplasty and the aberrant expression of MUC5AC - MUC7 by transposed segments is at present unclear.

Hippocampal memory consolidation during sleep: a comparison of mammals and birds

PubMed Central

Rattenborg, Niels C.; Martinez-Gonzalez, Dolores; Roth, Timothy C.; Pravosudov, Vladimir V.

2010-01-01

The transition from wakefulness to sleep is marked by pronounced changes in brain activity. The brain rhythms that characterize the two main types of mammalian sleep, slow-wave sleep (SWS) and rapid eye movement (REM) sleep, are thought to be involved in the functions of sleep. In particular, recent theories suggest that the synchronous slow-oscillation of neocortical neuronal membrane potentials, the defining feature of SWS, is involved in processing information acquired during wakefulness. According to the Standard Model of memory consolidation, during wakefulness the hippocampus receives input from neocortical regions involved in the initial encoding of an experience and binds this information into a coherent memory trace that is then transferred to the neocortex during SWS where it is stored and integrated within preexisting memory traces. Evidence suggests that this process selectively involves direct connections from the hippocampus to the prefrontal cortex (PFC), a multimodal, high-order association region implicated in coordinating the storage and recall of remote memories in the neocortex. The slow-oscillation is thought to orchestrate the transfer of information from the hippocampus by temporally coupling hippocampal sharp-wave/ripples (SWRs) and thalamocortical spindles. SWRs are synchronous bursts of hippocampal activity, during which waking neuronal firing patterns are reactivated in the hippocampus and neocortex in a coordinated manner. Thalamocortical spindles are brief 7–14 Hz oscillations that may facilitate the encoding of information reactivated during SWRs. By temporally coupling the readout of information from the hippocampus with conditions conducive to encoding in the neocortex, the slow-oscillation is thought to mediate the transfer of information from the hippocampus to the neocortex. Although several lines of evidence are consistent with this function for mammalian SWS, it is unclear whether SWS serves a similar function in birds, the only taxonomic group other than mammals to exhibit SWS and REM sleep. Based on our review of research on avian sleep, neuroanatomy, and memory, although involved in some forms of memory consolidation, avian sleep does not appear to be involved in transferring hippocampal memories to other brain regions. Despite exhibiting the slow-oscillation, SWRs and spindles have not been found in birds. Moreover, although birds independently evolved a brain region – the caudolateral nidopallium (NCL) – involved in performing high-order cognitive functions similar to those performed by the PFC, direct connections between the NCL and hippocampus have not been found in birds, and evidence for the transfer of information from the hippocampus to the NCL or other extra-hippocampal regions is lacking. Although based on the absence of evidence for various traits, collectively, these findings suggest that unlike mammalian SWS, avian SWS may not be involved in transferring memories from the hippocampus. Furthermore, it suggests that the slow-oscillation, the defining feature of mammalian and avian SWS, may serve a more general function independent of that related to coordinating the transfer of information from the hippocampus to the PFC in mammals. Given that SWS is homeostatically regulated (a process intimately related to the slow-oscillation) in mammals and birds, functional hypotheses linked to this process may apply to both taxonomic groups. PMID:21070585

Hippocampal memory consolidation during sleep: a comparison of mammals and birds.

PubMed

Rattenborg, Niels C; Martinez-Gonzalez, Dolores; Roth, Timothy C; Pravosudov, Vladimir V

