L-shaped right-to-left crossed-fused renal ectopia with left dysplastic ureter.

PubMed

Song, Wei; Yang, Jinrui; Zhu, Liang; Liu, Longfei

2012-01-01

Crossed-fused renal ectopia is a relatively rare congenital malformation. Herein, we report a case of L-shaped right- to-left crossed-fused renal ectopia with a left dysplastic ureter in a 5-year-old girl. She underwent a left nephrectomy and the postoperative course was uneventful. Copyright © 2011 S. Karger AG, Basel.

Exposure of smoke solutions from CNG-powered four-stroke auto-rickshaws induces distressed embryonic movements, embryonic hemorrhaging and ectopia cordis.

PubMed

Ejaz, Sohail; Ejaz, Ahmed; Sohail, Amara; Ahmed, Mukthar; Nasir, Amar; Lim, Chae Woong

2009-07-01

In south Asian countries, a campaign has launched to promote CNG-powered four-stroke auto-rickshaws (CNFAR) to decrease emission load in the environment. Even though, CNFAR are considered environmentally safe, emissions of some other toxic chemicals would amplify, which may effect the development of growing fetus and may result in different growth defects. By utilizing the in vivo chicken embryo model, this report analyzes the toxic potential of CNFAR smoke solutions (CNFARSS) on embryonic movements (EM) and cardiovascular development. Application of CNFARSS to embryos caused profound decline (p<0.001) in all four types of EMs. Several recovery attempts of all EMs were observed in oscillating fashion, however, EMs did not recover by the end of experiment. Exposure of CNFARSS escorted intense decline (p<0.001) with temperate recovery phases in the EM of tail. Macroscopic evaluation of all CNFARSS treated chicken embryos revealed several widespread hemorrhaging throughout the whole body. Moreover, four different types of ectopia cordis were prominently observed among all CNFARSS treated embryos, namely; incomplete ectopia cordis, complete ectopia cordis, cervico-thoracic ectopia cordis and thoraco-abdominal ectopia cordis.

Enhanced osteogenic activity and anti-inflammatory properties of Lenti-BMP-2-loaded TiO2 nanotube layers fabricated by lyophilization following trehalose addition

PubMed Central

Zhang, Xiaochen; Zhang, Zhiyuan; Shen, Gang; Zhao, Jun

2016-01-01

To enhance biocompatibility and osseointegration between titanium implants and surrounding bone tissue, numerous efforts have been made to modify the surface topography and composition of Ti implants. In this paper, Lenti-BMP-2-loaded TiO2 nanotube coatings were fabricated by lyophilization in the presence of trehalose to functionalize the surface. We characterized TiO2 nanotube layers in terms of the following: surface morphology; Lenti-BMP-2 and trehalose release; their ability to induce osteogenesis, proliferation, and anti-inflammation in vitro; and osseointegration in vivo. The anodized TiO2 nanotube surfaces exhibited an amorphous glassy matrix perpendicular to the Ti surface. Both Lenti-BMP-2 and trehalose showed sustained release over the course of 8 days. Results from real-time quantitative polymerase chain reaction studies demonstrated that lyophilized Lenti-BMP-2/TiO2 nanotubes constructed with trehalose (Lyo-Tre-Lenti-BMP-2) significantly promoted osteogenic differentiation of bone marrow stromal cells but not their proliferation. In addition, Lyo-Tre-Lenti-BMP-2 nanotubes effectively inhibited lipopolysaccharide-induced interleukin-1β and tumor necrosis factor-α production. In vivo, the formulation also promoted osseointegration. This study presents a promising new method for surface-modifying biomedical Ti-based implants to simultaneously enhance their osteogenic potential and anti-inflammatory properties, which can better satisfy clinical needs. PMID:26869786

Enhanced osteogenic activity and anti-inflammatory properties of Lenti-BMP-2-loaded TiO₂ nanotube layers fabricated by lyophilization following trehalose addition.

PubMed

Zhang, Xiaochen; Zhang, Zhiyuan; Shen, Gang; Zhao, Jun

2016-01-01

To enhance biocompatibility and osseointegration between titanium implants and surrounding bone tissue, numerous efforts have been made to modify the surface topography and composition of Ti implants. In this paper, Lenti-BMP-2-loaded TiO2 nanotube coatings were fabricated by lyophilization in the presence of trehalose to functionalize the surface. We characterized TiO2 nanotube layers in terms of the following: surface morphology; Lenti-BMP-2 and trehalose release; their ability to induce osteogenesis, proliferation, and anti-inflammation in vitro; and osseointegration in vivo. The anodized TiO2 nanotube surfaces exhibited an amorphous glassy matrix perpendicular to the Ti surface. Both Lenti-BMP-2 and trehalose showed sustained release over the course of 8 days. Results from real-time quantitative polymerase chain reaction studies demonstrated that lyophilized Lenti-BMP-2/TiO2 nanotubes constructed with trehalose (Lyo-Tre-Lenti-BMP-2) significantly promoted osteogenic differentiation of bone marrow stromal cells but not their proliferation. In addition, Lyo-Tre-Lenti-BMP-2 nanotubes effectively inhibited lipopolysaccharide-induced interleukin-1β and tumor necrosis factor-α production. In vivo, the formulation also promoted osseointegration. This study presents a promising new method for surface-modifying biomedical Ti-based implants to simultaneously enhance their osteogenic potential and anti-inflammatory properties, which can better satisfy clinical needs.

Lentivirus-ABCG1 instillation reduces lipid accumulation and improves lung compliance in GM-CSF knock-out mice

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

Malur, Anagha; Huizar, Isham; Wells, Greg

2011-11-18

Highlights: Black-Right-Pointing-Pointer Lentivirus-ABCG1 reduces lipid accumulation in lungs of GM-CSF knock-out mice. Black-Right-Pointing-Pointer Up-regulation of ABCG1 improves lung function. Black-Right-Pointing-Pointer Upregulation of ABCG1 improves surfactant metabolism. -- Abstract: We have shown decreased expression of the nuclear transcription factor, peroxisome proliferator-activated receptor-gamma (PPAR{gamma}) and the PPAR{gamma}-regulated ATP-binding cassette transporter G1 (ABCG1) in alveolar macrophages from patients with pulmonary alveolar proteinosis (PAP). PAP patients also exhibit neutralizing antibodies to granulocyte-macrophage colony stimulating factor (GM-CSF), an upregulator of PPAR{gamma}. In association with functional GM-CSF deficiency, PAP lung is characterized by surfactant-filled alveolar spaces and lipid-filled alveolar macrophages. Similar pathology characterizes GM-CSF knock-out (KO)more » mice. We reported previously that intratracheal instillation of a lentivirus (lenti)-PPAR{gamma} plasmid into GM-CSF KO animals elevated ABCG1 and reduced alveolar macrophage lipid accumulation. Here, we hypothesized that instillation of lenti-ABCG1 might be sufficient to decrease lipid accumulation and improve pulmonary function in GM-CSF KO mice. Animals received intratracheal instillation of lenti-ABCG1 or control lenti-enhanced Green Fluorescent Protein (eGFP) plasmids and alveolar macrophages were harvested 10 days later. Alveolar macrophage transduction efficiency was 79% as shown by lenti-eGFP fluorescence. Quantitative PCR analyses indicated a threefold (p = 0.0005) increase in ABCG1 expression with no change of PPAR{gamma} or ABCA1 in alveolar macrophages of lenti-ABCG1 treated mice. ABCG1 was unchanged in control lenti-eGFP and PBS-instilled groups. Oil Red O staining detected reduced intracellular neutral lipid in alveolar macrophages from lenti-ABCG1 treated mice. Extracellular cholesterol and phospholipids were also decreased as shown by analysis of bronchoalveolar lavage fluid. Lung compliance was diminished in untreated GMCSF KO mice but improved significantly after lenti-ABCG1 treatment. Data demonstrate that in vivo instillation of lenti-ABCG1 in GM-CSF KO mice is sufficient to restore pulmonary homeostasis by: (1) upregulating ABCG1; (2) reducing intra and extracellular lipids; and (3) improving lung function. Results suggest that the ABCG1 lipid transporter is the key downstream target of GM-CSF-induced PPAR{gamma} necessary for surfactant catabolism.« less

Novel variants in PAX6 gene caused congenital aniridia in two Chinese families.

PubMed

Zhang, R; Linpeng, S; Wei, X; Li, H; Huang, Y; Guo, J; Wu, Q; Liang, D; Wu, L

2017-06-01

PurposeTo reveal the underlying genetic defect in two four-generation Chinese families with aniridia and explore the pathologic mechanism.MethodsFull ophthalmic examinations were performed in two families with aniridia. The PAX6 gene was directly sequenced in patients of two families, and the detected variants were screened in unaffected family members and two hundred unrelated healthy controls. Real-time quantitative PCR was used to explore pathologic mechanisms of the two variants.ResultsAniridia, cataract, and oscillatory nystagmus were observed in patients of the two families. In addition, we observed corneal opacity and microphthalmus in family 1, and strabismus, left ectopia lentis, microphthalmus, and microcornea in family 2. Sanger sequencing detected a novel 1-bp duplication (c.50dupA) in family 1 and a novel 2-bp splice site deletion (c.765+1_765+2delGT) in family 2. Sequencing of cDNA indicated skipping of exon 9 caused by the splice site deletion, being predicted to cause a premature stop codon, as well as the duplication. The PAX6 mRNA significantly lower in patients with aniridia than in unaffected family members in both families, suggesting that the duplication and splice site deletion caused nonsense-mediated mRNA decay.ConclusionsOur study identified two novel PAX6 variants in two families with aniridia and revealed the pathogenicity of the variants; this would expand the variant spectrum of PAX6 and help us better understand the molecular basis of aniridia, thus facilitating genetic counseling.

[Crossed renal ectopia in a patient with a complicated sigma neoplasia].

PubMed

Pérez-Sánchez, Luis Eduardo; Burneo-Esteves, Mauricio; Rosat-Rodrigo, Adriá; Baz-Figueroa, Caleb; Pérez-Álvarez, Antonio Dámaso; Barrera-Gómez, Manuel Ángel

2017-12-01

Crossed renal ectopia is a rare pathology that is often asymptomatic. Intraoperative detection with a sigma complicated neoplasia is more infrequent and requires correct management to avoid a renal ureteral injury. To present a case report of a patient with a sigma complicated neoplasia and a crossed renal ectopia detected incidentally. We present the case of a 62-year-old man that was submitted for emergency surgery for a sigma perforated neoplasm, and who presented with a previously undiagnosed left-side CRE. During surgery there was a need to insert 2-double-J stents as a guide to both ureters and to avoid any injury to them. Crossed renal ectopia is a rare, often asymptomatic entity, the diagnosis of which is usually incidental. In our case, the detection of a concomitant complicated neoplasm, required identification of both ureters due the anatomic doubt of its localization and to avoid them being injured. In conclusion, upon finding a casual crossed renal ectopia during an emergency surgery of sigma, we recommend the identification of the ureters to facilitate its location and to avoid any injury to the ureters. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

Immobilization of laccase of Pycnoporus sanguineus CS43.

PubMed

Gonzalez-Coronel, Luis A; Cobas, Marta; Rostro-Alanis, Magdalena de J; Parra-Saldívar, Roberto; Hernandez-Luna, Carlos; Pazos, Marta; Sanromán, M Ángeles

2017-10-25

Laccase from Pycnoporus sanguineus CS43 was successfully immobilized onto Immobead-150 and Eupergit-C by covalent binding and by entrapment in LentiKats. The highest immobilization was onto Immobead-150 (97.1±1.2%) compared to the other supports, LentiKats (89±1.1%) and Eupergit-C (83.2±1.4%). All three immobilized enzyme systems showed increased thermostability and better mechanical properties than free laccase. Moreover, after 5 cycles of reuse of these systems, 90% of initial laccase activity was retained. Immobead-150 and LentiKats systems exhibited the highest efficiencies in removal of m-cresol under the combined actions of biodegradation and adsorption, while laccase entrapped in LentiKats showed a high ability for degradation of m-cresol within 24h. In addition, the typical Michaelis-Menten enzymatic model effectively described the kinetic profile of m-cresol degradation by the enzyme entrapped in LentiKats. Based on the results obtained in the present study, it can be established that the immobilized biocatalysts developed here possess significant potential for wastewater treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

[Influence and mechanism of PinX1 gene on the chemotherapy sensitivity of nasopharyngeal carcinoma cells in response to Cisplatin].

PubMed

Shen, Congxiang; Liu, Yanhui; Wen, Zhong; Yang, Keke; Li, Guanxue; Zhang, Shenhua; Zhang, Xinyu

2015-06-23

To explore the influence and mechanism of PinX1 gene on the chemotherapy sensitivity of nasopharyngeal carcinoma cells in response to Cisplatin. Transfected nasopharyngeal carcinoma 5-8F cell lines with pCDH-CMV-PinX1-copGFP vector constructed by lentivirus to generate Lenti-PinX1-5-8F cells containing PinX1 gene, using Lenti-Ctrl-5-8F cell (blank vector without PinX1 gene was used to transfect 5-8F cell lines) and 5-8F cell as controls. Expression of PinX1 gene, telomerase activity, the inhibition of cancer cells proliferation, combined anticancer effect with Cisplatin and the expression of lung resistance protein (LRP) and Bcl-2 were detected with fluorescent quantitation polymerase chain reaction (PCR), flow cytometry, thiazolyl blue (MTT) method, areole test, Western blot and drug sensitivity test, respectively, in four groups (Lenti-PinX1-5-8F cell + Cisplatin, Lenti-PinX1-5-8F cell, Cisplatin and 5-8F cell) so as to explore the influence and mechanism of PinX1 gene on the chemotherapy sensitivity of nasopharyngeal carcinoma cells in response to Cisplatin. The telomerase activity in Lenti-PinX1-5-8F cell (0.146 ± 0.004) was lower than those in the other two control cells (Lenti-Ctrl-5-8F cell: 0.967 ± 0.016, 5-8F cell: 1.000 ± 0.034, both P < 0.01). The cancer cell biological activity could be intensively inhibited by 16 µg/ml Cisplatin after lower level telomerase activity induced by PinX1 gene. Proliferation index (PI) (%) in Lenti-PinX1-5-8F cell + Cisplatin (14.39 ± 3.66) was also less than the other groups (Lenti-PinX1-5-8F cell, Cisplatin and 5-8F cell groups, 32.97 ± 3.00, 31.18 ± 4.24 and 47.19 ± 4.19, all P < 0.01). And same time, the expressions of LRP (0.64 ± 0.14) and Bcl-2 (0.57 ± 0.12) protein in Lenti-PinX1-5-8F cells were obviously reduced than those in other two group cells (Lenti-Ctrl-5-8F cell: 0.84 ± 0.19 and 0.81 ± 0.16; 5-8F cell: 0.83 ± 0.35 and 0.78 ± 0.27; all P < 0.01). PinX1 gene can enhance the chemotherapy sensitivity of nasopharyngeal carcinoma cells in response to Cisplatin, which may be mediated by the down-regulation of telomerase activity and the inhibition of LRP and Bcl-2 gene in nasopharyngeal carcinoma cells.

Microenvironmental Regulation by Fibrillin-1

PubMed Central

Sengle, Gerhard; Tsutsui, Ko; Keene, Douglas R.; Tufa, Sara F.; Carlson, Eric J.; Charbonneau, Noe L.; Ono, Robert N.; Sasaki, Takako; Wirtz, Mary K.; Samples, John R.; Fessler, Liselotte I.; Fessler, John H.; Sekiguchi, Kiyotoshi; Hayflick, Susan J.; Sakai, Lynn Y.

2012-01-01

Fibrillin-1 is a ubiquitous extracellular matrix molecule that sequesters latent growth factor complexes. A role for fibrillin-1 in specifying tissue microenvironments has not been elucidated, even though the concept that fibrillin-1 provides extracellular control of growth factor signaling is currently appreciated. Mutations in FBN1 are mainly responsible for the Marfan syndrome (MFS), recognized by its pleiotropic clinical features including tall stature and arachnodactyly, aortic dilatation and dissection, and ectopia lentis. Each of the many different mutations in FBN1 known to cause MFS must lead to similar clinical features through common mechanisms, proceeding principally through the activation of TGFβ signaling. Here we show that a novel FBN1 mutation in a family with Weill-Marchesani syndrome (WMS) causes thick skin, short stature, and brachydactyly when replicated in mice. WMS mice confirm that this mutation does not cause MFS. The mutation deletes three domains in fibrillin-1, abolishing a binding site utilized by ADAMTSLIKE-2, -3, -6, and papilin. Our results place these ADAMTSLIKE proteins in a molecular pathway involving fibrillin-1 and ADAMTS-10. Investigations of microfibril ultrastructure in WMS humans and mice demonstrate that modulation of the fibrillin microfibril scaffold can influence local tissue microenvironments and link fibrillin-1 function to skin homeostasis and the regulation of dermal collagen production. Hence, pathogenetic mechanisms caused by dysregulated WMS microenvironments diverge from Marfan pathogenetic mechanisms, which lead to broad activation of TGFβ signaling in multiple tissues. We conclude that local tissue-specific microenvironments, affected in WMS, are maintained by a fibrillin-1 microfibril scaffold, modulated by ADAMTSLIKE proteins in concert with ADAMTS enzymes. PMID:22242013

Associations of Age and Sex with Marfan Phenotype: The NHLBI GenTAC Registry

PubMed Central

Roman, Mary J.; Devereux, Richard B.; Preiss, Liliana R.; Asch, Federico M.; Eagle, Kim A.; Holmes, Kathryn W.; LeMaire, Scott A.; Maslen, Cheryl L.; Milewicz, Dianna M.; Morris, Shaine A.; Prakash, Siddharth K.; Pyeritz, Reed E.; Ravekes, William J.; Shohet, Ralph V.; Song, Howard K.; Weinsaft, Jonathan W.

2017-01-01

Background The associations of age and sex with phenotypic features of Marfan syndrome have not been systematically examined in a large cohort of both children and adults. Methods and Results We evaluated 789 Marfan patients enrolled in the NHLBI GenTAC Registry (53% male; mean age 31 [range: 1–86 years]). Females aged≥15 and males aged≥16 years were considered adults based on average age of skeletal maturity. Adults (n=606) were more likely than children (n=183) likely to have spontaneous pneumothorax, scoliosis, and striae, but were comparable in revised Ghent systemic score, ectopia lentis, and most phenotypic features, including prevalence of aortic root dilatation. Prophylactic aortic root replacement and mitral valve surgery were rare during childhood vs. adulthood (2 vs. 35% and 1 vs. 9%, respectively, both p<0.0001). Adult males were more likely than females to have aortic root dilatation (92 vs. 84%), aortic regurgitation (55 vs. 36%) and to have undergone prophylactic aortic root replacement (47 vs. 24%), all p<0.001. Prevalence of prior aortic dissection tended to be higher in males than females (25 vs. 18%, p=0.06); 44% of dissections were type B. Type B dissection was strongly associated with previous prophylactic aortic root replacement. Conclusions Pulmonary, skeletal and aortic complications, but not other phenotypic features, are more prevalent in adults than children in Marfan syndrome. Aortic aneurysms and prophylactic aortic surgery are more common in men. Aortic dissection, commonly type B, occurs in an appreciable proportion of Marfan patients, especially in men and following previous prophylactic aortic root replacement. PMID:28600386

Changes in Aggressiveness of the Ascochyta lentis Population in Southern Australia

PubMed Central

Davidson, Jennifer; Smetham, Gabriel; Russ, Michelle H.; McMurray, Larn; Rodda, Matthew; Krysinska-Kaczmarek, Marzena; Ford, Rebecca

2016-01-01

Anecdotal evidence identified a change in the reaction of the resistant lentil cv Nipper to ascochyta blight in South Australia in 2010 and subsequent seasons, leading to infection. This study investigated field reactions of lentil cultivars against Ascochyta lentis and the pathogenic variability of the A. lentis population in southern Australia on commonly grown cultivars and on parental germplasm used in the Australian lentil breeding program. Disease data recorded in agronomic and plant breeder field trials from 2005 to 2014 in southern Australia confirmed the change in reaction on the foliage of the previously resistant cvs Nipper and Northfield. Cultivar responses to seed staining from A. lentis did not change. The change in foliar response was confirmed in a series of controlled environment experiments using single, conidium-derived, isolates of A. lentis collected over different years and inoculated onto differential host sets. Specific isolate/cultivar interactions produced a significant range of disease reactions from high to low aggressiveness with a greater percentage of isolates more aggressive on cvs Nipper, Northfield and PBA Flash than previously detected. Specific isolates were tested against Australian lentil cultivars and breeding lines in controlled conditions, again verifying the aggressiveness on cv Nipper. A small percentage of isolates collected prior to the commercial release of cv Nipper were also able to infect this cultivar indicating a natural variability of the A. lentis population which subsequently may have been selected in response to high cropping intensity of cv Nipper. Spore release studies from naturally infested lentil stubbles collected from commercial crops also resulted in a high percentage of infection on the previously resistant cvs Nipper and Northfield. Less than 10% of the lesions developed on the resistant differentials ILL7537 and cv Indianhead. Pathogenic variation within the seasonal populations was not affected by the cultivar from which the stubble was sourced, further indicating a natural variability in aggressiveness. The impact of dominant cultivars in cropping systems and loss of effective disease resistance is discussed. Future studies are needed to determine if levels of aggressiveness among A. lentis isolates are increasing against a range of elite cultivars. PMID:27065073

Headache in children with Chiari I malformation.

PubMed

Toldo, Irene; Tangari, Marta; Mardari, Rodica; Perissinotto, Egle; Sartori, Stefano; Gatta, Michela; Calderone, Milena; Battistella, Pier Antonio

2014-05-01

Headache is the most common symptom of Chiari 1 malformation, a condition characterized by the herniation of cerebellar tonsils through the foramen magnum. However, the headache pattern of cases with Chiari 1 malformations is not well defined in the literature, especially in children. The aim of this retrospective chart review was to evaluate the frequency and the characteristics of headache in children with Chiari 1 malformation at initial evaluation and during follow up. Forty-five cases with tonsillar ectopia were selected among 9947 cases under 18 years of age who underwent neuroimaging between 2002 and 2010. A semistructured clinical interview (mean follow-up: 5.2 years) was conducted. Headache was classified according to the second edition of the International Classification of Headache Disorders. Possible associations between clinical picture, in particular headache pattern, but also other signs and symptoms attributable to Chiari 1 malformation, and the extent of tonsillar ectopia were found for 3 different groups: those with borderline (<5 mm, N = 12), mild (5-9 mm, N = 27), and severe tonsillar ectopia (≥10 mm, N = 6), respectively. Twenty-four out of 33 (73%) cases with Chiari 1 malformation complained of headache, and 9/33 (27%) of those patients (5 with mild and 4 with severe tonsillar ectopia) reported headache attributed to Chiari 1 malformation. In our studied pediatric population, the most common symptom for cases diagnosed with Chiari 1 malformation was headache, and headache attributed to Chiari 1 malformation was the most common headache pattern in patients with Chiari 1 malformation. The presence of headache attributed to Chiari 1 malformation along with 3 other signs or symptoms of Chiari 1 malformation were highly predictive of severe tonsillar ectopia. © 2014 American Headache Society.

STAT3/NF-κB-Regulated Lentiviral TK/GCV Suicide Gene Therapy for Cisplatin-Resistant Triple-Negative Breast Cancer

PubMed Central

Kuo, Wei-Ying; Hwu, Luen; Wu, Chun-Yi; Lee, Jhih-Shian; Chang, Chi-Wei; Liu, Ren-Shyan

2017-01-01

Triple-negative breast cancer (TNBC) represents approximately 20% of all breast cancers and appears resistance to conventional cytotoxic chemotherapy, demonstrating a particularly poor prognosis and a significantly worse clinical outcome than other types of cancer. Suicide gene therapy has been used for the in vivo treatment of various solid tumors in recent clinical trials. In tumor microenvironment, STAT3/NF-κB pathways are constitutively activated in stromal cells as well as in cancer stem cells (CSCs). In this study, we have cloned a novel STAT3/NF-κB-based reporter system to drive the expression of herpes simplex virus thymidine kinase (HSV-TK) against breast cancer. Lentiviral vector expressing HSV-TK under the regulation of STAT3/NF-κB fused response element was developed. In this setting, we exploited the constitutive STAT3/NF-κB activation in tumors to achieve higher transgene expression than that driven by a constitutively active CMV promotor in vivo. An orthotropic MDA-MB-231 triple negative breast cancer mouse model was used for evaluating the feasibility of STAT3-NF-κB-TK/GCV suicide gene therapy system. The basal promoter activity of Lenti-CMV-TK and Lenti-STAT3-NF-κB-TK in MDA-MB-231 cells was compared by 3H-FEAU uptake assay. The Lenti-CMV-TK showed ~5 fold higher 3H-FEAU uptake then Lenti -STAT3-NF-κB-TK. In clonogenic assay, cells expressing Lenti-CMV-TK were 2-fold more sensitive to GCV than Lenti-STAT3-NF-κB-TK transduced cells. In vitro effect of STAT3-NF-κB-induced transgene expression was determined by 10ng/mL TNF-α induction and confirmed by western blot analysis and DsRedm fluorescent microscopy. In vivo evaluation of therapeutic effect by bioluminescence and [18F]FHBG microPET imaging indicated that Lenti-STAT3-NF-κB-TK showed more tumor growth retardation than Lenti-CMV-TK when GCV (20 mg/kg) was administered. The invasiveness and expression of cancer stem cell markers were both decreased after STAT3/NF-κB-regulated HSV-TK/GCV therapy. Moreover, STAT3/NF-κB signaling targeting could further sensitize tumor cells to cisplatin. This study successfully established a theranositic approach to treat triple-negative breast cancer via STAT3-NF-κB responsive element-driven suicide gene therapy. This platform may also be an alternative strategy to handle with drug-resistant cancer cells. PMID:28255357

[Intramuscular injection of lentivirus-mediated EPAS1 gene improves hind limb ischemia and its mechanism in a rat model of peripheral artery vascular disease].

PubMed

Wang, Zhihong; Gu, Hongbin; Yang, Fan; Xie, Huajie; Sheng, Lei; Li, Mingfei

2017-11-01

Objective To investigate the effect of over-expressed endothelial Per-Arnt-Sim domain protein 1 (EPAS1) on peripheral arterial disease (PAD) in a rat model. Methods PAD rat model was established by external iliac artery ligation followed by lentivirus-mediated EPAS1 gene injection into rat right adductor magnus. The models were evaluated by quantitative analysis of gait disturbance. The changes of blood flow in the posterior extremity of the rats were detected using laser Doppler. The expressions of EPAS1, hepatocyte growth factor (HGF), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) mRNAs were tested by real-time quantitative PCR. The expression of α-smooth muscle actin (αSMA) was detected by immunohistochemical staining. Results Compared with lenti-EGFP group, rat hind limb function and circulation got recovered obviously 7 days after lenti-EPAS1 injection. The mRNA expressions of EPAS1, HGF, bFGF, and VEGF were up-regulated in the lenti-EPAS1-treated sites.The expression of αSMA showed an obvious increase in the lenti-EPAS1-treated muscles. Conclusion Over-expressed lenti-EPAS1 can promote angiogenesis via the up-regulation of EPAS1-related angiogenic factors in the muscles of the affected hind limb and reduce gait disturbance.

Image quality comparison of two multifocal IOLs: influence of the pupil.

PubMed

García-Domene, Mari Carmen; Felipe, Adelina; Peris-Martínez, Cristina; Navea, Amparo; Artigas, Jose M; Pons, Álvaro M

2015-04-01

To evaluate the effect of pupil size on image quality of a sectorial multifocal intraocular lens (IOL), the Lentis Mplus (Oculentis GmbH, Berlin, Germany), and the Acri.LISA IOL (Carl Zeiss Meditec, Jena, Germany). The authors measured the MTFs of the Lentis Mplus LS-312 IOL and the Acri.LISA 366D IOL with three different sizes of pupil diameters: 3, 4, and 5 mm. The MTF was calculated from the cross-line spread function recorded with the OPAL Vector System (Image Science Ltd., Oxford, UK) by using fast Fourier-transform techniques. In distance focus, the image quality provided by the Lentis Mplus IOL was better than that of the Acri. LISA IOL with all pupil diameters. In near focus, the MTF of the Acri.LISA IOL was better with a 3-mm pupil, but poor with larger pupils. The aberration effect was equal in both IOLs in distance focus, but in near focus and with a 3-mm pupil, the Acri.LISA IOL was less affected by the aberration than the Lentis Mplus IOL. The Lentis Mplus IOL provides better distance image quality than the Acri.LISA IOL, whereas the near image quality of the Acri.LISA IOL is better with small-pupil diameter. The sectorial design makes this IOL more suitable for patients with a pupil diameter greater than 3 mm. Copyright 2015, SLACK Incorporated.

Morphological and molecular characterization of Pratylenchus lentis n. sp. (Nematoda: Pratylenchidae) from Sicily

USDA-ARS?s Scientific Manuscript database

Pratylenchus lentis n. sp. parasitizing roots of lentil in Sicily, Italy, is described and illustrated. The new species is characterized by a high lip region with three annuli, stylet mean length of 16 micrometers with anteriorly flattened knobs, cylindrical body with a relatively anterior vulva, l...

Cytological and histopathological abnormalities of the cervix in genital Chlamydia trachomatis infections.

PubMed

Cevenini, R; Costa, S; Rumpianesi, F; Donati, M; Guerra, B; Diana, R; Antonini, M P

1981-10-01

Since genital infection with Chlamydia trachomatis may be associated with cervical abnormalities 160 patients with grandular ectopia attending a gynaecological outpatient clinic were examined for antibodies against C trachomatis, the presence of C trachomatis infection, and cytological and histopathological abnormalities of the cervix.A significantly higher incidence of histological dysplasia was found in women with glandular ectopia who had antichlamydial antibodies than in those without.

Cytological and histopathological abnormalities of the cervix in genital Chlamydia trachomatis infections

PubMed Central

Cevenini, R; Costa, S; Rumpianesi, F; Donati, M; Guerra, B; Diana, R; Antonini, M P

1981-01-01

Since genital infection with Chlamydia trachomatis may be associated with cervical abnormalities 160 patients with grandular ectopia attending a gynaecological outpatient clinic were examined for antibodies against C trachomatis, the presence of C trachomatis infection, and cytological and histopathological abnormalities of the cervix. A significantly higher incidence of histological dysplasia was found in women with glandular ectopia who had antichlamydial antibodies than in those without. PMID:7296254

Biometric and structural ocular manifestations of Marfan syndrome.

PubMed

Gehle, Petra; Goergen, Barbara; Pilger, Daniel; Ruokonen, Peter; Robinson, Peter N; Salchow, Daniel J

2017-01-01

To study biometric and structural ocular manifestations of Marfan syndrome (MFS). Observational, retrospective, comparative cohort study in a tertiary referral center on 285 MFS patients and 267 controls. Structural and biometric ocular characteristic were compared. MFS eyes were longer (axial length 24.25 ± 1.74 mm versus 23.89 ± 1.31 mm, p < 0.001) and had a flatter cornea than control eyes (mean keratometry 41.78 ± 1.80 diopters (D) versus 43.05 ± 1.51 D, p < 0.001). Corneal astigmatism was greater and the central cornea was thinner in MFS eyes (530.14 ± 41.31 μm versus 547.02 ± 39.18 μm, p < 0.001). MFS eyes were more myopic than control eyes (spherical equivalent -2.16 ± 3.75 D versus -1.17 ± 2.58 D, p < 0.001). Visual acuity was reduced (0.13 ± 0.25 logMAR versus 0.05 ± 0.18 logMAR, p < 0.001) and intraocular pressure was lower in MFS eyes (14.6 ± 3.4 mmHg versus 15.1 ± 3.2 mmHg, p = 0.01). Iris transillumination defects (ITD) were significantly more common in MFS eyes (odds ratio for MFS in the presence of ITD, 3.7). Ectopia lentis (EL) was only present in MFS eyes (33.4%). History of retinal detachment was significantly more common in MFS eyes. Glaucoma was equally common in both groups. ITD and EL are most characteristic findings in MFS. ITD and corneal curvature should be studied as diagnostic criteria for MFS. Visual acuity is reduced in MFS. MFS patients need regular eye exams to identify serious ocular complications.

Visual outcomes after lensectomy and iris claw artisan intraocular lens implantation in patients with Marfan syndrome.

PubMed

Rabie, Hossein Mohammad; Malekifar, Parviz; Javadi, Mohammad Ali; Roshandel, Danial; Esfandiari, Hamed

2017-08-01

To review our experience with crystalline lens extraction and iris claw Artisan IOL implantation in patients with lens subluxation secondary to Marfan syndrome. A retrospective analysis of 12 eyes of 9 patients with lens subluxation due to Marfan syndrome who underwent crystalline lens removal and Artisan IOL (Ophtec, Groningen, Netherlands) implantation. A questionnaire of pre- and post-operative data, including demographics, pre- and postoperative comorbidities and complications was completed. Patients were evaluated for visual outcome and occurrence of complications. Uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), and spherical equivalents (SE) were compared before and after lens extraction and IOL insertion. The mean age of the participants was 30.03 ± 15.02 years, and mean post-operative follow-up time was 44.5 ± 16.4 months. Mean BCVA also showed a significant improvement from 0.5 ± 0.3 at the baseline to 0.2 ± 0.2 post-operatively (P = 0.006). SE changed significantly from -11.38 ± 1.99 preoperatively to -0.45 ± 1.65 post-operatively (P = 0.003). All eyes had the IOL implanted at desired position. Post-operative complications were retinal detachment in one case and IOL dislocation in another patient. No other complication such as ocular hypertension, angle abnormalities, clinical cystoids macular edema, and corneal decompensation was observed during the follow-up period. Artisan IOL implantation after lens extraction appears to be an attractive alternative for optical correction in cases of Marfan syndrome with ectopia lentis. It confers a significant improvement in visual acuity with reasonable risk profile.

Clinical and mutation-type analysis from an international series of 198 probands with a pathogenic FBN1 exons 24–32 mutation

PubMed Central

Faivre, L; Collod-Beroud, G; Callewaert, B; Child, A; Binquet, C; Gautier, E; Loeys, B L; Arbustini, E; Mayer, K; Arslan-Kirchner, M; Stheneur, C; Kiotsekoglou, A; Comeglio, P; Marziliano, N; Wolf, J E; Bouchot, O; Khau-Van-Kien, P; Beroud, C; Claustres, M; Bonithon-Kopp, C; Robinson, P N; Adès, L; De Backer, J; Coucke, P; Francke, U; De Paepe, A; Jondeau, G; Boileau, C

2009-01-01

Mutations in the FBN1 gene cause Marfan syndrome (MFS) and a wide range of overlapping phenotypes. The severe end of the spectrum is represented by neonatal MFS, the vast majority of probands carrying a mutation within exons 24–32. We previously showed that a mutation in exons 24–32 is predictive of a severe cardiovascular phenotype even in non-neonatal cases, and that mutations leading to premature truncation codons are under-represented in this region. To describe patients carrying a mutation in this so-called ‘neonatal' region, we studied the clinical and molecular characteristics of 198 probands with a mutation in exons 24–32 from a series of 1013 probands with a FBN1 mutation (20%). When comparing patients with mutations leading to a premature termination codon (PTC) within exons 24–32 to patients with an in-frame mutation within the same region, a significantly higher probability of developing ectopia lentis and mitral insufficiency were found in the second group. Patients with a PTC within exons 24–32 rarely displayed a neonatal or severe MFS presentation. We also found a higher probability of neonatal presentations associated with exon 25 mutations, as well as a higher probability of cardiovascular manifestations. A high phenotypic heterogeneity could be described for recurrent mutations, ranging from neonatal to classical MFS phenotype. In conclusion, even if the exons 24–32 location appears as a major cause of the severity of the phenotype in patients with a mutation in this region, other factors such as the type of mutation or modifier genes might also be relevant. PMID:19002209

Biometric and structural ocular manifestations of Marfan syndrome

PubMed Central

Gehle, Petra; Goergen, Barbara; Pilger, Daniel; Ruokonen, Peter; Robinson, Peter N.

2017-01-01

Background To study biometric and structural ocular manifestations of Marfan syndrome (MFS). Methods Observational, retrospective, comparative cohort study in a tertiary referral center on 285 MFS patients and 267 controls. Structural and biometric ocular characteristic were compared. Results MFS eyes were longer (axial length 24.25 ± 1.74 mm versus 23.89 ± 1.31 mm, p < 0.001) and had a flatter cornea than control eyes (mean keratometry 41.78 ± 1.80 diopters (D) versus 43.05 ± 1.51 D, p < 0.001). Corneal astigmatism was greater and the central cornea was thinner in MFS eyes (530.14 ± 41.31 μm versus 547.02 ± 39.18 μm, p < 0.001). MFS eyes were more myopic than control eyes (spherical equivalent -2.16 ± 3.75 D versus -1.17 ± 2.58 D, p < 0.001). Visual acuity was reduced (0.13 ± 0.25 logMAR versus 0.05 ± 0.18 logMAR, p < 0.001) and intraocular pressure was lower in MFS eyes (14.6 ± 3.4 mmHg versus 15.1 ± 3.2 mmHg, p = 0.01). Iris transillumination defects (ITD) were significantly more common in MFS eyes (odds ratio for MFS in the presence of ITD, 3.7). Ectopia lentis (EL) was only present in MFS eyes (33.4%). History of retinal detachment was significantly more common in MFS eyes. Glaucoma was equally common in both groups. Conclusions ITD and EL are most characteristic findings in MFS. ITD and corneal curvature should be studied as diagnostic criteria for MFS. Visual acuity is reduced in MFS. MFS patients need regular eye exams to identify serious ocular complications. PMID:28931008

Novel association of VACTERL, neural tube defect and crossed renal ectopia: sonic hedgehog signaling: a point of coherence?

PubMed

Vaze, Dhananjay; Mahalik, Santosh; Rao, Katragadda L N

2012-12-01

The present case report describes two patients with a novel combination of VACTERL (vertebral, anorectal, cardiac, tracheoesophageal, renal, limb), neural tube defect and crossed renal ectopia. Though cases of VACTERL associated with crossed renal ectopia have been described, the present case report is the first to describe its combination with neural tube defect. The cases reported here are significant because central nervous system manifestations are scarce in VACTERL syndrome. The role of sonic hedgehog pathway has been proposed in VACTERL association and neural tube defects. Axial Sonic hedgehog signaling has also been implicated in the mediolateral positioning of the renal parenchyma. With this knowledge, the etiopathogenesis of this novel combination is discussed to highlight the role of sonic hedgehog signaling as a point of coherence. © 2011 The Authors. Congenital Anomalies © 2011 Japanese Teratology Society.

Androgen Receptor-Mediated Growth Suppression of HPr-1AR and PC3-Lenti-AR Prostate Epithelial Cells

PubMed Central

Bolton, Eric C.

2015-01-01

The androgen receptor (AR) mediates the developmental, physiologic, and pathologic effects of androgens including 5α-dihydrotestosterone (DHT). However, the mechanisms whereby AR regulates growth suppression and differentiation of luminal epithelial cells in the prostate gland and proliferation of malignant versions of these cells are not well understood, though they are central to prostate development, homeostasis, and neoplasia. Here, we identify androgen-responsive genes that restrain cell cycle progression and proliferation of human prostate epithelial cell lines (HPr-1AR and PC3-Lenti-AR), and we investigate the mechanisms through which AR regulates their expression. DHT inhibited proliferation of HPr-1AR and PC3-Lenti-AR, and cell cycle analysis revealed a prolonged G1 interval. In the cell cycle, the G1/S-phase transition is initiated by the activity of cyclin D and cyclin-dependent kinase (CDK) complexes, which relieve growth suppression. In HPr-1AR, cyclin D1/2 and CDK4/6 mRNAs were androgen-repressed, whereas CDK inhibitor, CDKN1A, mRNA was androgen-induced. The regulation of these transcripts was AR-dependent, and involved multiple mechanisms. Similar AR-mediated down-regulation of CDK4/6 mRNAs and up-regulation of CDKN1A mRNA occurred in PC3-Lenti-AR. Further, CDK4/6 overexpression suppressed DHT-inhibited cell cycle progression and proliferation of HPr-1AR and PC3-Lenti-AR, whereas CDKN1A overexpression induced cell cycle arrest. We therefore propose that AR-mediated growth suppression of HPr-1AR involves cyclin D1 mRNA decay, transcriptional repression of cyclin D2 and CDK4/6, and transcriptional activation of CDKN1A, which serve to decrease CDK4/6 activity. AR-mediated inhibition of PC3-Lenti-AR proliferation occurs through a similar mechanism, albeit without down-regulation of cyclin D. Our findings provide insight into AR-mediated regulation of prostate epithelial cell proliferation. PMID:26372468

Reduced 64Cu uptake and tumor growth inhibition by knockdown of human copper transporter 1 in xenograft mouse model of prostate cancer.

PubMed

Cai, Huawei; Wu, Jiu-sheng; Muzik, Otto; Hsieh, Jer-Tsong; Lee, Robert J; Peng, Fangyu

2014-04-01

Copper is an element required for cell proliferation and angiogenesis. Human prostate cancer xenografts with increased (64)Cu radioactivity were visualized previously by PET using (64)CuCl2 as a radiotracer ((64)CuCl2 PET). This study aimed to determine whether the increased tumor (64)Cu radioactivity was due to increased cellular uptake of (64)Cu mediated by human copper transporter 1 (hCtr1) or simply due to nonspecific binding of ionic (64)CuCl2 to tumor tissue. In addition, the functional role of hCtr1 in proliferation of prostate cancer cells and tumor growth was also assessed. A lentiviral vector encoding short-hairpin RNA specific for hCtr1 (Lenti-hCtr1-shRNA) was constructed for RNA interference-mediated knockdown of hCtr1 expression in prostate cancer cells. The degree of hCtr1 knockdown was determined by Western blot, and the effect of hCtr1 knockdown on copper uptake and proliferation were examined in vitro by cellular (64)Cu uptake and cell proliferation assays. The effects of hCtr1 knockdown on tumor uptake of (64)Cu were determined by PET quantification and tissue radioactivity assay. The effects of hCtr1 knockdown on tumor growth were assessed by PET/CT and tumor size measurement with a caliper. RNA interference-mediated knockdown of hCtr1 was associated with the reduced cellular uptake of (64)Cu and the suppression of prostate cancer cell proliferation in vitro. At 24 h after intravenous injection of the tracer (64)CuCl2, the (64)Cu uptake by the tumors with knockdown of hCtr1 (4.02 ± 0.31 percentage injected dose per gram [%ID/g] in Lenti-hCtr1-shRNA-PC-3 and 2.30 ± 0.59 %ID/g in Lenti-hCtr1-shRNA-DU-145) was significantly lower than the (64)Cu uptake by the control tumors without knockdown of hCtr1 (7.21 ± 1.48 %ID/g in Lenti-SCR-shRNA-PC-3 and 5.57 ± 1.20 %ID/g in Lenti-SCR-shRNA-DU-145, P < 0.001) by PET quantification. Moreover, the volumes of prostate cancer xenograft tumors with knockdown of hCtr1 (179 ± 111 mm(3) for Lenti-hCtr1-shRNA-PC-3 or 39 ± 22 mm(3) for Lenti-hCtr1-shRNA-DU-145) were significantly smaller than those without knockdown of hCtr1 (536 ± 191 mm(3) for Lenti- SCR-shRNA-PC-3 or 208 ± 104 mm(3) for Lenti-SCR-shRNA-DU-145, P < 0.01). Overall, data indicated that hCtr1 is a promising theranostic target, which can be further developed for metabolic imaging of prostate cancer using (64)CuCl2 PET/CT and personalized cancer therapy targeting copper metabolism.

Persistent hyperplastic tunica vasculosa lentis and persistent hyperplastic primary vitreous in transgenic line TgN3261Rpw.