2011-08-01

The transition from wakefulness to sleep is marked by pronounced changes in brain activity. The brain rhythms that characterize the two main types of mammalian sleep, slow-wave sleep (SWS) and rapid eye movement (REM) sleep, are thought to be involved in the functions of sleep. In particular, recent theories suggest that the synchronous slow-oscillation of neocortical neuronal membrane potentials, the defining feature of SWS, is involved in processing information acquired during wakefulness. According to the Standard Model of memory consolidation, during wakefulness the hippocampus receives input from neocortical regions involved in the initial encoding of an experience and binds this information into a coherent memory trace that is then transferred to the neocortex during SWS where it is stored and integrated within preexisting memory traces. Evidence suggests that this process selectively involves direct connections from the hippocampus to the prefrontal cortex (PFC), a multimodal, high-order association region implicated in coordinating the storage and recall of remote memories in the neocortex. The slow-oscillation is thought to orchestrate the transfer of information from the hippocampus by temporally coupling hippocampal sharp-wave/ripples (SWRs) and thalamocortical spindles. SWRs are synchronous bursts of hippocampal activity, during which waking neuronal firing patterns are reactivated in the hippocampus and neocortex in a coordinated manner. Thalamocortical spindles are brief 7-14 Hz oscillations that may facilitate the encoding of information reactivated during SWRs. By temporally coupling the readout of information from the hippocampus with conditions conducive to encoding in the neocortex, the slow-oscillation is thought to mediate the transfer of information from the hippocampus to the neocortex. Although several lines of evidence are consistent with this function for mammalian SWS, it is unclear whether SWS serves a similar function in birds, the only taxonomic group other than mammals to exhibit SWS and REM sleep. Based on our review of research on avian sleep, neuroanatomy, and memory, although involved in some forms of memory consolidation, avian sleep does not appear to be involved in transferring hippocampal memories to other brain regions. Despite exhibiting the slow-oscillation, SWRs and spindles have not been found in birds. Moreover, although birds independently evolved a brain region--the caudolateral nidopallium (NCL)--involved in performing high-order cognitive functions similar to those performed by the PFC, direct connections between the NCL and hippocampus have not been found in birds, and evidence for the transfer of information from the hippocampus to the NCL or other extra-hippocampal regions is lacking. Although based on the absence of evidence for various traits, collectively, these findings suggest that unlike mammalian SWS, avian SWS may not be involved in transferring memories from the hippocampus. Furthermore, it suggests that the slow-oscillation, the defining feature of mammalian and avian SWS, may serve a more general function independent of that related to coordinating the transfer of information from the hippocampus to the PFC in mammals. Given that SWS is homeostatically regulated (a process intimately related to the slow-oscillation) in mammals and birds, functional hypotheses linked to this process may apply to both taxonomic groups. © 2010 The Authors. Biological Reviews © 2010 Cambridge Philosophical Society.

A Social Ecology of Hyperactive Boys: Medication Effects in Structured Classroom Environments.

ERIC Educational Resources Information Center

Whalen, Carol K.; And Others

1979-01-01

Among the findings were that hyperactive Ss on placebo showed lower rates of task attention and higher rates of gross motor movement, regular and negative verbalization, noise making, physical contact, social initiation, and other responses than did normal Ss and hyperactive Ss on Ritalin. (Author/DLS)

Developmental and Psychoeducational Sequelae of Chronic Otitis Media.

ERIC Educational Resources Information Center

Zinkus, Peter W.; And Others

1978-01-01

American Medical Association, 535 N. Dearborn Street, Chicago, Illinois 60610. The developmental, psychological, and educational sequelae of chronic otitis media (a middle ear disease) occurring during the first 3 years of life were investigated in a group of children (ages 6-11 years) with educational difficulties. (Author/DLS)

Personality and Perceptions of the Gifted.

ERIC Educational Resources Information Center

Karamessinis, Nicholas P.

1980-01-01

The article reviews the recent literature on the personality attributes and self-perceptions of the gifted, and the attitudes and perceptions held about them. Among the conclusions are that the gifted appear to have higher self-esteem than others, and that gifted students are more popular with their peers than others. (Author/DLS)

Long-Term Outcome in Children with Temporal Lobe Seizures. II: Marriage, Parenthood and Sexual Indifference.

ERIC Educational Resources Information Center

Lindsay, Janet; And Others

1979-01-01

Among the findings were that female survivors, if not totally handicapped, were nearly all married; whereas surviving males who were not totally handicapped more often remained single. Journal availability: J. B. Lippincott Co., E. Washington Sq., Philadelphia, PA 19105. (Author/DLS)

Operant Control of Pathological Tongue Thrust in Spastic Cerebral Palsy.

ERIC Educational Resources Information Center

Thompson, George A., Jr.

1979-01-01

The behavior modification procedure, carried out at mealtime with a ten-year-old retarded boy who had spastic cerebral palsy, consisted of differential reinforcement and punishment, and resulted in substantial decreases in tongue thrust (reverse swallowing) and food expulsion, and a large increase in observed chewing. (Author/DLS)

Monodispersed magnetite nanoparticles optimized for magnetic fluid hyperthermia: Implications in biological systems

NASA Astrophysics Data System (ADS)

Khandhar, Amit P.; Ferguson, R. Matthew; Krishnan, Kannan M.

2011-04-01

Magnetite (Fe3O4) nanoparticles (MNPs) are suitable materials for Magnetic Fluid Hyperthermia (MFH), provided their size is carefully tailored to the applied alternating magnetic field (AMF) frequency. Since aqueous synthesis routes produce polydisperse MNPs that are not tailored for any specific AMF frequency, we have developed a comprehensive protocol for synthesizing highly monodispersed MNPs in organic solvents, specifically tailored for our field conditions (f = 376 kHz, H0 = 13.4 kA/m) and subsequently transferred them to water using a biocompatible amphiphilic polymer. These MNPs (σavg. = 0.175) show truly size-dependent heating rates, indicated by a sharp peak in the specific loss power (SLP, W/g Fe3O4) for 16 nm (diameter) particles. For broader size distributions (σavg. = 0.266), we observe a 30% drop in overall SLP. Furthermore, heating measurements in biological medium [Dulbecco's modified Eagle medium (DMEM) + 10% fetal bovine serum] show a significant drop for SLP (˜30% reduction in 16 nm MNPs). Dynamic Light Scattering (DLS) measurements show particle hydrodynamic size increases over time once dispersed in DMEM, indicating particle agglomeration. Since the effective magnetic relaxation time of MNPs is determined by fractional contribution of the Neel (independent of hydrodynamic size) and Brownian (dependent on hydrodynamic size) components, we conclude that agglomeration in biological medium modifies the Brownian contribution and thus the net heating capacity of MNPs.

Preserving the Pyramid of STI Using Buckets

NASA Technical Reports Server (NTRS)

Nelson, Michael L.; Maly, Kurt

2004-01-01

The product of research projects is information. Through the life cycle of a project, information comes from many sources and takes many forms. Traditionally, this body of information is summarized in a formal publication, typically a journal article. While formal publications enjoy the benefits of peer review and technical editing, they are also often compromises in media format and length. As such, we consider a formal publication to represent an abstract to a larger body of work: a pyramid of scientific and technical information (STI). While this abstract may be sufficient for some applications, an in-depth use or analysis is likely to require the supporting layers from the pyramid. We have developed buckets to preserve this pyramid of STI. Buckets provide an archive- and protocol-independent container construct in which all related information objects can be logically grouped together, archived, and manipulated as a single object. Furthermore, buckets are active archival objects and can communicate with each other, people, or arbitrary network services. Buckets are an implementation of the Smart Object, Dumb Archive (SODA) DL model. In SODA, data objects are more important than the archives that hold them. Much of the functionality traditionally associated with archives is pushed down into the objects, such as enforcing terms and conditions, negotiating display, and content maintenance. In this paper, we discuss the motivation, design, and implication of bucket use in DLs with respect to grey literature.

4-(Di­methyl­amino)­pyridinium trichlorido[4-(di­methyl­amino)­pyridine-κN]cobaltate(II)

PubMed Central

Guenifa, Fatiha; Hadjadj, Nasreddine; Zeghouan, Ouahida; Bendjeddou, Lamia; Merazig, Hocine

2013-01-01

In the anion of the title compound, (C7H11N2)[CoCl3(C7H10N2)], the CoII ion is coordinated by one N atom from a 4-(di­methyl­amino)­pyridine (DMAP) ligand and three Cl atoms, forming a CoNCl3 polyhedron with a distorted tetra­hedral geometry. In the crystal, cations and anions are linked via weak N—H⋯Cl and C—H⋯Cl hydrogen bonds. Double layers of complex anions stack along the b- axis direction, which alternate with double layers of 4-(di­methyl­amino)-pyridinium cations. PMID:24046560

Differential Analysis of Selected Prompts and Neurological Variables in Motor Assessment of Moderately Mentally Retarded Children.