PubMed

Colitz, C M; Malarkey, D E; Woychik, R P; Wilkinson, J E

2000-09-01

Persistent hyperplastic tunica vasculosa lentis and persistent hyperplastic primary vitreous are congenital ocular anomalies that can lead to cataract formation. A line of insertional mutant mice, TgN3261Rpw, generated at the Oak Ridge National Laboratory in a large-scale insertional mutagenesis program was found to have a low incidence (8/243; 3.29%) of multiple developmental ocular abnormalities. The ocular abnormalities include persistent hyperplastic primary vitreous, persistent hyperplastic tunica vasculosa lentis, failure of cleavage of the anterior segment, retrolental fibrovascular membrane, posterior polar cataract, and detached retina. This transgenic mouse line provides an ontogenetic model because of the high degree of similarity of this entity in humans, dogs, and mice.

Traumatic Transient Herniation Concomitant with Tonsillar Hemorrhagic Contusion in a Child

PubMed Central

Öğrenci, Ahmet; Koban, Orkun; Ekşi, Murat; Yaman, Onur; Dalbayrak, Sedat

2017-01-01

Downward displacement of cerebellar tonsils more than 5 mm below the foramen magnum is named as Chiari type I malformation and named benign tonsillar ectopia if herniation is less than 3 mm. It does not just depend on congenital causes. There are also some reasons for acquired Chiari Type 1 and benign tonsillar ectopia/herniation. Trauma is one of them. Trauma may increase tonsillar ectopia or may be the cause of new-onset Chiari type 1. The relationship between the tonsil contusion and its position is unclear. We present a case of pediatric age group with tonsillar herniation with a hemorrhagic contusion. Only 1 case has been presented so far in the literature. A case with unilateral tonsil contusion has not been presented to date. We will discuss the possible reasons for taking the place of the tonsils to the above level of the foramen magnum in the follow-up period, by looking at the literature. PMID:29104687

Persistent Mullerian Duct Syndrome: an interesting case report.

PubMed

Farag, S; Sutton, P; Leow, K S; Kosai, N R; Razman, J; Hanafiah, H; Das, S

2013-01-01

Transverse testicular ectopia is an uncommon disorder of testicular ectopia. Nearly thirty percent of the cases is associated with Persistent mullerian duct syndrome which is characterized by karyotypically normal males with retained mullerian derivatives. Understanding the natural process of the condition and the association with malignant potential will allow for a better understanding of the optimal surgical approach. This is a case report of young male presented a left sided inguinal hernia in which the sac contained both testes and uterus. The literature review of the syndrome will be discussed.

Behavior, cortical ectopias, and autoimmunity in BXSB-Yaa and BXSB-Yaa+ mice.

PubMed

Schrott, L M; Waters, N S; Boehm, G W; Sherman, G F; Morrison, L; Rosen, G D; Behan, P O; Galaburda, A M; Denenberg, V H

1993-09-01

The BXSB-Yaa recombinant inbred strain was created by crossing a male SB/Le with a female C57BL/6J. A Y chromosome factor derived from the SB/Le male, known as the autoimmune accelerator (Yaa), leads to an earlier onset and greater severity of autoimmune disease in males. In contrast, male BXSB mice, which lack the Yaa gene (called BXSB-Yaa+) because their Y chromosome is derived from the C57BL/6J, do not develop an autoimmune condition. To examine the influence of the Y chromosome on behavior, cortical ectopia incidence, and immune functioning, males and females of these two strains were compared. Significant strain differences (for both sexes) were found for behavioral measures including discrimination, spatial and avoidance learning, and activity. For immunological parameters, a sex difference was seen in the BXSB-Yaa (males more autoimmune), but not in the BXSB-Yaa+ strain. As expected, male BXSB-Yaas were more autoimmune than male BXSB-Yaa+s. However, there was also a strain difference for IgG in the females (BXSB-Yaa+ greater). No strain difference was found for the presence of ectopias. However, there was a sex difference across both strains, with males having a higher incidence. BXSB-Yaa and BXSB-Yaa+ mice have behavioral and immunological differences greater than would be predicted by their known genetic differences. The significant differences between the two female groups suggest that the two strains differ with respect to autosomal genes, in addition to the Y chromosome. The incidence of ectopias is independent of this genetic difference and is influenced by the subject's sex.

GABAergic excitation after febrile seizures induces ectopic granule cells and adult epilepsy.

PubMed

Koyama, Ryuta; Tao, Kentaro; Sasaki, Takuya; Ichikawa, Junya; Miyamoto, Daisuke; Muramatsu, Rieko; Matsuki, Norio; Ikegaya, Yuji

2012-08-01

Temporal lobe epilepsy (TLE) is accompanied by an abnormal location of granule cells in the dentate gyrus. Using a rat model of complex febrile seizures, which are thought to be a precipitating insult of TLE later in life, we report that aberrant migration of neonatal-generated granule cells results in granule cell ectopia that persists into adulthood. Febrile seizures induced an upregulation of GABA(A) receptors (GABA(A)-Rs) in neonatally generated granule cells, and hyperactivation of excitatory GABA(A)-Rs caused a reversal in the direction of granule cell migration. This abnormal migration was prevented by RNAi-mediated knockdown of the Na(+)K(+)2Cl(-) co-transporter (NKCC1), which regulates the excitatory action of GABA. NKCC1 inhibition with bumetanide after febrile seizures rescued the granule cell ectopia, susceptibility to limbic seizures and development of epilepsy. Thus, this work identifies a previously unknown pathogenic role of excitatory GABA(A)-R signaling and highlights NKCC1 as a potential therapeutic target for preventing granule cell ectopia and the development of epilepsy after febrile seizures.

[Arterial involvements in hereditary dysplasia of the connective tissue].

PubMed

Beylot, C; Doutre, M S; Beylot-Barry, M; Busquet, M

1994-03-01

Arterial involvement is an important feature of the diagnosis and, above all, prognosis of heritable disorders of connective tissue. In pseudoxanthoma elasticum, a progressive occlusive syndrome is associated with hemorrhage and especially with gastrointestinal bleeding. Aneurysms are uncommon. Hypertension occurs frequently. Cutaneous signs (yellowish pseudo xanthomatous papules of the large folds) the ocular changes (angioid streaks) and pathology showing numerous, thickened, fragmented, disorganized, calcified elastic fibers in the deep dermis and arterial walls, allow the diagnosis to be made. In the heterogeneous group of Ehlers-Danlos syndromes, type IV is characterized by sudden spontaneous rupture of the large arteries. Aneurysms and carotido-cavernous fistulae are rather frequent. Owing to friability of the arterial walls, arteriograms and other procedure requiring arterial puncture may prove hazardous and surgery difficult. Such patients have an acrogeric morphotype, and thin, fragile skin, but cutaneous hyperelasticity and joint hyperlaxity are usually minimal. Pathology evidences collagen hypoplasia in the skin and arterial walls. The severity of Marfan syndrome is due to aortic involvement. A fusiform aneurysm of the ascending aorta represents a vital risk of rupture. Aortic root dilatation is associated and responsible of severe aortic regurgitation. Aortic dissection is also a serious threat. Improved surgical techniques for repairing a dilated or dissected aortic root with simultaneous replacement of the aortic valve increases the life expectancy of such patients. Dolichomorphism is the characteristic skeletal abnormality, particularly with arachnodactyly and upward ectopia lentis, which is almost bilateral, is a very frequent feature of Marfan syndrome. The most typical histological finding is aortic cystic median necrosis. The basic defect in Marfan syndrome concerns the fibrillin, whose gene is located on chromosome 15. The three diseases detailed in this paper constitute the main areas of this subject, but arterial involvement may occur in other inheritable disorders of connective tissue (osteogenesis imperfecta, cutis laxa, Werner syndrome, Menkes syndrome, etc).

Differences in manifestations of Marfan syndrome, Ehlers-Danlos syndrome, and Loeys-Dietz syndrome.

PubMed

Meester, Josephina A N; Verstraeten, Aline; Schepers, Dorien; Alaerts, Maaike; Van Laer, Lut; Loeys, Bart L

2017-11-01

Many different heritable connective tissue disorders (HCTD) have been described over the past decades. These syndromes often affect the connective tissue of various organ systems, including heart, blood vessels, skin, joints, bone, eyes, and lungs. The discovery of these HCTD was followed by the identification of mutations in a wide range of genes encoding structural proteins, modifying enzymes, or components of the TGFβ-signaling pathway. Three typical examples of HCTD are Marfan syndrome (MFS), Ehlers-Danlos syndrome (EDS), and Loeys-Dietz syndrome (LDS). These syndromes show some degree of phenotypical overlap of cardiovascular, skeletal, and cutaneous features. MFS is typically characterized by cardiovascular, ocular, and skeletal manifestations and is caused by heterozygous mutations in FBN1 , coding for the extracellular matrix (ECM) protein fibrillin-1. The most common cardiovascular phenotype involves aortic aneurysm and dissection at the sinuses of Valsalva. LDS is caused by mutations in TGBR1/2 , SMAD2/3 , or TGFB2/3 , all coding for components of the TGFβ-signaling pathway. LDS can be distinguished from MFS by the unique presence of hypertelorism, bifid uvula or cleft palate, and widespread aortic and arterial aneurysm and tortuosity. Compared to MFS, LDS cardiovascular manifestations tend to be more severe. In contrast, no association is reported between LDS and the presence of ectopia lentis, a key distinguishing feature of MFS. Overlapping features between MFS and LDS include scoliosis, pes planus, anterior chest deformity, spontaneous pneumothorax, and dural ectasia. EDS refers to a group of clinically and genetically heterogeneous connective tissue disorders and all subtypes are characterized by variable abnormalities of skin, ligaments and joints, blood vessels, and internal organs. Typical presenting features include joint hypermobility, skin hyperextensibility, and tissue fragility. Up to one quarter of the EDS patients show aortic aneurysmal disease. The latest EDS nosology distinguishes 13 subtypes. Many phenotypic features show overlap between the different subtypes, which makes the clinical diagnosis rather difficult and highlights the importance of molecular diagnostic confirmation.

Differences in manifestations of Marfan syndrome, Ehlers-Danlos syndrome, and Loeys-Dietz syndrome

PubMed Central

Meester, Josephina A. N.; Verstraeten, Aline; Schepers, Dorien; Alaerts, Maaike; Van Laer, Lut

2017-01-01

Many different heritable connective tissue disorders (HCTD) have been described over the past decades. These syndromes often affect the connective tissue of various organ systems, including heart, blood vessels, skin, joints, bone, eyes, and lungs. The discovery of these HCTD was followed by the identification of mutations in a wide range of genes encoding structural proteins, modifying enzymes, or components of the TGFβ-signaling pathway. Three typical examples of HCTD are Marfan syndrome (MFS), Ehlers-Danlos syndrome (EDS), and Loeys-Dietz syndrome (LDS). These syndromes show some degree of phenotypical overlap of cardiovascular, skeletal, and cutaneous features. MFS is typically characterized by cardiovascular, ocular, and skeletal manifestations and is caused by heterozygous mutations in FBN1, coding for the extracellular matrix (ECM) protein fibrillin-1. The most common cardiovascular phenotype involves aortic aneurysm and dissection at the sinuses of Valsalva. LDS is caused by mutations in TGBR1/2, SMAD2/3, or TGFB2/3, all coding for components of the TGFβ-signaling pathway. LDS can be distinguished from MFS by the unique presence of hypertelorism, bifid uvula or cleft palate, and widespread aortic and arterial aneurysm and tortuosity. Compared to MFS, LDS cardiovascular manifestations tend to be more severe. In contrast, no association is reported between LDS and the presence of ectopia lentis, a key distinguishing feature of MFS. Overlapping features between MFS and LDS include scoliosis, pes planus, anterior chest deformity, spontaneous pneumothorax, and dural ectasia. EDS refers to a group of clinically and genetically heterogeneous connective tissue disorders and all subtypes are characterized by variable abnormalities of skin, ligaments and joints, blood vessels, and internal organs. Typical presenting features include joint hypermobility, skin hyperextensibility, and tissue fragility. Up to one quarter of the EDS patients show aortic aneurysmal disease. The latest EDS nosology distinguishes 13 subtypes. Many phenotypic features show overlap between the different subtypes, which makes the clinical diagnosis rather difficult and highlights the importance of molecular diagnostic confirmation. PMID:29270370

Biometry Characteristics in Adults and Children With Marfan Syndrome: From the Marfan Eye Consortium of Chicago.

PubMed

Kinori, Michael; Wehrli, Sarah; Kassem, Iris S; Azar, Nathalie F; Maumenee, Irene H; Mets, Marilyn B

2017-05-01

To report on the biometric findings of adults and children with Marfan syndrome (MFS) recruited from 2 annual National Marfan Foundation conferences (2012 and 2015). Cross-sectional study. Subjects diagnosed with MFS by Ghent 2 nosology were included for analysis. Subjects were divided into "adults" (≥16 years of age) and "children" (5-15 years of age). Biometric data included values for refractive error, axial length (AL), corneal curvature, anterior chamber depth, lens thickness, and central corneal thickness. Of the 117 subjects evaluated, 74 (35 adults, 32 children, and 7 children <5 years of age) had a definite diagnosis of MFS and were included in the study. The AL was longer (25.25 ± 0.32 mm vs 24.24 ± 0.33 mm, P = .03) and the lens was thicker (3.94 ± 0.09 mm vs 3.62 ± 0.10 mm, P = .03) in adults. Both groups had flat corneas (average keratometry [K med ] of 41.59 ± 0.35 diopters [D] in adults vs 40.89 ± 0.36 D in children, P = .17). A negative correlation was found between AL and K med (-0.33, P < .001). The corneas of patients with MFS with ectopia lentis (EL) were significantly flatter and with higher degree of corneal astigmatism compared to patients without EL (K med of 40.68 ± 0.31 D vs 41.75 ± 0.28 D, P < .01 and corneal astigmatism of 1.68 ± 0.16 D vs 1.13 ± 0.14 D, P = .01). Children with established MFS have flat corneas at least to the same degree as adults. Corneas of patients with MFS with EL are flatter and have a higher degree of corneal astigmatism. We strongly suggest that corneal parameters should be measured if MFS is suspected, especially in children that may not yet have developed EL. Copyright © 2017 Elsevier Inc. All rights reserved.

Biometry Characteristics in Adults and Children With Marfan Syndrome: From the Marfan Eye Consortium of Chicago

PubMed Central

KINORI, MICHAEL; WEHRLI, SARAH; KASSEM, IRIS S.; AZAR, NATHALIE F.; MAUMENEE, IRENE H.; METS, MARILYN B.

2017-01-01

PURPOSE To report on the biometric findings of adults and children with Marfan syndrome (MFS) recruited from 2 annual National Marfan Foundation conferences (2012 and 2015). DESIGN Cross-sectional study. METHODS Subjects diagnosed with MFS by Ghent 2 nosology were included for analysis. Subjects were divided into “adults” (≥16 years of age) and “children” (5–15 years of age). Biometric data included values for refractive error, axial length (AL), corneal curvature, anterior chamber depth, lens thickness, and central corneal thickness. RESULTS Of the 117 subjects evaluated, 74 (35 adults, 32 children, and 7 children <5 years of age) had a definite diagnosis of MFS and were included in the study. The AL was longer (25.25 ± 0.32 mm vs 24.24 ± 0.33 mm, P [ .03) and the lens was thicker (3.94 ± 0.09 mm vs 3.62 ± 0.10 mm, P [ .03) in adults. Both groups had flat corneas (average keratometry [Kmed] of 41.59 ± 0.35 diopters [D] in adults vs 40.89 ± 0.36 D in children, P [ .17). A negative correlation was found between AL and Kmed (L0.33, P < .001). The corneas of patients with MFS with ectopia lentis (EL) were significantly flatter and with higher degree of corneal astigmatism compared to patients without EL (Kmed of 40.68 ± 0.31 D vs 41.75 ± 0.28 D, P < .01 and corneal astigmatism of 1.68 ± 0.16 D vs 1.13 ± 0.14 D, P =.01). CONCLUSIONS Children with established MFS have flat corneas at least to the same degree as adults. Corneas of patients with MFS with EL are flatter and have a higher degree of corneal astigmatism. We strongly suggest that corneal parameters should be measured if MFS is suspected, especially in children that may not yet have developed EL. PMID:28257833

CANDIDA ENDOPHTHALMITIS FROM THE REACTIVATION OF A DORMANT LENTICULAR FUNGAL ABSCESS IN A PREMATURE INFANT.

PubMed

Yanoga, Fatoumata; Garcia-Gonzalez, Jose M; Greenwald, Mark; Shapiro, Michael J; Blair, Michael P

2017-01-01

To report a case of fungal endophthalmitis from reactivation of a dormant lenticular fungal abscess in a severely premature infant. Single retrospective case report. A female born at 23 and 6/7 weeks and weighing 620 g was diagnosed at age 29 weeks post menstrual age with persistent tunica vasculosa lentis, lenticular opacity, and aggressive posterior retinopathy of prematurity, and received bilateral intravitreal injection of bevacizumab. At the time of injection she was receiving systemic antibiotics for sepsis and fungemia. The retinopathy of prematurity regressed, as did the tunica vasculosa lentis, but a small plaque remained on the lens. At 5.5 months of age, patient presented with hypopyon and elevated intraocular pressure. Culture of intraocular fluid demonstrated Candida albicans. Candida lenticular abscess is a rare complication of systemic fungemia in premature infants. Bevacizumab-induced regression of tunica vasculosa lentis may have decreased the ability of systemically administered antifungal medications to reach the colonized lens.

Crossed Unfused Ectopic Pelvic Kidneys: A Case Illustration.

PubMed

Degheili, Jad A; AbuSamra, Murad M; El-Merhi, Fadi; El-Hajj, Albert

2018-01-01

Crossed unfused ectopia constitutes a very rare variant of ectopic kidneys, with an approximate incidence of 1 : 75000. We hereby describe a rare case of an incidental finding of crossed unfused ectopic kidneys, in a 45-year-old gentleman incidentally found to have a bladder lesion. The unique blood supply of his kidneys has also been described. The present case also highlights the different subtypes of renal ectopia, the different embryological hypotheses behind their presentation, and the various systematic anomalies, associated with them. Variations in vasculature of ectopic kidneys have been only described in case reports and are crucial to recognize in case any further intervention is needed.

Effect of NeuroD gene silencing on the migration and invasion of human pancreatic cancer cells PANC-1.

PubMed

Wang, Yang; Su, Dong Wei; Gao, Li; Ding, Gui Ling; Ni, Can Rong; Zhu, Ming Hua

2014-07-01

The aim of this study is to investigate the influence of Lenti-EGFP-NeuroD-miR, RNAi lentiviral expression vector, on the expression level of NeuroD and migration, and invasion of PANC-1 cell line. PANC-1 cells were cultured and cotransfected with Lenti-EGFP-NeuroD-miR and Lenti-GFP. The infection rate of lentivirus was determined by fluorescence. The interfering effection by the expression of NeuroD mRNA in PANC-1 cells was analyzed by real-time PCR after transfected. Biological behavior of PANC-1 cells transinfected was observed, and the migration and invasion were studied by transwell assay. Intrapancreatic allografts model in nude mice was established to observe the effects of NeuroD on tumorigenesis, tumor growth, and invasion in vivo. The expression of NeuroD mRNA decreased significantly after RNAi lentivirus transinfecting PANC-1 cell. The cell's migration and invasion ability decreased obviously as soon as down regulate of NeuroD in PANC-1 cells. Comparing with control group, the tumors were smaller in size and the invasiveness was inhibited after 8 weeks intrapancreatic allografts in nude mice. Lenti-EGFP-NeuroD-miR transfected into PANC-1 cells shows a stable, effective, and especial blocking expression of NeuroD in mRNA level. The RNAi of lentiviral vector target NeuroD can reduce the migration and invasion abilities of PANC-1 cells.

Crossed Unfused Ectopic Pelvic Kidneys: A Case Illustration

PubMed Central

AbuSamra, Murad M.; El-Merhi, Fadi

2018-01-01

Crossed unfused ectopia constitutes a very rare variant of ectopic kidneys, with an approximate incidence of 1 : 75000. We hereby describe a rare case of an incidental finding of crossed unfused ectopic kidneys, in a 45-year-old gentleman incidentally found to have a bladder lesion. The unique blood supply of his kidneys has also been described. The present case also highlights the different subtypes of renal ectopia, the different embryological hypotheses behind their presentation, and the various systematic anomalies, associated with them. Variations in vasculature of ectopic kidneys have been only described in case reports and are crucial to recognize in case any further intervention is needed. PMID:29854552

Cytogenetic and morphologic approaches of hybrids from experimental crosses between Triatoma lenti Sherlock & Serafim, 1967 and T. sherlocki Papa et al., 2002 (Hemiptera: Reduviidae).

PubMed

Mendonça, Vagner José; Alevi, Kaio Cesar Chaboli; Medeiros, Lívia Maria de Oliveira; Nascimento, Juliana Damieli; de Azeredo-Oliveira, Maria Tercília Vilela; da Rosa, João Aristeu

2014-08-01

The reproductive capacity between Triatoma lenti and Triatoma sherlocki was observed in order to verify the fertility and viability of the offspring. Cytogenetic, morphological and morphometric approaches were used to analyze the differences that were inherited. Experimental crosses were performed in both directions. The fertility rate of the eggs in crosses involving T. sherlocki females was 65% and 90% in F1 and F2 offspring, respectively. In reciprocal crosses, it was 7% and 25% in F1 and F2 offspring, respectively. The cytogenetic analyses of the male meiotic process of the hybrids were performed using lacto-acetic orcein, C-banding and Feulgen techniques. The male F1 offspring presented normal chromosome behavior, a finding that was similar to those reported in parental species. However, cytogenetic analysis of F2 offspring showed errors in chromosome pairing. This post-zygotic isolation, which prevents hybrids in nature, may represent the collapse of the hybrid. This phenomenon is due to a genetic dysregulation that occurs in the chromosomes of F1. The results were similar in the hybrids from both crosses. Morphological features, such as color and size of connexive and the presence of red-orange rings on the femora, were similar to T. sherlocki, while wins size was similar to T. lenti in F1 offspring. The eggshells showed characteristics that were similar to species of origin, whereas the median process of the pygophore resulted in intermediate characteristics in the F1 and a segregating pattern in F2 offspring. Geometric morphometric techniques used on the wings showed that both F1 and F2 offspring were similar to T. lenti. These studies on the reproductive capacity between T. lenti and T. sherlocki confirm that both species are evolutionarily closed; hence, they are included in the brasiliensis subcomplex. The extremely reduced fertility observed in the F2 hybrids confirmed the specific status of the species that were analyzed. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Left crossed fused renal ectopia L-shaped kidney type, with double nutcracker syndrome (anterior and posterior).

PubMed

Pupca, Gheorghe; Miclăuş, Graţian Dragoslav; Bucuraş, Viorel; Iacob, Nicoleta; Sas, Ioan; Matusz, Petru; Tubbs, R Shane; Loukas, Marios

2014-01-01

Crossed fused renal ectopia (CFRE) is the second most common fusion anomalies (FAs) of the kidneys after horseshoe kidney. Crossed fused renal ectopia (CFRE) results from one kidney crossing over to the opposite side and subsequent fusion of the parenchyma of the two kidneys. We report, by multidetector-row computed tomography (MDCT) angiography, an extremely rare case of a left CFRE (L-shaped kidney type), consisting of multiple renal arteries (one main renal artery for the upper renal parenchyma, and three renal arteries (one main and two additional) for the lower renal parenchyma) and two left renal veins, which produced a double nutcracker syndrome (both anterior and posterior). The L-shaped left kidney has a maximum length of 18.5 cm, a maximum width of 10.2 cm, and a maximum thickness of 5.3 cm. The upper pole of the kidney is located at the level of the lower third of T12 vertebral body (4.6 cm left to the mediosagittal plan); the lower pole is located along the lower half of the L5 vertebral body (1.5 cm left to the mediosagittal plan). The following case will focus on the relevant anatomy, embryology, and the clinical significance of this entity.

Intraocular Delivery of miR-146 Inhibits Diabetes-Induced Retinal Functional Defects in Diabetic Rat Model.

PubMed

Zhuang, Pei; Muraleedharan, Chithra K; Xu, Shunbin

2017-03-01

Previously, we showed that microRNA-146 (miR-146) is a pivotal negative feedback regulator of multiple nuclear factor kappa-B (NF-κB) activation pathways in retinal endothelial cells (RECs). We hypothesized that miR-146 plays an important role in diabetic retinopathy (DR) by inhibiting diabetes-induced inflammatory response in the retina. The purpose of the current study is to test this hypothesis in vivo. Lentiviruses expressing rno-miR-146a, lenti-miR-146a, and negative control oligonucleotide with scrambled sequence, lenti-miR-neg ctl, were produced. Young male Sprague-Dawley rats were injected with a single dose of streptozotocin ([STZ] 65 mg/kg) to induce diabetes. One week after diabetes, animals were injected with lentivirus intravitreally (4 μl, ∼106 CFU/mL). Three months after diabetes, retinal microvascular leakage was tested by Evans blue assay; retinal function by electroretinogram (ERG). Total RNA and protein lysate were isolated from the retina for quantitative (q)RT-PCR and Western blot analyses. Lenti-miR-146a robustly transduced human retinal endothelial cells (HRECs) and increased the expression of miR-146a in vitro. In vivo, intravitreal injection of lenti-miR-146a increased the expression of miR-146a in the retina, while its key downstream target genes, including CARD10, IRAK1, and TRAF6, were downregulated. Intravitreal delivery of miR-146 inhibited diabetes-induced upregulation of NF-κB downstream gene, Intercellular Adhesion Molecule 1 (ICAM1), as well as microvascular leakage and retinal functional defects. Intravitreal delivery of miR-146 inhibited diabetes-induced NF-κB activation and retinal microvascular and neuronal functional defects in a diabetic rat model.

Combining zonal refractive and diffractive aspheric multifocal intraocular lenses.

PubMed

Muñoz, Gonzalo; Albarrán-Diego, César; Javaloy, Jaime; Sakla, Hani F; Cerviño, Alejandro

2012-03-01

To assess visual performance with the combination of a zonal refractive aspheric multifocal intraocular lens (MIOL) (Lentis Mplus, Oculentis GmbH) and a diffractive aspheric MIOL (Acri.Lisa 366, Acri.Tech GmbH). This prospective interventional cohort study comprised 80 eyes from 40 cataract patients (mean age: 65.5±7.3 years) who underwent implantation of the Lentis Mplus MIOL in one eye and Acri.Lisa 366 MIOL in the fellow eye. The main outcome measures were refraction; monocular and binocular uncorrected and corrected distance, intermediate, and near visual acuities; monocular and binocular defocus curves; binocular photopic contrast sensitivity function compared to a monofocal intraocular lens (IOL) control group (40 age-matched pseudophakic patients implanted with the AR-40e [Abbott Medical Optics]); and quality of vision questionnaire. Binocular uncorrected visual acuities were 0.12 logMAR (0.76 decimal) or better at all distances measured between 6 m and 33 cm. The Lentis Mplus provided statistically significant better vision than the Acri.Lisa at distances between 2 m and 40 cm, and the Acri.Lisa provided statistically significant better vision than the Lentis Mplus at 33 cm. Binocular defocus curve showed little drop-off at intermediate distances. Photopic contrast sensitivity function for distance and near were similar to the monofocal IOL control group except for higher frequencies. Moderate glare (15%), night vision problems (12.5%), and halos (10%) were reported. Complete independence of spectacles was achieved by 92.5% of patients. The combination of zonal refractive aspheric and diffractive aspheric MIOLs resulted in excellent uncorrected binocular distance, intermediate, and near vision, with low incidence of significant photic phenomena and high patient satisfaction. Copyright 2012, SLACK Incorporated.

ALDH isozymes downregulation affects cell growth, cell motility and gene expression in lung cancer cells.

PubMed

Moreb, Jan S; Baker, Henry V; Chang, Lung-Ji; Amaya, Maria; Lopez, M Cecilia; Ostmark, Blanca; Chou, Wayne

2008-11-24

Aldehyde dehydrogenase isozymes ALDH1A1 and ALDH3A1 are highly expressed in non small cell lung cancer. Neither the mechanisms nor the biologic significance for such over expression have been studied. We have employed oligonucleotide microarrays to analyze changes in gene profiles in A549 lung cancer cell line in which ALDH activity was reduced by up to 95% using lentiviral mediated expression of siRNA against both isozymes (Lenti 1+3). Stringent analysis methods were used to identify gene expression patterns that are specific to the knock down of ALDH activity and significantly different in comparison to wild type A549 cells (WT) or cells similarly transduced with green fluorescent protein (GFP) siRNA. We confirmed significant and specific down regulation of ALDH1A1 and ALDH3A1 in Lenti 1+3 cells and in comparison to 12 other ALDH genes detected. The results of the microarray analysis were validated by real time RT-PCR on RNA obtained from Lenti 1+3 or WT cells treated with ALDH activity inhibitors. Detailed functional analysis was performed on 101 genes that were significantly different (P < 0.001) and their expression changed by > or = 2 folds in the Lenti 1+3 group versus the control groups. There were 75 down regulated and 26 up regulated genes. Protein binding, organ development, signal transduction, transcription, lipid metabolism, and cell migration and adhesion were among the most affected pathways. These molecular effects of the ALDH knock-down are associated with in vitro functional changes in the proliferation and motility of these cells and demonstrate the significance of ALDH enzymes in cell homeostasis with a potentially significant impact on the treatment of lung cancer.

Validity of automated refraction after segmented refractive multifocal intraocular lens implantation

PubMed Central

Albarrán-Diego, César; Muñoz, Gonzalo; Rohrweck, Stephanie; García-Lázaro, Santiago; Albero, José Ricardo

2017-01-01

AIM To evaluate the clinical utility of automated refraction (AR) and keratometry (KR) compared with subjective or manifest refraction (MR) after cataract or refractive lens exchange surgery with implantation of Lentis Mplus X (Oculentis GmbH) refractive multifocal intraocular lens (IOL). METHODS Eighty-six eyes implanted with the Lentis Mplus X multifocal IOL were included. MR was performed in all patients followed by three consecutive AR measurements using the Topcon KR-8000 autorefractor. Assessment of repeatability of consecutive AR before and after dilation with phenylephrine 10%, and comparison of the AR and KR with MR using vector analysis were performed at 3mo follow-up. RESULTS Analysis showed excellent repeatability of the AR measurements. Linear regression of AR versus MR showed good correlation for sphere and spherical equivalent, whereas the correlation for astigmatism was low. The mean difference AR-MR was -1.28±0.29 diopters (D) for sphere. Astigmatism showed better correlation between KR and MR. CONCLUSION We suggest AR sphere plus 1.25 D and the KR cylinder as the starting point for MR in eyes with a Lentis Mplus X multifocal IOL. If AR measurements are equal to MR, decentration of the IOL should be suspected. PMID:29181318

Validity of automated refraction after segmented refractive multifocal intraocular lens implantation.

PubMed

Albarrán-Diego, César; Muñoz, Gonzalo; Rohrweck, Stephanie; García-Lázaro, Santiago; Albero, José Ricardo

2017-01-01

To evaluate the clinical utility of automated refraction (AR) and keratometry (KR) compared with subjective or manifest refraction (MR) after cataract or refractive lens exchange surgery with implantation of Lentis Mplus X (Oculentis GmbH) refractive multifocal intraocular lens (IOL). Eighty-six eyes implanted with the Lentis Mplus X multifocal IOL were included. MR was performed in all patients followed by three consecutive AR measurements using the Topcon KR-8000 autorefractor. Assessment of repeatability of consecutive AR before and after dilation with phenylephrine 10%, and comparison of the AR and KR with MR using vector analysis were performed at 3mo follow-up. Analysis showed excellent repeatability of the AR measurements. Linear regression of AR versus MR showed good correlation for sphere and spherical equivalent, whereas the correlation for astigmatism was low. The mean difference AR-MR was -1.28±0.29 diopters (D) for sphere. Astigmatism showed better correlation between KR and MR. We suggest AR sphere plus 1.25 D and the KR cylinder as the starting point for MR in eyes with a Lentis Mplus X multifocal IOL. If AR measurements are equal to MR, decentration of the IOL should be suspected.

Crossed fused renal ectopia in a Persian cat

PubMed Central

Seo, Sang-Hyuk; Lee, Hyun-A; Suh, Sang-Il; Choi, Ran; Park, In-Chul; Hyun, Changbaig

2017-01-01

Case summary This report describes a rare case of crossed fused renal ectopia (CFRE) in a cat. A mature intact male Persian cat presented with bloody nasal discharge and ascites. Diagnostic studies revealed an ectopic left kidney fused with an orthotopic right kidney and a concurrent feline infectious peritonitis (FIP) infection. The FIP was responsible for clinical signs in this cat, while clinical signs associated with CFRE were not obvious. Despite receiving intensive treatment, the cat died. A post-mortem examination was not performed because the owners declined approval. Relevance and novel information To the best of our knowledge, this is the first report of L-shaped CFRE in a cat. In addition, this report describes the CT features of L-shaped CFRE in a cat. PMID:28491454

LentiPro26: novel stable cell lines for constitutive lentiviral vector production.

PubMed

Tomás, H A; Rodrigues, A F; Carrondo, M J T; Coroadinha, A S

2018-03-27

Lentiviral vectors (LVs) are excellent tools to promote gene transfer and stable gene expression. Their potential has been already demonstrated in gene therapy clinical trials for the treatment of diverse disorders. For large scale LV production, a stable producer system is desirable since it allows scalable and cost-effective viral productions, with increased reproducibility and safety. However, the development of stable systems has been challenging and time-consuming, being the selection of cells presenting high expression levels of Gag-Pro-Pol polyprotein and the cytotoxicity associated with some viral components, the main limitations. Hereby is described the establishment of a new LV producer cell line using a mutated less active viral protease to overcome potential cytotoxic limitations. The stable transfection of bicistronic expression cassettes with re-initiation of the translation mechanism enabled the generation of LentiPro26 packaging populations supporting high titers. Additionally, by skipping intermediate clone screening steps and performing only one final clone screening, it was possible to save time and generate LentiPro26-A59 cell line, that constitutively produces titers above 10 6 TU.mL -1 .day -1 , in less than six months. This work constitutes a step forward towards the development of improved LV producer cell lines, aiming to efficiently supply the clinical expanding gene therapy applications.

Genotype-Dependent Interaction of Lentil Lines with Ascochyta lentis

PubMed Central

Sari, Ehsan; Bhadauria, Vijai; Vandenberg, Albert; Banniza, Sabine

2017-01-01

Ascochyta blight of lentil is a prevalent disease in many lentil producing regions and can cause major yield and grain quality losses. The most environmentally acceptable and economically profitable method of control is to develop varieties with high levels of durable resistance. Genetic studies to date suggest that ascochyta blight resistance genes (R-gene) in lentil lines CDC Robin, ILL 7537, 964a-46, and ILL 1704 are non-allelic. To understand how different R-genes manifest resistance in these genotypes and an accession of Lens ervoides, L-01-827A, with high level of resistance to ascochyta blight, cellular and molecular defense responses were compared after inoculation with the causal pathogen Ascochyta lentis. Pathogenicity testing of the resistant lines to A. lentis inoculation revealed significantly lower disease severity on CDC Robin and ILL 7537 compared to ILL 1704 and 964a-46, and no symptoms of disease were observed on L-01-827A. Histological examinations indicated that cell death triggered by the pathogen might be disrupted as a mechanism of resistance in CDC Robin. In contrast, limiting colonization of epidermal cells by A. lentis is a suggested mechanism of resistance in 964a-46. A time-series comparison of the expressions of hallmark genes in salicylic acid (SA) and jasmonic acid (JA) signal transduction pathways between CDC Robin and 964a-46 was conducted. These partially resistant genotypes differed in the timing and the magnitude of SA and JA signaling pathway activation. The SA signaling pathway was only triggered in 964a-46, whereas the JA pathway was triggered in both partially resistant genotypes CDC Robin and 964a-46. The expression of JA-associated genes was lower in 964a-46 than CDC Robin. These observations corroborate the existence of diverse ascochyta blight resistance mechanisms in lentil genotypes carrying different R-genes. PMID:28539932

In situ reprogramming to transdifferentiate fibroblasts into cardiomyocytes using adenoviral vectors: Implications for clinical myocardial regeneration.

PubMed

Mathison, Megumi; Singh, Vivek P; Chiuchiolo, Maria J; Sanagasetti, Deepthi; Mao, Yun; Patel, Vivekkumar B; Yang, Jianchang; Kaminsky, Stephen M; Crystal, Ronald G; Rosengart, Todd K

2017-02-01

The reprogramming of cardiac fibroblasts into induced cardiomyocyte-like cells improves ventricular function in myocardial infarction models. Only integrating persistent expression vectors have thus far been used to induce reprogramming, potentially limiting its clinical applicability. We therefore tested the reprogramming potential of nonintegrating, acute expression adenoviral (Ad) vectors. Ad or lentivirus vectors encoding Gata4 (G), Mef2c (M), and Tbx5 (T) were validated in vitro. Sprague-Dawley rats then underwent coronary ligation and Ad-mediated administration of vascular endothelial growth factor to generate infarct prevascularization. Three weeks later, animals received Ad or lentivirus encoding G, M, or T (AdGMT or LentiGMT) or an equivalent dose of a null vector (n = 11, 10, and 10, respectively). Outcomes were analyzed by echocardiography, magnetic resonance imaging, and histology. Ad and lentivirus vectors provided equivalent G, M, and T expression in vitro. AdGMT and LentiGMT both likewise induced expression of the cardiomyocyte marker cardiac troponin T in approximately 6% of cardiac fibroblasts versus <1% cardiac troponin T expression in AdNull (adenoviral vector that does not encode a transgene)-treated cells. Infarcted myocardium that had been treated with AdGMT likewise demonstrated greater density of cells expressing the cardiomyocyte marker beta myosin heavy chain 7 compared with AdNull-treated animals. Echocardiography demonstrated that AdGMT and LentiGMT both increased ejection fraction compared with AdNull (AdGMT: 21% ± 3%, LentiGMT: 14% ± 5%, AdNull: -0.4% ± 2%; P < .05). Ad vectors are at least as effective as lentiviral vectors in inducing cardiac fibroblast transdifferentiation into induced cardiomyocyte-like cells and improving cardiac function in postinfarct rat hearts. Short-term expression Ad vectors may represent an important means to induce cardiac cellular reprogramming in humans. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Downregulation of Notch-regulated Ankyrin Repeat Protein Exerts Antitumor Activities against Growth of Thyroid Cancer.

PubMed

Chu, Bing-Feng; Qin, Yi-Yu; Zhang, Sheng-Lai; Quan, Zhi-Wei; Zhang, Ming-Di; Bi, Jian-Wei

2016-07-05

The Notch-regulated ankyrin repeat protein (NRARP) is recently found to promote proliferation of breast cancer cells. The role of NRARP in carcinogenesis deserves extensive investigations. This study attempted to investigate the expression of NRARP in thyroid cancer tissues and assess the influence of NRARP on cell proliferation, apoptosis, cell cycle, and invasion in thyroid cancer. Thirty-four cases with thyroid cancer were collected from the Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine between 2011 and 2012. Immunohistochemistry was used to detect the level of NRARP in cancer tissues. Lentivirus carrying NRARP-shRNA (Lenti-NRARP-shRNA) was applied to down-regulate NRARP expression. Cell viability was tested after treatment with Lenti-NRARP-shRNA using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptosis and cell cycle distribution were determined by flow cytometry. Cell invasion was tested using Transwell invasion assay. In addition, expressions of several cell cycle-associated and apoptosis-associated proteins were examined using Western blotting after transfection. Student's t-test, one-way analysis of variance (ANOVA), or Kaplan-Meier were used to analyze the differences between two group or three groups. NRARP was highly expressed in thyroid cancer tissues. Lenti-NRARP-shRNA showed significantly inhibitory activities against cell growth at a multiplicity of infection of 10 or higher (P < 0.05). Lenti-NRARP-shRNA-induced G1 arrest (BHT101: 72.57% ± 5.32%; 8305C: 75.45% ± 5.26%) by promoting p21 expression, induced apoptosis by promoting bax expression and suppressing bcl-2 expression, and inhibited cell invasion by suppressing matrix metalloproteinase-9 expression. Downregulation of NRARP expression exerts significant antitumor activities against cell growth and invasion of thyroid cancer, that suggests a potential role of NRARP in thyroid cancer targeted therapy.

Pupil Influence on the Visual Outcomes of a New-Generation Multifocal Toric Intraocular Lens With a Surface-Embedded Near Segment.

PubMed

Wang, Mengmeng; Corpuz, Christine Carole C; Huseynova, Tukezban; Tomita, Minoru

2016-02-01

To evaluate the influences of preoperative pupil parameters on the visual outcomes of a new-generation multifocal toric intraocular lens (IOL) model with a surface-embedded near segment. In this prospective study, patients with cataract had phacoemulsification and implantation of Lentis Mplus toric LU-313 30TY IOLs (Oculentis GmbH, Berlin, Germany). The visual and optical outcomes were measured and compared preoperatively and postoperatively. The correlations between preoperative pupil parameters (diameter and decentration) and 3-month postoperative visual outcomes were evaluated using the Spearman's rank-order correlation coefficient (Rs) for the nonparametric data. A total of 27 eyes (16 patients) were enrolled into the current study. Statistically significant improvements in visual and refractive performances were found after the implantation of Lentis Mplus toric LU-313 30TY IOLs (P < .05). Statistically significant correlations were present between preoperative pupil diameters and postoperative visual acuities (Rs > 0; P < .05). Patients with a larger pupil always have better postoperative visual acuities. Meanwhile, there was no statistically significant correlation between pupil decentration and visual acuities (P > .05). Lentis Mplus toric LU-313 30TY IOLs provided excellent visual and optical performances during the 3-month follow-up. The preoperative pupil size is an important parameter when this toric multifocal IOL model is contemplated for surgery. Copyright 2016, SLACK Incorporated.

Preclinical studies for a phase 1 clinical trial of autologous hematopoietic stem cell gene therapy for sickle cell disease.

PubMed

Urbinati, Fabrizia; Wherley, Jennifer; Geiger, Sabine; Fernandez, Beatriz Campo; Kaufman, Michael L; Cooper, Aaron; Romero, Zulema; Marchioni, Filippo; Reeves, Lilith; Read, Elizabeth; Nowicki, Barbara; Grassman, Elke; Viswanathan, Shivkumar; Wang, Xiaoyan; Hollis, Roger P; Kohn, Donald B

2017-09-01

Gene therapy by autologous hematopoietic stem cell transplantation (HSCT) represents a new approach to treat sickle cell disease (SCD). Optimization of the manufacture, characterization and testing of the transduced hematopoietic stem cell final cell product (FCP), as well as an in depth in vivo toxicology study, are critical for advancing this approach to clinical trials. Data are shown to evaluate and establish the feasibility of isolating, transducing with the Lenti/β AS3 -FB vector and cryopreserving CD34 + cells from human bone marrow (BM) at clinical scale. In vitro and in vivo characterization of the FCP was performed, showing that all the release criteria were successfully met. In vivo toxicology studies were conducted to evaluate potential toxicity of the Lenti/β AS3 -FB LV in the context of a murine BM transplant. Primary and secondary transplantation did not reveal any toxicity from the lentiviral vector. Additionally, vector integration site analysis of murine and human BM cells did not show any clonal skewing caused by insertion of the Lenti/β AS3 -FB vector in cells from primary and secondary transplanted mice. We present here a complete protocol, thoroughly optimized to manufacture, characterize and establish safety of a FCP for gene therapy of SCD. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

MISSION LentiPlex pooled shRNA library screening in mammalian cells.

PubMed

Coussens, Matthew J; Corman, Courtney; Fischer, Ashley L; Sago, Jack; Swarthout, John

2011-12-21

RNA interference (RNAi) is an intrinsic cellular mechanism for the regulation of gene expression. Harnessing the innate power of this system enables us to knockdown gene expression levels in loss of gene function studies. There are two main methods for performing RNAi. The first is the use of small interfering RNAs (siRNAs) that are chemically synthesized, and the second utilizes short-hairpin RNAs (shRNAs) encoded within plasmids. The latter can be transfected into cells directly or packaged into replication incompetent lentiviral particles. The main advantages of using lentiviral shRNAs is the ease of introduction into a wide variety of cell types, their ability to stably integrate into the genome for long term gene knockdown and selection, and their efficacy in conducting high-throughput loss of function screens. To facilitate this we have created the LentiPlex pooled shRNA library. The MISSION LentiPlex Human shRNA Pooled Library is a genome-wide lentiviral pool produced using a proprietary process. The library consists of over 75,000 shRNA constructs from the TRC collection targeting 15,000+ human genes. Each library is tested for shRNA representation before product release to ensure robust library coverage. The library is provided in a ready-to-use lentiviral format at titers of at least 5 x 10(8) TU/ml via p24 assay and is pre-divided into ten subpools of approximately 8,000 shRNA constructs each. Amplification and sequencing primers are also provided for downstream target identification. Previous studies established a synergistic antitumor activity of TRAIL when combined with Paclitaxel in A549 cells, a human lung carcinoma cell line. In this study we demonstrate the application of a pooled LentiPlex shRNA library to rapidly conduct a positive selection screen for genes involved in the cytotoxicity of A549 cells when exposed to TRAIL and Paclitaxel. One barrier often encountered with high-throughput screens is the cost and difficulty in deconvolution; we also detail a cost-effective polyclonal approach utilizing traditional sequencing.

Early morphogenesis of persistent hyperplastic tunica vasculosa lentis and primary vitreous (PHTVL/PHPV). Scanning electron microscopic observations.

PubMed

Boevé, M H; Vrensen, G F; Willekens, B L; Stades, F C; van der Linde-Sipman, J S

1993-01-01

This study provides scanning electron microscopic observations on the early morphogenesis of persistent hyperplastic tunica vasculosa lentis and primary vitreous (PHTVL/PHPV) in canine fetuses at days 28 35 postcoitum (D28 and D35). From previous studies regarding PHTVL/PHPV it is known that a retrolental plaque of fibrovascular tissue is present in eyes of affected canine fetuses from the D33 stage. The contribution of vitreous cells to the formation of the plaque is supported by the results of this study. The lens capsules at the stages described were not found to contain abnormalities such as transparent (thinner) parts or rents, as have been described for postnatal cases of PHTVL/PHPV. These findings support the hypothesis that the capsular anomalies observed in postnatal patients are secondary entities.

[GPER silence inhibits the stimulation of growth and inhibition of apoptosis induced by tamoxifen in breast cancer-associated fibroblasts].

PubMed

Yan, Yuzhao; Yu, Tenghua; Tu, Gang; Liu, Manran; Yuan, Jie; Yang, Guanglun

2015-09-01

To construct a lentiviral vector (Lenti-GPER-shRNA) targeting G-protein coupled estrogen receptor (GPER) and explore the role of GPER in the effect of tamoxifen on cell proliferation and apoptosis in breast cancer associated fibroblasts (BCAFs). The target sequence of GPER gene and negative control were cloned into lentiviral vectors. The recombinant lentivirus and control were extracted after HEK293T cells were transfected with the recombinant vector and helper vectors. After infection of BCAFs with the GPER lentiviral vector under the best interfering condition, GPER expression was detected by real-time quantitative PCR and Western blotting. BCAFs were divided into negative control group, GPER-RNAi group, negative control combined with tamoxifen (10(-8) mmol/L) group and GPER-RNAi combined with tamoxifen (10(-8) mmol/L) group. CCK-8 assay was used to detect the proliferation and annexin V-fluorescein isothiocyanate/propidium iodide (annexin V-FITC/PI) combined with flow cytometry was used to detect the apoptosis of BCAFs after the treatment of tamoxifen. Lenti-GPER-shRNA significantly interfered the expression of GPER in BCAFs. Tamoxifen promoted the growth of BCAFs, which could be attenuated by knockdown of GPER. Moreover, the apoptosis of BCAFs was reduced by tamoxifen, which was also reversed by knockdown of GPER. Lenti-GPER-shRNA could effectively silence the GPER expression in BCAFs. The ability of tamoxifen to accelerate cell proliferation and decrease cell apoptosis could be weakened by knockdown of GPER.

Intestinal atresia and ectopia in a bovine fetus.

PubMed

Lejeune, B; Miclard, J; Stoffel, M H; Meylan, M

2011-07-01

A 2-year-old Red Holstein cow was presented with uterine torsion at 235 days of pregnancy. The fetus extracted by cesarean section had weak vital signs and marked abdominal distention. An edematous pouch that contained tubular structures with peristaltic activity was associated with the umbilical cord. Because of poor prognosis, both dam and fetus were euthanized. At necropsy, the fetus had severe distention of the forestomachs, abomasum, and proximal small intestine; absence of distal small intestine, cecum, and proximal colon; atresia of the 2 blind ends of the intestine; and atrophy of distal colon and rectum. The tubular structures associated with the umbilical cord were identified as the segments of intestine that were absent in the fetus. Intestinal atresia combined with ectopia may be caused by local ischemia during temporary herniation and rotation of the fetal gut into the extraembryonic coelom. The close connection between ectopic intestine and amniotic sheath of the umbilical cord in this case may have facilitated vascularization and allowed development and viability of the ectopic intestine. © The Authors 2011

Acute deterioration in occult Chiari malformation following missile spinal trauma. Case report.

PubMed

Shahlaie, Kiarash; Hartman, Jonathan; Utter, Garth H; Schrot, Rudolph J

2008-04-01

Patients with Chiari malformation (CM) Type I typically experience chronic, slowly progressive symptoms. Rarely, however, do they suffer acute neurological deterioration following an iatrogenic decrease in caudal cerebrospinal fluid pressure due to, for example, a lumbar puncture. To our knowledge, acute neurological deterioration following missile spinal injury in CM has not been previously described. The authors report on a 16-year-old girl who was shot in the abdomen and lumbar spine. Although neurologically intact on initial workup, she developed precipitous quadriplegia and apnea in a delayed fashion. Tonsillar herniation with medullary compression and cerebellar infarction was diagnosed on magnetic resonance imaging. Suboccipital decompression resulted in significant neurological improvement. Well-formed tonsillar ectopia diagnosed at surgery suggested a preexisting CM. The authors conclude that missile spinal trauma can precipitate medullary compression and acute neurological decline, especially in patients with preexisting tonsillar ectopia. Immediate operative decompression to relieve impaction at the cervicomedullary junction can result in significant neurological recovery.

Evaluation of the True Wavefront Aberrations in Eyes Implanted With a Rotationally Asymmetric Multifocal Intraocular Lens.

PubMed

Akondi, Vyas; Pérez-Merino, Pablo; Martinez-Enriquez, Eduardo; Dorronsoro, Carlos; Alejandre, Nicolás; Jiménez-Alfaro, Ignacio; Marcos, Susana

2017-04-01

Standard evaluation of aberrations from wavefront slope measurements in patients implanted with a rotationally asymmetric multifocal intraocular lens (IOL), the Lentis Mplus (Oculentis GmbH, Berlin, Germany), results in large magnitude primary vertical coma, which is attributed to the intrinsic IOL design. The new proposed method analyzes aberrometry data, allowing disentangling the IOL power pupillary distribution from the true higher order aberrations of the eye. The new method of wavefront reconstruction uses retinal spots obtained at both the near and far foci. The method was tested using ray tracing optical simulations in a computer eye model virtually implanted with the Lentis Mplus IOL, with a generic cornea or with anterior segment geometry obtained from custom quantitative spectral-domain optical coherence tomography in a real patient. The method was applied to laser ray tracing aberrometry data at near and far fixation obtained in a patient implanted with the Lentis Mplus IOL. Higher order aberrations evaluated from simulated and real retinal spot diagrams following the new reconstruction approach matched the nominal aberrations (approximately 98%). Previously reported primary vertical coma in patients implanted with this IOL lost significance with the application of the proposed reconstruction. Custom analysis of ray tracing-based retinal spot diagrams allowed decoupling of the true higher order aberrations of the patient's eye from the power pupillary distribution of a rotationally asymmetric multifocal IOL, therefore providing the appropriate phase map to accurately evaluate through-focus optical quality. [J Refract Surg. 2017;33(4):257-265.]. Copyright 2017, SLACK Incorporated.

Persistent Mullerian duct syndrome with transverse testicular ectopia and seminoma.

PubMed

Alp, Bilal Fırat; Demirer, Zafer; Gürağaç, Ali; Babacan, Oğuzhan; Sarı, Erkan; Sarı, Sebahattin; Yavan, Ibrahim

2014-08-01

Persistent Mullerian duct syndrome (PMDS) is a rare form of the 46 XY disorders of sexual differentiation, characterized by the presence of a uterus and fallopian tubes due to the failure of Mullerian duct regression in genotypically normal males. More than 150 cases have been recorded, most of them in adults. In most cases, the PMDS is discovered during surgery for inguinal hernia or cryptorchidism, or by the presence of transverse testicular ectopia (TTE). The presence of PMDS with TTE is even more uncommon. In TTE, both testes descend through the same inguinal canal into the same scrotal sac. Patients with TTE present with symptoms of unilateral cryptorchidism and a contralateral inguinal hernia. For patients with inguinal hernia and cryptorchidism associated with TTE, PMDS should be kept in mind, and radiologic evaluation such as ultrasonography or magnetic resonance imaging of the genitourinary system and karyotyping are recommended. Whereas radiologic evaluation could be helpful in the diagnosis of TTE, it cannot diagnose the malignancy itself. The case explained in this report will offer urologists additional useful treatment strategies for patients with inguinal hernia and cryptorchidism.

Overexpression of c-Met in bone marrow mesenchymal stem cells improves their effectiveness in homing and repair of acute liver failure.

PubMed

Wang, Kun; Li, Yuwen; Zhu, Tiantian; Zhang, Yongting; Li, Wenting; Lin, Wenyu; Li, Jun; Zhu, Chuanlong

2017-07-05

Transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) has emerged as a novel therapy for acute liver failure (ALF). However, the homing efficiency of BMSCs to the injured liver sites appears to be poor. In this study, we aimed to determine if overexpression of c-Met in BMSCs could promote the homing ability of BMSCs to rat livers affected by ALF. Overexpression of c-Met in BMSCs (c-Met-BMSCs) was attained by transfection of naive BMSCs with the lenti-c-Met-GFP. The impact of transplanted c-Met-BMSCs on both homing and repair of ALF was evaluated and compared with lenti-GFP empty vector transfected BMSCs (control BMSCs). After cells were transfected with the lenti-c-Met-GFP vector, the BMSCs displayed very high expression of c-Met protein as demonstrated by Western blot. In addition, in vitro transwell migration assays showed that the migration ability of c-Met-BMSCs was significantly increased in comparison with that of control BMSCs (P < 0.05), and was dependent on hepatocyte growth factor (HGF). Furthermore, rats with ALF that received transplanted c-Met-BMSCs showed significantly improved homing ability to the injured liver; this was accompanied by elevated survival rates and liver function in the ALF rats. Parallel pathological examination further confirmed that transplantation of c-Met-BMSCs ameliorated liver injury with reduced hepatic activity index (HAI) scores, and that the effects of c-Met-BMSCs were more profound than those of control BMSCs. Overexpression of c-Met promotes the homing of BMSCs to injured hepatic sites in a rat model of ALF, thereby improving the efficacy of BMSC therapy for ALF repair.

Early morphogenesis of persistent hyperplastic tunica vasculosa lentis and primary vitreous. The dog as an ontogenetic model.

PubMed

Boevé, M H; van der Linde-Sipman, T; Stades, F C

1988-07-01

Observations on (postnatal) persistent hyperplastic tunica vasculosa lentis/persistent hyperplastic primary vitreous (PHTVL/PHPV) in man and dog have been published previously. Up to the present, no evidence on the etiology of this entity was available. The hereditary occurrence of the disease in the Dobermann pinscher dog and the similarity of ocular development in mammals has provided a useful model in providing ontogenetic data. The present study deals with the early morphogenesis of PHTVL/PHPV, from day 25 to 44 post-coitum (D25-D44), in genetically affected dog fetuses. Normal beagle dog fetuses served as reference material, which has been described separately. At D30, the hyaloid system, including the tunica vasculosa lentis posterior, had developed further than in the reference fetuses. From that stage onward, a retrolental fibrovascular membrane developed. In some of the eyes of D37, posterior polar subcapsular cataracts and preretinal glial proliferations were observed. Capsular anomalies and distortions of the lens shape as seen in clinical PHTVL/PHPV were not observed, and are believed to be secondary entities. Extrapolation of some of the obtained data from dog to man is possible by the use of comparable gestational time scales. The anterior form of (PHTVL/PHPV) in man probably develops its main features in the period of approximately 43 to 66 days of pregnancy. Recently, anti-angiogenetic properties of normal vitreous have been described. This, and the fact that overdevelopment and subsequent incomplete regression of the hyaloid system plays a major role in the pathogenesis of PHTVL/PHPV, gives rise to the hypothesis that a changed amount or effectiveness of such (humoral) factors is an important factor in the etiology of this disease.

Involvement of S6K1 in mitochondria function and structure in HeLa cells.

PubMed

Park, Jisoo; Tran, Quangdon; Mun, Kisun; Masuda, Kouhei; Kwon, So Hee; Kim, Seon-Hwan; Kim, Dong-Hoon; Thomas, George; Park, Jongsun

2016-12-01

The major biological function of mitochondria is to generate cellular energy through oxidative phosphorylation. Apart from cellular respiration, mitochondria also play a key role in signaling processes, including aging and cancer metabolism. It has been shown that S6K1-knockout mice are resistant to obesity due to enhanced beta-oxidation, with an increased number of large mitochondria. Therefore, in this report, the possible involvement of S6K1 in regulating mitochondria dynamics and function has been investigated in stable lenti-shS6K1-HeLa cells. Interestingly, S6K1-stably depleted HeLa cells showed phenotypical changes in mitochondria morphology. This observation was further confirmed by detailed image analysis of mitochondria shape. Corresponding molecular changes were also observed in these cells, such as the induction of mitochondrial fission proteins (Drp1 and Fis1). Oxygen consumption is elevated in S6K1-depeleted HeLa cells and FL5.12 cells. In addition, S6K1 depletion leads to enhancement of ATP production in cytoplasm and mitochondria. However, the relative ratio of mitochondrial ATP to cytoplasmic ATP is actually decreased in lenti-shS6K1-HeLa cells compared to control cells. Lastly, induction of mitophagy was found in lenti-shS6K1-HeLa cells with corresponding changes of mitochondria shape on electron microscope analysis. Taken together, our results indicate that S6K1 is involved in the regulation of mitochondria morphology and function in HeLa cells. This study will provide novel insights into S6K1 function in mitochondria-mediated cellular signaling. Copyright © 2016 Elsevier Inc. All rights reserved.

The Dutch complementary and alternative medicine (CAM) protocol: to ensure the safe and effective use of complementary and alternative medicine within Dutch mental health care.

PubMed

Hoenders, H J Rogier; Appelo, Martin T; van den Brink, Erik H; Hartogs, Bregje M A; de Jong, Joop T V M

2011-12-01

Complementary and alternative medicine (CAM) is subject to heated debates and prejudices. Studies show that CAM is widely used by psychiatric patients, usually without the guidance of a therapist and without the use of a solid working method, leading to potential health risks. The purpose of this study is to facilitate the judicious use of CAM alongside conventional psychiatry in an outpatient psychiatric clinic. A search was made through scientific and legal articles and discussion in focus groups. In the Centre for Integrative Psychiatry (CIP) of Lentis in The Netherlands, some carefully selected CAM are offered under strict conditions, alongside conventional treatments. Because of the controversy and the potential health risks, Lentis designed a protocol that is presented. The CIP hopes, by using this protocol, to better serve and respect the individual needs and preferences of the diversity of psychiatric patients in our Dutch multicultural society, and better protect them from harm.

A case-control study of cerebellar tonsillar ectopia (Chiari) and head/neck trauma (whiplash).

PubMed

Freeman, Michael D; Rosa, Scott; Harshfield, David; Smith, Francis; Bennett, Robert; Centeno, Christopher J; Kornel, Ezriel; Nystrom, Ake; Heffez, Dan; Kohles, Sean S

2010-01-01

Chiari malformation is defined as herniation of the cerebellar tonsils through the foramen magnum, also known as cerebellar tonsillar ectopia (CTE). CTE may become symptomatic following whiplash trauma. The purpose of the present study was to assess the frequency of CTE in traumatic vs non-traumatic populations. Case-control. Cervical MRI scans for 1200 neck pain patients were reviewed; 600 trauma (cases) and 600 non-trauma (controls). Half of the groups were scanned in a recumbent position and half were scanned in an upright position. Two radiologists interpreted the scans for the level of the cerebellar tonsils. A total of 1195 of 1200 scans were read. CTE was found in 5.7% and 5.3% in the recumbent and upright non-trauma groups vs 9.8% and 23.3% in the recumbent and upright trauma groups (p = 0.0001). The results described in the present investigation are first to demonstrate a neuroradiographic difference between neck pain patients with and without a recent history of whiplash trauma. The results of prior research on psychosocial causes of chronic pain following whiplash are likely confounded because of a failure to account for a possible neuropathologic basis for the symptoms.

Posterior odontoid process angulation in pediatric Chiari I malformation: an MRI morphometric external validation study.

PubMed

Ladner, Travis R; Dewan, Michael C; Day, Matthew A; Shannon, Chevis N; Tomycz, Luke; Tulipan, Noel; Wellons, John C

2015-08-01

OBJECT Osseous anomalies of the craniocervical junction are hypothesized to precipitate the hindbrain herniation observed in Chiari I malformation (CM-I). Previous work by Tubbs et al. showed that posterior angulation of the odontoid process is more prevalent in children with CM-I than in healthy controls. The present study is an external validation of that report. The goals of our study were 3-fold: 1) to externally validate the results of Tubbs et al. in a different patient population; 2) to compare how morphometric parameters vary with age, sex, and symptomatology; and 3) to develop a correlative model for tonsillar ectopia in CM-I based on these measurements. METHODS The authors performed a retrospective review of 119 patients who underwent posterior fossa decompression with duraplasty at the Monroe Carell Jr. Children's Hospital at Vanderbilt University; 78 of these patients had imaging available for review. Demographic and clinical variables were collected. A neuroradiologist retrospectively evaluated preoperative MRI examinations in these 78 patients and recorded the following measurements: McRae line length; obex displacement length; odontoid process parameters (height, angle of retroflexion, and angle of retroversion); perpendicular distance to the basion-C2 line (pB-C2 line); length of cerebellar tonsillar ectopia; caudal extent of the cerebellar tonsils; and presence, location, and size of syringomyelia. Odontoid retroflexion grade was classified as Grade 0, > 90°; Grade I,85°-89°; Grade II, 80°-84°; and Grade III, < 80°. Age groups were defined as 0-6 years, 7-12 years, and 13-17 years at the time of surgery. Univariate and multivariate linear regression analyses, Kruskal-Wallis 1-way ANOVA, and Fisher's exact test were performed to assess the relationship between age, sex, and symptomatology with these craniometric variables. RESULTS The prevalence of posterior odontoid angulation was 81%, which is almost identical to that in the previous report (84%). With increasing age, the odontoid height (p < 0.001) and pB-C2 length (p < 0.001) increased, while the odontoid process became more posteriorly inclined (p = 0.010). The pB-C2 line was significantly longer in girls (p = 0.006). These measurements did not significantly correlate with symptomatology. Length of tonsillar ectopia in pediatric CM-I correlated with an enlarged foramen magnum (p = 0.023), increasing obex displacement (p = 0.020), and increasing odontoid retroflexion (p < 0.001). CONCLUSIONS Anomalous bony development of the craniocervical junction is a consistent feature of CM-I in children. The authors found that the population at their center was characterized by posterior angulation of the odontoid process in 81% of cases, similar to findings by Tubbs et al. (84%). The odontoid process appeared to lengthen and become more posteriorly inclined with age. Increased tonsillar ectopia was associated with more posterior odontoid angulation, a widened foramen magnum, and an inferiorly displaced obex.

Hit and go CAS9 delivered through a lentiviral based self-limiting circuit.

PubMed

Petris, Gianluca; Casini, Antonio; Montagna, Claudia; Lorenzin, Francesca; Prandi, Davide; Romanel, Alessandro; Zasso, Jacopo; Conti, Luciano; Demichelis, Francesca; Cereseto, Anna

2017-05-22

In vivo application of the CRISPR-Cas9 technology is still limited by unwanted Cas9 genomic cleavages. Long-term expression of Cas9 increases the number of genomic loci non-specifically cleaved by the nuclease. Here we develop a Self-Limiting Cas9 circuit for Enhanced Safety and specificity (SLiCES) which consists of an expression unit for Streptococcus pyogenes Cas9 (SpCas9), a self-targeting sgRNA and a second sgRNA targeting a chosen genomic locus. The self-limiting circuit results in increased genome editing specificity by controlling Cas9 levels. For its in vivo utilization, we next integrate SLiCES into a lentiviral delivery system (lentiSLiCES) via circuit inhibition to achieve viral particle production. Upon delivery into target cells, the lentiSLiCES circuit switches on to edit the intended genomic locus while simultaneously stepping up its own neutralization through SpCas9 inactivation. By preserving target cells from residual nuclease activity, our hit and go system increases safety margins for genome editing.

Surface expression of anti-CD3scfv stimulates locoregional immunotherapy against hepatocellular carcinoma depending on the E1A-engineered human umbilical cord mesenchymal stem cells.

PubMed

Zhang, Qing; Yuan, Xiang-Fei; Lu, Yang; Li, Zhen-Zhen; Bao, Shi-Qi; Zhang, Xiao-Long; Yang, Yuan-Yuan; Fan, Dong-Mei; Zhang, Yi-Zhi; Wu, Chen-Xuan; Guo, Hong-Xing; Zhang, Yan-Jun; Ye, Zhou; Xiong, Dong-Sheng

2017-10-01

Tumor antigens is at the core of cancer immunotherapy, however, the ideal antigen selection is difficult especially in poorly immunogenic tumors. In this study, we designed a strategy to modify hepatocellular carcinoma (HCC) cells by surface expressing anti-CD3scfv within the tumor site strictly, which depended on the E1A-engineered human umbilical cord mesenchymal stem cells (HUMSC.E1A) delivery system. Subsequently, membrane-bound anti-CD3scfv actived the lymphocytes which lysed HCC cells bypassing the expression of antigens or MHC restriction. First, we constructed the anti-CD3scfv gene driven by human α-fetoprotein (AFP) promoter into an adenoviral vector and the E1A gene into the lentiviral vector. Our results showed that anti-CD3scfv could specifically express on the surface of HCC cells and activate the lymphocytes to kill target cells effectively in vitro. HUMSC infected by AdCD3scfv followed by LentiR.E1A could support the adenoviral replication and packaging in vitro 36 h after LentiR.E1A infection. Using a subcutaneous HepG2 xenograft model, we confirmed that AdCD3scfv and LentiR.E1A co-transfected HUMSC could migrate selectively to the tumor site and produce considerable adenoviruses. The new generated AdCD3scfv infected and modified tumor cells successfully. Mice injected with the MSC.E1A.AdCD3scfv and lymphocytes significantly inhibited the tumor growth compared with control groups. Furthermore, 5-fluorouracil (5-FU) could sensitize adenovirus infection at low MOI resulting in improved lymphocytes cytotoxicity in vitro and in vivo. In summary, this study provides a promising strategy for solid tumor immunotherapy. © 2017 UICC.

Molecular Characterization of Wetland Soil Bacterial Communities in Constructed Mesocosms

DTIC Science & Technology

2008-03-01

Acido., Acidobacteria; Actino., Actinobacteria ; Bacter., Bacteroidetes; Chloro., Chloroflexi; Firm., Firmicutes; Gemma., Gemmatimonadetes; Lenti...Planted sequences (B) using RDP Classifier. Abbreviations: Acidobacteria; Actino., Actinobacteria ; Bacter., Bacteroidetes; Chloro., Chloroflexi...4.2 4.79 Lentisphaerae 0.13 0 Actinobacteria 2.5 3.04 Nitrospira 1.18 1.07 Chloroflexi 3.55 3.04 Acidobacteria 16.16 12.87 Proteobacteria 34.95

[Study of sand flies (Diptera, Psychodidae, Phlebotominae) in the urban area of Campo Grande, Mato Grosso do Sul State, Brazil, from 1999 to 2000].

PubMed

de Oliveira, Alessandra Gutierrez; Andrade Filho, José Dilermando; Falcão, Alda Lima; Brazil, Reginaldo Peçanha

2003-01-01

From February 1999 to February 2000, sand flies were captured weekly with CDC light traps at five sites in the urban area of Campo Grande, Mato Grosso do Sul State, Brazil. Traps were placed in 11 different ecotopes in the environment (ground level, tree canopies, and forest edge) and the peridomicile (chicken coops and banana trees). A total of 1,245 sand flies were captured, belonging to 28 species: 4 species from genus Brumptomyia Fran a & Parrot, 1921 and 24 from genus Lutzomyia Fran a, 1924. The species were: B. avellari, B. brumpti, B. galindoi, B. pintoi, L. aragaoi, L. bourrouli, L. campograndensis, L. cerradincola, L. christenseni, L. claustrei, L. cortelezzii, L. corumbaensis, L. cruzi, L. damascenoi, L. flaviscutellata, L. hermanlenti, L. lenti, L. longipalpis, L. longipennis, L. migonei, L. punctigeniculata, L. quinquefer, L. renei, L. shannoni, L. sordellii, L. teratodes, L. termitophila, and L. whitmani. L. longipalpis and L. cruzi, vectors of visceral leishmaniasis, and L. whitmani, L. flaviscutellata and L. migonei, vectors of cutaneous leishmaniasis, were captured in the urban area. The most frequent species were L. termitophila, L. aragaoi, L. lenti, L. longipennis, and L. longipalpis.

Rotationally asymmetric multifocal IOL implantation with and without capsular tension ring: refractive and visual outcomes and intraocular optical performance.

PubMed

Alió, Jorge L; Plaza-Puche, Ana B; Piñero, David P

2012-04-01

To ascertain whether the refractive, visual, and intraocular optical quality outcomes of a rotationally asymmetric multifocal intraocular lens (IOL) are enhanced by the use of a capsular tension ring. Ninety consecutive eyes from 53 patients (age range: 36 to 82 years) were divided into two groups: the no ring group comprised 43 eyes implanted with the multifocal rotationally asymmetric Lentis Mplus LS-312 (Oculentis GmbH) without a capsular tension ring; and the ring group comprised 47 eyes with the same IOL with a capsular tension ring. Distance and near visual acuity and refractive outcomes were evaluated pre- and postoperatively. Contrast sensitivity, intraocular aberrations, and defocus curve were evaluated postoperatively. Significant postoperative differences between groups were found in sphere, spherical equivalent refraction, and near addition (P<.02). Regarding defocus curve, significantly better visual acuity was present in eyes with the capsular tension ring for intermediate vision conditions (P<.05). Intraocular aberrometry did not differ significantly between groups (P<.09). Refractive predictability and intermediate visual outcomes with the Lentis Mplus LS-312 IOL improved significantly when implanted in combination with a capsular tension ring. Copyright 2012, SLACK Incorporated.

Trypanosoma cruzi strains from triatomine collected in Bahia and Rio Grande do Sul, Brazil.

PubMed

Ribeiro, Aline Rimoldi; Mendonça, Vagner José; Alves, Renata Tomé; Martinez, Isabel; Araújo, Renato Freitas de; Mello, Fernanda; da Rosa, João Aristeu

2014-04-01

Collection of triatomines in domestic, peridomestic and sylvatic environments in states of Bahia and Rio Grande do Sul, Northeastern and Southern Brazil respectively, and isolation of Trypanosoma cruzi strains. First, the captured triatomines were identified using insect identification keys, then their intestinal content was examined by abdominal compression, and the samples containing trypanosomatid forms were inoculated in LIT medium and Swiss mice. Six triatomine species were collected in cities in Bahia, namely Panstrongylus geniculatus (01), Triatoma melanocephala (11), T. lenti (94), T. pseudomaculata (02), T. sherlocki (26) and T. sordida (460), and two in cities in Rio Grande do Sul, namely T. circummaculata (11) and T. rubrovaria (115). Out of the specimens examined, T. cruzi was isolated from 28 triatomine divided into four different species: T. melanocephala (one), T. lenti (one), T. rubrovaria (16) and T. sordida (10). Their index of natural infection by T. cruzi was 6.4%. The isolation of T. cruzi strains from triatomines found in domestic and peridomestic areas shows the potential risk of transmission of Chagas disease in the studied cities. The maintenance of those T. cruzi strains in laboratory is intended to promote studies that facilitate the understanding of the parasite-vector-host relationship.

Hematopoietic Stem-Cell Gene Therapy for Cerebral Adrenoleukodystrophy.

PubMed

Eichler, Florian; Duncan, Christine; Musolino, Patricia L; Orchard, Paul J; De Oliveira, Satiro; Thrasher, Adrian J; Armant, Myriam; Dansereau, Colleen; Lund, Troy C; Miller, Weston P; Raymond, Gerald V; Sankar, Raman; Shah, Ami J; Sevin, Caroline; Gaspar, H Bobby; Gissen, Paul; Amartino, Hernan; Bratkovic, Drago; Smith, Nicholas J C; Paker, Asif M; Shamir, Esther; O'Meara, Tara; Davidson, David; Aubourg, Patrick; Williams, David A

2017-10-26

In X-linked adrenoleukodystrophy, mutations in ABCD1 lead to loss of function of the ALD protein. Cerebral adrenoleukodystrophy is characterized by demyelination and neurodegeneration. Disease progression, which leads to loss of neurologic function and death, can be halted only with allogeneic hematopoietic stem-cell transplantation. We enrolled boys with cerebral adrenoleukodystrophy in a single-group, open-label, phase 2-3 safety and efficacy study. Patients were required to have early-stage disease and gadolinium enhancement on magnetic resonance imaging (MRI) at screening. The investigational therapy involved infusion of autologous CD34+ cells transduced with the elivaldogene tavalentivec (Lenti-D) lentiviral vector. In this interim analysis, patients were assessed for the occurrence of graft-versus-host disease, death, and major functional disabilities, as well as changes in neurologic function and in the extent of lesions on MRI. The primary end point was being alive and having no major functional disability at 24 months after infusion. A total of 17 boys received Lenti-D gene therapy. At the time of the interim analysis, the median follow-up was 29.4 months (range, 21.6 to 42.0). All the patients had gene-marked cells after engraftment, with no evidence of preferential integration near known oncogenes or clonal outgrowth. Measurable ALD protein was observed in all the patients. No treatment-related death or graft-versus-host disease had been reported; 15 of the 17 patients (88%) were alive and free of major functional disability, with minimal clinical symptoms. One patient, who had had rapid neurologic deterioration, had died from disease progression. Another patient, who had had evidence of disease progression on MRI, had withdrawn from the study to undergo allogeneic stem-cell transplantation and later died from transplantation-related complications. Early results of this study suggest that Lenti-D gene therapy may be a safe and effective alternative to allogeneic stem-cell transplantation in boys with early-stage cerebral adrenoleukodystrophy. Additional follow-up is needed to fully assess the duration of response and long-term safety. (Funded by Bluebird Bio and others; STARBEAM ClinicalTrials.gov number, NCT01896102 ; ClinicalTrialsRegister.eu number, 2011-001953-10 .).

Comparison of a new refractive multifocal intraocular lens with an inferior segmental near add and a diffractive multifocal intraocular lens.

PubMed

Alio, Jorge L; Plaza-Puche, Ana B; Javaloy, Jaime; Ayala, María José; Moreno, Luis J; Piñero, David P

2012-03-01

To compare the visual acuity outcomes and ocular optical performance of eyes implanted with a multifocal refractive intraocular lens (IOL) with an inferior segmental near add or a diffractive multifocal IOL. Prospective, comparative, nonrandomized, consecutive case series. Eighty-three consecutive eyes of 45 patients (age range, 36-82 years) with cataract were divided into 2 groups: group A, 45 eyes implanted with Lentis Mplus LS-312 (Oculentis GmbH, Berlin, Germany); group B, 38 eyes implanted with diffractive IOL Acri.Lisa 366D (Zeiss, Oberkochen, Germany). All patients underwent phacoemulsification followed by IOL implantation in the capsular bag. Distance corrected, intermediate, and near with the distance correction visual acuity outcomes and contrast sensitivity, intraocular aberrations, and defocus curve were evaluated postoperatively during a 3-month follow-up. Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), uncorrected near visual acuity (UNVA), corrected distance near and intermediate visual acuity (CDNVA), contrast sensitivity, intraocular aberrations, and defocus curve. A significant improvement in UDVA, CDVA, and UNVA was observed in both groups after surgery (P ≤ 0.04). Significantly better values of UNVA (P<0.01) and CDNVA (P<0.04) were found in group B. In the defocus curve, significantly better visual acuities were present in eyes in group A for intermediate vision levels of defocus (P ≤ 0.04). Significantly higher amounts of postoperative intraocular primary coma and spherical aberrations were found in group A (P<0.01). In addition, significantly better values were observed in photopic contrast sensitivity for high spatial frequencies in group A (P ≤ 0.04). The Lentis Mplus LS-312 and Acri.Lisa 366D IOLs are able to successfully restore visual function after cataract surgery. The Lentis Mplus LS-312 provided better intermediate vision and contrast sensitivity outcomes than the Acri.Lisa 366D. However, the Acri.Lisa design provided better distance and near visual outcomes and intraocular optical performance parameters. Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Congenital anatomic variants of the kidney and ureter: a pictorial essay.

PubMed

Srinivas, M R; Adarsh, K M; Jeeson, Riya; Ashwini, C; Nagaraj, B R

2016-03-01

Congenital renal parenchymal and pelvicalyceal abnormalities have a wide spectrum. Most of them are asymptomatic, like that of ectopia, cross fused kidney, horseshoe kidney, etc., while a few of them become complicated, leading to renal failure and death. It is very important for the radiologist to identify these anatomic variants and guide the clinicians for surgical and therapeutic procedures. Cross-sectional imaging with a volume rendered technique/maximum intensity projection has overcome ultrasonography and IVU for identification and interpretation of some of these variants.

MicroRNA-195 prevents dendritic degeneration and neuron death in rats following chronic brain hypoperfusion

PubMed Central

Chen, Xin; Jiang, Xue-Mei; Zhao, Lin-Jing; Sun, Lin-Lin; Yan, Mei-Ling; Tian, You; Zhang, Shuai; Duan, Ming-Jing; Zhao, Hong-Mei; Li, Wen-Rui; Hao, Yang-Yang; Wang, Li-Bo; Xiong, Qiao-Jie; Ai, Jing

2017-01-01

Impaired synaptic plasticity and neuron loss are hallmarks of Alzheimer’s disease and vascular dementia. Here, we found that chronic brain hypoperfusion (CBH) by bilateral common carotid artery occlusion (2VO) decreased the total length, numbers and crossings of dendrites and caused neuron death in rat hippocampi and cortices. It also led to increase in N-terminal β-amyloid precursor protein (N-APP) and death receptor-6 (DR6) protein levels and in the activation of caspase-3 and caspase-6. Further study showed that DR6 protein was downregulated by miR-195 overexpression, upregulated by miR-195 inhibition, and unchanged by binding-site mutation and miR-masks. Knockdown of endogenous miR-195 by lentiviral vector-mediated overexpression of its antisense molecule (lenti-pre-AMO-miR-195) decreased the total length, numbers and crossings of dendrites and neuron death, upregulated N-APP and DR6 levels, and elevated cleaved caspase-3 and caspase-6 levels. Overexpression of miR-195 using lenti-pre-miR-195 prevented these changes triggered by 2VO. We conclude that miR-195 is involved in CBH-induced dendritic degeneration and neuron death through activation of the N-APP/DR6/caspase pathway. PMID:28569780

[Construction and selection of effective mouse Smad6 recombinant lenti-virus interference vectors].

PubMed

Yu, Jing; Qi, Mengchun; Deng, Jiupeng; Liu, Gang; Chen, Huaiqing

2010-10-01

This experiment was designed to construct mouse Smad6 recombinant RNA interference vectors and determine their interference effects on bone marrow mesenchymal stem cells (BMSCs). Three recombinant Smad6 RNA interference vectors were constructed by molecular clone techniques with a lenti-virus vector expressing green fluorescent protein (GFP), and the correctness of recombinant vectors was verified by DNA sequencing. Mouse BMSCs were used for transfection experiments and BMP-2 was in use for osteogenic induction of MSCs. The transfection efficiency of recombinant vectors was examined by Laser confocal scanning microscope and the interference effect of recombinant vectors on Smad6 gene expression was determined by real-time RT-PCR and Western blot, respectively. Three Smad6 recombinant RNA interference vectors were successfully constructed and their correctness was proved by DNA sequencing. After transfection, GFPs were effectively expressed in MSCs and all of three recombinant vectors gained high transfection efficiency (> 95%). Both real-time PCR and Western blot examination indicated that among three recombinant vectors, No. 2 Svector had the best interference effect and the interference effect was nearly 91% at protein level. In conclusion, Mouse recombinant Smad6 RNA interference (RNAi) vector was successfully constructed and it provided an effective tool for further studies on BMP signal pathways.

Trypanosoma cruzi strains from triatomine collected in Bahia and Rio Grande do Sul, Brazil

PubMed Central

Ribeiro, Aline Rimoldi; Mendonça, Vagner José; Alves, Renata Tomé; Martinez, Isabel; de Araújo, Renato Freitas; Mello, Fernanda; da Rosa, João Aristeu

2014-01-01

OBJECTIVE Collection of triatomines in domestic, peridomestic and sylvatic environments in states of Bahia and Rio Grande do Sul, Northeastern and Southern Brazil respectively, and isolation of Trypanosoma cruzi strains. METHODS First, the captured triatomines were identified using insect identification keys, then their intestinal content was examined by abdominal compression, and the samples containing trypanosomatid forms were inoculated in LIT medium and Swiss mice. RESULTS Six triatomine species were collected in cities in Bahia, namely Panstrongylus geniculatus (01), Triatoma melanocephala (11), T. lenti (94), T. pseudomaculata (02), T. sherlocki (26) and T. sordida (460), and two in cities in Rio Grande do Sul, namely T. circummaculata (11) and T. rubrovaria (115). Out of the specimens examined, T. cruzi was isolated from 28 triatomine divided into four different species: T. melanocephala (one), T. lenti (one), T. rubrovaria (16) and T. sordida (10). Their index of natural infection by T. cruzi was 6.4%. CONCLUSIONS The isolation of T. cruzi strains from triatomines found in domestic and peridomestic areas shows the potential risk of transmission of Chagas disease in the studied cities. The maintenance of those T. cruzi strains in laboratory is intended to promote studies that facilitate the understanding of the parasite-vector-host relationship. PMID:24897051

Muscle Stem Cell Therapy for the Treatment of DMD Associated Cardiomyopathy

DTIC Science & Technology

2014-10-01

is shown in Figure 1. 2) Effect of hypoxia on the gene expression of human muscle derived stem cells (hMDSCs) Three populations of lenti-GFP...adipogenic differentiation of mesenchymal stem cells (MSCs) (5). Activation of RhoA-ROCK signaling in cultured MSCs in vitro induces their osteogenesis but...reduced osteoblastogenesis and enhanced adipogenesis of human mesenchymal stem cells in modeled microgravity. J Bone Miner Res. 2005;20(10):1858-66. PMCID

Definitions and Anatomic Considerations in Chiari I Malformation and Associated Syringomyelia.

PubMed

Tubbs, R Shane

2015-10-01

Current understanding of the hindbrain hernias known as Chiari I malformations is based on more than 100 years of pathologic and clinical experience. Over time, the definition of this finding has been analyzed and altered. The term Chiari I malformation is currently used to describe tonsillar ectopia in a wide range of patients with varying embryonic derailments. This article discusses this malformation, its various definitions, and varied anatomic traits. In addition, the morphology of the commonly associated syringomyelia is reviewed. Copyright © 2015 Elsevier Inc. All rights reserved.

Ibrutinib inhibits BTK-driven NF-κB p65 activity to overcome bortezomib-resistance in multiple myeloma

PubMed Central

Murray, Megan Y; Zaitseva, Lyubov; Auger, Martin J; Craig, Jenny IO; MacEwan, David J; Rushworth, Stuart A; Bowles, Kristian M

2015-01-01

Multiple Myeloma (MM) is a haematologic malignancy characterized by the accumulation of clonal plasma cells in the bone marrow. Over the last 10–15 y the introduction of the proteasome-inhibitor bortezomib has improved MM prognosis, however relapse due to bortezomib-resistance is inevitable and the disease, at present, remains incurable. To model bortezomib-resistant MM we generated bortezomib-resistant MM cell lines (n = 4 ) and utilised primary malignant plasma cells from patients relapsing after bortezomib treatment (n = 6 ). We identified enhanced Bruton's tyrosine kinase (BTK) activity in bortezomib-resistant MM cells and found that inhibition of BTK, either pharmacologically with ibrutinib (0.5 μM) or via lenti-viral miRNA-targeted BTK interference, re-sensitized previously bortezomib-resistant MM cells to further bortezomib therapy at a physiologically relevant concentration (5 nM). Further analysis of pro-survival signaling revealed a role for the NF-κB p65 subunit in MM bortezomib-resistance, thus a combination of BTK and NF-κB p65 inhibition, either pharmacologically or via further lenti-viral miRNA NF-κB p65 interference, also restored sensitivity to bortezomib, significantly reducing cell viability (37.5 ± 6 .9 %, ANOVA P ≤ 0 .001). Accordingly, we propose the clinical evaluation of a bortezomib/ibrutinib combination therapy, including in patients resistant to single-agent bortezomib. PMID:25565020

Sandflies (Diptera: Psychodidae) in an urban area of Northeastern Brazil.

PubMed

Agra, Maria Claudia Ribeiro; Costa, Pietra Lemos; Duque, Anderson Enio Silva; Soares, Efraim Naftali Lopes; Alves, Leucio Câmara; Ramos, Rafael Antonio Nascimento; Carvalho, Gílcia Aparecida de

2016-01-01

The sandfly fauna is well studied globally. In Brazil, sandfly fauna is very diverse in the Northeast region, especially in states such as Maranhão, Ceará, and Bahia. However, in the State of Pernambuco, the distribution of these insects is still not well known. Therefore, the objective of this study was to identify the different species that constitute the sandfly fauna in an urban area in the Northeast region of Brazil, where an outbreak of visceral leishmaniasis (VL) was recently reported. The sandflies were collected from an urban area endemic for VL, at five collection points. The collection of samples was carried out from November 2014 to December 2015, using CDC light traps installed in intradomiciliary and peridomiciliary fashion. The collected sandflies (n = 297) belonged to eight species: Lutzomyia lenti, Lutzomyia longipalpis, Lutzomyia sallesi, Lutzomyia migonei, Lutzomyia walkeri, Lutzomyia capixaba, Lutzomyia carmelinoi, and Lutzomyia whitmani. Most of the specimens collected were peridomiciliary (247/297, 83%). L. lenti (154/297, 52%) was the most frequently sampled species, followed by L. longipalpis (88/297, 29.6%), and L. sallesi (42/297, 14.1%), which together accounted for over 90% of the collected sandfly specimens. The continued presence of L. longipalpis in urban areas, including that in intradomiciliary areas, with a predominance of females, is crucial because of the high possibility of them causing VL outbreaks, since this species is the main vector of Leishmania infantum in Brazil.

Ibrutinib inhibits BTK-driven NF-κB p65 activity to overcome bortezomib-resistance in multiple myeloma.