ERIC Educational Resources Information Center

Ilmer, Steven; Drews, Judith

1980-01-01

The relative effectiveness of multisensory-, physical-, modeling-, and verbal-prompting assessment strategies upon the gross motor performance of 40 moderately retarded children (ages 5 to 15 years) was investigated, taking into account the impact of the Ss' levels of reflexive maturation and orthopedic functioning. (Author/DLS)

The Effects of Congenital Heart Disease on Cognitive Development, Illness Causality Concepts, and Vulnerability.

ERIC Educational Resources Information Center

Myers-Vando, Rosemary; And Others

1979-01-01

It was found, among other things, that Ss with cardiac disease responded at lower levels of development on attainment of conservation tasks than did normal controls, and that cardiac Ss appeared to feel somewhat more vulnerable to illness in general, especially when projecting to adult health status. (DLS)

Performance of Mentally Retarded Children on a Hierarchically Sequenced Introductory Mathematics Curriculum.

ERIC Educational Resources Information Center

Singh, Nirbhay N.; Ahrens, Michael G.

1979-01-01

Results at the end of one year showed that the experimental group mastered an average of 32 objectives while the control group averaged 15.5, suggesting that hierarchically sequenced mathematics curricula may provide an effective approach to the teaching of number concepts to the severely and moderately retarded. (Author/DLS)

The Use of Medication in a Residential Institution for Mentally Retarded Persons.

ERIC Educational Resources Information Center

Silva, Dennis A.

1979-01-01

Overall use of drugs was high, with the largest percentage of clients taking major tranquilizers (21.2 percent), followed closely by those taking anticonvulsants (20.4 percent). The data suggest a decrease over the years in the use of major tranquilizers in residential institutions for the retarded. (Author/DLS)

Warfighter IT Interoperability Standards Study

DTIC Science & Technology

2012-07-22

data (e.g. messages) between systems ? ii) What process did you used to validate and certify semantic interoperability between your...other systems at this time There was no requirement to validate and certify semantic interoperability The DLS program exchanges data with... semantics Testing for System Compliance with Data Models Verify and Certify Interoperability Using Data

Synthesis, characterization and applications of maghemite beads functionalized with rabbit antibodies.

PubMed

Rodriguez, A F R; Rocha, C O; Piazza, R D; Dos Santos, C C; Morales, M A; Faria, F S E D V; Iqbal, M Zubair; Barbosa, L; Chaves, Y O; Mariuba, L A; Jafelicci, M; Marques, R F C

2018-06-12

Magnetic nanoparticles (NPs) have attracted great attention owing to their applications in the biomedical field. In the present work, maghemite (γFe 2 O 3 ) NPs of 6.5 nm were prepared using a sonochemical method and used to prepare magnetic beads through silanization with 3-aminopropyltrimethoxysilane (APTS). Subsequently, amino groups in the resulting APTS-γFe 2 O 3 beads were converted to carboxylic acid (CARB-γFe 2 O 3 ) through the succinic anhydride reaction, as confirmed by transmission electron microscopy (TEM), Fourier transform infrared spectroscopy and dynamic light scattering (DLS) measurements. The size of these beads was measured as 12 nm and their hydrodynamic diameter as 490 nm, using TEM analysis and DLS, respectively. The CARB-γFe 2 O 3 beads were further functionalized by immobilizing rabbit antibodies on their surfaces; the immobilization was confirmed by flow cytometry and ionic strength. The samples were further characterized by Mössbauer spectroscopy and DC magnetization measurements. Studies on magnetic relaxivities showed that magnetic beads present great potential for application in MR imaging.

Fast optimization of binary clusters using a novel dynamic lattice searching method.

PubMed

Wu, Xia; Cheng, Wen

2014-09-28

Global optimization of binary clusters has been a difficult task despite of much effort and many efficient methods. Directing toward two types of elements (i.e., homotop problem) in binary clusters, two classes of virtual dynamic lattices are constructed and a modified dynamic lattice searching (DLS) method, i.e., binary DLS (BDLS) method, is developed. However, it was found that the BDLS can only be utilized for the optimization of binary clusters with small sizes because homotop problem is hard to be solved without atomic exchange operation. Therefore, the iterated local search (ILS) method is adopted to solve homotop problem and an efficient method based on the BDLS method and ILS, named as BDLS-ILS, is presented for global optimization of binary clusters. In order to assess the efficiency of the proposed method, binary Lennard-Jones clusters with up to 100 atoms are investigated. Results show that the method is proved to be efficient. Furthermore, the BDLS-ILS method is also adopted to study the geometrical structures of (AuPd)79 clusters with DFT-fit parameters of Gupta potential.