PubMed

Murray, Megan Y; Zaitseva, Lyubov; Auger, Martin J; Craig, Jenny Io; MacEwan, David J; Rushworth, Stuart A; Bowles, Kristian M

2015-01-01

Multiple Myeloma (MM) is a haematologic malignancy characterized by the accumulation of clonal plasma cells in the bone marrow. Over the last 10-15 y the introduction of the proteasome-inhibitor bortezomib has improved MM prognosis, however relapse due to bortezomib-resistance is inevitable and the disease, at present, remains incurable. To model bortezomib-resistant MM we generated bortezomib-resistant MM cell lines (n = 4 ) and utilised primary malignant plasma cells from patients relapsing after bortezomib treatment (n = 6 ). We identified enhanced Bruton's tyrosine kinase (BTK) activity in bortezomib-resistant MM cells and found that inhibition of BTK, either pharmacologically with ibrutinib (0.5 μM) or via lenti-viral miRNA-targeted BTK interference, re-sensitized previously bortezomib-resistant MM cells to further bortezomib therapy at a physiologically relevant concentration (5 nM). Further analysis of pro-survival signaling revealed a role for the NF-κB p65 subunit in MM bortezomib-resistance, thus a combination of BTK and NF-κB p65 inhibition, either pharmacologically or via further lenti-viral miRNA NF-κB p65 interference, also restored sensitivity to bortezomib, significantly reducing cell viability (37.5 ± 6 .9 %, ANOVA P ≤ 0 .001). Accordingly, we propose the clinical evaluation of a bortezomib/ibrutinib combination therapy, including in patients resistant to single-agent bortezomib.

Molecular cloning and production of caprine recombinant Oct4 protein for generation induced pluripotent stem cells.

PubMed

Singhal, Dinesh K; Singhal, Raxita; Malik, Hruda N; Singh, Surender; Kumar, Sudarshan; Kaushik, Jai K; Mohanty, Ashok K; Malakar, Dhruba

2015-12-01

Oct4, pluripotency marker and transcription factor, expresses in embryonic stem cells. It plays a pivotal role in determination of stem cells fate. Up and down regulation of Oct4 causes differentiation of embryonic stem cells. It is one of the main transcription factors which remained concerned in every study related to induced pluripotent stem cell. Here, we report the production of goat Oct4 protein using plasmid and lentiviral based vectors. Firstly, Oct4 ORF was cloned in pAcGFP1-N1 plasmid vector and positive clones were screened with colony PCR. Oct4 was over-expressed in CHO-K1 cell line and expression was confirmed by observing green florescent protein expression in CHO-K1 cells. Secondly, Oct4 lentiviral expression construct has been prepared using pLenti-gw vector. Oct4 ORF was cloned into pLenti4/V5-DEST vector and viral particles were produced in 293FT cells. Oct4 viral particles were used to infect goat fibroblast cells. Oct4 expression was observed and confirmed in transfected goat fibroblast cells using RT-PCR. Detection of Oct4 protein in western blotting assay affirmed the capacity of over-expression of our Oct4 lentiviral vector. The lentiviral expression construct and recombinant Oct4 protein may be used for reprogramming of somatic cell into induced pluripotent stem cell.

Surgical management and histologic and immunohistochemical features of a cataract and retrolental plaque secondary to persistent hyperplastic tunica vasculosa lentis/persistent hyperplastic primary vitreous (PHTVL/PHPV) in a Bloodhound puppy.

PubMed

Gemensky-Metzler, Anne J; Wilkie, David A

2004-01-01

The objective of this study was to describe the clinical, histologic and immunohistochemical features, the surgical treatment, and outcome of a cataract secondary to persistent hyperplastic tunica vasculosa lentis/persistent hyperplastic primary vitreous (PHTVL/PHPV) in a dog. A 4-month-old male Bloodhound dog presented for evaluation of a cataract. A complete ophthalmic examination and ocular ultrasonography were performed. A resorbing cataract with intralenticular hemorrhage, lens induced uveitis, and PHTVL/PHPV were diagnosed. Extracapsular cataract extraction using phacoemulsification was performed. A primary posterior capsulectomy was performed to remove a retrolental plaque with the posterior capsule; the excised plaque was submitted for histopathology and immunohistochemical staining. A 41-Diopter intraocular lens (IOL) was implanted. Functional vision was maintained postoperatively during the 21-month follow-up period. Histologically, the posterior capsule was coiled and exhibited duplication. The retrolental plaque was comprised of dense fibrous connective tissue, blood vessels, free red blood cells, hemosiderin-laden macrophages, a pocket of neural tissue and numerous perivascular mast cells. With immunohistochemical staining, the neural elements were determined to be glial cells compatible with astrocytes. Cataract secondary to PHTVL/PHPV can be successfully treated using phacoemulsification and planned posterior capsulectomy. Posterior lens capsule duplication, mast cells and astrocytic glial cells may be normal components of the fibrovascular retrolental plaque associated with PHTVL/PHPV.

Health assessment of gasoline and fuel oxygenate vapors: developmental toxicity in mice.

PubMed

Roberts, L G; Gray, T M; Marr, M C; Tyl, R W; Trimmer, G W; Hoffman, G M; Murray, F J; Clark, C R; Schreiner, C A

2014-11-01

CD-1 mice were exposed to baseline gasoline vapor condensate (BGVC) alone or to vapors of gasoline blended with methyl tertiary butyl ether (G/MTBE). Inhalation exposures were 6h/d on GD 5-17 at levels of 0, 2000, 10,000, and 20,000mg/m(3). Dams were evaluated for evidence of maternal toxicity, and fetuses were weighed, sexed, and evaluated for external, visceral, and skeletal anomalies. Exposure to 20,000mg/m(3) of BGVC produced slight reductions in maternal body weight/gain and decreased fetal body weight. G/MTBE exposure did not produce statistically significant maternal or developmental effects; however, two uncommon ventral wall closure defects occurred: gastroschisis (1 fetus at 10,000mg/m(3)) and ectopia cordis (1 fetus at 2000mg/m(3); 2 fetuses/1 litter at 10,000mg/m(3)). A second study (G/MTBE-2) evaluated similar exposure levels on GD 5-16 and an additional group exposed to 30,000mg/m(3) from GD 5-10. An increased incidence of cleft palate was observed at 30,000mg/m(3) G/MTBE. No ectopia cordis occurred in the replicate study, but a single observation of gastroschisis was observed at 30,000mg/m(3). The no observed adverse effect levels for maternal/developmental toxicity in the BGVC study were 10,000/2000mg/m(3), 20,000/20,000 for the G/MTBE study, and 10,000/20,000 for the G/MTBE-2 study. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

De Novo Chromosome Copy Number Variation in Fanconi Anemia-Associated Hematopoietic Defects

DTIC Science & Technology

2012-04-01

Appendix 1. Expansion of monoclonal populations of FA-A hTERT and FA-A + FANCA hTERT cells Appendix 2. Expansion of monoclonal populations of FA...marrow failure (BMF) and pronounced cancer susceptibility. The FA proteins and the major breast cancer susceptibility gene products BRCA1 and BRCA2...Correction of FA-A, FA-C, and FA-D2 hTERT cells with pLenti6.2/V5- FANCA , -FANCC, and FANCD2, respectively. Sub-task 1. Selection and expansion of clonal

De Novo Chromosome Copy Number Variation in Fanconi Anemia-Associated Hematopoietic Defects

DTIC Science & Technology

2014-08-01

protein, and not FANCA , is required for the suppression of spontaneous de novo CNV. These findings support a model whereby the FANCD2 protein, possibly...cancer susceptibility gene products BRCA1 and BRCA2 function cooperatively in the FA-BRCA pathway to repair damaged DNA. Recent studies have...the FA-BRCA pathway in the suppression of spontaneous de novo CNVs Task 1. Correction of FA-A, FA-C, and FA-D2 hTERT cells with pLenti6.2/V5- FANCA

Kinetics of Thermal Neutrons in a Time-of-Flight Spectrometer. I. Probability of Transmission of Neutrons through a Revolving Slit; CENETICA DEI NEUTRONI LENTI IN UNO SPETTROMETRO A TEMPO DI VOLO. I-PROBABILITA DI TRANSMISSIONE DEI NEUTRONI ATTRAVERSO UNA FENDITURA RUOTANTE

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

Marseguerra, M.; Pauli, G.

1958-07-01

The kinetic behavior of thermal neutrons in a time-offlight spectrometer is examined. An analytical method for obtaining the expressions for the probability for slow neutron transmission through a revolving slit (the general case of a curved slit is considered) is presented and discussed in detail. (auth)

Exploiting RhoA Mutations in Diffuse Gastric Adenocarcinoma and Targeting Intertwined RhoA and Yap1 Pathways for Therapeutic Advantage

DTIC Science & Technology

2017-10-01

fluorescent marker mOrange into MIT’s Dr. Zhang’s pLenti- Crispr -v2, making transfection into mammalian cells easier and visible under fluorescent...microscope, it the same time, those cells under Crispr editing are also selectable with puromycin. We have successfully knocked-out RhoA expression in cell...15. SUBJECT TERMS RHOA, YAP1, mouse model, CRISPR -CAS9, plasmid, cell lines, diffuse gastric adenocarcinoma, mutations, gastric adenocarcinoma 16

Investigating Cooperation between KEAP1 and LKB1 Inactivation in Lung Adenocarcinoma

DTIC Science & Technology

2017-08-01

cell culture conditions (Figures 2A, 6). To test the effects of KEAP1 deletion in LKB1-deficient LA (LKB1-), we 4 utilized CRISPR (Clustered...sgRNA sequences to murine Keap1 using an online design tool (http://crispr.mit.edu/) that were cloned into the pLentiV2 CRISPR vector. Following...performed CRISPR mediated deletion of Keap1 in a murine LA cell line wildtype for Lkb1, but carrying an oncogenic mutation to Kras and found t increased

[Congenital anomalies of poor prognosis. Genetics Consensus Committee].

PubMed

Pardo Vargas, Rosa A; Aracena, Mariana; Aravena, Teresa; Cares, Carolina; Cortés, Fanny; Faundes, Víctor; Mellado, Cecilia; Passalacqua, Cristóbal; Sanz, Patricia; Castillo Taucher, Silvia

The Genetic Branch of the Chilean Society of Paediatrics, given the draft Law governing the decriminalisation of abortion on three grounds, focusing on the second ground, which considers the "embryo or foetus suffering from a congenital structural anomaly or a genetic disorder incompatible with life outside the womb", met to discuss the scientific evidence according to which congenital anomalies (CA) may be included in this draft law. Experts in clinical genetics focused on 10 CA, reviewed the literature evidence, and met to discuss it. It was agreed not to use the term "incompatible with life outside the womb", as there are exceptions and longer survivals, and change to "congenital anomaly of poor prognosis (CAPP)". Ten CA were evaluated: serious defects of neural tube closure: anencephaly, iniencephaly and craniorachischisis, pulmonary hypoplasia, acardiac foetus, ectopia cordis, non-mosaic triploidy, "limb body wall" complex, "body stalk" anomaly, trisomy 13, trisomy 18, and bilateral renal agenesis. Findings on the prevalence, natural history, prenatal diagnostic methods, survival, and reported cases of prolonged survival were analysed. Post-natal survival, existence of treatments, and outcomes, as well as natural history without intervention, were taken into account in classifying a CA as a CAPP. A CAPP would be: anencephaly, severe pulmonary hypoplasia, acardiac foetus, cervical ectopia cordis, non-mosaic triploidy, limb body wall complex, body stalk anomaly, non-mosaic trisomy 13, non-mosaic trisomy 18, and bilateral renal agenesis. For their diagnosis, it is required that all pregnant women have access to assessments by foetal anatomy ultrasound and occasionally MRI, and cytogenetic and molecular testing. Copyright © 2016 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Calcification of Hydrophilic Acrylic Intraocular Lenses With a Hydrophobic Surface: Laboratory Analysis of 6 Cases.

PubMed

Gartaganis, Sotirios P; Prahs, Philipp; Lazari, Eftichia D; Gartaganis, Panos S; Helbig, Horst; Koutsoukos, Petros G

2016-08-01

To investigate the nature and characteristic features of deposits causing opacification of intraocular lenses (IOLs) based on the examination of clinical findings using scanning electron microscopy (SEM) and energy-dispersive x-ray spectroscopy (EDX) analysis. Retrospective, observational case series. This is a multicenter study of 6 hydrophilic acrylic IOLs (Lentis LS-502-1; Oculentis GmbH, Berlin, Germany) with a hydrophobic surface that were explanted from 5 patients because of opacification. Three patients had an uncomplicated phacoemulsification. One patient underwent combined phacoemulsification and pars plana vitrectomy for retinal detachment and later silicone oil endotamponade owing to redetachment. The last patient had a pars plana vitrectomy and silicone oil instillation combined with phacoemulsification for tractive retinal detachment and diabetic retinopathy. The explanted lenses were submitted to our laboratory and were examined by SEM and EDX in order to identify the morphologic features and the composition of the deposits. SEM and EDX analyses confirmed the presence of calcific deposits in the interior of the opacified hydrophilic IOLs, with a pattern showing the formation of lumps on the surface. The lumps were due to subsurface formation of calcium phosphate crystalline deposits. The crystallite clusters seemed to diffuse from the IOL interior to the surface. We demonstrated the calcification pattern of the hydrophilic IOL (Lentis LS-502-1) with a hydrophobic surface. Although hydrophilic acrylic lenses have a hydrophobic surface, the development of calcification is a possible threat initiating from the hydrophilic subsurface of the IOLs. Copyright © 2016 Elsevier Inc. All rights reserved.

[In Vitro Evaluation of the Optical Quality of Segmental Refractive Multifocal Intraocular Lenses].

PubMed

Yildirim, Timur Mert; Auffarth, Gerd Uwe; Tandogan, Tamer; Liebing, Stephanie; Labuz, Grzegorz; Choi, Chul Young; Khoramnia, Ramin

2017-11-08

In customised patient care, it is important to know the optical quality of different intraocular lenses (IOL). In this study, the optical quality of three segmental intraocular lenses were compared. The LENTIS Comfort LS-313 MF15, LENTIS Mplus X LS-313 MF30 and LENTIS High Add IOL LS-313 MF80 (Oculentis, Berlin, Germany) with a far power of + 21 D were analysed at the optical bench OptiSpheric IOL PRO (Trioptics GmbH, Wedel, Germany). The lenses have almost the same optical design but differ in the power of the near segment. The MF15 has a + 1.5 D addition to improve vision in intermediate distances, the MF30 has a near addition of + 3 D and the MF80 has a near addition of + 8 D. The modulation transfer function area (MTFa) and the Strehl ratio were examined for apertures of 3 mm (photopic) and 4.5 mm (mesopic). The MTFa values for the far focus are 33.34/30.80/51.53 (MF15/MF30/MF80) with an aperture of 3 mm and 25.38/22.52/43.15 for 4.5 mm. The MTFa values for the intermediate focus are 29.85/16.21/6.25 for a 3 mm aperture and 23.92/8.05/3.08 for 4.5 mm. The MTFa values for the near focus are 9.75/21.49/33.12 for an aperture of 3 mm and 4.95/22.70/31.68 for 4.5 mm. The Strehl ratio of the far focus is 0.34/0.30/0.52 for an aperture of 3 mm and 0.24/0.22/0.43 for 4.5 mm. For the intermediate focus, the Strehl ratio is 0.30/0.17/0.07 for an aperture of 3 mm and 0.24/0.08/0.03 for 4.5 mm. The Strehl ratio of the near focus is 0.10/0.22/0.33 for an aperture of 3 mm and 0.05/0.23/0.32 for 4.5 mm. We confirmed that the addition influences the optical quality of segmental bifocal intraocular lenses. For the far focus, the results of the MF15 and MF30 are similar. In intermediate distances, the MF15 achieves the best results. For near distances, the MF30 achieves better optical values than the MF15. The lens MF80, which has been designed for patients with maculopathies, achieves good results for far and near distances. Georg Thieme Verlag KG Stuttgart · New York.

Study of sand flies (Diptera: Psychodidae) in visceral and cutaneous leishmaniasis areas in the central-western state of Minas Gerais, Brazil.

PubMed

Nascimento, Bruno Warlley Leandro; Saraiva, Lara; Neto, Rafael Gonçalves Teixeira; Meira, Paula Cavalcante Lamy Serra e; Sanguinette, Cristiani de Castilho; Tonelli, Gabriel Barbosa; Botelho, Helbert Antônio; Belo, Vinícius Silva; Silva, Eduardo Sérgio da; Gontijo, Célia Maria Ferreira; Filho, José Dilermando Andrade

2013-03-01

The transmission of Leishmania involves several species of sand flies that are closely associated with various parasites and reservoirs, with differing transmission cycles in Brazil. A study on the phlebotomine species composition has been conducted in the municipality of Divinópolis, Minas Gerais, Brazil, an endemic area for cutaneous leishmaniasis (CL), which has intense occurrence of visceral leishmaniasis (VL) cases. In order to study the sand flies populations and their seasonality, CDC light traps (HP model) were distributed in 15 houses which presented at least one case of CL or VL and in five urban parks (green areas). Collections were carried out three nights monthly from September 2010 to August 2011. A total of 1064 phlebotomine specimens were collected belonging to two genera and seventeen species: Brumptomyia brumpti, Lutzomyia bacula, Lutzomyia cortelezzii, Lutzomyia lenti, Lutzomyia sallesi, Lutzomyia longipalpis, Lutzomyia migonei, Lutzomyia intermedia, Lutzomyia neivai, Lutzomyia whitmani, Lutzomyia christenseni, Lutzomyia monticola, Lutzomyia pessoai, Lutzomyia aragaoi, Lutzomyia brasiliensis, Lutzomyia lutziana, and Lutzomyia sordellii. L. longipalpis, the main vector of Leishmania infantum in Brazil, was the most frequent species, accounting for 76.9% of the total, followed by L. lenti with 8.3%, this species is not a proven vector. Green and urban areas had different sand flies species composition, whereas the high abundance of L. longipalpis in urban areas and the presence of various vector species in both green and urban areas were also observed. Our data point out to the requirement of control measures against phlebotomine sand flies in the municipality of Divinópolis and adoption of strategies aiming entomological surveillance. Copyright © 2012 Elsevier B.V. All rights reserved.

ATP synthase β-subunit abnormality in pancreas islets of rats with polycystic ovary syndrome and type 2 diabetes mellitus.

PubMed

Li, Wei; Li, Sai-Jiao; Yin, Tai-Lang; Yang, Jing; Cheng, Yan

2017-04-01

This study investigated the abnormal expression of ATP synthase β-subunit (ATPsyn-β) in pancreas islets of rat model of polycystic ovary syndrome (PCOS) with type 2 diabetes mellitus (T2DM), and the secretion function changes after up-regulation of ATP5b. Sixty female SD rats were divided into three groups randomly and equally. The rat model of PCOS with T2DM was established by free access to the high-carbohydrate/high-fat diet, subcutaneous injections of DHEA, and a single injection of streptozotocin. The pancreas was removed for the detection of the ATPsyn-β expression by immunohistochemical staining, Western blotting and reverse transcription-PCR (RT-PCR). The pancreas islets of the rats were cultured, isolated with collagenase V and purified by gradient centrifugation, and the insulin secretion after treatment with different glucose concentrations was tested. Lentivirus ATP5b was successfully constructed with the vector of GV208 and transfected into the pancreas islets for the over-expression of ATPsyn-β. The insulin secretion and intracellular ATP content were determined after transfection of the PCOS-T2DM pancreas islets with Lenti-ATP5b. The results showed that the expression of ATPsyn-β protein and mRNA was significantly decreased in the pancreas of PCOS-T2DM rats. The ATP content in the pancreas islets was greatly increased and the insulin secretion was improved after the up-regulation of ATPsyn-β in the pancreas islets transfected with lenti-ATP5b. These results indicated that for PCOS, the ATPsyn-β might be one of the key factors for the attack of T2DM.

Correlation of visual performance with quality of life and intraocular aberrometric profile in patients implanted with rotationally asymmetric multifocal IOLs.

PubMed

Ramón, María L; Piñero, David P; Pérez-Cambrodí, Rafael J

2012-02-01

To examine the visual performance of a rotationally asymmetric multifocal intraocular lens (IOL) by correlating the defocus curve of the IOL-implanted eye with the intraocular aberrometric profile and impact on the quality of life. A prospective, consecutive, case series study including 26 eyes from 13 patients aged between 50 and 83 years (mean: 65.54±7.59 years) was conducted. All patients underwent bilateral cataract surgery with implantation of a rotationally asymmetric multifocal IOL (Lentis Mplus LS-312 MF30, Oculentis GmbH). Distance and near visual acuity outcomes, intraocular aberrations, defocus curve, and quality of life (assessed using the National Eye Institute Visual Functioning Questionnaire-25) were evaluated postoperatively (mean follow-up: 6.42±2.24 months). A significant improvement in distance visual acuity was found postoperatively (P<.01). Mean postoperative logMAR distance-corrected near visual acuity was 0.19±0.12 (∼20/30). Corrected distance visual acuity and near visual acuity of 20/20 or better were achieved by 30.8% and 7.7% of eyes, respectively. Of all eyes, 96.2% had a postoperative addition between 0 and 1.00 diopter (D). The defocus curve showed two peaks of maximum visual acuity (0 and 3.00 D of defocus), with an acceptable range of intermediate vision. LogMAR visual acuity corresponding to near defocus was directly correlated with some higher order intraocular aberrations (r⩾0.44, P⩽.04). Some difficulties evaluated with the quality of life test correlated directly with near and intermediate visual acuity (r⩾0.50, P⩽.01). The Lentis Mplus multifocal IOL provides good distance, intermediate, and near visual outcomes; however, the induced intraocular aberrometric profile may limit the potential visual benefit. Copyright 2012, SLACK Incorporated.

Correlating optical bench performance with clinical defocus curves in varifocal and trifocal intraocular lenses.

PubMed

Plaza-Puche, Ana B; Alió, Jorge L; MacRae, Scott; Zheleznyak, Len; Sala, Esperanza; Yoon, Geunyoung

2015-05-01

To investigate the correlations existing between a trifocal intraocular lens (IOL) and a varifocal IOL using the "ex vivo" optical bench through-focus image quality analysis and the clinical visual performance in real patients by study of the defocus curves. This prospective, consecutive, nonrandomized, comparative study included a total of 64 eyes of 42 patients. Three groups of eyes were differentiated according to the IOL implanted: 22 eyes implanted with the varifocal Lentis Mplus LS-313 IOL (Oculentis GmbH, Berlin, Germany); 22 eyes implanted with the trifocal FineVision IOL (Physiol, Liege, Belgium), and 20 eyes implanted with the monofocal Acrysof SA60AT IOL (Alcon Laboratories, Inc., Fort Worth, TX). Visual outcomes and defocus curve were evaluated postoperatively. Optical bench through-focus performance was quantified by computing an image quality metric and the cross-correlation coefficient between an unaberrated reference image and captured retinal images from a model eye with a 3.0-mm artificial pupil. Statistically significant differences among defocus curves of different IOLs were detected for the levels of defocus from -4.00 to -1.00 diopters (D) (P < .01). Significant correlations were found between the optical bench image quality metric results and logMAR visual acuity scale in all groups (Lentis Mplus group: r = -0.97, P < .01; FineVision group: r = -0.82, P < .01; Acrys of group: r = -0.99, P < .01). Linear predicting models were obtained. Significant correlations were found between logMAR visual acuity and image quality metric for the multifocal and monofocal IOLs analyzed. This finding enables surgeons to predict visual outcomes from the optical bench analysis. Copyright 2015, SLACK Incorporated.

Error induced by the estimation of the corneal power and the effective lens position with a rotationally asymmetric refractive multifocal intraocular lens

PubMed Central

Piñero, David P.; Camps, Vicente J.; Ramón, María L.; Mateo, Verónica; Pérez-Cambrodí, Rafael J.

2015-01-01

AIM To evaluate the prediction error in intraocular lens (IOL) power calculation for a rotationally asymmetric refractive multifocal IOL and the impact on this error of the optimization of the keratometric estimation of the corneal power and the prediction of the effective lens position (ELP). METHODS Retrospective study including a total of 25 eyes of 13 patients (age, 50 to 83y) with previous cataract surgery with implantation of the Lentis Mplus LS-312 IOL (Oculentis GmbH, Germany). In all cases, an adjusted IOL power (PIOLadj) was calculated based on Gaussian optics using a variable keratometric index value (nkadj) for the estimation of the corneal power (Pkadj) and on a new value for ELP (ELPadj) obtained by multiple regression analysis. This PIOLadj was compared with the IOL power implanted (PIOLReal) and the value proposed by three conventional formulas (Haigis, Hoffer Q and Holladay I). RESULTS PIOLReal was not significantly different than PIOLadj and Holladay IOL power (P>0.05). In the Bland and Altman analysis, PIOLadj showed lower mean difference (-0.07 D) and limits of agreement (of 1.47 and -1.61 D) when compared to PIOLReal than the IOL power value obtained with the Holladay formula. Furthermore, ELPadj was significantly lower than ELP calculated with other conventional formulas (P<0.01) and was found to be dependent on axial length, anterior chamber depth and Pkadj. CONCLUSION Refractive outcomes after cataract surgery with implantation of the multifocal IOL Lentis Mplus LS-312 can be optimized by minimizing the keratometric error and by estimating ELP using a mathematical expression dependent on anatomical factors. PMID:26085998

Error induced by the estimation of the corneal power and the effective lens position with a rotationally asymmetric refractive multifocal intraocular lens.

PubMed

Piñero, David P; Camps, Vicente J; Ramón, María L; Mateo, Verónica; Pérez-Cambrodí, Rafael J

2015-01-01

To evaluate the prediction error in intraocular lens (IOL) power calculation for a rotationally asymmetric refractive multifocal IOL and the impact on this error of the optimization of the keratometric estimation of the corneal power and the prediction of the effective lens position (ELP). Retrospective study including a total of 25 eyes of 13 patients (age, 50 to 83y) with previous cataract surgery with implantation of the Lentis Mplus LS-312 IOL (Oculentis GmbH, Germany). In all cases, an adjusted IOL power (PIOLadj) was calculated based on Gaussian optics using a variable keratometric index value (nkadj) for the estimation of the corneal power (Pkadj) and on a new value for ELP (ELPadj) obtained by multiple regression analysis. This PIOLadj was compared with the IOL power implanted (PIOLReal) and the value proposed by three conventional formulas (Haigis, Hoffer Q and Holladay I). PIOLReal was not significantly different than PIOLadj and Holladay IOL power (P>0.05). In the Bland and Altman analysis, PIOLadj showed lower mean difference (-0.07 D) and limits of agreement (of 1.47 and -1.61 D) when compared to PIOLReal than the IOL power value obtained with the Holladay formula. Furthermore, ELPadj was significantly lower than ELP calculated with other conventional formulas (P<0.01) and was found to be dependent on axial length, anterior chamber depth and Pkadj. Refractive outcomes after cataract surgery with implantation of the multifocal IOL Lentis Mplus LS-312 can be optimized by minimizing the keratometric error and by estimating ELP using a mathematical expression dependent on anatomical factors.

Overexpression of SARAF Ameliorates Pressure Overload-Induced Cardiac Hypertrophy Through Suppressing STIM1-Orai1 in Mice.

PubMed

Dai, Fengdan; Zhang, Yan; Wang, Qiang; Li, De; Yang, Yongjian; Ma, Shuangtao; Yang, Dachun

2018-01-01

Activation of stromal interaction molecule 1 (STIM1) and Orai1 participates in the development of cardiac hypertrophy. Store-operated Ca2+ entry-associated regulatory factor (SARAF) is an intrinsic inhibitor of STIM1-Orai1 interaction. Thus, we hypothesized that SARAF could prevent cardiac hypertrophy. Male C57BL/6 mice, aged 8 weeks, were randomly divided into sham and abdominal aortic constriction surgery groups and were infected with lentiviruses expressing SARAF and GFP (Lenti-SARAF) or GFP alone (Lenti-GFP) via intramyocardial injection. At 4 weeks after aortic constriction, left ventricular structure and function were assessed by echocardiography and hemodynamic assays. The gene and protein expressions of SARAF, STIM1, and Orai1 were measured by quantitative PCR and Western blot, respectively. Gene and protein expressions of SARAF were significantly decreased, while STIM1 and Orai1 were increased in the heart tissue compared with sham group. Overexpression of SARAF in the heart prevented the upregulation of STIM1 and Orai1, and importantly, attenuated aortic constriction-induced decrease in maximal rate of left ventricular pressure decay and increases in thickness of interventricular septum and left ventricular posterior wall, heart weight/body weight ratio, and size of cardiomyocytes. Blood pressure detected through the carotid artery and left ventricular systolic function were not affected by SARAF overexpression. In addition, overexpression of SARAF also attenuated angiotensin II-induced upregulation of STIM1 and Orai1 and hypertrophy of cultured cardiomyocytes. Overexpression of SARAF in the heart prevents cardiac hypertrophy, probably through suppressing the upregulation of STIM1/Orai1. © 2018 The Author(s). Published by S. Karger AG, Basel.

Alterations of the tunica vasculosa lentis in the rat model of retinopathy of prematurity.

PubMed

Favazza, Tara L; Tanimoto, Naoyuki; Munro, Robert J; Beck, Susanne C; Garcia Garrido, Marina; Seide, Christina; Sothilingam, Vithiyanjali; Hansen, Ronald M; Fulton, Anne B; Seeliger, Mathias W; Akula, James D

2013-08-01

To study the relationship between retinal and tunica vasculosa lentis (TVL) disease in retinopathy of prematurity (ROP). Although the clinical hallmark of ROP is abnormal retinal blood vessels, the vessels of the anterior segment, including the TVL, are also altered. ROP was induced in Long-Evans pigmented and Sprague Dawley albino rats; room-air-reared (RAR) rats served as controls. Then, fluorescein angiographic images of the TVL and retinal vessels were serially obtained with a scanning laser ophthalmoscope near the height of retinal vascular disease, ~20 days of age, and again at 30 and 64 days of age. Additionally, electroretinograms (ERGs) were obtained prior to the first imaging session. The TVL images were analyzed for percent coverage of the posterior lens. The tortuosity of the retinal arterioles was determined using Retinal Image multiScale Analysis (Gelman et al. in Invest Ophthalmol Vis Sci 46:4734-4738, 2005). In the youngest ROP rats, the TVL was dense, while in RAR rats, it was relatively sparse. By 30 days, the TVL in RAR rats had almost fully regressed, while in ROP rats, it was still pronounced. By the final test age, the TVL had completely regressed in both ROP and RAR rats. In parallel, the tortuous retinal arterioles in ROP rats resolved with increasing age. ERG components indicating postreceptoral dysfunction, the b-wave, and oscillatory potentials were attenuated in ROP rats. These findings underscore the retinal vascular abnormalities and, for the first time, show abnormal anterior segment vasculature in the rat model of ROP. There is delayed regression of the TVL in the rat model of ROP. This demonstrates that ROP is a disease of the whole eye.

Alterations of the Tunica Vasculosa Lentis in the Rat Model of Retinopathy of Prematurity

PubMed Central

Favazza, Tara L; Tanimoto, Naoyuki; Munro, Robert J.; Beck, Susanne C.; Garrido, Marina G.; Seide, Christina; Sothilingam, Vithiyanjali; Hansen, Ronald M.; Fulton, Anne B.; Seeliger, Mathias W.; Akula, James D

2013-01-01

Purpose To study the relation between retinal and tunica vasculosa lentis (TVL) disease in ROP. Although the clinical hallmark of retinopathy of prematurity (ROP) is abnormal retinal blood vessels, the vessels of the anterior segment, including the TVL, are also altered. Methods ROP was induced in Long Evans pigmented and Sprague-Dawley albino rats; room-air-reared (RAR) rats served as controls. Then, fluorescein angiographic images of the TVL and retinal vessels were serially obtained with a scanning laser ophthalmoscope (SLO) near the height of retinal vascular disease, ∼20 days-of-age, and again at 30 and 64 days-of-age. Additionally, electroretinograms (ERGs) were obtained prior to the first imaging session. The TVL images were analyzed for percent coverage of the posterior lens. The tortuosity of the retinal arterioles was determined using Retinal Image multiScale Analysis (RISA; Gelman et al., 2005). Results In the youngest ROP rats, the TVL was dense, while in RAR rats, it was relatively sparse. By 30 days, the TVL in RAR rats had almost fully regressed, while in ROP rats it was still pronounced. By the final test age, the TVL had completely regressed in both ROP and RAR rats. In parallel, the tortuous retinal arterioles in ROP rats resolved with increasing age. ERG components indicating postreceptoral dysfunction, the b-wave and oscillatory potentials (OPs), were attenuated in ROP rats. Conclusions These findings underscore the retinal vascular abnormalities and, for the first time, show abnormal anterior segment vasculature in the rat model of ROP. There is delayed regression of the TVL in the rat model of ROP. This demonstrates that ROP is a disease of the whole eye. PMID:23748796

Kinetics of Slow Neutrons in a Time-of-flight Spectrometer. II. Probability of Transmission Across a Rotating Slit and Distribution after the Flight of Neutrons with Velocity Spectrum F (v); CINETICA DEI NEUTRONI LENTI IN UNO SPETTROMETRO A TEMPO DI VOLO. II. PROBABILITA DI TRANSMISSIONE ATTRAVERSO UNA FENDITURA RUOTANTE E DISTRIBUZIONE DOPO IL VOLO DI NEUTRONI CON SPETTRO DI VELOCITA F (V)

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

Marsequerra, M.; Pauli, G.

1958-12-01

On the basis of the results obtained in Part I (CNC-1), expressions are derived for the transmission probability through a revolving curved slit for neutrons having a velocity distribution f(v), the distribution shown by the neutrons after the flight, and the uncertainty in the energy of neutrons detected in an infinitesimal time interval. (auth)

[Opacification of an intraocular lens: calcification of hydrophilic intraocular lenses after gas tamponade of the anterior chamber].

PubMed

Schmidinger, G; Pemp, B; Werner, L

2013-11-01

A patient with endothelial dystrophy was treated with Descemet stripping automated endothelial keratoplasty (DSAEK) combined with cataract extraction and implantation of a hydrophilic intraocular lens (IOL, Lentis-L312, Oculentis) but visual acuity dropped from 0.15 logMAR to 0.52 logMAR 18 months later due to calcification of the IOL. With new methods of lamellar corneal transplantation being used more frequently the number of necessary anterior chamber tamponades with air/gas are increasing. In cataract cases in which a gas tamponade and transplantation might be necessary later on (cornea guttata), hydrophilic IOLs should be avoided.

Marfan Syndrome in an Iranian Family: A Case Series

PubMed Central

Davari, Mohammad Hossein; Kazemi, Toba

2014-01-01

Marfan syndrome (MFS) is a genetic disorder which is inherited by autosomal dominant traits. In MFS, lens displacement and cardiovascular involvement are important causes of morbidity and mortality in the clinical course of the disease. In this case study, the ocular involvement in a family with severe penetration of MFS is reported. Twelve members of a family (father, two daughters, three sons, and six grandchildren) had MFS. Lens ectopia was the most common ophthalmic involvement among the family (100%). Other ocular involvements were as follows; Hypoplastic iris or ciliary’s muscle hypoplasia (50%), on gated eyeball (42%), flat cornea (30%), glaucoma and cataract (25%), retinal detachment (16%). Three members of the family underwent eye surgery including lens extraction, glaucoma surgery and retinal surgery. PMID:25031493

Giant serous cystadenoma arising from an accessory ovary in a morbidly obese 11-year-old girl: a case report.

PubMed

Sharatz, Steven M; Treviño, Taína A; Rodriguez, Luís; West, Jared H

2008-01-18

Ectopic ovarian tissue is an unusual entity, especially if it is an isolated finding thought to be of embryological origin. An 11-year-old, morbidly obese female presented with left flank pain, nausea, and irregular menses. Various diagnostic procedures suggested a large ovarian cyst, and surgical resection was performed. Histologically, the resected mass was not of tubal origin as suspected, but a serous cystadenoma arising from ovarian tissue. The patient's two normal, eutopic ovaries were completely uninvolved and unaffected. A tumor arising from ectopic ovarian tissue of embryological origin seems the most likely explanation. We suggest refining the descriptive nomenclature so as to more precisely characterize the various presentations of ovarian ectopia.

Cat eye syndrome and growth hormone deficiency with pituitary anomalies: a case report and review of the literature.

PubMed

Melo, Cláudia; Gama-de-Sousa, Susana; Almeida, Filipa; Rendeiro, Paula; Tavares, Purificação; Cardoso, Helena; Carvalho, Sónia

2013-10-15

Cat eye syndrome is a rare congenital disease characterized by the existence of a supernumerary chromosome derived from chromosome 22, with a variable phenotype comprising anal atresia, coloboma of the iris and preauricular tags or pits. We report a girl with cat eye syndrome, presenting short stature, with growth hormone deficiency due to posterior pituitary ectopia. Short stature is a common feature of this syndrome, and the association with a structural pituitary anomaly has been described, however growth hormone deficiency and the underlying mechanisms are rarely reported. A review on short stature and growth hormone deficiency in cat eye syndrome is conducted. © 2013 Elsevier B.V. All rights reserved.

Abdominal aortic aneurysm associated with congenital solitary pelvic kidney treated with novel hybrid technique.

PubMed

Malinowski, Michael J; Al-Nouri, Omar; Hershberger, Richard; Halandras, Pegge M; Aulivola, Bernadette; Cho, Jae S

2014-08-01

Renal ectopia in the rare condition of associated abdominal aortic aneurysm presents a difficult clinical challenge with respect to access to the aorto-iliac segment and preservation of renal function because of its anomalous renal arterial anatomy and inevitable renal ischemia at the time of open repair. Multiple operative techniques are described throughout the literature to cope with both problems. We report a case of a 57-year-old male with an aorto-iliac aneurysm and a congenital solitary pelvic kidney successfully treated by hybrid total renal revascularization using iliorenal bypass followed by unilateral internal iliac artery coil embolization and conventional endovascular aortic aneurysm repair without any clinical evidence of renal impairment. Copyright © 2014 Elsevier Inc. All rights reserved.

Absence of mutations in PAX8, NKX2.5, and TSH receptor genes in patients with thyroid dysgenesis.

PubMed

Brust, Ester S; Beltrao, Cristine B; Chammas, Maria C; Watanabe, Tomoco; Sapienza, Marcelo T; Marui, Suemi

2012-04-01

To precisely classify the various forms of TD, and then to screen for mutations in transcription factor genes active in thyroid development. Patients underwent ultrasound, thyroid scan, and serum thyroglobulin measurement to accurately diagnose the form of TD. DNA was extracted from peripheral leukocytes. The PAX8, and NKX2.5 genes were evaluated in all patients, and TSH receptor (TSHR) gene in those with hypoplasia. In 27 nonconsanguineous patients with TD, 13 were diagnosed with ectopia, 11 with hypoplasia, and 3 with athyreosis. No mutations were detected in any of the genes studied. Sporadic cases of TD are likely to be caused by epigenetic factors, rather than mutations in thyroid transcription factors or genes involved in thyroid development.

Horseshoe kidney: a review of anatomy and pathology.

PubMed

Natsis, Konstantinos; Piagkou, Maria; Skotsimara, Antonia; Protogerou, Vassilis; Tsitouridis, Ioannis; Skandalakis, Panagiotis

2014-08-01

Horseshoe kidney (HSK) is the most common renal fusion, which is characterized by three anatomic anomalies: ectopia, malrotation and vascular changes. Patients with HSK are prone to a variety of complications, genitourinary and non-genitourinary. In this paper, the anatomy of HSK is delineated with a great emphasis on its blood supply. After reviewing the literature, the arterial supply patterns found by each author were categorized according to the classification system proposed by Graves. The majority of HSKs were found to be supplied by renal arteries derived from the abdominal aorta below the isthmus or by vessels originating from the common iliac arteries. In addition, the abnormalities associated with HSK are highlighted and classified in anatomical variations, congenital anomalies as well as in pathologic conditions related to HSK.

Modulating drug resistance by targeting BCRP/ABCG2 using retrovirus-mediated RNA interference.

PubMed

Xie, Ni; Mou, Lisha; Yuan, Jianhui; Liu, Wenlan; Deng, Tingting; Li, Zigang; Jing, Yi; Jin, Yi; Hu, Zhangli

2014-01-01

The BCRP/ABCG2 transporter, which mediates drug resistance in many types of cells, depends on energy provided by ATP hydrolysis. Here, a retrovirus encoding a shRNA targeting the ATP-binding domain of this protein was used to screen for highly efficient agents that could reverse drug resistance and improve cell sensitivity to drugs, thus laying the foundation for further studies and applications. To target the ATP-binding domain of BCRP/ABCG2, pLenti6/BCRPsi shRNA recombinant retroviruses, with 20 bp target sequences starting from the 270th, 745th and 939th bps of the 6th exon, were constructed and packaged. The pLenti6/BCRPsi retroviruses (V-BCRPi) that conferred significant knockdown effects were screened using a drug-sensitivity experiment and flow cytometry. The human choriocarcinoma cell line JAR, which highly expresses endogenous BCRP/ABCG2, was injected under the dorsal skin of a hairless mouse to initiate a JAR cytoma. After injecting V-BCRPi-infected JAR tumor cells into the dorsal skin of hairless mice, BCRP/ABCG2 expression in the tumor tissue was determined using immunohistochemistry, fluorescent quantitative RT-PCR and Western blot analyses. After intraperitoneal injection of BCRP/ABCG2-tolerant 5-FU, the tumor volume, weight change, and apoptosis rate of the tumor tissue were determined using in situ hybridization. V-BCRPi increased the sensitivity of the tumor histiocytes to 5-FU and improved the cell apoptosis-promoting effects of 5-FU in the tumor. The goal of the in vivo and in vitro studies was to screen for an RNA interference recombinant retrovirus capable of stably targeting the ATP-binding domain of BCRP/ABCG2 (V-BCRPi) to inhibit its function. A new method to improve the chemo-sensitivity of breast cancer and other tumor cells was discovered, and this method could be used for gene therapy and functional studies of malignant tumors.

Interfering RNA against PKC-α inhibits TNF-α-induced IP3R1 expression and improves glomerular filtration rate in rats with fulminant hepatic failure.

PubMed

Wang, Dong-Lei; Dai, Wen-Ying; Wang, Wen; Wen, Ying; Zhou, Ying; Zhao, Yi-Tong; Wu, Jian; Liu, Pei

2018-05-01

We have reported that tumor necrosis factor-α (TNF-α) is critical for reduction of glomerular filtration rate (GFR) in rats with fulminant hepatic failure (FHF). The present study aims to evaluate the underlying mechanisms of decreased GFR during acute hepatic failure. Rats with FHF induced by d-galactosamine plus lipopolysaccharide (GalN/LPS) were injected intravenously with recombinant lentivirus harboring short hairpin RNA against the protein kinase C-α ( PKC-α) gene (Lenti-shRNA-PKC-α). GFR, serum levels of aminotransferases, creatinine, urea nitrogen, potassium, sodium, chloride, TNF-α, and endothelin-1 (ET-1), as well as type 1 inositol 1,4,5-trisphosphate receptor (IP 3 R1) expression in renal tissue were assessed. The effects of PKC-α silencing on TNF-α-induced IP 3 R1, specificity protein 1 (SP-1), and c-Jun NH 2 -terminal kinase (JNK) expression, as well as cytosolic calcium content were determined in glomerular mesangial cell (GMCs) with RNAi against PKC-α. Renal IP 3 R1 overexpression was abrogated by pre-treatment with Lenti-shRNA-PKC-α. The PKC-α silence significantly improved the compromised GFR, reduced Cr levels, and reversed the decrease in glomerular inulin space and the increase in glomerular calcium content in GalN/LPS-exposed rats. TNF-α treatment increased expression of PKC-α, IP 3 R1, specificity protein 1 (SP-1), JNK, and p-JNK in GMCs and increased Ca 2 + release and binding activity of SP-1 to the IP 3 R1 promoter. These effects were blocked by transfection of siRNA against the PKC-α gene, and the PKC-α gene silence also restored cytosolic Ca 2+ concentration. RNAi targeting PKC-α inhibited TNF-α-induced IP 3 R1 overexpression and in turn improved compromised GFR in the development of acute kidney injury during FHF in rats.