Characterization of interaction between esculin and human serum albumin in membrane mimetic environments

NASA Astrophysics Data System (ADS)

Zhang, Yaheng; Li, Jiazhong; Dong, Lijun; Li, Ying; Chen, Xingguo

2008-10-01

In this study the interaction between esculin and human serum albumin (HSA) in AOT/isooctane/water microemulsions was studied for the first time using fluorescence quenching technique in combination with UV absorption spectroscopy, Fourier transform infrared (FT-IR) spectroscopy, circular dichroism (CD) spectroscopy and dynamic light scattering (DLS) technique. Fluorescence data in ω o 20 microemulsions revealed the presence of the binding site of esculin on HSA and its binding constants at four different temperatures were obtained. The affinities in microemulsions are similar to that in buffer solution. The alterations of protein secondary structure in the microemulsions in the absence and presence of esculin compared with the free form of HSA in buffer were qualitatively and quantitatively analyzed by the evidence from CD and FT-IR spectroscopes. The displacement experiments confirmed that esculin could bind to the site I of HSA, which was in agreement with the result of the molecular modeling study. Furthermore, the DLS data suggested that HSA may locate at the interface of the microemulsion and esculin could interact with them.

Evaluating scintillator performance in time-resolved hard X-ray studies at synchrotron light sources.

PubMed

Rutherford, Michael E; Chapman, David J; White, Thomas G; Drakopoulos, Michael; Rack, Alexander; Eakins, Daniel E

2016-05-01

The short pulse duration, small effective source size and high flux of synchrotron radiation is ideally suited for probing a wide range of transient deformation processes in materials under extreme conditions. In this paper, the challenges of high-resolution time-resolved indirect X-ray detection are reviewed in the context of dynamic synchrotron experiments. In particular, the discussion is targeted at two-dimensional integrating detector methods, such as those focused on dynamic radiography and diffraction experiments. The response of a scintillator to periodic synchrotron X-ray excitation is modelled and validated against experimental data collected at the Diamond Light Source (DLS) and European Synchrotron Radiation Facility (ESRF). An upper bound on the dynamic range accessible in a time-resolved experiment for a given bunch separation is calculated for a range of scintillators. New bunch structures are suggested for DLS and ESRF using the highest-performing commercially available crystal LYSO:Ce, allowing time-resolved experiments with an interframe time of 189 ns and a maximum dynamic range of 98 (6.6 bits).

Evaluating scintillator performance in time-resolved hard X-ray studies at synchrotron light sources

PubMed Central

Rutherford, Michael E.; Chapman, David J.; White, Thomas G.; Drakopoulos, Michael; Rack, Alexander; Eakins, Daniel E.

2016-01-01

The short pulse duration, small effective source size and high flux of synchrotron radiation is ideally suited for probing a wide range of transient deformation processes in materials under extreme conditions. In this paper, the challenges of high-resolution time-resolved indirect X-ray detection are reviewed in the context of dynamic synchrotron experiments. In particular, the discussion is targeted at two-dimensional integrating detector methods, such as those focused on dynamic radiography and diffraction experiments. The response of a scintillator to periodic synchrotron X-ray excitation is modelled and validated against experimental data collected at the Diamond Light Source (DLS) and European Synchrotron Radiation Facility (ESRF). An upper bound on the dynamic range accessible in a time-resolved experiment for a given bunch separation is calculated for a range of scintillators. New bunch structures are suggested for DLS and ESRF using the highest-performing commercially available crystal LYSO:Ce, allowing time-resolved experiments with an interframe time of 189 ns and a maximum dynamic range of 98 (6.6 bits). PMID:27140147

Evaluation of antibacterial and Antibiofilm activity of Synthesized Zinc-Hydroxyapatite Biocomposites from Labeo rohita fish scale waste

NASA Astrophysics Data System (ADS)

Sathiskumar, Swamiappan; Vanaraj, Sekar; Sabarinathan, Devaraj; Preethi, Kathirvel