Mesenchymal stem cell-based NK4 gene therapy in nude mice bearing gastric cancer xenografts

PubMed Central

Zhu, Yin; Cheng, Ming; Yang, Zhen; Zeng, Chun-Yan; Chen, Jiang; Xie, Yong; Luo, Shi-Wen; Zhang, Kun-He; Zhou, Shu-Feng; Lu, Nong-Hua

2014-01-01

Mesenchymal stem cells (MSCs) have been recognized as promising delivery vehicles for gene therapy of tumors. Gastric cancer is the third leading cause of worldwide cancer mortality, and novel treatment modalities are urgently needed. NK4 is an antagonist of hepatocyte growth factor receptors (Met) which are often aberrantly activated in gastric cancer and thus represent a useful candidate for targeted therapies. This study investigated MSC-delivered NK4 gene therapy in nude mice bearing gastric cancer xenografts. MSCs were transduced with lentiviral vectors carrying NK4 complementary DNA or enhanced green fluorescent protein (GFP). Such transduction did not change the phenotype of MSCs. Gastric cancer xenografts were established in BALB/C nude mice, and the mice were treated with phosphate-buffered saline (PBS), MSCs-GFP, Lenti-NK4, or MSCs-NK4. The tropism of MSCs toward gastric cancer cells was determined by an in vitro migration assay using MKN45 cells, GES-1 cells and human fibroblasts and their presence in tumor xenografts. Tumor growth, tumor cell apoptosis and intratumoral microvessel density of tumor tissue were measured in nude mice bearing gastric cancer xenografts treated with PBS, MSCs-GFP, Lenti-NK4, or MSCs-NK4 via tail vein injection. The results showed that MSCs migrated preferably to gastric cancer cells in vitro. Systemic MSCs-NK4 injection significantly suppressed the growth of gastric cancer xenografts. MSCs-NK4 migrated and accumulated in tumor tissues after systemic injection. The microvessel density of tumor xenografts was decreased, and tumor cellular apoptosis was significantly induced in the mice treated with MSCs-NK4 compared to control mice. These findings demonstrate that MSC-based NK4 gene therapy can obviously inhibit the growth of gastric cancer xenografts, and MSCs are a better vehicle for NK4 gene therapy than lentiviral vectors. Further studies are warranted to explore the efficacy and safety of the MSC-based NK4 gene therapy in animals and cancer patients. PMID:25525335

Influence on Visual Quality of Intraoperative Orientation of Asymmetric Intraocular Lenses.

PubMed

Bonaque-González, Sergio; Ríos, Susana; Amigó, Alfredo; López-Gil, Norberto

2015-10-01

To evaluate visual quality when changing the intraocular orientation of the Lentis Mplus LS-312MF nonrotational symmetric +3.00 diopters aspheric multifocal intraocular lens ([IOL] Oculentis GmbH, Berlin, Germany) in normal eyes. An artificial eye was used to measure the in vitro wavefront of the IOL. The corneal topography of 20 healthy patients was obtained. For each eye, a computational analysis simulated the implantation of the IOL. The modulation transfer function (MTF) and an image quality parameter (visually modulated transfer function [VSMTF] metric) were calculated for a 5.0-mm pupil and for three conditions: distance, intermediate, and near vision. The procedure was repeated for each eye after a rotation of the IOL with respect to the cornea from 0° to 360° in 1° steps. Statistical analysis showed significant differences in mean VSMTF values between orientations for distance vision. Optimal orientation of the IOL (different for each eye) showed a mean improvement of 58% ± 19% (range: 20% to 121%) in VSMTF values with respect to the worst possible orientation. For these orientations, intermediate and near vision quality were statistically indistinguishable. The MTFs were different between orientations, showing a mean difference of approximately 5 cycles per degree in the maximum spatial frequencies that can be transferred between the best and the worst orientations for distance vision. The results suggest that implantation of this nonrotational symmetric IOL should improve visual outcomes if it is oriented to coincide with a customized meridian. A simple, practical method is proposed to find an approximation to the angle that an Mplus IOL should be inserted. Copyright 2015, SLACK Incorporated.

High pressure vaginography to diagnose vaginal ureteral ectopia in patients with continuous urinary incontinence.

PubMed

Zuckerman, Jack M; Shekarriz, Bijan; Upadhyay, Jyoti

2013-02-01

Continuous urinary incontinence in female patients can be a diagnostic dilemma if traditional imaging fails to identify a source. Vaginography has been used to diagnose vaginal ectopic ureters in the past with mixed results. Institutional review board approval was obtained for a retrospective review. Five teenage females with continuous incontinence and prior negative imaging work ups underwent high pressure vaginography. Their findings and treatment outcomes are reviewed. A vaginal ectopic ureter was diagnosed in each of the five patients at a mean age 15.8 years. Each had undergone prior magnetic resonance urography that was non-diagnostic. Four of the five were managed surgically with resolution of their incontinence. One was lost to follow up. High pressure vaginogram should be considered during the work up of female patients with continuous urinary incontinence, especially when other imaging modalities fail to identify an etiology.

Mature Teratoma in a Supernumerary Ovary in a Child: Report of the First Case.

PubMed

Gupta, Ruchika; Verma, Sarika; Bansal, Kalpana; Jain, Vishesh; Sengar, Mamta; Mohta, Anup

2016-02-01

Supernumerary ovary (ie, ovarian ectopia having no anatomic connection with the normally placed ovaries) is a rare gynecologic condition. To the best of our knowledge, only 1 pediatric case of supernumerary ovary has been reported to date in the English literature. A 4-year-old girl was assessed for foul-smelling vestibular discharge and was found to have a fistulous tract with opening near the vaginal orifice. Fistuloscopy revealed hair in the lumen of the tract. Computed tomography scan showed a retroperitoneal mass in continuation of the tract. Excision of the mass revealed a mature teratoma in a retroperitoneal supernumerary ovary. Supernumerary ovary, a gynecologic rarity, is even more uncommon in children. Hence, a thorough clinical-radiological-pathological correlation is mandatory to diagnose extragonadal ovarian tumors arising in supernumerary ovaries. Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Functional fixation of autotransplanted tooth germs by using bioresorbable membranes.

PubMed

Gérard, Eric; Membre, Hervé; Gaudy, Jean-François; Mahler, Patrick; Bravetti, Pierre

2002-12-01

The purpose of this study was to evaluate the contribution of a bioresorbable membrane placement to the healing of immature teeth after autotransplantation of tooth buds. Six cases were selected: 2 transplantations of wisdom teeth, 2 for premolar agenesis, 1 for ectopia, and 1 premolar in an incisor position. The crown of each tooth germ and the marginal alveolar bone were covered with a resorbable membrane. The radicular edification was nearly complete, neither ankylosis nor inflammatory resorption was observable, the pulp vitality was preserved, and the periodontal integration was identical to that of other teeth. The membrane ensured contention and stabilization of the transplant, allowed functional stimulation, permitted protection of the coagulum and periodontal cells, and kept the epithelium at a distance. The transplantations of immature teeth were improved by the use of a resorbable membrane, which caused an optimal functional fixation of the transplanted tooth.

Endometriosis of umbilical cicatrix: case report and review of the literature.

PubMed

Rosina, Paolo; Pugliarello, Silvia; Colato, Chiara; Girolomoni, Giampiero

2008-01-01

Umbilical endometriosis has an estimated incidence of 0.5%-1% of all patients with endometrial ectopia. It is a very rare disease, but should be considered on the differential diagnosis of umbilical lesions. We report on a case of spontaneous umbilical endometriosis in a 38-year-old woman, with a dark brown nodule periodically bleeding, associated with severe abdominal pain. There was no history of endometriosis and she had not been pregnant before. Laparoscopic visualization of pelvic cavity showed bilateral ovarian endometrioma (it was removed while sparing the ovaries). Surgical treatment proved effective. Cutaneous endometriosis could be a sign of internal endometriosis. Presentations may be atypical and pose diagnostic difficulty, mimicking other acute diseases, e.g., skin neoplasm, folliculitis, etc., but it should be suspected in any female presenting with a painful or bleeding mass close to the umbilicus or abdominal surgical scar.

Chiari I Malformation in Nephropathic Cystinosis

PubMed Central

Rao, Kavya I; Hesselink, John; Trauner, Doris A

2015-01-01

Objective To determine the relative incidence of Chiari I malformations in children with cystinosis compared with those in the general population. Study design Magnetic resonance imaging (MRI) scans were performed on 53 patients with nephropathic cystinosis and 120 controls, age range 3-18 years. Results Ten of 53 (18.9%) cystinosis patients had Chiari I or tonsillar ectopia, and only 2 of 120 controls (1.6%) had a similar finding. At least 2 of the patients had symptoms or signs thought to be related to the malformation, and one had surgical decompression. Two had an associated cervical syrinx. Conclusions Children with cystinosis have a 12-fold higher prevalence of Chiari I malformations than the general pediatric population. Chiari I malformations should be high on the differential diagnosis when individuals with cystinosis develop neurologic signs and symptoms, and MRI scans should be performed on children with cystinosis who present with new-onset headache, ataxia, incontinence, or other unexplained neurologic symptoms. PMID:26265281

Using HSV-TK/GCV suicide gene therapy to inhibit lens epithelial cell proliferation for treatment of posterior capsular opacification

PubMed Central

Jiang, Yong-Xiang; Liu, Tian-Jing; Yang, Jin; Chen, Yan; Fang, Yan-Wen

2011-01-01

Purpose To establish a novel, targeted lentivirus-based HSV-tk (herpes simplex virus thymidine kinase)/GCV (ganciclovir) gene therapy system to inhibit lens epithelial cell proliferation for treatment of posterior capsular opacification (PCO) after cataract surgery. Methods An enhanced Cre recombinase (Cre/loxP) system with a lentiviral vector expressing Cre under the control of the lens-specific promoter LEP503 (Lenti-LEP503-HSVtk-Cre [LTKCRE]) was constructed, as well as another lentiviral vector containing a switching unit. The latter vector contains a stuffer sequence encoding EGFP (Lenti-hPGK-Loxp-EGFP-pA-Loxp-HSVtk [PGFPTK]) with a functional polyadenylation signal between two loxP sites, followed by the herpes simplex virus thymidine kinase (HSV-tk) gene, both under the control of the human posphoglycerate kinase (hPGK) promoter. Expression of the downstream gene (HSV-tk) is activated by co-expression of Cre. Human lens epithelial cells (HLECs) or retinal pigmental epithelial cells (RPECs) were co-infected with LTKCRE and PGFPTK. The inhibitory effects on HLECs and RPECs infected by the enhanced specific lentiviral vector combination at the concentration of 20 µg/ml GCV were assayed and compared. Results The specific gene expression of Cre and HSV-tk in HLECs is activated by the LEP503 promoter. LTKCRE and PGFPTK co-infected HLECs, but not RPECs, expressed high levels of the HSV-tk protein. After 96 h of GCV treatment, the percentage of apoptotic HLECs infected by the enhanced specific lentiviral vector combination was 87.23%, whereas that of apoptotic RPECs was only 10.12%. Electron microscopy showed that GCV induced apoptosis and necrosis of the infected HLECs. Conclusions The enhanced specific lentiviral vector combination selectively and effectively expressed HSV-tk in HLECs. A concentration of 20 µg/ml, GCV is effective against the proliferation of HLECs in vitro. This cell-type-specific gene therapy using a Cre/loxP lentivirus system may be a feasible treatment strategy to prevent PCO. PMID:21283526

Regression of vessels in the tunica vasculosa lentis is initiated by coordinated endothelial apoptosis: a role for vascular endothelial growth factor as a survival factor for endothelium.

PubMed

Mitchell, C A; Risau, W; Drexler, H C

1998-11-01

The development of the embryonic lens is dependent on the formation and regression of the tunica vasculosa lentis (TVL), which is a transiently occurring capillary plexus that surrounds the posterior part of the lens. In this study, by using the terminal deoxy-nucleotidyl transferase mediated nick end-labelling technique (TUNEL), electron microscopy, radioactive end-labelling of DNA extracted from TVL, and the Comet assay, we show that widespread apoptosis of the endothelial cells that constitute the TVL is occurring already at embryonic day 17.5 (E17.5) of mouse development, much earlier than was reported previously (Jack [1972a] Am. J. Ophthalmol. 74:261-272; Lang [1997] Cell Death Diff. 4:12-20). In addition to apoptotic cell death, regression of this structure is associated with loss of capillary integrity, leakage of erythrocytes into the vitreal compartment, and phagocytosis of the apoptotic endothelium by tissue macrophages (hyalocytes). In situ hybridization experiments with probes for the flk-1 receptor and its high-affinity ligand, vascular endothelial growth factor (VEGF; Terman et al. [1992] Biochem. Biophys. Res. Commun. 187:1579-1586; Millauer et al. [1993] Cell 72:835-846), revealed strong endothelial cell expression for flk-1 in the eyes of E13.5-E17.5 embryos. VEGF mRNA was detected in lens epithelial cells located at the posterior pole of the developing lens in E13.5 embryos, in close proximity to the TVL capillaries. At later times (E14.5-E17.5), when the lens epithelial cells have differentiated into primary lens fiber cells, and a thick lenticular capsule is formed, the expression of VEGF mRNA becomes restricted to the anterior and equatorial portions of the lens. The physical separation of the VEGF-producing cells from the flk-1-expressing endothelium (due to the differentiation of the lens epithelial cells into lens fiber cells and the formation of the lenticular capsule) may deprive the endothelium of an essential survival factor and, thus, may constitute the primary mechanism that is responsible for the induction of endothelial cell apoptosis in this model.

Outcomes after Intravitreal Bevacizumab versus Laser Photocoagulation for Retinopathy of Prematurity: A 5-Year Retrospective Analysis

PubMed Central

Hwang, Christopher K.; Hubbard, G. Baker; Hutchinson, Amy K.; Lambert, Scott R.

2014-01-01

Purpose To determine the relative effectiveness, major complications, and refractive errors associated with intravitreal bevacizumab (IVB) versus panretinal photocoagulation (PRP) to treat Type 1 retinopathy of prematurity (ROP). Subjects Consecutive infants with Type 1 ROP who received either IVB or PRP between January 2008 and December 2012 and had at least six months of follow-up. Design Retrospective case series. Methods The data from infants treated with either IVB or PRP for Type 1 ROP between January 2008 and December 2012 were recorded from two medical centers in Atlanta, Georgia. Main Outcome Measures Recurrence rate, complication rate, refractive error. Results A total of 54 eyes (28 patients) with Type 1 ROP were evaluated: 22 eyes (11 patients) received IVB, and 32 eyes (17 patients) received PRP. Among the 22 eyes treated with IVB, 16 eyes had Zone I ROP and 6 eyes had posterior Zone II ROP. The number of Zone I and Zone II ROP eyes treated with PRP were 5 and 27 eyes, respectively. Mean gestational age, birth weight, postmenstrual age at the initial treatment, and follow-up period for the infants receiving IVB were 24.2 weeks, 668.1 grams, 35.1 weeks, and 21.7 weeks, respectively, and for the infants receiving PRP were 24.8, 701.4 grams, 36.1 weeks, and 34.5 weeks, respectively. ROP recurred in 3/22 (14%) IVB-treated eyes and in 1/32 (3%) PRP-treated eyes. None of IVB-treated eyes progressed to retinal detachment or developed macular ectopia. Only one eye went on to retinal detachment and five eyes developed macular ectopia in PRP-treated eyes. Mean spherical equivalent and postgestational age at the last refraction for IVB-treated eyes were −2.4 D and 22.4 months, respectively, and for PRP-treated eyes were −5.3 D and 37.1 months, respectively. Mean spherical equivalent for Zone I ROP eyes treated with IVB and PRP were −3.7 D and −10.1 D, respectively, and for Zone II ROP eyes were 0.6 D and −4.7 D, respectively. Conclusions Both IVB and PRP are effective treatment options for Type 1 ROP with low complication rates. Zone I ROP was associated with high minus refractive errors in eyes treated with either IVB or PRP. PMID:25687024

Optical reprogramming with ultrashort femtosecond laser pulses

NASA Astrophysics Data System (ADS)

Uchugonova, Aisada; Breunig, Hans G.; Batista, Ana; König, Karsten

2015-03-01

The use of sub-15 femtosecond laser pulses in stem cell research is explored with particular emphasis on the optical reprogramming of somatic cells. The reprogramming of somatic cells into induced pluripotent stem (iPS) cells can be evoked through the ectopic expression of defined transcription factors. Conventional approaches utilize retro/lenti-viruses to deliver genes/transcription factors as well as to facilitate the integration of transcription factors into that of the host genome. However, the use of viruses may result in insertional mutations caused by the random integration of genes and as a result, this may limit the use within clinical applications due to the risk of the formation of cancer. In this study, a new approach is demonstrated in realizing non-viral reprogramming through the use of ultrashort laser pulses, to introduce transcription factors into the cell so as to generate iPS cells.

A chemical approach to myocardial protection and regeneration.

PubMed

Piccoli, Marco; Cirillo, Federica; Tettamanti, Guido; Anastasia, Luigi

2016-04-28

The possibility of generating induced pluripotent stem cells from mouse embryonic fibroblasts and human adult fibroblasts has introduced new perspectives for possible therapeutic strategies to repair damaged hearts. However, obtaining large numbers of adult stem cells is still an ongoing challenge, and the safety of genetic reprogramming with lenti- or retro-viruses has several drawbacks not easy to be addressed. Furthermore, the majority of adult stem cell-based clinical trials for heart regeneration have had generally poor and controversial results. Nonetheless, it is now clear that the injected cells activate the growth and differentiation of progenitor cells that are already present in the heart. This is achieved by the release of signalling factors and/or exosomes carrying them. Along this line, chemistry may play a major role in developing new strategies for activating resident stem cells to regenerate the heart. In particular, this review focuses on small molecule approaches for cell reprogramming, cell differentiation, and activation of cell protection.

HOXA13 is a potential GBM diagnostic marker and promotes glioma invasion by activating the Wnt and TGF-β pathways

PubMed Central

Duan, Ran; Han, Lei; Wang, Qixue; Wei, Jianwei; Chen, Luyue; Zhang, Jianning; Kang, Chunsheng; Wang, Lei

2015-01-01

Homeobox (HOX) genes, including HOXA13, are involved in human cancer. We found that HOXA13 expression was associated with glioma grade and prognosis. Bioinformatics analysis revealed that most of the HOXA13-associated genes were enriched in cancer-related signaling pathways and mainly involved in the regulation of transcription. We transfected four glioma cell lines with Lenti-si HOXA13. HOXA13 increased cell proliferation and invasion and inhibited apoptosis. HOXA13 decreased β-catenin, phospho-SMAD2, and phospho-SMAD3 in the nucleus and increased phospho-β-catenin in the cytoplasm. Furthermore, downregulation of HOXA13 in orthotopic tumors decreased tumor growth. We suggest that HOXA13 promotes glioma progression in part via Wnt- and TGF-β-induced EMT and is a potential diagnostic biomarker for glioblastoma and an independent prognostic factor in high-grade glioma. PMID:26356815

[Occurrence of sand flies (Diptera, Psychodidae) in leishmaniasis foci in an ecotourism area around the Lençóis Maranhenses National Park, Brazil].

PubMed

Rebêlo, José Manuel Macário; Assunção Júnior, Antonildes Nascimento; Silva, Orleans; Moraes, Jorge Luiz Pinto

2010-01-01

The distribution and relative abundance of sand fly species were studied in the municipality of Barreirinhas, Maranhão State, Brazil, around the Lençóis Maranhenses National Park, from January to June 2005, August 2004, July 2005, and September/2008. A total of 6,658 specimens were captured. The most frequent species were Lutzomyia whitmani (46.6%), L. longipalpis (29.9%), L. evandroi (17.1%), and L. lenti (4.8%), while L. termitophila, L. flaviscutellata, L. migonei, L. infraspinosa, L. sordellii, L. wellcomei, L. antunesi, and L. trinidadensis represented 1.6%. The presence of Leishmania vector species explains the high detection rate for tegumentary leishmaniasis in 2000 (308.2), 2001 (310.9), 2002 (338.2), and 2005 (313.6) and active foci of human visceral leishmaniasis in the municipality of Barreirinhas.

Distribution of Nidogen in the Murine Eye and Ocular Phenotype of the Nidogen-1 Knockout Mouse

PubMed Central

May, Christian Albrecht

2012-01-01

Distribution and lack of nidogen-1, part of numerous basement membranes, were studied in the mouse eye. For that purpose, eyes of C57BL/6 and nidogen-1 knockout mice were stained immunohistochemically for nidogen-1, and intraocular pressure measurements and light- and electron microscopy were used to study the nidogen-1 knockout animals. In normal mice, nidogen-1 was present in many basement membranes, but showed irregularities underneath the corneal epithelium, in Bruch's membrane and in the iris. Homozygous knockout of nidogen-1 in the mouse showed only mild pathological changes. In the anterior eye segment, small interruptions were noted in the nonpigmented ciliary epithelium without further consequences. In the posterior eye segment, interruptions of the inner limiting membrane led to small retinal ectopias and subsequent changes in the optic nerve. In summary, the knockout of nidogen-1 showed mild but significant morphological changes pointing to the importance of this protein which can in part, but not completely; be replaced by nidogen-2. PMID:24555126

Thoracic meningocele in lumbo-costo-vertebral syndrome in a child: possible enlargement with repeated motion by anchoring to the diaphragm.

PubMed

Wataya, Takafumi; Horikawa, Kyohei; Kitagawa, Masashi; Tashiro, Yuzuru

2016-08-01

Lumbo-costo-vertebral syndrome (LCVS) is a rare disorder in children that is characterized by hemivertebrae, congenital absence of ribs, meningocele, and hypoplasia of the truncal and abdominal wall presenting as a congenital lumbar hernia. An otherwise healthy 12-month-old girl was referred to the authors' hospital with soft swelling on her left middle back; scoliosis had been present since birth. Imaging revealed a thoracic meningocele, ectopia of the spleen suggesting lumbar hernia, multiple anomalies of the thoracic vertebral columns, and defects of the ribs; thus, LCVS was diagnosed. Surgical observation revealed that the meningocele was firmly anchored to part of the diaphragm, which created stretching tension in the meningocele continuously with exhalation. Once detached, the meningocele shrank spontaneously and never developed again after cauterization. In this case, continuous or pulsatile pressure in the presence of a vertebral defect was thus considered to be an important factor for formation of the thoracic meningocele.

Not all cases of nyctalopia are benign: Unusual and serendipitous presentation of Arnold–Chiari Type 1 malformation at a Pediatric Tertiary Care Center

PubMed Central

Patra, Kailash Chandra; Kirtane, Abhijeet Prakash

2016-01-01

The Arnold–Chiari Type 1 malformation (CM1) is a rare congenital abnormality characterized by ectopia or caudal herniation of the cerebellar tonsils through the foramen magnum into the cervical spine, resulting in crowding at the craniocervical junction. It seldom presents in childhood with symptoms and a normal neurological examination. More typically, CM1 presents in young adult women with neurological symptoms including a headache, cervical pain, cranial nerve palsies, neurosensory deficit, and ataxia. Ocular manifestations associated with Chiari I include third and sixth cranial nerve paresis and convergence/divergence abnormalities. Papilledema is a rare manifestation of Chiari I with a clinical presentation often similar to that of idiopathic intracranial hypertension. To underscore this noteworthy complication, the authors report a case of an 8-year-old boy who presented with nyctalopia and suboccipital headaches, but was diagnosed serendipitously as a case of papilledema due to Chiari I malformation. PMID:27857798

Not all cases of nyctalopia are benign: Unusual and serendipitous presentation of Arnold-Chiari Type 1 malformation at a Pediatric Tertiary Care Center.

PubMed

Patra, Kailash Chandra; Kirtane, Abhijeet Prakash

2016-01-01

The Arnold-Chiari Type 1 malformation (CM1) is a rare congenital abnormality characterized by ectopia or caudal herniation of the cerebellar tonsils through the foramen magnum into the cervical spine, resulting in crowding at the craniocervical junction. It seldom presents in childhood with symptoms and a normal neurological examination. More typically, CM1 presents in young adult women with neurological symptoms including a headache, cervical pain, cranial nerve palsies, neurosensory deficit, and ataxia. Ocular manifestations associated with Chiari I include third and sixth cranial nerve paresis and convergence/divergence abnormalities. Papilledema is a rare manifestation of Chiari I with a clinical presentation often similar to that of idiopathic intracranial hypertension. To underscore this noteworthy complication, the authors report a case of an 8-year-old boy who presented with nyctalopia and suboccipital headaches, but was diagnosed serendipitously as a case of papilledema due to Chiari I malformation.

PAF53 is essential in mammalian cells: CRISPR/Cas9 fails to eliminate PAF53 expression.

PubMed

Rothblum, Lawrence I; Rothblum, Katrina; Chang, Eugenie

2017-05-15

When mammalian cells are nutrient and/or growth factor deprived, exposed to inhibitors of protein synthesis, stressed by heat shock or grown to confluence, rDNA transcription is essentially shut off. Various mechanisms are available to accomplish this downshift in ribosome biogenesis. Muramatsu's laboratory (Hanada et al., 1996) first demonstrated that mammalian PAF53 was essential for specific rDNA transcription and that PAF53 levels were regulated in response to growth factors. While S. cerevisae A49, the homologue of vertebrate PAF53, is not essential for viability (Liljelund et al., 1992), deletion of yA49 results in colonies that grow at 6% of the wild type rate at 25°C. Experiments described by Wang et al. (2015) identified PAF53 as a gene "essential for optimal proliferation". However, they did not discriminate genes essential for viability. Hence, in order to resolve this question, we designed a series of experiments to determine if PAF53 was essential for cell survival. We set out to delete the gene product from mammalian cells using CRISPR/CAS9 technology. Human 293 cells were transfected with lentiCRISPR v2 carrying genes for various sgRNA that targeted PAF53. In some experiments, the cells were cotransfected in parallel with plasmids encoding FLAG-tagged mouse PAF53. After treating the transfected cells with puromycin (to select for the lentiCRISPR backbone), cells were cloned and analyzed by western blots for PAF53 expression. Genomic DNA was amplified across the "CRISPRd" exon, cloned and sequenced to identify mutated PAF53 genes. We obtained cell lines in which the endogenous PAF53 gene was "knocked out" only when we rescued with FLAG-PAF53. DNA sequencing demonstrated that in the absence of ectopic PAF53 expression, cells demonstrated unique means of surviving; including recombination or the utilization of alternative reading frames. We never observed a clone in which one PAF53 gene is expressed, unless there was also ectopic expression In the absence of ectopic gene expression, the gene products of both endogenous genes were expressed, irrespective of whether they were partially mutant proteins or not. Copyright © 2016 Elsevier B.V. All rights reserved.

Direct pelvic access percutaneous nephrolithotomy in management of ectopic kidney stone: a case report and literature review.

PubMed

Mehmet, Rifaioglu Murat; Rustu, Yalcinkaya Fatih; Hanefi, Bayarogullari; Mursel, Davarci; Fusun, Aydogan; Mehmet, Inci

2013-01-01

Percutaneous nephrolithotomy (PNL) is an effective procedure for the treatment of patients with large or complex stones. PNL is challenging in anomalous kidneys, certain patients, such as those with renal ectopia. It is unable to undergo PNL in conventional technique safely in these cases. We presented a case report of laparoscopic-assisted PNL via direct pelvic puncture in a pelvic kidney stone and discussed previous published literature. A 49-year-old man presented with right lower quadrant pain and hematuria. Intravenous pyelography and three-dimensional computerized tomography revealed an opaque 2.7 × 1.7 cm pelvis renalis stone in a right side ectopic pelvic kidney with grade III hydronephrosis. Laparoscopic-assisted tubeless PNL was performed to remove the calculus. Laparoscopic-assisted PNL as a minimally invasive therapy in ectopic kidney has many advantages. Our case showed that, in pelvic ectopic kidney with pelvic stones greater than 1.5 cm in size, laparoscopic-assisted PNL via direct pelvis puncture is a safe and effective technique.

Sleep disturbance: a forgotten syndrome in patients with Chiari I malformation.

PubMed

Ferré Masó, A; Poca, M A; de la Calzada, M D; Solana, E; Romero Tomás, O; Sahuquillo, J

2014-06-01

Chiari type I malformation (CM-I) is characterised by caudal ectopia of the cerebellar tonsils through the foramen magnum. This is associated with brain stem, high spinal cord, and cranial nerve compression phenomena. The most frequent symptoms are occipital headaches and dizziness. Less well-known symptoms are sleep disorders and nocturnal respiratory abnormalities. MEDLINE and information from patients evaluated at the Neurosurgery and Clinical Neurophysiology Departments at Hospital Universitario Vall d'Hebron. Review article based on data obtained from MEDLINE articles since 1966, using combinations of the following keywords: «Chiari malformation» or «Arnold-Chiari malformation» and «sleep apnea» or «sleep disorders». CM-I patients show a higher prevalence of sleep disorders than that observed in the general population. Some studies report a 50% prevalence of sleep apnea-hypopnea syndrome (SAHS), probably associated with sudden death in some cases. These results support analysing sleep respiratory parameters in theses patients. Identifying SAHS symptoms may help optimise treatment, thereby improving quality of life and prognosis. Copyright © 2010 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

Editing of mouse and human immunoglobulin genes by CRISPR-Cas9 system.

PubMed

Cheong, Taek-Chin; Compagno, Mara; Chiarle, Roberto

2016-03-09

Applications of the CRISPR-Cas9 system to edit the genome have widely expanded to include DNA gene knock-out, deletions, chromosomal rearrangements, RNA editing and genome-wide screenings. Here we show the application of CRISPR-Cas9 technology to edit the mouse and human immunoglobulin (Ig) genes. By delivering Cas9 and guide-RNA (gRNA) with retro- or lenti-virus to IgM(+) mouse B cells and hybridomas, we induce class-switch recombination (CSR) of the IgH chain to the desired subclass. Similarly, we induce CSR in all human B cell lines tested with high efficiency to targeted IgH subclass. Finally, we engineer mouse hybridomas to secrete Fab' fragments instead of the whole Ig. Our results indicate that Ig genes in mouse and human cells can be edited to obtain any desired IgH switching helpful to study the biology of normal and lymphoma B cells. We also propose applications that could transform the technology of antibody production.

Excision of a viral reprogramming cassette by delivery of synthetic Cre mRNA

PubMed Central

Loh, Yuin-Han; Yang, Jimmy Chen; De Los Angeles, Alejandro; Guo, Chunguang; Cherry, Anne; Rossi, Derrick J.; Park, In-Hyun; Daley, George Q.

2012-01-01

The generation of patient-specific induced pluripotent stem (iPS) cells provides an invaluable resource for cell therapy, in vitro modeling of human disease, and drug screening. To date, most human iPS cells have been generated with integrating retro- and lenti-viruses and are limited in their potential utility because residual transgene expression may alter their differentiation potential or induce malignant transformation. Alternatively, transgene-free methods using adenovirus and protein transduction are limited by low efficiency. This report describes a protocol for the generation of transgene-free human induced pluripotent stem cells using retroviral transfection of a single vector, which includes the coding sequences of human OCT4, SOX2, KLF4, and cMYC linked with picornaviral 2A plasmids. Moreover, after reprogramming has been achieved, this cassette can be removed using mRNA transfection of Cre recombinase. The method described herein to excise reprogramming factors with ease and efficiency facilitates the experimental generation and use of transgene-free human iPS cells. PMID:22605648

Teratogenic effects of the neonicotinoid thiacloprid on chick embryos (Gallus gallus domesticus).

PubMed

Salvaggio, Antonio; Antoci, Francesco; Messina, Antonino; Ferrante, Margherita; Copat, Chiara; Ruberto, Claudia; Scalisi, Elena Maria; Pecoraro, Roberta; Brundo, Maria Violetta

2018-06-19

Thiacloprid is an insecticide belonging to the family of neonicotinoids, substances initially underestimated for their potential adverse effects, that they may manifest in the long term leading to an extensive use. The objective of this study was to evaluate the effect at increasing concentrations of thiacloprid on chick embryos development. The research was carried out on 75 fertile eggs of Gallus gallus domesticus. The eggs were opened after 10, 15 and 20 days of incubation and in treated embryos were observed developmental alterations, growth retardation, limbs defects and ectopia viscerale. The histological analysis showed hepatic steatosis and haemorrhages both in the liver and in the lungs. Moreover, the immunohistochemical analysis performed on the liver sections showed a strong positivity only for the erythrocytes to the anti-CYP1A antibody. Thiacloprid exposure increases the risks of teratogenic effects especially at the higher doses tested, therefore its use should be more controlled and limited. Since the literature on the topic is lacking, then the human health impacts resulting from neonicotinoids exposure is not yet fully understood, and, our data will be helpful to allow the assessment of an oral reference dose and health risk characterization. Copyright © 2018. Published by Elsevier Ltd.

Radiographic assessment of dental anomalies in patients with ectopic maxillary canines.

PubMed

Sørensen, Helle Budtz; Artmann, Lone; Larsen, Helle Juul; Kjaer, Inger

2009-03-01

The aetiology of palatally and labially located ectopic maxillary canines is multifactorial. Accordingly, early prediction of this eruptional disturbance is in most cases not possible. The purpose of this study was to analyse dental deviations in cases with either palatal or labial ectopic canines. Panoramic and intra-oral radiographs from 50 patients with palatally located (38 females and 12 males) and 19 patients with labially located ectopic canines (11 females and 8 males), aged 10 years, 2 months-18 years, 1 month, were analysed. Dental deviations registered were crown and root malformations, agenesis, and eruption deviations. Registrations were performed in the maxillary incisor field and in the dentition in general. The study documented that palatally as well as labially located ectopic canines can occur in dentitions without other dental deviations. Dental deviations occurred in approximately two-thirds of all cases, more often in females and in cases with palatally located canines. More than half of the females with palatally located canines had deviations in the maxillary incisors and in the dentition in general. Dental deviations may be considered a risk factor for maxillary canine ectopia. Early identification of patients at risk and appropriate interceptive treatment may reduce ectopic eruption of maxillary canines.

[Clinical results after implantation of a new segmental refractive multifocal intraocular lens].

PubMed

Thomas, B C; Auffarth, G U; Philips, R; Novák, J; Blazek, J; Adamkova, H; Rabsilber, T M

2013-11-01

The aim of the study was a clinical evaluation of an intraocular lens (IOL) with a segmental multifocal optic design and near addition of + 3.0 D as part of a CE approval study. In a multicenter study the LENTIS Mplus LS-312 MF IOL (Oculentis) was implanted in 134 eyes of 79 patients with a mean age of 68 ± 12 years. The multifocality is achieved by implementation of a distance part and a segmented near sector. Three months after surgery, uncorrected and best corrected distance visual acuity (UCDVA and BCDVA, respectively), near visual acuity (UCNVA and BCNVA, respectively), contrast vision and patient satisfaction (questionnaire) were evaluated. The IOLs were implanted uneventfully either unilaterally or bilaterally and 3 months postoperatively (n = 86 eyes) the following mean visual acuities were obtained (logMAR): UCDVA = 0.05, BCDVA = - 0.01, UCNVA = 0.09 and BCNVA = 0.02. Contrast sensitivity (n = 25 eyes) was within normal limits. Of the 66 questioned patients 10.6% spontaneously reported halos and 3% glare. This new innovative multifocal IOL concept showed very good functional results as well as high patient satisfaction.

Experimental Model for Successful Liver Cell Therapy by Lenti TTR-YapERT2 Transduced Hepatocytes with Tamoxifen Control of Yap Subcellular Location

PubMed Central

Yovchev, Mladen; Jaber, Fadi L.; Lu, Zhonglei; Patel, Shachi; Locker, Joseph; Rogler, Leslie E.; Murray, John W.; Sudol, Marius; Dabeva, Mariana D.; Zhu, Liang; Shafritz, David A.

2016-01-01

Liver repopulation by transplanted hepatocytes has not been achieved previously in a normal liver microenvironment. Here we report that adult rat hepatocytes transduced ex vivo with a lentivirus expressing a human YapERT2 fusion protein (hYapERT2) under control of the hepatocyte-specific transthyretin (TTR) promoter repopulate normal rat liver in a tamoxifen-dependent manner. Transplanted hepatocytes expand very slowly but progressively to produce 10% repopulation at 6 months, showing clusters of mature hepatocytes that are fully integrated into hepatic parenchyma, with no evidence for dedifferentiation, dysplasia or malignant transformation. Thus, we have developed the first vector designed to regulate the growth control properties of Yap that renders it capable of producing effective cell therapy. The level of liver repopulation achieved has significant translational implications, as it is 2-3x the level required to cure many monogenic disorders of liver function that have no underlying hepatic pathology and is potentially applicable to diseases of other tissues and organs. PMID:26763940

The Colletotrichum destructivum species complex – hemibiotrophic pathogens of forage and field crops

PubMed Central

Damm, U.; O'Connell, R.J.; Groenewald, J.Z.; Crous, P.W.

2014-01-01

Colletotrichum destructivum is an important plant pathogen, mainly of forage and grain legumes including clover, alfalfa, cowpea and lentil, but has also been reported as an anthracnose pathogen of many other plants worldwide. Several Colletotrichum isolates, previously reported as closely related to C. destructivum, are known to establish hemibiotrophic infections in different hosts. The inconsistent application of names to those isolates based on outdated species concepts has caused much taxonomic confusion, particularly in the plant pathology literature. A multilocus DNA sequence analysis (ITS, GAPDH, CHS-1, HIS3, ACT, TUB2) of 83 isolates of C. destructivum and related species revealed 16 clades that are recognised as separate species in the C. destructivum complex, which includes C. destructivum, C. fuscum, C. higginsianum, C. lini and C. tabacum. Each of these species is lecto-, epi- or neotypified in this study. Additionally, eight species, namely C. americae-borealis, C. antirrhinicola, C. bryoniicola, C. lentis, C. ocimi, C. pisicola, C. utrechtense and C. vignae are newly described. PMID:25492986

The Evolving Landscape of the Columbia River Gorge: Lewis and Clark and Cataclysms on the Columbia

USGS Publications Warehouse

O'Connor, James E.

2004-01-01

Travelers reacting Lewis and Clark's journey to the Pacific over the past two hundred years have witnessed tremendous change to the Columbia River Gorge and its primary feature, the Columbia River. Dams, reservoirs, timer harvest, altered fisheries, transportation infrastructure, and growth and shrinkage of communities have transformed the river and valley. This radically different geography of human use and habitation is  commonly contrasted with the sometimes romantic view of a prior time provided both by early nineteenth-century chronicle and present day critics of the modern condition - an ectopia of plentiful and perpetual resources sustaining a stable culture from time immemorial. Reality is more complicated. Certainly the human-caused changes to the Columbia River and the gorge since Lewis and Clark have been profound; by the geologic history of immense floods, landslides, and volcanic eruptions that occurred before the journey had equally, if not more, acute effects on landscapes and societies of the gorge. In many ways, the Lewis and Clark Expidition can be viewed as a hinge point for the Columbia River, the changes engineered to the river and its valley in the two hundred years since their visit mirrored by tremendous cchanges geologically engendered in the thousands of years before. 

Reelin Promotes Neuronal Orientation and Dendritogenesis during Preplate Splitting

PubMed Central

Nichols, Anna J.

2010-01-01

The secreted ligand Reelin is thought to regulate the translocation and positioning of prospective layer 6 (L6) neurons into the preplate, a plexus of neurons overlying the ventricular zone. We examined wild type and Reelin-deficient cortices and found that L6 neurons were equivalently positioned beneath the pia during the period of preplate splitting and initial cortical plate (CP) formation. The absence of detectable L6 ectopia in “reeler” cortices at this developmental time point indicates that Reelin-signaling might not regulate L6 neuron migration or gross positioning during preplate splitting. To explore the acute response of L6 neurons to Reelin, subpial injections of Reelin were made into Reelin-deficient explants. Reelin injection caused L6 neurons to orient their nuclei and polarize their Golgi toward the pia while initiating exuberant dendritic (MAP2+) outgrowth within 4 h. This rapid Reelin-dependent neuronal orientation and alignment created CP-like histology without any significant change in the mean position of the population of L6 neurons. Conversely, subplate cells and chondroitin sulfate proteoglycan immunoreactivity were found at significantly deeper positions from the pial surface after injection, suggesting that Reelin partially rescues preplate splitting within 4 h. Thus, Reelin has a direct role in promoting rapid morphological differentation and orientation of L6 neurons during preplate splitting. PMID:20064940

Cerebrospinal fluid leakage and Chiari I malformation with Gorham's disease of the skull base: A case report.

PubMed

Nagashima, Hiroaki; Mizukawa, Katsu; Taniguchi, Masaaki; Yamamoto, Yusuke; Kohmura, Eiji

Gorham's syndrome is a rare bone disorder characterized by massive osteolysis of unknown etiology. There are no reports of comorbidity involving cerebrospinal fluid (CSF) leakage and Chiari I malformation with Gorham's syndrome. Here, we report an unusual case of an acute presyrinx state complicated by bacterial meningitis due to CSF leakage and Chiari I malformation associated with Gorham's disease of the skull base. A 25-year-old woman with Chiari I malformation associated with Gorham's syndrome presented with aggressive paresthesia following bacterial meningitis. Axial magnetic resonance imaging (MRI) and computed tomography (CT) cisternography revealed CSF leakage in the right petrous apex. A presyrinx state was diagnosed based on the clinical symptoms and MRI findings. With resolution of the bacterial meningitis, the spinal edema and tonsillar ectopia also improved. Surgical repair of the CSF leakage was performed by an endoscopic endonasal transsphenoidal approach to prevent recurrence of meningitis. The postoperative course was uneventful. Skull base osteolysis in Gorham's syndrome may induce Chiari I malformation and CSF leakage. We should pay attention to acute progression of clinical symptoms because Gorham's syndrome may predispose to development of Chiari I malformation and may be complicated by CSF leakage. Copyright © 2017 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Morphofunctional Alterations in Zebrafish (Danio rerio) Gills after Exposure to Mercury Chloride

PubMed Central

Macirella, Rachele; Brunelli, Elvira

2017-01-01

Mercury (Hg) is a global pollutant that may exert its toxic effects on living organisms and is found in both aquatic and terrestrial ecosystems in three chemical forms; elemental, organic, and inorganic. The inorganic form (iHg) tends to predominantly accumulate in aquatic environments. The gill apparatus is a very dynamic organ that plays a fundamental role in gas exchange, osmoregulation, acid-base regulation, detoxification, and excretion, and the gills are the primary route of waterborne iHg entrance in fish. In the present work we investigated the morphofunctional and ultrastructural effects in Danio rerio gills after 96 h exposure to two low HgCl2 concentrations (7.7 and 38.5 µg/L). Our results clearly demonstrated that a short-term exposure to low concentrations of mercury chloride resulted in gill morphology alterations and in the modifications of both Na+/K+-ATPase and metallothioneins (MTs) expression pattern. The main morphological effects recorded in this work were represented by hyperplasia and ectopia of chloride cells (CCs), lamellar fusion, increased mucous secretion, alteration of pavement cells (PVCs), detachment of the secondary epithelium, pillar cell degeneration, degeneration, and apoptosis. Trough immunohistochemistry and real-time PCR analysis also showed a dose-related modulation of Na+/K+-ATPase and MTs. PMID:28406445

Anthropophily of Lutzomyia wellcomei (Diptera: Psychodidae) in an Atlantic Forest Conservation Unit in Northeast Brazil.