2018-02-01

Materials based on hydroxyapatite (HAp) Synthesized from bio-wastes have been regarded as useful, novel, eco-friendly medical applications that are targeted primarily for their antibacterial nature. In the present study, HAp was Synthesized from the fish scales of Labeo rohita using alkaline heat treatment and subsequently mixed with 1, 2 and 3 wt% of zinc (Zn) at 800 °C using calcination method to yield Zn-HAp composites. A detailed characterization of the generated composites was analysed by XRD, FT-IR, SEM, EDX and DLS methods. Further, antibacterial and biofilm inhibitory activity of the generated composites was determined using strains of Staphylococcus aureus and Escherichia coli. The confirmation of the presence of zinc, confirmed by EDAX spectra, XRD, FT-IR, SEM and DLS observations, established that HAp and Zn-HAp composites were without impurities, irregular in shape and were 848 nm sized particles. Although 1-3 wt% Zn-HAp composites showed antibacterial activity, the 3 wt% Zn-HAp composite was found suitable to kill the surrounding bacterial growth and showed potent inhibitory activity against biofilm formation.

Non-invasive, quantitative, and remote detection of early radiation cataracts for applications in bio-astronautics and bio-informatics

NASA Astrophysics Data System (ADS)

Ansari, Rafat R.; Giblin, Frank J.; King, James F.

2001-02-01

Human exploration of Mars may be a possibility in the next twenty years. Maintaining good vision is an essential aspect of achieving a successful mission. Continuous radiation exposure is a risk factor for radiation-induced cataracts in astronauts. A compact device based on the technique of dynamic light scattering (DLS) is designed for monitoring an astronaut's ocular health during long-duration space travel. Preliminary data on the simulated effects of ionizing radiation exposure to the ocular tissues of non-human animals and results on the sensitivity of DLS over established clinical procedures in investigating cataracts are presented. This capability of early diagnosis, unmatched by any other clinical technique in use today, may enable prompt initiation of preventive/curative therapy. An inter-net web based system integrating photon correlation data and controlling the hardware to monitor cataract development in vivo at a remote site in real time (tele-ophthalmology) is currently being developed. Cataract studies on-board the International Space Station (ISS) will be helpful in designing better protective radiation shields for future space vehicles and space suits. .

Golgi Study of Medium Spiny Neurons from Dorsolateral Striatum of the Turtle Trachemys scripta elegans.

PubMed

González, Carolina; Mendoza, Janeth; Avila-Costa, María Rosa; Arias, Juan M; Barral, Jaime

2013-10-25

Comparative anatomy has shown similarities between reptilian and mammalian basal ganglia. Here the morphological characteristics of the medium spiny neurons (MSN) in the dorsolateral striatum (DLS) of the turtle are described after staining them with the Golgi technique. The soma of MSN in DLS showed three main forms: spherical, ovoid, and fusiform. The number of primary dendritic branches (3-4 dendrites/cell) was less than observed in mammals. The MSN axon originates mainly from the soma, and randomly it emerges at the beginning of the primary dendrite. The main differences between turtle and mammalian MSN were detected on dendritic spines. Short, thin, bifurcated and fungiform types of dendritic spines were observed in the turtle's MSN, according to their shape. In most of the analyzed spines, it was found that its length considerably exceeded that reported in mammals, with dendritic spines up to 8μm in length. These differences could play an important role in the modulation of motor networks preserved along the vertebrate evolution. Copyright © 2013. Published by Elsevier Ireland Ltd.

Non-Invasive, Quantitative, and Remote Detection of Early Radiation Cataracts for Applications in Bio-Astronautics and Bio-Informatics

NASA Technical Reports Server (NTRS)

Ansari, Rafat R.; Giblin, Frank J.; King, James F.; Singh, B. (Technical Monitor)

2002-01-01

Human exploration of Mars may be a possibility in the next twenty years. Maintaining good vision is an essential aspect of achieving a successful mission. Continuous radiation exposure is a risk factor for radiation-induced cataracts in astronauts. A compact device based on the technique of dynamic light scattering (DLS) is designed for monitoring an astronaut's ocular health during long-duration space travel. Preliminary data on the simulated effects of ionizing radiation exposure to the ocular tissues of nonhuman animals and results on the sensitivity of DLS over established clinical procedures in investigating cataracts are presented. This capability of early diagnosis, unmatched by any other clinical technique in use today, may enable prompt initiation of preventive/curative therapy. An internet web based system integrating photon correlation data and controlling the hardware to monitor cataract development in vivo at a remote site in real time (teleophthalmology) is currently being developed. Cataract studies on-board the International Space Station (ISS) will be helpful in designing better protective radiation shields for future space vehicles and space suits.

Synthesis of Silver Nanoparticles from Microbial Source-A Green Synthesis Approach, and Evaluation of its Antimicrobial Activity against Escherichia coli

NASA Astrophysics Data System (ADS)

Behera, S. S.; Jha, S.; Arakha, M.; Panigrahi, T. K.

2012-03-01

TRACT Nanoparticles synthesis by biological methods using various microorganisms, plants, and plant extracts and enzymes have attracted a great attention as these are cost effective, nontoxic, eco-friendly and an alternative to physical and chemical methods. In this research, Silver nanoparticles (Ag-NPs) were synthesized from AgNO3 solution by green synthesis process with the assistance of microbial source only. The detailed characterization of the Ag NPs were carried out using UV-visible spectroscopy, Scanning electron microscopy (SEM), Energy dispersive X-ray Spectroscopy (EDS), Dynamic light scattering (DLS) analysis, and their antimicrobial evaluation was done against Escherichia coli. The UV-visible spectroscopy analysis showed the surface plasmon resonance property of nanoparticles. The DLS analysis showed the particle distribution of synthesized silver nanoparticles in solution, and SEM analysis showed the morphology of nanoparticles. The elemental composition of synthesized sample was confirmed by EDS analysis. Antibacterial assay of synthesized Ag NP was carried out in solid (Nutrient Agar) growth medium against E.coli. The presence of zone of inhibition clearly indicated the antibacterial activity of silver nanoparticles.

Online submicron particle sizing by dynamic light scattering using autodilution

NASA Technical Reports Server (NTRS)

Nicoli, David F.; Elings, V. B.

1989-01-01

Efficient production of a wide range of commercial products based on submicron colloidal dispersions would benefit from instrumentation for online particle sizing, permitting real time monitoring and control of the particle size distribution. Recent advances in the technology of dynamic light scattering (DLS), especially improvements in algorithms for inversion of the intensity autocorrelation function, have made it ideally suited to the measurement of simple particle size distributions in the difficult submicron region. Crucial to the success of an online DSL based instrument is a simple mechanism for automatically sampling and diluting the starting concentrated sample suspension, yielding a final concentration which is optimal for the light scattering measurement. A proprietary method and apparatus was developed for performing this function, designed to be used with a DLS based particle sizing instrument. A PC/AT computer is used as a smart controller for the valves in the sampler diluter, as well as an input-output communicator, video display and data storage device. Quantitative results are presented for a latex suspension and an oil-in-water emulsion.

Phagocytosis of PLGA Microparticles in Rat Peritoneal Exudate Cells: A Time-Dependent Study

NASA Astrophysics Data System (ADS)

Gomes, Anderson De Jesus; Nain Lunardi, Claure; Henrique Caetano, Flávio; Orive Lunardi, Laurelúcia; da Hora Machado, Antonio Eduardo

2006-07-01

With the purpose of enhancing the efficacy of microparticle-encapsulated therapeutic agents, in this study we evaluated the phagocytic ability of rat peritoneal exudate cells and the preferential location of poly(D,L-lactide-co-glycolic acid) (PLGA) microparticles inside these cells. The microparticles used were produced by a solvent evaporation method and were characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). Size distribution analysis using DLS and SEM showed that the particles were spherical, with diameters falling between 0.5 and 1.5 [mu]m. Results from cell adhesion by SEM assay, indicated that the PLGA microparticles are not toxic to cells and do not cause any distinct damage to them as confirmed by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay. Among the large variety of cell populations found in the peritoneal exudates (neutrophils, eosinophils, monocytes, and macrophages), TEM showed that only the latter phagocytosed PLGA microparticles, in a time-dependent manner. The results obtained indicate that the microparticles studied show merits as possible carriers of drugs for intracellular delivery.