PubMed

Pinheiro, Marcos Paulo Gomes; Silva, José Hilário Tavares da; Inacio, Cássio Lázaro Silva; Ximenes, Maria de Fátima Freire de Melo

2016-11-01

Lutzomyia wellcomei (Fraiha, Shaw & Lainson) (Diptera: Psychodidae) can act as an important vector of Leishmania (Viannia) braziliensis This study presents the results of collections carried out in a fragment of Atlantic Forest in a Conservation Unit of Rio Grande do Norte state. Collections occurred over 12 consecutive months using Shannon and CDC traps. A total of 777 sand flies from eight species were collected: Lutzomyia walkeri (Newstead), Lutzomyia evandroi (Costa Lima & Antunes), Lutzomyia wellcomei (Fraiha, Shaw & Lainson), Lutzomyia sordellii (Shannon & Del Ponte), Lutzomyia brasiliensis (Costa Lima), Lutzomyia lenti (Mangabeira), Lutzomyia longipalpis (Lutz & Neiva), and Lutzomyia abonnenci (Floch & Chassignet). Lutzomyia wellcomei was the most abundant species using the Shannon trap (97%) and L. walkeri in the CDC trap (81%). It is important to note the abundance of L. wellcomei in Shannon trap collections, which favors the capture of anthropophilic species. Lutzomyia wellcomei was only present in months where rainfall was above 100 mm, confirming it as a species adapted to wetter months. © The Authors 2016. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Lo Gnomone Clementino Astronomia Meridiana in Basilica

NASA Astrophysics Data System (ADS)

Sigismondi, Costantino

2014-05-01

Costruito per chiara volontà del papa 70 anni dopo il caso Galileo, lo Gnomone Clementino è un grande telescopio solare che non fa uso di lenti a 92 anni dall’invenzione del cannocchiale. Queste due caratteristiche basterebbero da sole a giustificare l’interesse verso questo strumento. L’astronomia meridiana è alla base dell’astrometria e dell’astrofisica moderna. Lo Gnomone Clementino sta oggi all’astronomia, come il veliero “Amerigo Vespucci” sta alla Marina Italiana. E’ possibile svolgere ogni genere di osservazione e studio su questo strumento, e dal 2002 vi tengo lezioni teorico-pratiche del corso di Storia dell’Astronomia e La Terra nel Sistema Solare della Sapienza, Università di Roma, Facoltà di Lettere e Filosofia. Questo testo aggiunge alcuni tasselli alla ricerca storica sulla meridiana, appoggiandosi, com’è naturale, sulle spalle di giganti che mi hanno preceduto in questi studi. In particolare la misura dell’azimut della meridiana, ed il suo inquadramento tra gli strumenti simili ed alcuni studi di astrometria sui dati del 1701-1703 di Bianchini, che sono apparsi fin’ora soltanto su riviste specializzate ed in Inglese vengono qui proposti in Italiano e semplificati, per valorizzare sempre più questa straordinaria opera d’arte e di scienza.

Sand fly captures with Disney traps in area of occurrence of Leishmania (Leishmania) amazonensis in the state of Mato Grosso do Sul, mid-western Brazil.

PubMed

Dorval, Maria Elizabeth Cavalheiros; Alves, Tulia Peixoto; Cristaldo, Geucira; Rocha, Hilda Carlos da; Alves, Murilo Andrade; Oshiro, Elisa Teruya; Oliveira, Alessandra Gutierrez de; Brazil, Reginaldo Peçanha; Galati, Eunice Aparecida Bianchi; Cunha, Rivaldo Venancio da

2010-01-01

The work was conducted to study phlebotomine fauna (Diptera: Psychodidae) and aspects of American cutaneous leishmaniasis transmission in a forested area where Leishmania (Leishmania) amazonensis occurs, situated in the municipality of Bela Vista, State of Mato Grosso do Sul, Brazil. The captures were conducted with modified Disney traps, using hamster (Mesocricetus auratus) as bait, from May 2004 to January 2006. Ten species of phlebotomine sandflies were captured: Brumptomyia avellari, Brumptomyia brumpti, Bichromomyia flaviscutellata, Evandromyia bourrouli, Evandromyia lenti, Lutzomyia longipalpis, Psathyromyia campograndensis, Psathyromyia punctigeniculata, Psathyromyia shannoni and Sciopemyia sordellii. The two predominant species were Ev bourrouli (57.3%) and Bi flaviscutellata (41.4%), present at all sampling sites. Two of the 36 hamsters used as bait presented natural infection with Leishmania. The parasite was identified as Leishmania (Leishmania) amazonensis. Analysis of the results revealed the efficiency of Disney traps for capturing Bichromomyia flaviscutellata and the simultaneous presence of both vector and the Leishmania species transmitted by the same can be considered a predictive factor of the occurrence of leishmaniasis outbreaks for the human population that occupies the location.

MicroRNA-133 regulates the expression of GLUT4 by targeting KLF15 and is involved in metabolic control in cardiac myocytes.

PubMed

Horie, Takahiro; Ono, Koh; Nishi, Hitoo; Iwanaga, Yoshitaka; Nagao, Kazuya; Kinoshita, Minako; Kuwabara, Yasuhide; Takanabe, Rieko; Hasegawa, Koji; Kita, Toru; Kimura, Takeshi

2009-11-13

GLUT4 shows decreased levels in failing human adult hearts. We speculated that GLUT4 expression in cardiac muscle may be fine-tuned by microRNAs. Forced expression of miR-133 decreased GLUT4 expression and reduced insulin-mediated glucose uptake in cardiomyocytes. A computational miRNA target prediction algorithm showed that KLF15 is one of the targets of miR-133. It was confirmed that over-expression of miR-133 reduced the protein level of KLF15, which reduced the level of the downstream target GLUT4. Cardiac myocytes infected with lenti-decoy, in which the 3'UTR with tandem sequences complementary to miR-133 was linked to the luciferase reporter gene, had decreased miR-133 levels and increased levels of GLUT4. The expression levels of KLF15 and GLUT4 were decreased at the left ventricular hypertrophy and congestive heart failure stage in a rat model. The present results indicated that miR-133 regulates the expression of GLUT4 by targeting KLF15 and is involved in metabolic control in cardiomyocytes.

Broad-spectrum non-toxic antiviral nanoparticles with a virucidal inhibition mechanism

NASA Astrophysics Data System (ADS)

Cagno, Valeria; Andreozzi, Patrizia; D'Alicarnasso, Marco; Jacob Silva, Paulo; Mueller, Marie; Galloux, Marie; Le Goffic, Ronan; Jones, Samuel T.; Vallino, Marta; Hodek, Jan; Weber, Jan; Sen, Soumyo; Janeček, Emma-Rose; Bekdemir, Ahmet; Sanavio, Barbara; Martinelli, Chiara; Donalisio, Manuela; Rameix Welti, Marie-Anne; Eleouet, Jean-Francois; Han, Yanxiao; Kaiser, Laurent; Vukovic, Lela; Tapparel, Caroline; Král, Petr; Krol, Silke; Lembo, David; Stellacci, Francesco

2018-02-01

Viral infections kill millions yearly. Available antiviral drugs are virus-specific and active against a limited panel of human pathogens. There are broad-spectrum substances that prevent the first step of virus-cell interaction by mimicking heparan sulfate proteoglycans (HSPG), the highly conserved target of viral attachment ligands (VALs). The reversible binding mechanism prevents their use as a drug, because, upon dilution, the inhibition is lost. Known VALs are made of closely packed repeating units, but the aforementioned substances are able to bind only a few of them. We designed antiviral nanoparticles with long and flexible linkers mimicking HSPG, allowing for effective viral association with a binding that we simulate to be strong and multivalent to the VAL repeating units, generating forces (~190 pN) that eventually lead to irreversible viral deformation. Virucidal assays, electron microscopy images, and molecular dynamics simulations support the proposed mechanism. These particles show no cytotoxicity, and in vitro nanomolar irreversible activity against herpes simplex virus (HSV), human papilloma virus, respiratory syncytial virus (RSV), dengue and lenti virus. They are active ex vivo in human cervicovaginal histocultures infected by HSV-2 and in vivo in mice infected with RSV.

Percutaneous nephrolithotomy in ectopically located kidneys and in patients with musculoskeletal deformities.

PubMed

Srivastava, A; Gupta, P; Chaturvedi, S; Singh, P; Kapoor, R; Dubey, D; Kumar, A

2010-01-01

To assess the feasibility, safety and results of percutaneous nephrolithotomy (PNL) in ectopically located kidneys and in patients with musculoskeletal deformities. Thirteen such patients underwent PNL between June 2005 and May 2008. Mean stone size was 27.4 mm (16-37 mm). Six patients had severe kyphoscoliosis, 2 patients each had achondroplasia, cross-fused ectopia and pelvic ectopic kidney, and 1 patient had thoracic kidney. All had a preoperative CT scan of the abdomen. Preoperative ultrasound- or CT-guided percutaneous nephrostomy (PCN) was done in 10 patients. Three patients underwent laparoscopic-assisted PNL. All underwent standard PNL. The stone-free rate, complication rate and need for secondary intervention were evaluated. PNL was successfully completed in all. A second ultrasound-guided intraoperative puncture was required in 2 patients. Re-look PNL was required in 1 patient and the same patient later required shock wave lithotripsy for complete stone clearance. The remaining 12 patients (92.3%) were rendered stone-free in a single sitting. PNL is a feasible and effective modality in anomalous kidneys. Preoperative planning with CT and image-guided PCN is helpful in these situations. Laparoscopic-assisted PNL can be safely performed in patients where access to a renal collecting system by fluoroscopy or image-guided assistance (ultrasound or CT scan) is not possible. Copyright (c) 2010 S. Karger AG, Basel.

Mayer-Rokitansky-Kuster-Hauser Syndrome: Embryology, Genetics and Clinical and Surgical Treatment

PubMed Central

Sturlese, Emanuele; Retto, Giovanni; Retto, Annalisa; De Dominici, Rosanna; Puzzolo, Domenico

2013-01-01

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a pathological condition characterized by primary amenorrhea and infertility and by congenital aplasia of the uterus and of the upper vagina. The development of secondary sexual characters is normal as well as that the karyotype (46,XX). Etiologically, this syndrome may be caused by the lack of development of the Müllerian ducts between the fifth and the sixth weeks of gestation. To explain this condition, it has been suggested that in patients with MRKH syndrome, there is a very strong hyperincretion of Müllerian-inhibiting factor (MIF), which would provoke the lack of development of the Müllerian ducts from primitive structures (as what normally occurs in male phenotype). These alterations are commonly associated with renal agenesis or ectopia. Specific mutations of several genes such as WT1, PAX2, HOXA7-HOXA13, PBX1, and WNT4 involved in the earliest stages of embryonic development could play a key role in the etiopathogenesis of this syndrome. Besides, it seems that the other two genes, TCF2 (HNF1B) and LHX1, are involved in the determinism of this pathology. Currently, the most widely nonsurgical used techniques include the “Frank's dilators method,” while the surgical ones most commonly used are those developed by McIndoe, Williams, Vecchietti, Davydov, and Baldwin. PMID:23431465

Marfan Syndrome: new diagnostic criteria, same anesthesia care? Case report and review.

PubMed

Araújo, Maria Rita; Marques, Céline; Freitas, Sara; Santa-Bárbara, Rita; Alves, Joana; Xavier, Célia

2016-01-01

Marfan's Syndrome (MFS) is a disorder of connective tissue, mainly involving the cardiovascular, musculoskeletal, and ocular systems. The most severe problems include aortic root dilatation and dissection. Anesthetic management is vital for the improvement on perioperative morbidity. 61-year-old male with MFS, presenting mainly with pectus carinatum, scoliosis, ectopia lens, previous spontaneous pneumothorax and aortal aneurysm and dissection submitted to thoracoabdominal aortic prosthesis placement. Underwent routine laparoscopic cholecystectomy due to lithiasis. Important findings on preoperative examination were thoracolumbar kyphoscoliosis, metallic murmur on cardiac exam. Chest radiograph revealed Cobb angle of 70°. Echocardiogram showed evidence of aortic mechanical prosthesis with no deficits. Preoperative evaluation should focus on cardiopulmonary abnormalities. The anesthesiologist should be prepared for a potentially difficult intubation. Proper positioning and limb support prior to induction is crucial in order to avoid joint injuries. Consider antibiotic prophylaxis for subacute bacterial endocarditis. The patient should be carefully positioned to avoid joint injuries. Intraoperatively cardiovascular monitoring is mandatory: avoid maneuvers that can lead to tachycardia or hypertension, control airway pressure to prevent pneumothorax and maintain an adequate volemia to decrease chances of prolapse, especially if considering laparoscopic surgery. No single intraoperative anesthetic agent or technique has demonstrated superiority. Adequate postoperative pain management is vitally important to avoid the detrimental effects of hypertension and tachycardia. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

Beckwith-Wiedemann syndrome and Chiari I malformation--a case-based review of central nervous system involvement in hemihypertrophy syndromes.

PubMed

Udayakumaran, Suhas; Onyia, Chiazor U

2015-05-01

Beckwith-Wiedemann syndrome (BWS) is an unusual complex of abnormalities that includes mainly omphalocele, macroglossia, gigantism, visceromegaly, and neonatal hypoglycemia. Type I Chiari malformation, on the other hand, is defined as ectopia of the cerebellar tonsils below the plane of the foramen magnum. Only one case of association of BWS with Chiari I malformation has been previously reported in the literature. Several conditions involving congenital hemihypertrophy have been previously reported in association with Type I Chiari malformation. The pathophysiological mechanism for most of these associations is thought to be quite complex and still remains unclear. However, the presence of tonsillar herniation in BWS has been explained by Tubbs and Oakes in the only one existing case report of BWS with Type I Chiari malformation in the literature, to be due to associated hemihypertrophy of the skull base. We additionally suggest that cerebellar hypertrophy may also contribute to the tonsillar herniation and fourth ventricular outlet obstruction. We now report our recent experience on this association following a review of the literature on association of other hemihypertrophy syndromes with the central nervous system anomalies. We believe that a common pathogenesis of Type I Chiari malformation occurs in conditions of hemihypertrophy including BWS, probably secondary to dysmorphology involving the posterior cranial fossa, and is not just an associated finding.

[Marfan Syndrome: new diagnostic criteria, same anesthesia care? Case report and review].

PubMed

Araújo, Maria Rita; Marques, Céline; Freitas, Sara; Santa-Bárbara, Rita; Alves, Joana; Xavier, Célia

2016-01-01

Marfan's Syndrome (MFS) is a disorder of connective tissue, mainly involving the cardiovascular, musculoskeletal, and ocular systems. The most severe problems include aortic root dilatation and dissection. Anesthetic management is vital for the improvement on perioperative morbidity. 61-year-old male with MFS, presenting mainly with pectus carinatum, scoliosis, ectopia lens, previous spontaneous pneumothorax and aortal aneurysm and dissection submitted to thoracoabdominal aortic prosthesis placement. Underwent routine laparoscopic cholecystectomy due to lithiasis. Important findings on preoperative examination were thoracolumbar kyphoscoliosis, metallic murmur on cardiac exam. Chest radiograph revealed Cobb angle of 70°. Echocardiogram showed evidence of aortic mechanical prosthesis with no deficits. Preoperative evaluation should focus on cardiopulmonary abnormalities. The anesthesiologist should be prepared for a potentially difficult intubation. Proper positioning and limb support prior to induction is crucial in order to avoid joint injuries. Consider antibiotic prophylaxis for subacute bacterial endocarditis. The patient should be carefully positioned to avoid joint injuries. Intraoperatively cardiovascular monitoring is mandatory: avoid maneuvers that can lead to tachycardia or hypertension, control airway pressure to prevent pneumothorax and maintain an adequate volemia to decrease chances of prolapse, especially if considering laparoscopic surgery. No single intraoperative anesthetic agent or technique has demonstrated superiority. Adequate postoperative pain management is vitally important to avoid the detrimental effects of hypertension and tachycardia. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

Selective pathologies of the head and neck in children: a developmental perspective.

PubMed

Ozolek, John A

2009-09-01

The range of pathology seen in the head and neck region is truly amazing and to a large extent probably mirrors the complex signaling pathways and careful orchestration of events that occurs between the primordial germ layers during the development of this region. As is true in general for the entire discipline of pediatric pathology, the head and neck pathology within this age group is as diverse and different as its adult counterpart. Cases that come across the pediatric head and neck surgical pathology bench are more heavily weighted toward developmental and congenital lesions such as branchial cleft anomalies, thyroglossal duct cysts, ectopias, heterotopias, choristomas, and primitive tumors. Many congenital "benign" lesions can cause significant morbidity and even mortality if they compress the airway or other vital structures. Exciting investigations into the molecular embryology of craniofacial development have begun to shed light on the pathogenesis of craniofacial developmental lesions and syndromes. Much more investigation is needed, however, to intertwine aberrations in the molecular ontogeny and development of the head and neck regions to the represented pathology. This review will integrate traditional morphologic embryology with some of the recent advances in the molecular pathways of head and neck development followed by a discussion of a variety of developmental lesions finishing with tumors presumed to be derived from pluripotent/progenitor cells and tumors that show anomalous or aborted development.

Genetic variants in microRNAs predict non-small cell lung cancer prognosis in Chinese female population in a prospective cohort study.

PubMed

Lingzi, Xia; Zhihua, Yin; Xuelian, Li; Yangwu, Ren; Haibo, Zhang; Yuxia, Zhao; Baosen, Zhou

2016-12-13

To investigate the prognostic effect of microRNA single nucleotide polymorphisms (SNP) on non-small cell lung cancer (NSCLC) patients, 658 female participants from northeast China were enrolled in our prospective cohort study and followed up from 2010 to 2015. C-containing genotypes of miR-149 rs2292832 were associated with better overall survival (OS). The joint effect of miR-149 and miR-196a2 and the joint effect of miR-149 and miR-608 were also observed in our study. To verify the function of miR-149 rs2292832, A549 cell lines were stably transfected with lenti-virus containing miR-149-C vector, miR-149-T vector and empty vector. Cells containing C allele assumed a higher expression level of miR-149, a decrease in cell growth and the sensitivity to anticancer drug when compared with cells containing T allele. The role of miR-149 playing in cancer prognosis may function through DNA topoisomerases 1 (TOP1) pathway, according to the results from luciferase reporter assays. In conclusion, miR-149 C allele may be a prognostic biomarker for better NSCLC OS.

Genetic variants in microRNAs predict non-small cell lung cancer prognosis in Chinese female population in a prospective cohort study

PubMed Central

Lingzi, Xia; Zhihua, Yin; Xuelian, Li; Yangwu, Ren; Haibo, Zhang; Yuxia, Zhao; Baosen, Zhou

2016-01-01

To investigate the prognostic effect of microRNA single nucleotide polymorphisms (SNP) on non-small cell lung cancer (NSCLC) patients, 658 female participants from northeast China were enrolled in our prospective cohort study and followed up from 2010 to 2015. C-containing genotypes of miR-149 rs2292832 were associated with better overall survival (OS). The joint effect of miR-149 and miR-196a2 and the joint effect of miR-149 and miR-608 were also observed in our study. To verify the function of miR-149 rs2292832, A549 cell lines were stably transfected with lenti-virus containing miR-149-C vector, miR-149-T vector and empty vector. Cells containing C allele assumed a higher expression level of miR-149, a decrease in cell growth and the sensitivity to anticancer drug when compared with cells containing T allele. The role of miR-149 playing in cancer prognosis may function through DNA topoisomerases 1 (TOP1) pathway, according to the results from luciferase reporter assays. In conclusion, miR-149 C allele may be a prognostic biomarker for better NSCLC OS. PMID:27825117

Geographic distribution of phlebotomine sandfly species (Diptera: Psychodidae) in Central-West Brazil.

PubMed

Almeida, Paulo Silva de; Andrade, Andrey José de; Sciamarelli, Alan; Raizer, Josué; Menegatti, Jaqueline Aparecida; Hermes, Sandra Cristina Negreli Moreira; Carvalho, Maria do Socorro Laurentino de; Gurgel-Gonçalves, Rodrigo

2015-06-01

This study updates the geographic distributions of phlebotomine species in Central-West Brazil and analyses the climatic factors associated with their occurrence. The data were obtained from the entomology services of the state departments of health in Central-West Brazil, scientific collections and a literature review of articles from 1962-2014. Ecological niche models were produced for sandfly species with more than 20 occurrences using the Maxent algorithm and eight climate variables. In all, 2,803 phlebotomine records for 127 species were analysed. Nyssomyia whitmani, Evandromyia lenti and Lutzomyia longipalpis were the species with the greatest number of records and were present in all the biomes in Central-West Brazil. The models, which were produced for 34 species, indicated that the Cerrado areas in the central and western regions of Central-West Brazil were climatically more suitable to sandflies. The variables with the greatest influence on the models were the temperature in the coldest months and the temperature seasonality. The results show that phlebotomine species in Central-West Brazil have different geographical distribution patterns and that climate conditions in essentially the entire region favour the occurrence of at least one Leishmania vector species, highlighting the need to maintain or intensify vector control and surveillance strategies.

Geographic distribution of phlebotomine sandfly species (Diptera: Psychodidae) in Central-West Brazil

PubMed Central

de Almeida, Paulo Silva; de Andrade, Andrey José; Sciamarelli, Alan; Raizer, Josué; Menegatti, Jaqueline Aparecida; Hermes, Sandra Cristina Negreli Moreira; de Carvalho, Maria do Socorro Laurentino; Gurgel-Gonçalves, Rodrigo

2015-01-01

This study updates the geographic distributions of phlebotomine species in Central-West Brazil and analyses the climatic factors associated with their occurrence. The data were obtained from the entomology services of the state departments of health in Central-West Brazil, scientific collections and a literature review of articles from 1962-2014. Ecological niche models were produced for sandfly species with more than 20 occurrences using the Maxent algorithm and eight climate variables. In all, 2,803 phlebotomine records for 127 species were analysed. Nyssomyia whitmani, Evandromyia lenti and Lutzomyia longipalpis were the species with the greatest number of records and were present in all the biomes in Central-West Brazil. The models, which were produced for 34 species, indicated that the Cerrado areas in the central and western regions of Central-West Brazil were climatically more suitable to sandflies. The variables with the greatest influence on the models were the temperature in the coldest months and the temperature seasonality. The results show that phlebotomine species in Central-West Brazil have different geographical distribution patterns and that climate conditions in essentially the entire region favour the occurrence of at least one Leishmania vector species, highlighting the need to maintain or intensify vector control and surveillance strategies. PMID:26018450

Implantation of refractive multifocal intraocular lens with a surface-embedded near section for cataract eyes complicated with a coexisting ocular pathology

PubMed Central

Ouchi, M; Kinoshita, S

2015-01-01

Purpose To evaluate the postoperative outcomes of cataract eyes complicated with coexisting ocular pathologies that underwent implantation of a refractive multifocal intraocular lens (MIOL) with a surface-embedded near section. Methods LENTIS MPlus (Oculentis GmbH) refractive MIOLs were implanted in 15 eyes with ocular pathologies other than cataract (ie, six high-myopia eyes with an axial length longer than 28 mm, two fundus albipunctatus eyes, two branch retinal-vein occlusion eyes, four glaucoma eyes (one with high myopia), and two keratoconus eyes). Uncorrected or corrected distance and near visual acuity (VA) (UDVA, UNVA, CDVA, and CNVA), contrast sensitivity, and defocus curve were measured at 1 day and 6 months postoperatively, and each patient completed a 6-month postoperative questionnaire regarding vision quality and eyeglass use. Results Thirteen eyes (87%) registered 0 or better in CDVA and 12 eyes (73%) registered better than 0 in CNVA. Contrast sensitivity in the eyes of all patients was comparable to that of normal healthy subjects. No patient required eyeglasses for distance vision, but three patients (20%) required them for near vision. No patient reported poor or very poor vision quality. Conclusion With careful case selection, sectorial refractive MIOL implantation is effective for treating cataract eyes complicated with ocular pathologies. PMID:25744442

Implantation of refractive multifocal intraocular lens with a surface-embedded near section for cataract eyes complicated with a coexisting ocular pathology.

PubMed

Ouchi, M; Kinoshita, S

2015-05-01

To evaluate the postoperative outcomes of cataract eyes complicated with coexisting ocular pathologies that underwent implantation of a refractive multifocal intraocular lens (MIOL) with a surface-embedded near section. LENTIS MPlus (Oculentis GmbH) refractive MIOLs were implanted in 15 eyes with ocular pathologies other than cataract (ie, six high-myopia eyes with an axial length longer than 28 mm, two fundus albipunctatus eyes, two branch retinal-vein occlusion eyes, four glaucoma eyes (one with high myopia), and two keratoconus eyes). Uncorrected or corrected distance and near visual acuity (VA) (UDVA, UNVA, CDVA, and CNVA), contrast sensitivity, and defocus curve were measured at 1 day and 6 months postoperatively, and each patient completed a 6-month postoperative questionnaire regarding vision quality and eyeglass use. Thirteen eyes (87%) registered 0 or better in CDVA and 12 eyes (73%) registered better than 0 in CNVA. Contrast sensitivity in the eyes of all patients was comparable to that of normal healthy subjects. No patient required eyeglasses for distance vision, but three patients (20%) required them for near vision. No patient reported poor or very poor vision quality. With careful case selection, sectorial refractive MIOL implantation is effective for treating cataract eyes complicated with ocular pathologies.

Implantation of a multifocal toric intraocular lens with a surface-embedded near segment after repeated LASIK treatments.

PubMed

Khoramnia, Ramin; Auffarth, Gerd U; Rabsilber, Tanja M; Holzer, Mike P

2012-11-01

We report a 66-year-old patient who presented with increasing hyperopia, astigmatism, and presbyopia in both eyes 8 years after bilateral laser in situ keratomileusis (LASIK) and LASIK enhancement in the left eye aiming for spectacle independence. Bilateral multifocal toric Lentis Mplus intraocular lenses (IOLs) with an embedded near segment and individually customized cylinder correction were implanted uneventfully following phacoemulsification. The Haigis-L formula after previous hyperopia correction was chosen for IOL power calculation and provided reliable results. Emmetropia was targeted and achieved. Three months postoperatively, the uncorrected distance visual acuity had increased from 0.40 logMAR to 0.10 logMAR in the right eye and from 0.20 logMAR to 0.00 logMAR in the left eye. The patient gained 6 lines of uncorrected near visual acuity: 0.20 logMAR in the right eye and 0.10 logMAR in the left eye. This case shows that customized premium IOL implantation can provide accurate results even in challenging cases. The International Vision Correction Research Centre, Department of Ophthalmology, University of Heidelberg, Heidelberg, Germany, has received research grants, lecture fees, and travel reimbursement from Oculentis GmbH. Copyright © 2012 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Differentiation of Human Mesenchymal Stem Cells into Insulin Producing Cells by Using A Lentiviral Vector Carrying PDX1.

PubMed

Allahverdi, Amir; Abroun, Saied; Jafarian, Arefeh; Soleimani, Masoud; Taghikhani, Mohammad; Eskandari, Fatemeh

2015-01-01

Type I diabetes is an immunologically-mediated devastation of insulin producing cells (IPCs) in the pancreatic islet. Stem cells that produce β-cells are a new promising tool. Adult stem cells such as mesenchymal stem cells (MSCs) are self renewing multi potent cells showing capabilities to differentiate into ectodermal, mesodermal and endodermal tissues. Pancreatic and duodenal homeobox factor 1 (PDX1) is a master regulator gene required for embryonic development of the pancreas and is crucial for normal pancreatic islets activities in adults. We induced the over-expression of the PDX1 gene in human bone marrow MSCs (BM-MSCs) by Lenti-PDX1 in order to generate IPCs. Next, we examine the ability of the cells by measuring insulin/c-peptide production and INSULIN and PDX1 gene expressions. After transduction, MSCs changed their morphology at day 5 and gradually differentiated into IPCs. INSULIN and PDX1 expressions were confirmed by real time polymerase chain reaction (RT-PCR) and immunostaining. IPC secreted insulin and C-peptide in the media that contained different glucose concentrations. MSCs differentiated into IPCs by genetic manipulation. Our result showed that lentiviral vectors could deliver PDX1 gene to MSCs and induce pancreatic differentiation.

A GMP-compliant protocol to expand and transfect cancer patient T cells with mRNA encoding a tumor-specific chimeric antigen receptor.

PubMed

Krug, Christian; Wiesinger, Manuel; Abken, Hinrich; Schuler-Thurner, Beatrice; Schuler, Gerold; Dörrie, Jan; Schaft, Niels

2014-10-01

Chimeric antigen receptors (CARs), which combine an antibody-derived binding domain (single chain fragment variable) with T-cell-activating signaling domains, have become a promising tool in the adoptive cellular therapy of cancer. Retro- and lenti-viral transductions are currently the standard methods to equip T cells with a CAR; permanent CAR expression, however, harbors several risks like uncontrolled auto-reactivity. Modification of T cells by electroporation with CAR-encoding RNA to achieve transient expression likely circumvents these difficulties. We here present a GMP-compliant protocol to activate and expand T cells for clinical application. The protocol is optimized in particular to produce CAR-modified T cells in clinically sufficient numbers under full GMP-compliance from late-stage cancer patients. This protocol allows the generation of 6.7 × 10(8) CAR-expressing T cells from one patient leukapheresis. The CAR-engineered T cells produced pro-inflammatory cytokines after stimulation with antigen-bearing tumor cells and lysed tumor cells in an antigen-specific manner. This functional capacity was maintained after cryopreservation. Taken together, we provide a clinically applicable protocol to transiently engineer sufficient numbers of antigen-specific patient T cells for use in adoptive cell therapy of cancer.

Sandflies in an urban area of transmission of visceral leishmaniasis in midwest Brazil

PubMed Central

Dorval, Maria Elizabeth Cavalheiros; Oshiro, Elisa Teruya; Brilhante, Andreia Fernandes; Nunes, Vânia Lúcia Brandão; Cristaldo, Geucira; Lima Júnior, Manoel Sebastião Costa; Galati, Eunice Aparecida Bianchi

2016-01-01

The phlebotomine fauna of Campo Grande city, capital of Mato Grosso do Sul state in Brazil, an endemic area for visceral leishmaniasis, has been thoroughly investigated, but all the insect collections were undertaken with automatic light traps. The present study sought to investigate the fauna in this city using Shannon and Disney traps, having human beings and hamsters, respectively, as bait. Both types of traps were installed in forest fragment and peridomiciliary areas in the period from 2007 to 2009. The phlebotomine females were analyzed by PCR for Leishmania identification. Lutzomyia longipalpis was the only species collected in the peridomiciles and rendered a total of 574 specimens with a 5.2:1 male:female ratio. A total of eight species were attracted to the two traps (one of each type) installed in the forest fragment, including: Bichromomyia flaviscutellata, Evandromyia bourrouli, Evandromyia lenti, Lutzomyia longipalpis, Nyssomyia whitmani, Pintomyia christenseni, Psathyromyia bigeniculata, and Sciopemyia sordellii. A total of 143 specimens were collected, Bi. flaviscutellata accounting for 81% and Lu. longipalpis for 1.4% of them. In one female of Lu. longipalpis collected in a Disney trap installed in a peridomicile, Leishmania (Leishmania) infantum DNA was found, thus strengthening the hypothesis that the transmission of leishmaniasis is in fact occurring in the anthropic environment. PMID:27593433

Co-occurrence of severe Goltz-Gorlin syndrome and pentalogy of Cantrell - Case report and review of the literature.

PubMed

Smigiel, Robert; Jakubiak, Aleksandra; Lombardi, Maria Paola; Jaworski, Wojciech; Slezak, Ryszard; Patkowski, Dariusz; Hennekam, Raoul C

2011-05-01

Goltz-Gorlin syndrome is a highly variable disorder affecting many body parts of meso-ectodermal origin. Mutations in X-linked PORCN have been identified in almost all patients with a classical Goltz-Gorlin phenotype. The pentalogy of Cantrell is an infrequently described congenital disorder characterized by the combination of five anomalies: a midline supra-umbilical abdominal wall defect; absent or cleft lower part of the sternum; deficiency of the diaphragmatic pericardium; deficiency of the anterior diaphragm; and congenital heart anomalies. Etiology and pathogenesis are unknown. We report on an infant with findings fitting both Goltz-Gorlin syndrome (sparse hair; anophthalmia; clefting; bifid nose; irregular vermillion of both lips; asymmetrical limb malformations; caudal appendage; linear aplastic skin defects; unilateral hearing loss) and the pentalogy of Cantrell (absent lower sternum; anterior diaphragmatic hernia; ectopia cordis; omphalocele). The clinical diagnosis Goltz-Gorlin syndrome was confirmed molecularly by a point mutation in PORCN (c.727C>T). The presence of molecularly confirmed Goltz-Gorlin syndrome and pentalogy of Cantrell in a single patient has been reported twice before. The present patient confirms that the pentalogy of Cantrell can be caused in some patients by a PORCN mutation. It remains at present uncertain whether this can be explained by the type or localization of the mutation within PORCN, or whether the co-occurrence of the two entities is additionally determined by mutations or polymorphisms in other genes, environmental factors, and/or epigenetic influences. Copyright © 2011 Wiley-Liss, Inc.

Magnesium in cardioplegia: Is it necessary?

PubMed Central

Shakerinia, Tooraj; Ali, Idris M.; Sullivan, John A.P.

1996-01-01

Objective To study the effectiveness of magnesium in cardioplegic solution in preventing postoperative arrhythmias and perioperative ischemia. Design Randomized, control study. Setting The cardiovascular surgery division of a major referral centre for the maritime provinces of Canada. Patients Fifty patients scheduled to undergo coronary artery bypass who had a normal ejection fraction, normal preoperative serum magnesium level and no history of atrial or ventricular arrhythmia were randomized into two groups of 25 patients. One group received magnesium sulfate (15 mmol/L) in the cardioplegic solution (group 1), the other (control) group did not receive magnesium sulfate in the cardioplegic solution (group 2). Intervention Coronary artery bypass grafting during which myocardial protection was provided by intermittent cold blood cardioplegia. Outcome Measures Postoperative serum magnesium levels, cardiac-related death, infarction and arrhythmias. Results All group 2 patients had a lower postoperative serum magnesium level than group 1 patients. There were no cardiac-related deaths in either group. More group 2 patients had ischemic electrocardiographic changes than group 1 patients (p < 0.03). Non-Q-wave myocardial infarction occurred in two patients (one in each group). Eight patients in group 2 had atrial fibrillation compared with five patients in group 1. Ventricular ectopia occurred significantly (p < 0.01) more frequently in group 2 than in group 1. Conclusion The addition of magnesium to the cardioplegic solution is beneficial in reducing the incidence of perioperative ischemia and ventricular arrhythmia in patients who undergo coronary bypass grafting. PMID:8857989

Peripheral retinopathy in offspring of carriers of Norrie disease gene mutations. Possible transplacental effect of abnormal Norrin.

PubMed

Mintz-Hittner, H A; Ferrell, R E; Sims, K B; Fernandez, K M; Gemmell, B S; Satriano, D R; Caster, J; Kretzer, F L

1996-12-01

The Norrie disease (ND) gene (Xp11.3) (McKusick 310600) consists of one untranslated exon and two exons partially translated as the Norrie disease protein (Norrin). Norrin has sequence homology and computer-predicted tertiary structure of a growth factor containing a cystine knot motif, which affects endothelial cell migration and proliferation. Norrie disease (congenital retinal detachment), X-linked primary retinal dysplasia (congenital retinal fold), and X-linked exudative vitreoretinopathy (congenital macular ectopia) are allelic disorders. Blood was drawn for genetic studies from members of two families to test for ND gene mutations. Sixteen unaffected family members were examined ophthalmologically. If any retinal abnormality were identified, fundus photography and fluorescein angiography was performed. Family A had ND (R109stp), and family B had X-linked exudative vitreoretinopathy (R121L). The retinas of 11 offspring of carrier females were examined: three of seven carrier females, three of three otherwise healthy females, and one of one otherwise healthy male had peripheral inner retinal vascular abnormalities. The retinas of five offspring of affected males were examined: none of three carrier females and none of two otherwise healthy males had this peripheral retinal finding. Peripheral inner retinal vascular abnormalities similar to regressed retinopathy of prematurity were identified in seven offspring of carriers of ND gene mutations in two families. These ophthalmologic findings, especially in four genetically healthy offspring, strongly support the hypothesis that abnormal Norrin may have an adverse transplacental (environmental) effect on normal inner retinal vasculogenesis.

Surgical correction of ectopic penis and scrotum associated with bilateral orchidopexy.

PubMed

Sobral, Daniel Santos Rocha; Silva, Helder Damásio da; Damázio, Eulálio

2017-01-01

Ectopic penis is usually associated with penoscrotal transposition, and it is rarely observed in isolation. We report a surgical approach for an extremely rare case. A 10-year-old male patient with bilateral cryptorchidism and ectopic penis and scrotum in perineal area, with no penoscrotal transposition, representing an association not yet described in literature. A previous orchiopexy failed due to ectopic scrotum. By means of an inverted Y incision, the penis was mobilized and a perineal skin flap in form of a testicular sac was prepared. Finally orchiopexy was performed. The surgery was essential to treat cryptorchidism and to improve the self-image of the patient. RESUMO O pênis ectópico geralmente ocorre associado à transposição peno-escrotal, sendo raro isoladamente. Relatamos uma abordagem cirúrgica para um caso extremamente raro. Tratava-se de paciente do sexo masculino, 10 anos, com criptorquidia bilateral e pênis e escroto ectópicos, na região perineal, sem transposição peno-escrotal, representando uma associação ainda não descrita na literatura. Orquidopexia prévia sem sucesso, devido à ectopia do escroto. Por meio de uma incisão em Y invertido, mobilizou-se o pênis e preparou-se um retalho da pele perineal em forma de bolsa testicular. Por fim, realizou-se a orquidopexia. A cirurgia foi fundamental para tratar a criptorquidia e promover ganho na autoimagem do paciente.

SAND FLIES (DIPTERA: PSYCHODIDAE) IN AN ENDEMIC AREA OF LEISHMANIASIS IN AQUIDAUANA MUNICIPALITY, PANTANAL OF MATO GROSSO DO SUL , BRAZIL

PubMed Central

de FIGUEIREDO, Helen Rezende; SANTOS, Mirella Ferreira da Cunha; CASARIL, Aline Etelvina; INFRAN, Jucelei Oliveira de Moura; RIBEIRO, Leticia Moraes; FERNANDES, Carlos Eurico dos Santos; de OLIVEIRA, Alessandra Gutierrez

2016-01-01

SUMMARY The Aquidauana municipality is considered an endemic area of leishmaniasis and an important tourist site in Mato Grosso do Sul State. The aim of this study was to investigate the sand fly fauna in the city of Aquidauana. Captures were carried out twice a month, from April 2012 to March 2014 with automatic light traps and active aspiration, in the peridomicile and domicile of six residences. A total of 9,338 specimens were collected, 3,179 and 6,159 using light traps and active aspiration, respectively. The fauna consisted of: Brumptomyia brumpti, Evandromyia aldafalcaoae, Ev. evandroi, Ev. lenti, Ev. orcyi, Ev. sallesi, Ev. termitophila, Ev. walkeri, Lutzomyia longipalpis and Psathyromyia bigeniculata. The most abundant species captured was Lutzomyia longipalpis, present in all the ecotopes, predominantly in peridomicile areas, and mainly males. Leishmania DNA was not detected in the insects. It was observed the abundance of the sand fly fauna in the region, as well as the high frequency of Lu. longipalpis, the main vector of L. infantum. The results of this study show the need to increase the monitoring and more effective control measures. It is noteworthy that the studied region presents several activities related to tourism and recreation, increasing the risk of transmission of leishmaniasis to this particular human population. PMID:27982353

Activation of concurrent apoptosis and necroptosis by SMAC mimetics for the treatment of refractory and relapsed ALL.

PubMed

McComb, Scott; Aguadé-Gorgorió, Júlia; Harder, Lena; Marovca, Blerim; Cario, Gunnar; Eckert, Cornelia; Schrappe, Martin; Stanulla, Martin; von Stackelberg, Arend; Bourquin, Jean-Pierre; Bornhauser, Beat C

2016-05-18

More precise treatment strategies are urgently needed to decrease toxicity and improve outcomes for treatment-refractory leukemia. We used ex vivo drug response profiling of high-risk, relapsed, or refractory acute lymphoblastic leukemia (ALL) cases and identified a subset with exquisite sensitivity to small-molecule mimetics of the second mitochondria-derived activator of caspases (SMAC) protein. Potent ex vivo activity of the SMAC mimetic (SM) birinapant correlated with marked in vivo antileukemic effects, as indicated by delayed engraftment, decreased leukemia burden, and prolonged survival of xenografted mice. Antileukemic activity was dependent on simultaneous execution of apoptosis and necroptosis, as demonstrated by functional genomic dissection with a multicolored lentiCRISPR approach to simultaneously disrupt multiple genes in patient-derived ALL. SM specifically targeted receptor-interacting protein kinase 1 (RIP1)-dependent death, and CRISPR-mediated disruption of RIP1 completely blocked SM-induced death yet had no impact on the response to standard antileukemic agents. Thus, SM compounds such as birinapant circumvent escape from apoptosis in leukemia by activating a potent dual RIP1-dependent apoptotic and necroptotic cell death, which is not exploited by current therapy. Ex vivo drug activity profiling could provide important functional diagnostic information to identify patients who may benefit from targeted treatment with birinapant in early clinical trials. Copyright © 2016, American Association for the Advancement of Science.

NADPH oxidase mediates depressive behavior induced by chronic stress in mice.

PubMed

Seo, Ji-Seon; Park, Jin-Young; Choi, Juli; Kim, Tae-Kyung; Shin, Joo-Hyun; Lee, Ja-Kyeong; Han, Pyung-Lim

2012-07-11

Stress is a potent risk factor for depression, yet the underlying mechanism is not clearly understood. In the present study, we explored the mechanism of development and maintenance of depression in a stress-induced animal model. Mice restrained for 2 h daily for 14 d showed distinct depressive behavior, and the altered behavior persisted for >3 months in the absence of intervention. Acute restraint induced a surge of oxidative stress in the brain, and stress-induced oxidative stress progressively increased with repetition of stress. In vitro, the stress hormone glucocorticoid generated superoxide via upregulation of NADPH oxidase. Consistently, repeated restraints increased the expression of the key subunits of NADPH oxidase, p47phox and p67phox, in the brain. Moreover, stressed brains markedly upregulated the expression of p47phox to weak restress evoked in the poststress period, and this molecular response was reminiscent of amplified ROS surge to restress. Pharmacological inhibition of NADPH oxidase by the NADPH oxidase inhibitor apocynin during the stress or poststress period completely blocked depressive behavior. Consistently, heterozygous p47phox knock-out mice (p47phox(+/-)) or molecular inhibition of p47phox with Lenti shRNA-p47phox in the hippocampus suppressed depressive behavior. These results suggest that repeated stress promotes depressive behavior through the upregulation of NADPH oxidase and the resultant metabolic oxidative stress, and that the inhibition of NADPH oxidase provides beneficial antidepression effects.

Transduction of Human Primitive Repopulating Hematopoietic Cells With Lentiviral Vectors Pseudotyped With Various Envelope Proteins

PubMed Central

Kim, Yoon-Sang; Wielgosz, Matthew M; Hargrove, Phillip; Kepes, Steven; Gray, John; Persons, Derek A; Nienhuis, Arthur W

2010-01-01

Lentiviral vectors are useful for transducing primitive hematopoietic cells. We examined four envelope proteins for their ability to mediate lentiviral transduction of mobilized human CD34+ peripheral blood cells. Lentiviral particles encoding green fluorescent protein (GFP) were pseudotyped with the vesicular stomatitis virus envelope glycoprotein (VSV-G), the amphotropic (AMPHO) murine leukemia virus envelope protein, the endogenous feline leukemia viral envelope protein or the feline leukemia virus type C envelope protein. Because the relative amount of genome RNA per ml was similar for each pseudotype, we transduced CD34+ cells with a fixed volume of each vector preparation. Following an overnight transduction, CD34+ cells were transplanted into immunodeficient mice which were sacrificed 12 weeks later. The average percentages of engrafted human CD45+ cells in total bone marrow were comparable to that of the control, mock-transduced group (37–45%). Lenti-particles pseudotyped with the VSV-G envelope protein transduced engrafting cells two- to tenfold better than particles pseudotyped with any of the γ-retroviral envelope proteins. There was no correlation between receptor mRNA levels for the γ-retroviral vectors and transduction efficiency of primitive hematopoietic cells. These results support the use of the VSV-G envelope protein for the development of lentiviral producer cell lines for manufacture of clinical-grade vector. PMID:20372106

In Vitro Generation of Functional Liver Organoid-Like Structures Using Adult Human Cells.

PubMed

Ramachandran, Sarada Devi; Schirmer, Katharina; Münst, Bernhard; Heinz, Stefan; Ghafoory, Shahrouz; Wölfl, Stefan; Simon-Keller, Katja; Marx, Alexander; Øie, Cristina Ionica; Ebert, Matthias P; Walles, Heike; Braspenning, Joris; Breitkopf-Heinlein, Katja

2015-01-01

In this study we used differentiated adult human upcyte® cells for the in vitro generation of liver organoids. Upcyte® cells are genetically engineered cell strains derived from primary human cells by lenti-viral transduction of genes or gene combinations inducing transient proliferation capacity (upcyte® process). Proliferating upcyte® cells undergo a finite number of cell divisions, i.e., 20 to 40 population doublings, but upon withdrawal of proliferation stimulating factors, they regain most of the cell specific characteristics of primary cells. When a defined mixture of differentiated human upcyte® cells (hepatocytes, liver sinusoidal endothelial cells (LSECs) and mesenchymal stem cells (MSCs)) was cultured in vitro on a thick layer of Matrigel™, they self-organized to form liver organoid-like structures within 24 hours. When further cultured for 10 days in a bioreactor, these liver organoids show typical functional characteristics of liver parenchyma including activity of cytochromes P450, CYP3A4, CYP2B6 and CYP2C9 as well as mRNA expression of several marker genes and other enzymes. In summary, we hereby describe that 3D functional hepatic structures composed of primary human cell strains can be generated in vitro. They can be cultured for a prolonged period of time and are potentially useful ex vivo models to study liver functions.

Advanced glycation end product-induced astrocytic differentiation of cultured neurospheres through inhibition of Notch-Hes1 pathway-mediated neurogenesis.

PubMed

Guo, Yijing; Wang, Pin; Sun, Haixia; Cai, Rongrong; Xia, Wenqing; Wang, Shaohua

2013-12-23

This study aims to investigate the roles of the Notch-Hes1 pathway in the advanced glycation end product (AGE)-mediated differentiation of neural stem cells (NSCs). We prepared pLentiLox3.7 lentiviral vectors that express short hairpin RNA (shRNA) against Notch1 and transfected it into NSCs. Cell differentiation was analyzed under confocal laser-scanning microscopy. The percentage of neurons and astrocytes was quantified by normalizing the total number of TUJ1+ (Neuron-specific class III β-tubulin) and GFAP+ (Glial fibrillary acidic protein) cells to the total number of Hoechst 33342-labeled cell nuclei. The protein and gene expression of Notch-Hes1 pathway components was examined via western blot analysis and real-time PCR. After 1 week of incubation, we found that AGE-bovine serum albumin (BSA) (400 μg/mL) induced the astrocytic differentiation of cultured neurospheres and inhibited neuronal formation. The expression of Notch-Hes1 pathway components was upregulated in the cells in the AGE-BSA culture medium. Immunoblot analysis indicated that shRNA silencing of Notch1 expression in NSCs significantly increases neurogenesis and suppresses astrocytic differentiation in NSCs incubated with AGE-BSA. AGEs promote the astrocytic differentiation of cultured neurospheres by inhibiting neurogenesis through the Notch-Hes1 pathway, providing a potential therapeutic target for hyperglycemia-related cognitive deficits.

SCF increases in utero-labeled stem cells migration and improves wound healing.

PubMed

Zgheib, Carlos; Xu, Junwang; Mallette, Andrew C; Caskey, Robert C; Zhang, Liping; Hu, Junyi; Liechty, Kenneth W

2015-01-01

Diabetic skin wounds lack the ability to heal properly and constitute a major and significant complication of diabetes. Nontraumatic lower extremity amputations are the number one complication of diabetic skin wounds. The complexity of their pathophysiology requires an intervention at many levels to enhance healing and wound closure. Stem cells are a promising treatment for diabetic skin wounds as they have the ability to correct abnormal healing. Stem cell factor (SCF), a chemokine expressed in the skin, can induce stem cells migration, however the role of SCF in diabetic skin wound healing is still unknown. We hypothesize that SCF would correct the impairment and promote the healing of diabetic skin wounds. Our results show that SCF improved wound closure in diabetic mice and increased HIF-1α and vascular endothelial growth factor (VEGF) expression levels in these wounds. SCF treatment also enhanced the migration of red fluorescent protein (RFP)-labeled skin stem cells via in utero intra-amniotic injection of lenti-RFP at E8. Interestingly these RFP+ cells are present in the epidermis, stain negative for K15, and appear to be distinct from the already known hair follicle stem cells. These results demonstrate that SCF improves diabetic wound healing in part by increasing the recruitment of a unique stem cell population present in the skin. © 2015 by the Wound Healing Society.

AIDS: the frightening facts.

PubMed

Ryan, M

1986-01-01

Aquired Immune Deficiency Syndrome (AIDS) has succeeded in creating an unprecedented wave of panic among the Western public and some sections of the medical profession. Research clearly shows that the AIDS virus is transmissible in a number of ways: from man to woman and vice versa during sexual intercourse, through semen and possibly vaginal fluids; from mothers to their children through breast milk; through exchange of saliva (but not through just a casual kiss); and through blood and blood products. Far from being exclusive to homosexuals, studies in Europe have shown that female virus carriers can transmit AIDS to healthy men through sexual intercourse--the predominant means by which transmission appears to occur in Central Africa. Although cases of AIDS began being diagnosed in a few Central African countries at the beginning of the 1980s, at the same time as they were first being observed in Europe and North America, many commentators assumed that the virus originated in Africa. Yet, it is safe to say that the nature of the virus, let alone its origins, remains controversial among scientists and virologists. 1 supporter of the theory that the AIDS virus has African origins is Robert Gall of the US National Institute of Health (NIH). He is one of the co-discoverers of the virus, which he named HTLV3 (Human T-cell Lymphotropic Virus 3). The virus also was discovered at France's Pasteur Institute by Luc Montaigner, who called it LAV (Lymphadenpathy Associated Virus). Gallo named the virus as he did because he believes it to be related to a pair of other viruses, HTLV1 and HTLV2, which like the AIDS virus attack the body's immunity system. Unlike AIDS, these 2 viruses, do not destroy the T-cells but cause them to replicate into cancer tumors. In Gallo's view, HTLV1 has long been endemic to some parts of Africa, from where he believes it spread via the slave trade to other parts of the world. Montaigner does not agree. He denies that the AIDS virus is related to either HTLV1 or HTLV2, claiming that ist shape and behavior makes it closer to a group of viruses known as lenti-viruses, so called because they can lie dormant in an animal host for between 5-20 years before becoming active. Prior to the appearance of AIDS, lenti-viruses were hardly ever found in humans. Due to this controversy, the virus has been HTLV3/LAV by the scientific community. What is evident from studies of the disease in Africa, Europe, and the US, is that there are no easy remedies for this highly complex syndrome. Nor is it possible to generalize about it from 1 country to another, let alone 1 continent from another. The way the disease presents itself in Zaire is different from the way it presents itself in Uganda, and both are very different from the way it presents itself in Europe and the US. In Zaire, chronic diarrhea, tuberculosis, pneumonia, and cryptococcal meningitis could all be symptoms of the AIDS patient. AIDS is a recognized public health problem in a number of Central African countries. In those areas where the disease's presence has been confirmed, sexual promiscuity has been singled out as a high risk factor for its transmission. In all affected countries, health authorities are aware of the need to launch health education campaigns.

[Computerized evaluation of reparative processes of the cervix uteri].

PubMed

Pasquinucci, C; Contini, V

1990-01-01

This study was aimed to evaluate the effect of polydeoxyribonucleotide (PDRN), as reported in relevant literature, on cervical epithelia dynamics. Particularly, the interactions taking place between columnar epithelium and the squamous one have been examined. For the purposes of the study, the following computerized techniques, already widely known, have been used: The colposcope is joined to a videocamera connected with a computer (AT compatible). The computer is equipped with a graphic card capable to record and to digit the image, i.e. to make it recognizable by the computer itself. Thereafter, many operations can be performed on the colposcopic images: reductions, enlargements, retouches, record, recall, analysis, etc. Moreover, irregular epithelial areas can be easily determined to a good approximation and, using pre-established enlargement ratios, their evolution can be evaluated. By means of this technique 12 out-patients with uterine cervix ectopias, with or without normal transformation zone (NTZ), have been examined. The monthly therapy was 12 pessaries, each containing 5 mg polydeoxyribonucleotide (POLIDES 5--Farmigea), from the 7th to the 18th day of the cycle, repeated for 3 months. Since the first month of treatment a reduction of the ectopic columnar epithelium has been noted in most patients (9 on 12), with a squamous epithelium increase (peripheral reparative process). This process has kept on increasing during the following months in the 9 patients responding to the treatment, whose ectopic areas were covered by squamous epithelium (average 55% of the area; range 33%-78%). No response to the treatment has been shown in 3 cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Management of upper urinary tract calculi in crossed fused renal ectopic anomaly

PubMed Central

Huang, Liang; Lin, Yong; Tang, Zhengyan; Lie, Dongjie; Wang, Zhao; Chen, Hequn; Wang, Guilin

2018-01-01

The aim of the present study was to summarize the management of upper urinary tract calculi in crossed fused renal ectopia (CFRE). Two patients were retrospectively studied in Xiangya Hospital (Changsha, China) and all relevant literature published in English between 1996 and 2016 was reviewed. All patients, including those reported in the literature, were characterized by age, sex, manifestation, therapy history, ectopic side, stone location, surgery and outcome. The patients had a mean age of 42.3±18.5 years, a male: Female ratio of 5:4 and the ratio of renal ectopic side was 9:8 (left:right). All patients suffered from different degrees of pain on the affected side, with or without hematuria. Up to 89% of patients presented with renal stones. These patients received treatments including conservative management in 2, extracorporeal shock wave lithotripsy (ESWL) in 2, percutaneous nephrolithotomy (PCNL) in 11, laparoscope nephrolithotomy in 1 and retrograde intrarenal surgery (RIRS) in 3. Complete stone clearance was achieved in 14 patients (73.7%). In addition, 3 patients had a history of failed ESWL. No obvious intraoperative or postoperative complications occurred. The results suggested that, for the treatment of CFRE with upper urinary tract calculi, conservative treatment and ESWL are insufficient. PCNL is a safe and effective treatment for renal calculus, and laparoscopic nephrolithotomy is an alternative choice for treating large or staghorn renal stones. RIRS may become the first line of treatment for renal stones (≤3.5 cm) due to its multiple merits, including higher stone-free rates, minimal invasion and fewer complications. PMID:29375692

Management of upper urinary tract calculi in crossed fused renal ectopic anomaly.

PubMed

Huang, Liang; Lin, Yong; Tang, Zhengyan; Lie, Dongjie; Wang, Zhao; Chen, Hequn; Wang, Guilin

2018-01-01

The aim of the present study was to summarize the management of upper urinary tract calculi in crossed fused renal ectopia (CFRE). Two patients were retrospectively studied in Xiangya Hospital (Changsha, China) and all relevant literature published in English between 1996 and 2016 was reviewed. All patients, including those reported in the literature, were characterized by age, sex, manifestation, therapy history, ectopic side, stone location, surgery and outcome. The patients had a mean age of 42.3±18.5 years, a male: Female ratio of 5:4 and the ratio of renal ectopic side was 9:8 (left:right). All patients suffered from different degrees of pain on the affected side, with or without hematuria. Up to 89% of patients presented with renal stones. These patients received treatments including conservative management in 2, extracorporeal shock wave lithotripsy (ESWL) in 2, percutaneous nephrolithotomy (PCNL) in 11, laparoscope nephrolithotomy in 1 and retrograde intrarenal surgery (RIRS) in 3. Complete stone clearance was achieved in 14 patients (73.7%). In addition, 3 patients had a history of failed ESWL. No obvious intraoperative or postoperative complications occurred. The results suggested that, for the treatment of CFRE with upper urinary tract calculi, conservative treatment and ESWL are insufficient. PCNL is a safe and effective treatment for renal calculus, and laparoscopic nephrolithotomy is an alternative choice for treating large or staghorn renal stones. RIRS may become the first line of treatment for renal stones (≤3.5 cm) due to its multiple merits, including higher stone-free rates, minimal invasion and fewer complications.

Invesigation of prevalence of dental anomalies by using digital panoramic radiographs.

PubMed

Bilge, Nebiha Hilal; Yeşiltepe, Selin; Törenek Ağırman, Kübra; Çağlayan, Fatma; Bilge, Osman Murat

2017-09-21

This study was performed to evaluate the prevalence of all types and subtypes of dental anomalies among 6 to 40 year-old patients by using panoramic radiographs. This cross-sectional study was conducted by analyzing digital panoramic radiographs of 1200 patients admitted to our clinic in 2014. Dental anomalies were examined under 5 types and 16 subtypes. Dental anomalies were divided into five types: (a) number (including hypodontia, oligodontia and hyperdontia); (b) size (including microdontia and macrodontia); (c) structure (including amelogenesis imperfecta, dentinogenesis imperfecta and dentin dysplasia); (d) position (including transposition, ectopia, displacement, impaction and inversion); (e) shape (including fusion-gemination, dilaceration and taurodontism); RESULTS: The prevalence of dental anomalies diagnosed by panoramic radiographs was 39.2% (men (46%), women (54%)). Anomalies of position (60.8%) and shape (27.8%) were the most common types of abnormalities and anomalies of size (8.2%), structure (0.2%) and number (17%) were the least in both genders. Anomalies of impaction (45.5%), dilacerations (16.3%), hypodontia (13.8%) and taurodontism (11.2%) were the most common subtypes of dental anomalies. Taurodontism was more common in the age groups of 13-19 years. The age range of the most frequent of all other anomalies was 20-29. Anomalies of tooth position were the most common type of dental anomalies and structure anomalies were the least in this Turkish dental population. The frequency and type of dental anomalies vary within and between populations, confirming the role of racial factors in the prevalence of dental anomalies. Digital panoramic radiography is a very useful method for the detection of dental anomalies.

Low and high dietary folic acid levels perturb postnatal cerebellar morphology in growing rats.

PubMed

Partearroyo, Teresa; Pérez-Miguelsanz, Juliana; Peña-Melián, Ángel; Maestro-de-Las-Casas, Carmen; Úbeda, Natalia; Varela-Moreiras, Gregorio

2016-06-01

The brain is particularly sensitive to folate metabolic disturbances, because methyl groups are critical for brain functions. This study aimed to investigate the effects of different dietary levels of folic acid (FA) on postnatal cerebellar morphology, including the architecture and organisation of the various layers. A total of forty male OFA rats (a Sprague-Dawley strain), 5 weeks old, were classified into the following four dietary groups: FA deficient (0 mg/kg FA); FA supplemented (8 mg/kg FA); FA supra-supplemented (40 mg/kg FA); and control (2 mg/kg FA) (all n 10 per group). Rats were fed ad libitum for 30 d. The cerebellum was quickly removed and processed for histological and immunohistochemical analysis. Slides were immunostained for glial fibrillary acidic protein (to label Bergmann glia), calbindin (to label Purkinje cells) and NeuN (to label post-mitotic neurons). Microscopic analysis revealed two types of defect: partial disappearance of fissures and/or neuronal ectopia, primarily in supra-supplemented animals (incidence of 80 %, P≤0·01), but also in deficient and supplemented groups (incidence of 40 %, P≤0·05), compared with control animals. The primary fissure was predominantly affected, sometimes accompanied by defects in the secondary fissure. Our findings show that growing rats fed an FA-modified diet, including both deficient and supplemented diets, have an increased risk of disturbances in cerebellar corticogenesis. Defects caused by these diets may have functional consequences in later life. The present study is the first to demonstrate that cerebellar morphological defects can arise from deficient, as well as high, FA levels in the diet.

Analysis of Expression Pattern and Genetic Deletion of Netrin5 in the Developing Mouse

PubMed Central

Garrett, Andrew M.; Jucius, Thomas J.; Sigaud, Liam P. R.; Tang, Fu-Lei; Xiong, Wen-Cheng; Ackerman, Susan L.; Burgess, Robert W.

2016-01-01

Boundary cap cells (BCC) are a transient, neural-crest-derived population found at the motor exit point (MEP) and dorsal root entry zone (DREZ) of the embryonic spinal cord. These cells contribute to the central/peripheral nervous system (CNS/PNS) boundary, and in their absence neurons and glia from the CNS migrate into the PNS. We found Netrin5 (Ntn5), a previously unstudied member of the netrin gene family, to be robustly expressed in BCC. We generated Ntn5 knockout mice and examined neurodevelopmental and BCC-related phenotypes. No abnormalities in cranial nerve guidance, dorsal root organization, or sensory projections were found. However, Ntn5 mutant embryos did have ectopic motor neurons (MNs) that migrated out of the ventral horn and into the motor roots. Previous studies have implicated semaphorin6A (Sema6A) in BCC signaling to plexinA2 (PlxnA2)/neuropilin2 (Nrp2) in MNs in restricting MN cell bodies to the ventral horn, particularly in the caudal spinal cord. In Ntn5 mutants, ectopic MNs are likely to be a different population, as more ectopias were found rostrally. Furthermore, ectopic MNs in Ntn5 mutants were not immunoreactive for NRP2. The netrin receptor deleted in colorectal cancer (DCC) is a potential receptor for NTN5 in MNs, as similar ectopic neurons were found in Dcc mutant mice, but not in mice deficient for other netrin receptors. Thus, Ntn5 is a novel netrin family member that is expressed in BCC, functioning to prevent MN migration out of the CNS. PMID:26858598

Transgene Reactivation in Induced Pluripotent Stem Cell Derivatives and Reversion to Pluripotency of Induced Pluripotent Stem Cell-Derived Mesenchymal Stem Cells

PubMed Central

Galat, Yekaterina; Perepitchka, Mariana; Jennings, Lawrence J.; Iannaccone, Philip M.; Hendrix, Mary J.C.

2016-01-01

Induced pluripotent stem cells (iPSCs) have enormous potential in regenerative medicine and disease modeling. It is now felt that clinical trials should be performed with iPSCs derived with nonintegrative constructs. Numerous studies, however, including those describing disease models, are still being published using cells derived from iPSCs generated with integrative constructs. Our experimental work presents the first evidence of spontaneous transgene reactivation in vitro in several cellular types. Our results show that the transgenes were predominantly silent in parent iPSCs, but in mesenchymal and endothelial iPSC derivatives, the transgenes experienced random upregulation of Nanog and c-Myc. Additionally, we provide evidence of spontaneous secondary reprogramming and reversion to pluripotency in mesenchymal stem cells derived from iPSCs. These findings strongly suggest that the studies, which use cellular products derived from iPSCs generated with retro- or lentiviruses, should be evaluated with consideration of the possibility of transgene reactivation. The in vitro model described here provides insight into the earliest events of culture transformation and suggests the hypothesis that reversion to pluripotency may be responsible for the development of tumors in cell replacement experiments. The main goal of this work, however, is to communicate the possibility of transgene reactivation in retro- or lenti-iPSC derivatives and the associated loss of cellular fidelity in vitro, which may impact the outcomes of disease modeling and related experimentation. PMID:27193052

[Refractive precision and objective quality of vision after toric lens implantation in cataract surgery].

PubMed

Debois, A; Nochez, Y; Bezo, C; Bellicaud, D; Pisella, P-J

2012-10-01

To study efficacy and predictability of toric IOL implantation for correction of preoperative corneal astigmatism by analysing spherocylindrical refractive precision and objective quality of vision. Prospective study of 13 eyes undergoing micro-incisional cataract surgery through a 1.8mm corneal incision with toric IOL implantation (Lentis L313T(®), Oculentis) to treat over one D of preoperative corneal astigmatism. Preoperative evaluation included keratometry, subjective refraction, and total and corneal aberrometry (KR-1(®), Topcon). Six months postoperatively, measurements included slit lamp photography, documenting IOL rotation, tilt or decentration, uncorrected visual acuity, best-corrected visual acuity and objective quality of vision measurement (OQAS(®) Visiometrics, Spain). Postoperatively, mean uncorrected distance visual acuity was 8.33/10 ± 1.91 (0.09 ± 0.11 LogMar). Mean postoperative refractive sphere was 0.13 ± 0.73 diopters. Mean refractive astigmatism was -0.66 ± 0.56 diopters with corneal astigmatism of 2.17 ± 0.68 diopters. Mean IOL rotation was 4.4° ± 3.6° (range 0° to 10°). Mean rotation of this IOL at 6 months was less than 5°, demonstrating stability of the optic within the capsular bag. Objective quality of vision measurements were consistent with subjective uncorrected visual acuity. Implantation of the L313T(®) IOL is safe and effective for correction of corneal astigmatism in 1.8mm micro-incisional cataract surgery. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Influence of Near-Segment Positioning in a Rotationally Asymmetric Multifocal Intraocular Lens.

PubMed

Song, In Seok; Yoon, Sam Young; Kim, Jae Yong; Kim, Myoung Joon; Tchah, Hungwon

2016-04-01

To compare visual performance and higher order aberrations (HOAs) based on the position of the near segment in eyes with rotationally asymmetric multifocal intraocular lenses (IOLs). Asymmetric multifocal IOLs (Lentis Mplus LS-313; Oculentis Optikgeräte GmbH, Wetzlar, Germany) were implanted with the near segment positioned either inferiorly, superiorly, or temporally. Uncorrected distance (UDVA), intermediate (UIVA), and near (UNVA) visual acuity, corrected distance visual acuity (CDVA), and distance-corrected intermediate (DCIVA) and near (DCNVA) visual acuity, contrast sensitivity, HOAs, and subjective symptom questionnaires were compared at 1 month postoperatively. Forty-five eyes from 45 patients were evaluated (n = 25, 9, and 11 eyes in the inferior, superior, and temporal groups, respectively). No significant differences in UDVA, UIVA, UNVA, CDVA, DCIVA, or DCNVA were found between the three groups (P > .05). The temporal group showed the best results in UDVA, CDVA, and DCNVA, but the inferior group showed the best results in DCIVA and UNVA and the superior group showed the best results in UIVA. Contrast sensitivity and the subjective symptom questionnaire also did not demonstrate any significant differences (P > .05). Total HOA and spherical aberration did not demonstrate any statistically significant differences (P > .05), but vertical coma and horizontal coma demonstrated significant differences based on near segment position (P < .001). The position of the near segment in eyes with rotationally asymmetric multifocal IOLs demonstrates no significant effect on visual performance. Copyright 2016, SLACK Incorporated.

Lentiviral gene ontology (LeGO) vectors equipped with novel drug-selectable fluorescent proteins: new building blocks for cell marking and multi-gene analysis.

PubMed

Weber, K; Mock, U; Petrowitz, B; Bartsch, U; Fehse, B

2010-04-01

Vector-encoded fluorescent proteins (FPs) facilitate unambiguous identification or sorting of gene-modified cells by fluorescence-activated cell sorting (FACS). Exploiting this feature, we have recently developed lentiviral gene ontology (LeGO) vectors (www.LentiGO-Vectors.de) for multi-gene analysis in different target cells. In this study, we extend the LeGO principle by introducing 10 different drug-selectable FPs created by fusing one of the five selection marker (protecting against blasticidin, hygromycin, neomycin, puromycin and zeocin) and one of the five FP genes (Cerulean, eGFP, Venus, dTomato and mCherry). All tested fusion proteins allowed both fluorescence-mediated detection and drug-mediated selection of LeGO-transduced cells. Newly generated codon-optimized hygromycin- and neomycin-resistance genes showed improved expression as compared with their ancestors. New LeGO constructs were produced at titers >10(6) per ml (for non-concentrated supernatants). We show efficient combinatorial marking and selection of various cells, including mesenchymal stem cells, simultaneously transduced with different LeGO constructs. Inclusion of the cytomegalovirus early enhancer/chicken beta-actin promoter into LeGO vectors facilitated robust transgene expression in and selection of neural stem cells and their differentiated progeny. We suppose that the new drug-selectable markers combining advantages of FACS and drug selection are well suited for numerous applications and vector systems. Their inclusion into LeGO vectors opens new possibilities for (stem) cell tracking and functional multi-gene analysis.

In Vitro Aberrometric Assessment of a Multifocal Intraocular Lens and Two Extended Depth of Focus IOLs

PubMed Central

Tolosa, Angel; de Fez, Dolores; Caballero, María T.; Miret, Juan J.

2017-01-01

Purpose To analyze the “in vitro” aberrometric pattern of a refractive IOL and two extended depth of focus IOLs. Methods A special optical bench with a Shack-Hartmann wavefront sensor (SH) was designed for the measurement. Three presbyopia correction IOLs were analyzed: Mini WELL (MW), TECNIS Symfony ZXR00 (SYM), and Lentis Mplus X LS-313 MF30 (MP). Three different pupil sizes were used for the comparison: 3, 4, and 4.7 mm. Results MW generated negative primary and positive secondary spherical aberrations (SA) for the apertures of 3 mm (−0.13 and +0.12 μm), 4 mm (−0.12 and +0.08 μm), and 4.7 mm (−0.11 and +0.08 μm), while the SYM only generated negative primary SA for 4 and 4.7 mm apertures (−0.12 μm and −0.20 μm, resp.). The MP induced coma and trefoil for all pupils and showed significant HOAs for apertures of 4 and 4.7 mm. Conclusions In an optical bench, the MW induces negative primary and positive secondary SA for all pupils. The SYM aberrations seem to be pupil dependent; it does not produce negative primary SA for 3 mm but increases for higher pupils. Meanwhile, the HOAs for the MW and SYM were not significant. The MP showed in all cases the highest HOAs. PMID:29318040

In Vitro Aberrometric Assessment of a Multifocal Intraocular Lens and Two Extended Depth of Focus IOLs.

PubMed

Camps, Vicente J; Tolosa, Angel; Piñero, David P; de Fez, Dolores; Caballero, María T; Miret, Juan J

2017-01-01

To analyze the "in vitro" aberrometric pattern of a refractive IOL and two extended depth of focus IOLs. A special optical bench with a Shack-Hartmann wavefront sensor (SH) was designed for the measurement. Three presbyopia correction IOLs were analyzed: Mini WELL (MW), TECNIS Symfony ZXR00 (SYM), and Lentis Mplus X LS-313 MF30 (MP). Three different pupil sizes were used for the comparison: 3, 4, and 4.7 mm. MW generated negative primary and positive secondary spherical aberrations (SA) for the apertures of 3 mm (-0.13 and +0.12  μ m), 4 mm (-0.12 and +0.08  μ m), and 4.7 mm (-0.11 and +0.08  μ m), while the SYM only generated negative primary SA for 4 and 4.7 mm apertures (-0.12  μ m and -0.20  μ m, resp.). The MP induced coma and trefoil for all pupils and showed significant HOAs for apertures of 4 and 4.7 mm. In an optical bench, the MW induces negative primary and positive secondary SA for all pupils. The SYM aberrations seem to be pupil dependent; it does not produce negative primary SA for 3 mm but increases for higher pupils. Meanwhile, the HOAs for the MW and SYM were not significant. The MP showed in all cases the highest HOAs.

The influence of habitat fragmentation on helminth communities in rodent populations from a Brazilian Mountain Atlantic Forest.

PubMed

Cardoso, T S; Simões, R O; Luque, J L F; Maldonado, A; Gentile, R

2016-07-01

The influence of habitat structure on helminth communities of three sigomdontinae rodent species (Akodon cursor, A. montensis and Oligoryzomys nigripes) was investigated in forest fragments within an agricultural landscape in south-eastern Brazil. This is a pionner study correlating the occurrence of helminth species of rodent hosts with microhabitat characteristics. Rodents were collected from 12 fragments and in a continuous conserved area. Up to 13 nematode, three cestode and two trematode species were identified, and habitat fragmentation was found to have more influence on the helminth composition of O. nigripes compared to the other two rodent species. Fragmentation appeared to limit the development of some helminths' life cycles, e.g. with some species such as Trichofreitasia lenti, Protospirura numidica, Cysticercus fasciolaris and Avellaria sp., occurring mostly in areas with less anthropic impact. However, fragmentation did not seem to affect the life cycles of other dominant helminths, such as the trematode Canaania obesa, the nematodes Stilestrongylus lanfrediae, S. eta and S. aculeata, and the cestode Rodentolepis akodontis. The helminth community structure followed a nested pattern of distribution in A. montensis and O. nigripes. Stilestrongylus lanfrediae seemed to be more associated with dense understorey, C. obesa with open canopy and dense understorey, and Guerrerostrongylus zetta with organic matter on the ground. Their presence in each area may be explained by aspects of their life cycles that take place in the external environment outside the host.

Novel Lethal Form of Congenital Hypopituitarism Associated With the First Recessive LHX4 Mutation

PubMed Central

Gregory, L. C.; Humayun, K. N.; Turton, J. P. G.; McCabe, M. J.; Rhodes, S. J.

2015-01-01

Background: LHX4 encodes a member of the LIM-homeodomain family of transcription factors that is required for normal development of the pituitary gland. To date, only incompletely penetrant heterozygous mutations in LHX4 have been described in patients with variable combined pituitary hormone deficiencies. Objective/Hypothesis: To report a unique family with a novel recessive variant in LHX4 associated with a lethal form of congenital hypopituitarism that was identified through screening a total of 97 patients. Method: We screened 97 unrelated patients with combined pituitary hormone deficiency, including 65% with an ectopic posterior pituitary, for variants in the LHX4 gene using Sanger sequencing. Control databases (1000 Genomes, dbSNP, Exome Variant Server, ExAC Browser) were consulted upon identification of variants. Results: We identified the first novel homozygous missense variant (c.377C>T, p.T126M) in two deceased male patients of Pakistani origin with severe panhypopituitarism associated with anterior pituitary aplasia and posterior pituitary ectopia. Both were born small for gestational age with a small phallus, undescended testes, and mid-facial hypoplasia. The parents' first-born child was a female with mid-facial hypoplasia (DNA was unavailable). Despite rapid commencement of hydrocortisone and T4 in the brothers, all three children died within the first week of life. The LHX4(p.T126M) variant is located within the LIM2 domain, in a highly conserved location. The absence of homozygosity for the variant in over 65 000 controls suggests that it is likely to be responsible for the phenotype. Conclusion: We report, for the first time to our knowledge, a novel homozygous mutation in LHX4 associated with a lethal phenotype, implying that recessive mutations in LHX4 may be incompatible with life. PMID:25871839

A Novel Rasopathy Caused by Recurrent De Novo Missense Mutations In PPP1CB Closely Resembles Noonan Syndrome with Loose Anagen Hair

PubMed Central

Gripp, Karen W.; Aldinger, Kimberly A.; Bennett, James T.; Baker, Laura; Tusi, Jessica; Powell-Hamilton, Nina; Stabley, Deborah; Sol-Church, Katia; Timms, Andrew E.; Dobyns, William B.

2016-01-01

Noonan syndrome is a rasopathy caused by mutations in multiple genes encoding components of the RAS/MAPK pathway. Despite its variable phenotype, limited genotype-phenotype correlations exist. Noonan syndrome with loose anagen hair (NS-LAH) is characterized by its distinctive hair anomalies, developmental differences and structural brain abnormalities and is caused by a single recurrent missense SHOC2 mutation. SHOC2 forms a complex with protein phosphatase 1 (PP1C). Protein phosphatases counterbalance kinases and control activation of signaling proteins, such as the mitogen activated protein kinases of the RAS/MAPK pathway. Here we report four patients with de novo missense mutations in protein phosphatase 1 catalytic subunit beta (PPP1CB), sharing a recognizable phenotype. Three individuals had the recurrent PPP1CB c.146G>C, p.Pro49Arg mutation, the fourth had a c.166G>C, p.Ala56Pro change. All had relative or absolute macrocephaly, low-set and posteriorly angulated ears and developmental delay. Slow growing and/or sparse hair and/or an unruly hair texture was present in all. Three individuals had feeding difficulties requiring feeding tubes. One of two males had cryptorchidism, another had pectus excavatum. Short stature was present in three. A female with the recurrent mutation had a Dandy-Walker malformation and optic nerve hypoplasia. Mild ventriculomegaly occurred in all, cerebellar tonsillar ectopia was seen in two and progressed to Chiari 1 malformation in one individual. Based on the combination of phenotypic findings and PPP1CB’s effect on RAF dephosphorylation within the RAS/MAPK pathway, this novel condition can be considered a rasopathy, most similar to NS-LAH. Collectively, these mutations meet the standardized criteria for pathogenicity. PMID:27264673

Clinical characteristics of children with severe visual impairment but favorable retinal structural outcomes from the Early Treatment for Retinopathy of Prematurity (ETROP) study.

PubMed

Siatkowski, R Michael; Good, William V; Summers, C Gail; Quinn, Graham E; Tung, Betty

2013-04-01

To describe visual function and associated characteristics at the 6-year examination in children enrolled in the Early Treatment for Retinopathy of Prematurity Study who had unfavorable visual outcomes despite favorable structural outcomes in one or both eyes. The clinical examination records of children completing the 6-year follow-up examination were retrospectively reviewed. Eligible subjects were those with visual acuity of ≤20/200 in each eye (where recordable) and a normal fundus or straightening of the temporal retinal vessels with or without macular ectopia in at least one eye. Data regarding visual function, retinal structure, presence of nystagmus, optic atrophy, optic disk cupping, seizures/shunts, and Functional Independence Measure for Children (ie, WeeFIM: pediatric functional independence measure) developmental test scores were reviewed. Of 342 participants who completed the 6-year examination, 39 (11%) met inclusion criteria. Of these, 29 (74%) had normal retinal structure, 18 (46%) had optic atrophy, and 3 (8%) had increased cupping of the optic disk in at least one eye. Latent and/or manifest nystagmus occurred in 30 children (77%). The presence of nystagmus was not related to the presence of optic atrophy. Of the 39 children, 28 (72%) had a below-normal WeeFIM score. In 25 participants (7%) completing the 6-year examination, cortical visual impairment was considered the primary cause of visual loss. The remainder likely had components of both anterior and posterior visual pathway disease. Clinical synthesis of ocular anatomy and visual and neurologic function is required to determine the etiology of poor vision in these children. Copyright © 2013 American Association for Pediatric Ophthalmology and Strabismus. Published by Mosby, Inc. All rights reserved.

Expanding the SHOC2 mutation associated phenotype of Noonan syndrome with loose anagen hair: structural brain anomalies and myelofibrosis.

PubMed

Gripp, Karen W; Zand, Dina J; Demmer, Laurie; Anderson, Carol E; Dobyns, William B; Zackai, Elaine H; Denenberg, Elizabeth; Jenny, Kim; Stabley, Deborah L; Sol-Church, Katia

2013-10-01

Noonan syndrome is a heterogenous rasopathy typically presenting with short stature, characteristic facial features, cardiac abnormalities including pulmonic valve stenosis, ASD and hypertrophic cardiomyopathy (HCM), cryptorchidism, ectodermal abnormalities, and learning differences. The phenotype is variable, and limited genotype phenotype correlation exists with SOS1 mutations often associated with normal cognition and stature, RAF1 mutations entailing a high HCM risk, and certain PTPN11 mutations predisposing to juvenile myelomonocytic leukemia. The recently identified SHOC2 mutation (p.Ser2Gly) causes Noonan syndrome with loose anagen hair. We report five patients with this mutation. All had skin hyperpigmentation, sparse light colored hair, increased fine wrinkles, ligamentous laxity, developmental delay, and 4/4 had a structural cardiac anomaly. Hypotonia and macrocephaly occurred in 4/5 (80%); 3/5 (60%) had polyhydramnios, increased birth weight or required use of a feeding tube. Distinctive brain abnormalities included relative megalencephaly and enlarged subarachnoid spaces suggestive of benign external hydrocephalus, and a relatively small posterior fossa as indicated by a vertical tentorium. The combination of a large brain with a small posterior fossa likely resulted in the high rate of cerebellar tonsillar ectopia (3/4; 75%). Periventricular nodular heterotopia was seen in one patient with a thick and dysplastic corpus callosum. We report on the first hematologic neoplasm, myelofibrosis, in a 2-year-old patient with SHOC2 mutation. Myelofibrosis is exceedingly rare in children and young adults. The absence of a somatic JAK2 mutation, seen in the majority of patients with myelofibrosis, is noteworthy as it suggests that germline or somatic SHOC2 mutations are causally involved in myelofibrosis. Copyright © 2013 Wiley Periodicals, Inc.

Use of a percutaneously controlled hydraulic occluder for treatment of refractory urinary incontinence in three female cats.

PubMed

Wilson, Kendall E; Berent, Allyson C; Weisse, Chick W

2016-03-01

CASE DESCRIPTION 3 cats were referred for evaluation of chronic urinary incontinence. CLINICAL FINDINGS A presumptive diagnosis of urethral sphincter mechanism incompetence (USMI) was made in all 3 cats. Preoperatively, incontinence was mild in 1 cat (incontinence during sleep) and moderate to severe (incontinence while awake and at rest) in 2. Structural abnormalities noted during cystoscopy included urethrovestibular junction stenosis (n = 1), vaginal stenosis (1), short urethra (1), and intrapelvic bladder (1). TREATMENT AND OUTCOME All 3 cats were treated by means of implantation of an inflatable silicone hydraulic occluder (HO) via a ventral midline celiotomy. Immediately prior to HO implantation, patients underwent cystoscopy to detect any anatomic abnormalities and confirm the absence of ureteral ectopia. Following surgery, all 3 patients attained complete continence, needing 0 or 1 inflation of the device. Complications included cystoscopy-associated urethral tear (n = 1), constipation (1), stranguria (1), hematuria (2), and urinary tract infection (2). Device explantation was performed 14 weeks after surgery in 1 cat because of postoperative constipation. Constipation persisted and urinary incontinence recurred but was markedly improved following device removal in this cat (leakage of urine only when sleeping at follow-up 29 months after surgery [26 months after device explantation]). At the time of last follow-up, 2 of the 3 cats remained fully continent approximately 3 and 6 years after device implantation. CLINICAL RELEVANCE Findings suggested that implantation of an HO may be a safe and effective long-term treatment for some cats with USMI. Further studies are necessary to evaluate the potential for treatment-related complications and the long-term outcome.

Acute Presentation of Chiari I Malformation with Hemiparesis in a Pediatric Patient.

PubMed

Miranda, Stephen P; Kimmell, Kristopher T; Silberstein, Howard J

2016-01-01

Chiari I malformation (CM-I) is defined by cerebellar tonsillar herniation through the foramen magnum. Patients typically present with chronic complaints, including headache, dizziness, and numbness, although there are few reports in the literature of pediatric patients presenting acutely with neurological deficit caused by CM-I. We report a child who presented acutely with hemiparesis and magnetic resonance imaging findings consistent with CM-I and spinal cord edema. A 3-year old boy with normal development presented with difficulty walking and increased drooling. His mother stated he was running into objects and had balance issues for several days. Neurological examination showed ataxia with falling to the right after a few steps and weakness of the right arm and leg. His medical history was remarkable only for mild asthma, although he had recently been treated for an upper respiratory viral infection. Computed tomography of the head demonstrated no brainstem mass. Magnetic resonance imaging of the head and cervical spine showed tonsillar ectopia approximately 2 cm below the craniocervical junction with increased T2 signal in the spinal cord from C1 to C3 consistent with syringomyelia and cord edema. The patient underwent suboccipital craniectomy with removal of the posterior arch of C1 and dural patch graft. His postoperative course was unremarkable, with complete resolution of his symptoms at his 1-month follow-up visit. This case highlights an unusual presentation of CM-I with neurological deficit related to spinal cord edema, possibly precipitated by the "water-hammer" effect of this patient's coughing fits. Providers should be aware of the acute presentations of CM-I. Copyright © 2016 Elsevier Inc. All rights reserved.

Differential expression of endothelial nutrient transporters (MCT1 and GLUT1) in the developing eyes of mice.

PubMed

Kishimoto, Ayuko; Takahashi-Iwanaga, Hiromi; Watanabe M, Masahiko; Iwanaga, Toshihiko

2016-12-01

The blood-brain barrier in the neonatal brain expresses the monocarboxylate transporter (MCT)-1 rather than the glucose transporter (GLUT)-1, due to the special energy supply during the suckling period. The hyaloid vascular system, consisting of the vasa hyaloidea propria and tunica vasculosa lentis, is a temporary vasculature present only during the early development of mammalian eyes and later regresses. Although the ocular vasculature manifests such a unique developmental process, no information is available concerning the expression of endothelial nutrient transporters in the developing eye. The present immunohistochemical study using whole mount preparations of murine eyes found that the hyaloid vascular system predominantly expressed GLUT1 in the endothelium, in contrast to the brain endothelium. Characteristically, the endothelium in peripheral regions of the neonatal hyaloid vessels displayed a mosaic pattern of MCT1-immunoreactive cells scattered within the GLUT1-expressing endothelium. The proper retinal vessels first developed by sprouting angiogenesis endowed with filopodia, which were absolutely free from the immunoreactivities of GLUT1 and MCT1. The remodeling retinal capillary networks and veins in the surface layer of the retina mainly expressed MCT1 until the weaning period. Immunostaining of MCT1 in the retina revealed fine radicular processes projecting from the endothelium, differing from the MCT1-immunonegative filopodia. These findings suggest that the expression of nutrient transporters in the ocular blood vessels is differentially regulated at a cellular level and that the neonatal eyes provide an interesting model for research on nutrient transporters in the endothelium. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comparison of the visual and intraocular optical performance of a refractive multifocal IOL with rotational asymmetry and an apodized diffractive multifocal IOL.

PubMed

Alió, Jorge L; Plaza-Puche, Ana B; Javaloy, Jaime; Ayala, María José

2012-02-01

To compare the visual outcomes and intraocular optical quality observed postoperatively in patients implanted with a rotationally asymmetric multifocal intraocular lens (IOL) and an apodized diffractive multifocal IOL. Seventy-four consecutive eyes of 40 cataract patients (age range: 36 to 79 years) were divided into two groups: zonal refractive group, 39 eyes implanted with a rotationally asymmetric multifocal IOL (Lentis Mplus LS-312 IOL, Oculentis GmbH); and diffractive group, 35 eyes implanted with an apodized diffractive multifocal IOL (ReSTOR SN6AD3, Alcon Laboratories Inc). Distance and near visual acuity outcomes, contrast sensitivity, intraocular optical quality, and defocus curves were evaluated during 3-month follow-up. Calculation of the intraocular aberrations was performed by subtracting corneal aberrations from total ocular aberrations. Uncorrected near visual acuity and distance-corrected near visual acuity were better in the diffractive group than in the zonal refractive group (P=.01), whereas intermediate visual acuity (defocus +1.00 and +1.50 diopters) was better in the zonal refractive group. Photopic contrast sensitivity was significantly better in the zonal refractive group (P=.04). Wavefront aberrations (total, higher order, tilt, primary coma) were significantly higher in the zonal refractive group than in the diffractive group (P=.02). Both multifocal IOLs are able to successfully restore visual function after cataract surgery. The zonal refractive multifocal IOL provides better results in contrast sensitivity and intermediate vision, whereas the diffractive multifocal IOL provides better near vision at a closer distance. Copyright 2012, SLACK Incorporated.

Coinfection of Ugandan Red Colobus (Procolobus [Piliocolobus] rufomitratus tephrosceles) with Novel, Divergent Delta-, Lenti-, and Spumaretroviruses ▿

PubMed Central

Goldberg, Tony L.; Sintasath, David M.; Chapman, Colin A.; Cameron, Kenneth M.; Karesh, William B.; Tang, Shaohua; Wolfe, Nathan D.; Rwego, Innocent B.; Ting, Nelson; Switzer, William M.

2009-01-01

Nonhuman primates host a plethora of potentially zoonotic microbes, with simian retroviruses receiving heightened attention due to their roles in the origins of human immunodeficiency viruses type 1 (HIV-1) and HIV-2. However, incomplete taxonomic and geographic sampling of potential hosts, especially the African colobines, has left the full range of primate retrovirus diversity unexplored. Blood samples collected from 31 wild-living red colobus monkeys (Procolobus [Piliocolobus] rufomitratus tephrosceles) from Kibale National Park, Uganda, were tested for antibodies to simian immunodeficiency virus (SIV), simian T-cell lymphotrophic virus (STLV), and simian foamy virus (SFV) and for nucleic acids of these same viruses using genus-specific PCRs. Of 31 red colobus tested, 22.6% were seroreactive to SIV, 6.4% were seroreactive to STLV, and 97% were seroreactive to SFV. Phylogenetic analyses of SIV polymerase (pol), STLV tax and long terminal repeat (LTR), and SFV pol and LTR sequences revealed unique SIV and SFV strains and a novel STLV lineage, each divergent from corresponding retroviral lineages previously described in Western red colobus (Procolobus badius badius) or black-and-white colobus (Colobus guereza). Phylogenetic analyses of host mitochondrial DNA sequences revealed that red colobus populations in East and West Africa diverged from one another approximately 4.25 million years ago. These results indicate that geographic subdivisions within the red colobus taxonomic complex exert a strong influence on retroviral phylogeny and that studying retroviral diversity in closely related primate taxa should be particularly informative for understanding host-virus coevolution. PMID:19692478

Exploring the optimum step size for defocus curves.

PubMed

Wolffsohn, James S; Jinabhai, Amit N; Kingsnorth, Alec; Sheppard, Amy L; Naroo, Shehzad A; Shah, Sunil; Buckhurst, Phillip; Hall, Lee A; Young, Graeme

2013-06-01

To evaluate the effect of reducing the number of visual acuity measurements made in a defocus curve on the quality of data quantified. Midland Eye, Solihull, United Kingdom. Evaluation of a technique. Defocus curves were constructed by measuring visual acuity on a distance logMAR letter chart, randomizing the test letters between lens presentations. The lens powers evaluated ranged between +1.50 diopters (D) and -5.00 D in 0.50 D steps, which were also presented in a randomized order. Defocus curves were measured binocularly with the Tecnis diffractive, Rezoom refractive, Lentis rotationally asymmetric segmented (+3.00 D addition [add]), and Finevision trifocal multifocal intraocular lenses (IOLs) implanted bilaterally, and also for the diffractive IOL and refractive or rotationally asymmetric segmented (+3.00 D and +1.50 D adds) multifocal IOLs implanted contralaterally. Relative and absolute range of clear-focus metrics and area metrics were calculated for curves fitted using 0.50 D, 1.00 D, and 1.50 D steps and a near add-specific profile (ie, distance, half the near add, and the full near-add powers). A significant difference in simulated results was found in at least 1 of the relative or absolute range of clear-focus or area metrics for each of the multifocal designs examined when the defocus-curve step size was increased (P<.05). Faster methods of capturing defocus curves from multifocal IOL designs appear to distort the metric results and are therefore not valid. No author has a financial or proprietary interest in any material or method mentioned. Copyright © 2013 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

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

Baker, Anna D.; Malur, Anagha; Barna, Barbara P.

Peroxisome proliferator-activated receptor-gamma (PPAR{gamma}) is a nuclear transcription factor involved in lipid metabolism that is constitutively expressed in the alveolar macrophages of healthy individuals. PPAR{gamma} has recently been implicated in the catabolism of surfactant by alveolar macrophages, specifically the cholesterol component of surfactant while the mechanism remains unclear. Studies from other tissue macrophages have shown that PPAR{gamma} regulates cholesterol influx, efflux, and metabolism. PPAR{gamma} promotes cholesterol efflux through the liver X receptor-alpha (LXR{alpha}) and ATP-binding cassette G1 (ABCG1). We have recently shown that macrophage-specific PPAR{gamma} knockout (PPAR{gamma} KO) mice accumulate cholesterol-laden alveolar macrophages that exhibit decreased expression of LXR{alpha} andmore » ABCG1 and reduced cholesterol efflux. We hypothesized that in addition to the dysregulation of these cholesterol efflux genes, the expression of genes involved in cholesterol synthesis and influx was also dysregulated and that replacement of PPAR{gamma} would restore regulation of these genes. To investigate this hypothesis, we have utilized a Lentivirus expression system (Lenti-PPAR{gamma}) to restore PPAR{gamma} expression in the alveolar macrophages of PPAR{gamma} KO mice. Our results show that the alveolar macrophages of PPAR{gamma} KO mice have decreased expression of key cholesterol synthesis genes and increased expression of cholesterol receptors CD36 and scavenger receptor A-I (SRA-I). The replacement of PPAR{gamma} (1) induced transcription of LXR{alpha} and ABCG1; (2) corrected suppressed expression of cholesterol synthesis genes; and (3) enhanced the expression of scavenger receptors CD36. These results suggest that PPAR{gamma} regulates cholesterol metabolism in alveolar macrophages.« less

Analysis of sandflies (Diptera: Psychodidae) in Barra do Garças, State of Mato Grosso, Brazil, and the influence of environmental variables on the vector density of Lutzomyia longipalpis (Lutz & Neiva, 1912).

PubMed

Queiroz, Mirian Francisca Martins; Varjão, Jane Ramos; Moraes, Sinara Cristina de; Salcedo, Gladys Elena

2012-06-01

Leishmaniasis is an infectious and parasitic zoonotic, non-contagious, vector-borne disease caused by protozoa of the genus Leishmania. In Brazil, the major vector of Leishmania (Leishmania) infantum chagasi (Cunha & Chagas, 1934) is Lutzomyia longipalpis. Barra do Garças, State of Mato Grosso, was designated as a priority area by the Brazilian Ministry of Health for american visceral leishmaniasis, and it is important to identify the vector species present in this municipality. Our objective was to raise sandflies and study the influence of environmental variables on the vector density of Lutzomyia longipalpis. We performed entomological monitoring in 3 districts using Centers for Disease Control and Prevention (CDC) light traps and recorded human cases of american visceral leishmaniasis in the city. We calculated the relative frequency and richness of sandflies and applied a transfer function model to the vector density correlate with relative humidity. The sandfly population was composed of 2 genera and 27 species, totaling 8,097 individuals. Monitoring identified Lutzomyia longipalpis (44%), followed by Lutzomyia lenti (18.9%), Lutzomyia whitmani (13.9%), Lutzomyia carmelinoi (9.1%), Lutzomyia evandroi (5.1%), Lutzomyia termitophila (3.3%), Lutzomyia sordellii (1.9%), and 20 other species (<4%). The male:female ratio was 3.5:1. We observed high species diversity (Dα = 6.65). Lutzomyia longipalpis showed occurrence peaks during the rainy season; there was a temporal correlation with humidity, but not with frequency or temperature. The presence of Lutzomyia longipalpis in the urban area of Barra do Garças underscores the changing disease profile, which was previously restricted to the wild environment.

Progression and timing of treatment of zone I retinopathy of prematurity.

PubMed

Soh, Yuka; Fujino, Takahiro; Hatsukawa, Yoshikazu

2008-09-01

To clarify the progression of zone I retinopathy of prematurity (ROP) and elucidate the most suitable time and method of treatment. Interventional case series. Forty-six eyes of 23 zone I ROP infants were studied at a single institution. Birth weight ranged from 448 to 954 g, and gestational age ranged from 22 to 26 weeks. Fundus examination was started at 29 or 30 weeks postmenstrual age and was performed once or more per week. The first treatment was performed using laser photocoagulation or cryotherapy when zone I ROP progressed to the following criteria. Treatment criteria A included 35 eyes of 18 cases of zone I any stage ROP with plus disease (Early Treatment for Retinopathy of Prematurity [ETROP] type 1), criteria B included five eyes of three cases of zone I stage 3 ROP with or without plus disease (ETROP type 1), criteria C included six eyes of four cases of stage 1 or stage 2 ROP without plus disease; the demarcation lines belonged, in large part, within the zone I area. Hazy media such as corneal opacity, miotic pupil, tunica vasculosa lentis, and hazy vitreous persisted until approximately 32 weeks postmenstrual age. The mean period between stage 1 and stage 3 mild was one week, that between stage 1 and stage 3 moderate was 1.7 weeks, and that between stage 1 and stage 3 severe was 1.3 weeks. The period between stage 1 and the first treatment was zero to 20 days, and 60.9% of all the cases were treated within 10 days after stage 1. Six of 46 eyes had unfavorable outcomes. Surgical results of our treatment were comparable or better than those of other reports. Immediate treatment was required when zone I ROP was diagnosed behind persistent hazy media.

Simultaneous correction of post-traumatic aphakia and aniridia with the use of artificial iris and IOL implantation.

PubMed

Forlini, Cesare; Forlini, Matteo; Rejdak, Robert; Prokopiuk, Agata; Levkina, Oxana; Bratu, Adriana; Rossini, Paolo; Cagampang, Perfecto R; Cavallini, Gian Maria

2013-03-01

Combined post-traumatic aniridia and aphakia demand extensive and complex reconstructive surgery. We present our approach for simultaneous correction of this surgical situation with the use of the ArtificialIris (Dr. Schmidt Intraocularlinsen GmbH, Germany) with a foldable acrylic IOL Lentis L-313 (Oculentis, GmbH, Germany) sutured to its surface. The novelty (our first operation was on June 2010) of this surgical technique is based on the combined use of foldable (with closed haptics) IOL and Artificialiris to correct post-traumatic aniridia and aphakia. Four consecutive cases of combined post-traumatic lesions of iris and lens, corrected with complex device ArtificialIris and foldable IOL. In two cases, the compound implant was sutured to the sclera in sulcus during the penetrating keratoplasty; in another case, it was positioned through a corneal incision of about 5.0 mm with transscleral fixation, and in one patient with preserved capsular support and possibility of IOL in-the-bag implantation the ArtificialIris was placed in sulcus sutureless through a clear corneal tunnel. Maximal follow-up was 6 months. The complex device was placed firmly fixed within the sulcus, including in the eye implanted without sutures, and showed a stable and centered position without any tilt or torque. Management of post-traumatic aniridia combined with aphakia by haptic fixation of a foldable acrylic IOL on a foldable iris prosthesis appears to be a promising approach which gives the surgeon the possibility to correct a complex lesion with one procedure, which is less traumatic and faster. Existence of foldable materials, both iris and IOL, permits relatively small corneal incisions (4.0-5.0 mm). Moreover, the custom-tailored iris prosthesis gives a perfect aesthetic result.

Piggyback intraocular lens implantation to correct pseudophakic refractive error after segmental multifocal intraocular lens implantation.

PubMed

Venter, Jan A; Oberholster, Andre; Schallhorn, Steven C; Pelouskova, Martina

2014-04-01

To evaluate refractive and visual outcomes of secondary piggyback intraocular lens implantation in patients diagnosed as having residual ametropia following segmental multifocal lens implantation. Data of 80 pseudophakic eyes with ametropia that underwent Sulcoflex aspheric 653L intraocular lens implantation (Rayner Intraocular Lenses Ltd., East Sussex, United Kingdom) to correct residual refractive error were analyzed. All eyes previously had in-the-bag zonal refractive multifocal intraocular lens implantation (Lentis Mplus MF30, models LS-312 and LS-313; Oculentis GmbH, Berlin, Germany) and required residual refractive error correction. Outcome measurements included uncorrected distance visual acuity, corrected distance visual acuity, uncorrected near visual acuity, distance-corrected near visual acuity, manifest refraction, and complications. One-year data are presented in this study. The mean spherical equivalent ranged from -1.75 to +3.25 diopters (D) preoperatively (mean: +0.58 ± 1.15 D) and reduced to -1.25 to +0.50 D (mean: -0.14 ± 0.28 D; P < .01). Postoperatively, 93.8% of eyes were within ±0.50 D and 98.8% were within ±1.00 D of emmetropia. The mean uncorrected distance visual acuity improved significantly from 0.28 ± 0.16 to 0.01 ± 0.10 logMAR and 78.8% of eyes achieved 6/6 (Snellen 20/20) or better postoperatively. The mean uncorrected near visual acuity changed from 0.43 ± 0.28 to 0.19 ± 0.15 logMAR. There was no significant change in corrected distance visual acuity or distance-corrected near visual acuity. No serious intraoperative or postoperative complications requiring secondary intraocular lens removal occurred. Sulcoflex lenses proved to be a predictable and safe option for correcting residual refractive error in patients diagnosed as having pseudophakia. Copyright 2014, SLACK Incorporated.

Quality of vision, patient satisfaction and long-term visual function after bilateral implantation of a low addition multifocal intraocular lens.

PubMed

Pedrotti, Emilio; Mastropasqua, Rodolfo; Bonetto, Jacopo; Demasi, Christian; Aiello, Francesco; Nucci, Carlo; Mariotti, Cesare; Marchini, Giorgio

2017-07-17

The aim of the current study was to compare the quality of vision, contrast sensitivity and patient satisfaction with a biaspheric, segmented, rotationally asymmetric IOL (Lentis Comfort LS-313 MF 15-Oculentis GmbH, Berlin, Germany) as opposed to those of a monofocal IOL. This prospective single-blind comparative study included two groups of patients affected by bilateral senile cataract who underwent lens extraction and IOL implantation. The first group received a bilateral implantation of a monofocal IOL, and the second group received a bilateral implantation of the Comfort IOL. Twelve months after surgery uncorrected and corrected visual acuity at different distances (30, 50, 70 cm and 4 m), defocus curve and contrast sensitivity were assessed. Patient's satisfaction and spectacle independence were evaluated by mean of the NEI RQL-42 questionnaire. No significant differences were found between the groups in terms of near vision. The group of patients implanted with a Comfort IOL obtained the best results at intermediate distances (50 and 70 cm P < .001). Both groups showed an excellent uncorrected distance visual acuity (4 m). No statistically significant differences were found in terms of corrected near, intermediate and distance visual acuity. Concerning contrast sensitivity, no statistically significant differences between the groups were observed at any cycles per degree. The NEI RQL-42 questionnaire showed statistically significant differences between the group for "near vision" (P = .015), "dependence on correction" (P = .048) and "suboptimal correction" (P < .001) subscales. Our findings indicated that the Comfort IOL +1.5 D provides a good intermediate spectacle independence together with a high quality of vision, with a low amount of subjective symptoms and a contrast sensitivity similar to those obtained with a monofocal IOL.

Evaluation of rotation and visual outcomes after implantation of monofocal and multifocal toric intraocular lenses.

PubMed

Garzón, Nuria; Poyales, Francisco; de Zárate, Begoña Ortíz; Ruiz-García, Jose Luis; Quiroga, Juan Antonio

2015-02-01

To evaluate rotational stability and its influence on postoperative visual acuity of different monofocal and multifocal toric intraocular lenses (IOLs). A prospective interventional study was designed. Ninety-one patients with a mean age of 71.65 ± 11.82 years were implanted with toric IOLs after phacoemulsification. Three monofocal toric IOLs (the Lentis LT [Oculentis, Berlin, Germany], enVista [Bausch & Lomb, Rochester, NY], and AcrySof IQ [Alcon Laboratories, Inc., Fort Worth, TX]) and one multifocal toric IOL (AcrySof IQ ReSTOR; Alcon Laboratories, Inc.) were implanted. Preoperative and postoperative images were taken to calculate the misalignment due to the marking method. To evaluate rotation in the different follow-up visits, another photograph was taken 1 hour and 1, 7 and 30 days postoperatively. Refraction, uncorrected distance visual acuity (UDVA), and corrected distance visual acuity were measured 30 days postoperatively. Postoperative UDVA was 0.1 logMAR or better in 64.6% of eyes implanted with monofocal IOLs and 46.4% of eyes implanted with multifocal IOLs. The enVista toric IOL showed the best UDVA compared to the other monofocal IOLs, with 81% of eyes with 0.1 logMAR or better. The mean misalignment in the total group studied was 0.07° ± 0.60°; 69.6% of monofocal IOLs and 67.9% of multifocal IOLs showed less than 5° of rotation. A correlation was found between postoperative UDVA and rotation in the monofocal and multifocal IOLs implanted (r = 0.439 [P < .011] and = 0.787 [P = .001], respectively). At 1 month postoperatively, UDVA was slightly more affected by IOL rotation in multifocal than monofocal toric IOLs. The marking method was also effective. Copyright 2015, SLACK Incorporated.

Clinical Evaluation of Reading Performance Using the Salzburg Reading Desk With a Refractive Rotational Asymmetric Multifocal Intraocular Lens.

PubMed

Linz, Katharina; Attia, Mary S A; Khoramnia, Ramin; Tandogan, Tamer; Kretz, Florian T; Auffarth, Gerd Uwe

2016-08-01

To evaluate functional results and reading performance using the Salzburg Reading Desk after implantation of a sector-shaped near-embedded, rotational asymmetrical multifocal intraocular lens (IOL) and a multifocal toric IOL with a +3.00 diopter (D) near addition. In a prospective study, the LentisMplus and Mplus toric IOLs (Oculentis GmbH, Berlin, Germany) were implanted in 34 eyes of 18 patients at the University Eye Hospital of Heidelberg. Uncorrected and corrected distance visual acuity (UDVA, CDVA) and uncorrected and corrected near visual acuity (UNVA, CNVA) were evaluated using standardized visual acuity charts (ETDRS). The Salzburg Reading Desk was used to analyze unilateral and bilateral uncorrected and corrected reading acuity, reading distance, reading speed, and the smallest log-scaled print size that could be read effectively at a set (40 cm/80 cm) and subjective chosen near and intermediate distance. Postoperatively, the median UDVA was 0.08 logMAR (20/25 Snellen) and the median CDVA was 0.01 logMAR (20/20 Snellen). The median UNVA was 0.12 logMAR (20/25 Snellen) and the median CNVA was 0.03 logMAR (20/20 Snellen). The median uncorrected reading acuity measured with the Salzburg Reading Desk for near distance at 40 cm was 0.18 logMAR (20/32 Snellen). The subjectively preferred near distance was 39 cm and revealed similar visual acuity results. The best reading acuity for intermediate distance with a median of 0.22 logMAR (20/32 Snellen) was achieved at a median distance of 62 cm. Reading performance of the multifocal IOL corresponded for near standardized and individual distance, whereas reading function was better at the patient's preferred intermediate distance. [J Refract Surg. 2016;32(8):526-532.]. Copyright 2016, SLACK Incorporated.

Clinical and optical intraocular performance of rotationally asymmetric multifocal IOL plate-haptic design versus C-loop haptic design.

PubMed

Alió, Jorge L; Plaza-Puche, Ana B; Javaloy, Jaime; Ayala, María José; Vega-Estrada, Alfredo

2013-04-01

To compare the visual and intraocular optical quality outcomes with different designs of the refractive rotationally asymmetric multifocal intraocular lens (MFIOL) (Lentis Mplus; Oculentis GmbH, Berlin, Germany) with or without capsular tension ring (CTR) implantation. One hundred thirty-five consecutive eyes of 78 patients with cataract (ages 36 to 82 years) were divided into three groups: 43 eyes implanted with the C-Loop haptic design without CTR (C-Loop haptic only group); 47 eyes implanted with the C-Loop haptic design with CTR (C-Loop haptic with CTR group); and 45 eyes implanted with the plate-haptic design (plate-haptic group). Visual acuity, contrast sensitivity, defocus curve, and ocular and intraocular optical quality were evaluated at 3 months postoperatively. Significant differences in the postoperative sphere were found (P = .01), with a more myopic postoperative refraction for the C-Loop haptic only group. No significant differences were detected in photopic and scotopic contrast sensitivity among groups (P ⩾ .05). Significantly better visual acuities were present in the C-Loop haptic with CTR group for the defocus levels of -2.0, -1.5, -1.0, and -0.50 D (P ⩽.03). Statistically significant differences among groups were found in total intraocular root mean square (RMS), high-order intraocular RMS, and intraocular coma-like RMS aberrations (P ⩽.04), with lower values from the plate-haptic group. The plate-haptic design and the C-Loop haptic design with CTR implantation both allow good visual rehabilitation. However, better refractive predictability and intraocular optical quality was obtained with the plate-haptic design without CTR implantation. The plate-haptic design seems to be a better design to support rotational asymmetric MFIOL optics. Copyright 2013, SLACK Incorporated.

Inducing indel mutation in the SOX6 gene by zinc finger nuclease for gamma reactivation: An approach towards gene therapy of beta thalassemia.

PubMed

Modares Sadeghi, Mehran; Shariati, Laleh; Hejazi, Zahra; Shahbazi, Mansoureh; Tabatabaiefar, Mohammad Amin; Khanahmad, Hossein

2018-03-01

β-thalassemia is a common autosomal recessive disorder characterized by a deficiency in the synthesis of β-chains. Evidences show that increased HbF levels improve the symptoms in patients with β-thalassemia or sickle cell anemia. In this study, ZFN technology was applied to induce a mutation in the binding domain region of SOX6 to reactivate γ-globin expression. The sequences coding for ZFP arrays were designed and sub cloned in TDH plus as a transfer vector. The ZFN expression was confirmed using Western blot analysis. In the next step, using the site-directed mutagenesis strategy through the overlap PCR, a missense mutation (D64V) was induced in the catalytic domain of the integrase gene in the packaging plasmid and verified using DNA sequencing. Then, the integrase minus lentivirus containing ZFN cassette was packaged. Transduction of K562 cells with this virus was performed. Mutation detection assay was performed. The indel percentage of the cells transducted with lenti virus containing ZFN was 31%. After 5 days of erythroid differentiation with 15 μg/mL cisplatin, the levels of γ-globin mRNA were sixfold in the cells treated with ZFN compared to untreated cells. In the meantime, the measurement of HbF expression levels was carried out using hemoglobin electrophoresis and showed the same results. Integrase minus lentivirus can provide a useful tool for efficient transient gene expression and helps avoid disadvantages of gene targeting using the native virus. The ZFN strategy applied here to induce indel on SOX6 gene in adult erythroid progenitors may provide a method to activate fetal hemoglobin expression in individuals with β-thalassemia. © 2017 Wiley Periodicals, Inc.

Biological and Molecular Characterization of Trypanosoma cruzi Strains from Four States of Brazil.

PubMed

Ribeiro, Aline Rimoldi; Lima, Luciana; de Almeida, Larissa Aguiar; Monteiro, Joana; Moreno, Cláudia Jassica Gonçalves; Nascimento, Juliana Damieli; de Araújo, Renato Freitas; Mello, Fernanda; Martins, Luciamáre Perinetti Alves; Graminha, Márcia Aparecida Silva; Teixeira, Marta Maria Geraldes; Silva, Marcelo Sousa; Steindel, Mário; da Rosa, João Aristeu

2018-02-01

Chagas disease affects between six and seven million people. Its etiological agent, Trypanosoma cruzi , is classified into six discrete typing units (DTUs). The biological study of 11 T. cruzi strains presented here included four parameters: growth kinetics, parasitemia curves, rate of macrophage infection, and serology to evaluate IgM, total IgG, IgG1, IgG2a, and IgG3. Sequencing of small subunit of ribosomal RNA (SSU rRNA)was performed and the T. cruzi strains were classified into three DTUs. When their growth in liver infusion tryptose medium was represented in curves, differences among the strains could be noted. The parasitemia profile varied among the strains from the TcI, TcII, and TcIII groups, and the 11 T. cruzi strains produced distinct parasitemia levels in infected BALB/c. The TcI group presented the highest rate of macrophage infection by amastigotes, followed by TcII and TcIII. Reactivity to immunoglobulins was observed in the TcI, TcII, and TcIII; all the animals infected with the different strains of T. cruzi showed anti- T. cruzi antibodies. The molecular study presented here resulted in the classification of the T. cruzi strains into the TcI (Bolivia, T lenti, Tm, SC90); TcII (Famema, SC96, SI8, Y); and TcIII (QMM3, QMM5, SI5) groups. These biological and molecular results from 11 T. cruzi strains clarified the factors involved in the biology of the parasite and its hosts. The collection of triatomine (vector) species, and the study of geographic distribution, as well as biological and molecular characterization of the parasite, will contribute to the reporting and surveillance measures in Brazilian states.

MicroRNA-548j functions as a metastasis promoter in human breast cancer by targeting Tensin1.

PubMed

Zhan, Yun; Liang, Xiaoshuan; Li, Lin; Wang, Baona; Ding, Fang; Li, Yi; Wang, Xiang; Zhan, Qimin; Liu, Zhihua

2016-06-01

MicroRNAs (miRNAs) are single-stranded, small non-coding RNA molecules that participate in important biological processes. Although the functions of many miRNAs in breast cancer metastasis have been established, the role of others remains to be characterized. To identify additional miRNAs involved in metastasis, we performed a genetic screen by transducing a Lenti-miR™ virus library into MCF-7 cells. Using transwell invasion assays we identified human miR-548j as an invasion-inducing miRNA. The endogenous levels of miR-548j expression in breast cancer cell lines were shown to correlate with invasiveness. Moreover, miR-548j was shown to stimulate breast cancer cell invasion and metastasis in vitro and in vivo, but had no effect on proliferation. Next, using a series of in vitro and in vivo experiments, we found that Tensin1 served as a direct and functional target of miR-548j. Both miR-548j and Tensin1 modulated the activation of Cdc42 to regulate cell invasion and siCdc42 or the selective Cdc42 inhibitor ML141 suppressed the pathway of miR-548j-mediated cell invasion. Furthermore, a strong correlation between miR-548j, Tensin1, metastasis and survival was observed using two sets of clinical breast cancer samples. Our findings demonstrate that miR-548j functions as a metastasis-promoting miRNA to regulate breast cancer cell invasion and metastasis by targeting Tensin1 and activating Cdc42, suggesting a potential therapeutic application in breast cancer. Copyright © 2016 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Insect (food) allergy and allergens.

PubMed

de Gier, Steffie; Verhoeckx, Kitty

2018-05-03

Insects represent an alternative for meat and fish in satisfying the increasing demand for sustainable sources of nutrition. Approximately two billion people globally consume insects. They are particularly popular in Asia, Latin America, and Africa. Most research on insect allergy has focussed on occupational or inhalation allergy. Research on insect food safety, including allergenicity, is therefore of great importance. The objective of this review is to provide an overview of cases reporting allergy following insect ingestion, studies on food allergy to insects, proteins involved in insect allergy including cross-reactive proteins, and the possibility to alter the allergenic potential of insects by food processing and digestion. Food allergy to insects has been described for silkworm, mealworm, caterpillars, Bruchus lentis, sago worm, locust, grasshopper, cicada, bee, Clanis bilineata, and the food additive carmine, which is derived from female Dactylopius coccus insects. For cockroaches, which are also edible insects, only studies on inhalation allergy have been described. Various insect allergens have been identified including tropomyosin and arginine kinase, which are both pan-allergens known for their cross-reactivity with homologous proteins in crustaceans and house dust mite. Cross-reactivity and/or co-sensitization of insect tropomyosin and arginine kinase has been demonstrated in house dust mite and seafood (e.g. prawn, shrimp) allergic patients. In addition, many other (allergenic) species (various non-edible insects, arachnids, mites, seafoods, mammals, nematoda, trematoda, plants, and fungi) have been identified with sequence alignment analysis to show potential cross-reactivity with allergens of edible insects. It was also shown that thermal processing and digestion did not eliminate insect protein allergenicity. Although purified natural allergens are scarce and yields are low, recombinant allergens from cockroach, silkworm, and Indian mealmoth are readily available, giving opportunities for future research on diagnostic allergy tests and vaccine candidates. Copyright © 2018 Elsevier Ltd. All rights reserved.

The effect of repeated eye examinations and breeding advice on the prevalence and incidence of cataracts and progressive retinal atrophy in German dachshunds over a 13-year period.

PubMed

Koll, Sarah; Reese, Sven; Medugorac, Ivica; Rosenhagen, Carsten U; Sanchez, Rick F; Köstlin, Roberto

2017-03-01

To analyze the change in prevalence and incidence of hereditary eye diseases (HED) in dachshunds due to breeding regulations based on biennial examinations performed by the German panel of veterinary ophthalmologists (DOK) from 1998 to 2011. A total of 12 242 dachshunds examined by the DOK and pedigree data of 318 852 dachshunds provided by the German Dachshund Club (DTK). The prevalence of congenital cataract (CC), distichiasis (DIST), hereditary cataract (HC), persistent pupillary membranes (PPMs), persistent hyperplastic tunica vasculosa lentis / persistent hyperplastic primary vitreous (PHTVL/PHPV), progressive retinal atrophy (PRA), retinal dysplasia (RD), and findings such as fiberglass-like cataract (FGC) and prominent suture lines (PSLs) was analyzed. The significance (P), confidence interval (CI), odds ratio (OR), relative risk (RR) and inbreeding coefficients (F) were calculated and P < 0.05 was considered significant. The incidence was evaluated based on affected dogs within birth cohorts from 1993 to 2006. The prevalent conditions studied were as follows: CC 0.5%, DIST 6.7%, HC 3.9%, PPMs 8.4%, PHTVL/PHPV 0.4%, PRA 1.5%, RD 0.2%, FGC 2.2%, and PSL 1.5%. The incidence of PRA decreased significantly from 6.0% to 0.6% for dogs born from 1993 to 2006, while HC showed a decreasing trend from 8.7% to 3.1%. More males than females were diagnosed with HC and PRA. Dachshunds with HEDs had an F that was not significantly higher than that of healthy dachshunds. The decreasing incidence of PRA and HC in dachshunds supports the use of frequent HED examinations in combination with breeding control. © 2016 American College of Veterinary Ophthalmologists.

Comparative Agronomic Performance and Reaction to Fusarium wilt of Lens culinaris × L. orientalis and L. culinaris × L. ervoides derivatives.

PubMed

Singh, Mohar; Rana, Jai C; Singh, Badal; Kumar, Sandeep; Saxena, Deep R; Saxena, Ashok; Rizvi, Aqeel H; Sarker, Ashutosh

2017-01-01

The development of transgressive phenotype in the segregating populations has been speculated to contribute to niche divergence of hybrid lineages, which occurs most frequently at larger genetic distances. Wild Lens species are considered to be more resistant against major biotic and abiotic stresses than that of the cultivated species. In the present study, we assessed the comparative agronomic performance of lentil ( Lens culinaris subsp. culinaris ) inter-sub-specific ( L. culinaris subsp. orientalis ) and interspecific ( L. ervoides ) derivatives, also discussed its probable basis of occurrence. The F 3 , F 4 , and F 5 inter sub-specific and interspecific populations of ILL8006 × ILWL62 and ILL10829 × ILWL30, respectively revealed a substantial range of variation for majority of agro-morphological traits as reflected by the range, mean and coefficient of variation. A high level of fruitful heterosis was also observed in F 3 and F 4 progeny for important traits of interest. Phenotypic coefficient of variation (PCV) was higher in magnitude than genotypic coefficient of variation (GCV) in all generations for several quantitative characters. The results showed high heritability estimates for majority of traits in conjunction with low to high genetic advance in F 3 and F 4 generations. Further, F 5 progeny of ILL10829 × ILWL30, manifested resistant disease reaction for fifteen recombinant inbred lines (RILs) against ( Fusarium oxysporum f. sp. lentis ( Vasd. Srin .) Gord.). The multilocation agronomic evaluation of both crosses showed better results for earliness, desirable seed yield and Fusarium wilt resistance under two agro-ecological regions of north-western India. These better performing recombinants of ILL8006 × ILWL62 and ILL10829 × ILWL30 can be advanced for further genetic improvement and developing high yielding disease resistant cultivars of lentil.

When Closure Fails: What the Radiologist Needs to Know About the Embryology, Anatomy, and Prenatal Imaging of Ventral Body Wall Defects.

PubMed

Torres, Ulysses S; Portela-Oliveira, Eduardo; Braga, Fernanda Del Campo Braojos; Werner, Heron; Daltro, Pedro Augusto Nascimento; Souza, Antônio Soares

2015-12-01

Ventral body wall defects (VBWDs) are one of the main categories of human congenital malformations, representing a wide and heterogeneous group of defects sharing a common feature, that is, herniation of one or more viscera through a defect in the anterior body wall. Gastroschisis and omphalocele are the 2 most common congenital VBWDs. Other uncommon anomalies include ectopia cordis and pentalogy of Cantrell, limb-body wall complex, and bladder and cloacal exstrophy. Although VBWDs are associated with multiple abnormalities with distinct embryological origins and that may affect virtually any system organs, at least in relation to anterior body wall defects, they are thought (except for omphalocele) to share a common embryologic mechanism, that is, a failure involving the lateral body wall folds responsible for closing the thoracic, abdominal, and pelvic portions of the ventral body wall during the fourth week of development. Additionally, many of the principles of diagnosis and management are similar for these conditions. Fetal ultrasound (US) in prenatal care allows the diagnosis of most of such defects with subsequent opportunities for parental counseling and optimal perinatal management. Fetal magnetic resonance imaging may be an adjunct to US, providing global and detailed anatomical information, assessing the extent of defects, and also helping to confirm the diagnosis in equivocal cases. Prenatal imaging features of VBWDs may be complex and challenging, often requiring from the radiologist a high level of suspicion and familiarity with the imaging patterns. Because an appropriate management is dependent on an accurate diagnosis and assessment of defects, radiologists should be able to recognize and distinguish between the different VBWDs and their associated anomalies. In this article, we review the relevant embryology of VBWDs to facilitate understanding of the pathologic anatomy and diagnostic imaging approach. Features will be illustrated with prenatal US and magnetic resonance imaging and correlated with postnatal and clinical imaging. Copyright © 2015 Elsevier Inc. All rights reserved.

A novel rasopathy caused by recurrent de novo missense mutations in PPP1CB closely resembles Noonan syndrome with loose anagen hair.

PubMed

Gripp, Karen W; Aldinger, Kimberly A; Bennett, James T; Baker, Laura; Tusi, Jessica; Powell-Hamilton, Nina; Stabley, Deborah; Sol-Church, Katia; Timms, Andrew E; Dobyns, William B

2016-09-01

Noonan syndrome is a rasopathy caused by mutations in multiple genes encoding components of the RAS/MAPK pathway. Despite its variable phenotype, limited genotype-phenotype correlations exist. Noonan syndrome with loose anagen hair (NS-LAH) is characterized by its distinctive hair anomalies, developmental differences, and structural brain abnormalities and is caused by a single recurrent missense SHOC2 mutation. SHOC2 forms a complex with protein phosphatase 1 (PP1C). Protein phosphatases counterbalance kinases and control activation of signaling proteins, such as the mitogen-activated protein kinases of the RAS/MAPK pathway. Here we report four patients with de novo missense mutations in protein phosphatase one catalytic subunit beta (PPP1CB), sharing a recognizable phenotype. Three individuals had the recurrent PPP1CB c.146G>C, p.Pro49Arg mutation, the fourth had a c.166G>C, p.Ala56Pro change. All had relative or absolute macrocephaly, low-set and posteriorly angulated ears, and developmental delay. Slow growing and/or sparse hair and/or an unruly hair texture was present in all. Three individuals had feeding difficulties requiring feeding tubes. One of two males had cryptorchidism, another had pectus excavatum. Short stature was present in three. A female with the recurrent mutation had a Dandy-Walker malformation and optic nerve hypoplasia. Mild ventriculomegaly occurred in all, cerebellar tonsillar ectopia was seen in two and progressed to Chiari 1 malformation in one individual. Based on the combination of phenotypic findings and PPP1CB's effect on RAF dephosphorylation within the RAS/MAPK pathway, this novel condition can be considered a rasopathy, most similar to NS-LAH. Collectively, these mutations meet the standardized criteria for pathogenicity. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

UMG Lenti: novel lentiviral vectors for efficient transgene- and reporter gene expression in human early hematopoietic progenitors.

PubMed

Chiarella, Emanuela; Carrà, Giovanna; Scicchitano, Stefania; Codispoti, Bruna; Mega, Tiziana; Lupia, Michela; Pelaggi, Daniela; Marafioti, Maria G; Aloisio, Annamaria; Giordano, Marco; Nappo, Giovanna; Spoleti, Cristina B; Grillone, Teresa; Giovannone, Emilia D; Spina, Raffaella; Bernaudo, Francesca; Moore, Malcolm A S; Bond, Heather M; Mesuraca, Maria; Morrone, Giovanni

2014-01-01

Lentiviral vectors are widely used to investigate the biological properties of regulatory proteins and/or of leukaemia-associated oncogenes by stably enforcing their expression in hematopoietic stem and progenitor cells. In these studies it is critical to be able to monitor and/or sort the infected cells, typically via fluorescent proteins encoded by the modified viral genome. The most popular strategy to ensure co-expression of transgene and reporter gene is to insert between these cDNAs an IRES element, thus generating bi-cistronic mRNAs whose transcription is driven by a single promoter. However, while the product of the gene located upstream of the IRES is generally abundantly expressed, the translation of the downstream cDNA (typically encoding the reporter protein) is often inconsistent, which hinders the detection and the isolation of transduced cells. To overcome these limitations, we developed novel lentiviral dual-promoter vectors (named UMG-LV5 and -LV6) where transgene expression is driven by the potent UBC promoter and that of the reporter protein, EGFP, by the minimal regulatory element of the WASP gene. These vectors, harboring two distinct transgenes, were tested in a variety of human haematopoietic cell lines as well as in primary human CD34+ cells in comparison with the FUIGW vector that contains the expression cassette UBC-transgene-IRES-EGFP. In these experiments both UMG-LV5 and UMG-LV6 yielded moderately lower transgene expression than FUIGW, but dramatically higher levels of EGFP, thereby allowing the easy distinction between transduced and non-transduced cells. An additional construct was produced, in which the cDNA encoding the reporter protein is upstream, and the transgene downstream of the IRES sequence. This vector, named UMG-LV11, proved able to promote abundant expression of both transgene product and EGFP in all cells tested. The UMG-LVs represent therefore useful vectors for gene transfer-based studies in hematopoietic stem and progenitor cells, as well as in non-hematopoietic cells.

Vertical stratification and development aspects of phlebotomine sand flies (Diptera: Psychodidae) in an area of Atlantic Forest tree species in a metropolitan region in northeastern Brazil.

PubMed

Cortez, A M; Silva, V P M; Queiroz, P V S; Andrade, H T A; Loiola, M I B; Ximenes, M F F M

2007-12-01

In the state of Rio Grande do Norte in northeast Brazil, cases of visceral leishmaniasis (VL) occur mainly in the periurban areas of the city of Natal. Lutzomyia longipalpis Lutz & Neiva 1912 (Diptera: Psychodidae), a vector of Leishmania chagasi (Protozoa: Trypanosomatidae) to humans, is found throughout the state. Flora and fauna influence the distribution of sand fly species, whose horizontal or vertical stratification can be used as a parameter for identifying potential vectors, considering the presence of vertebrate hosts in the area. The purpose of this study was to obtain information about the vertical stratification of phlebotomine sand flies in an endemic area of leishmaniasis in Rio Grande do Norte, and associate it with the presence of other animals in the peridomiciliary environment as well as to analyze, under laboratory conditions, aspects of L. longipalpis reproduction in wild females. The sand flies were captured with light traps hung at different heights in species of Atlantic Forest trees and in a peridomiciliary environment in animal shelters. The traps were placed between 17:30 and 6:00 of the following day, in a peridomiciliary and extradomiciliary area of a forest fragment in both dry and rainy months. In the extradomiciliary environment, the traps were installed at 1, 3 and 5 m above the ground. The biological cycle of L. longipalpis was followed from the eggs of 200 wild females. Specimens of L. lenti, L. walkeri, and L. migonei were captured. The comparison and statistical analysis showed that L. longipalpis is more abundant at a height of 3 m and L. evandroi at 1 m. In the animal shelters (chickens, horses, and armadillos), we captured mainly specimens of L. longipalpis and L. evandroi. The duration of the biological cycle of L. longipalpis was approximately 38 days at a temperature of 28 degrees C.

Upregulation of CD147 Promotes Metastasis of Cholangiocarcinoma by Modulating the Epithelial-to-Mesenchymal Transitional Process.

PubMed

Dana, Paweena; Kariya, Ryusho; Vaeteewoottacharn, Kulthida; Sawanyawisuth, Kanlayanee; Seubwai, Wunchana; Matsuda, Kouki; Okada, Seiji; Wongkham, Sopit

2017-08-07

CD147 is a transmembrane protein that can induce the expression and activity of matrix metalloproteinases (MMPs). Expression of CD147 has been shown to potentiate cell migration, invasion, and metastasis of cancer. In this study, the critical role of CD147 in metastasis was elucidated using CD147-overexpressing cholangiocarcinoma (CCA) cells in vitro and in vivo. The molecular mechanism, demonstrated herein, supported the hypothesis that metastasis increased in CD147-overexpressing cells. Five CD147-overexpressing clones (Ex-CD147) were established from a low CD147-expressing CCA cell line, KKU-055, using lentivirus containing pReceiver-Lenti-CD147. The metastatic capability was determined using the tail vein injection mouse model and an in vitro 3D invasion assay. Liver colonization was assessed using anti-HLA class I immunohistochemistry. Adhesion abilities, cytoskeletal arrangements, MMP activities, the expressions of adhesion molecules, and epithelial-mesenchymal transitional markers were analyzed. All Ex-CD147 clones exhibited a high CD147 expression and high liver colonization in the tail vein-injected mouse model, whereas parental cells lacked this ability. Ex-CD147 clones exhibited metastatic phenotypes (i.e., an increase in F-actin rearrangement) and cell invasion and a decrease in cell adhesion. The molecular mechanisms were shown to be via the induction of MMP-2 activity and enhancement of epithelial-mesenchymal transitions. An increase in mesenchymal markers Slug, vimentin, and N-cadherin, and a decrease in epithelial markers E-cadherin and claudin-1, together with suppression of the adhesion molecule ICAM-1, were observed in the Ex-CD147 clones. Moreover, suppression of CD147 expression using siCD147 in two CCA cell lines with high CD147 expression significantly decreased cell migration and invasion of these CCA cells. These findings emphasize the essential role of CD147 in CCA metastasis and suggest CD147 as a promising target for the effective treatment of CCA.

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

Haffar, T.; Montreal Heart Institute; Bérubé-Simard, F.

A major cause for diabetic cardiomyopathy is excess lipid accumulation. To elucidate mechanisms of lipotoxicity mediated diabetic heart disease we need to further our understanding of how lipid metabolism is altered in the diabetic heart. Here we investigated the role of lipid clearance by oxidation as a regulator of lipid-mediated toxicity (lipotoxicity). We evaluated the effect of pre-treating rat neonatal cardiomyocytes (NCMs) with either oleate (mono-unsaturated fatty acid) or palmitate (saturated fatty acid) on fatty acid oxidation (FAO) by measuring {sup 14}C–CO{sub 2} production. We evaluated carnitine palmitoyltransferase (Cpt1b) expression by western blotting and mitochondrial membrane potential by quantitative andmore » qualitative fluorescence analyses using the JC-1 dye. We inhibited the Cpt1b pharmacologically using etomoxir and genetically by knocking down its expression using LentiVector mediated transduction of siRNAs targeting the Cpt1b gene. We found that palmitate had a slower clearance rate from NCMs than oleate, and this was associated with a significant decrease in FAO. This impairment in FAO was not the result of either loss of Cpt1b protein or mitochondrial integrity. Enhancing FAO with either oleate or carnitine was associated with a significant attenuation of palmitate mediated lipotoxicity. In contrast impairing FAO in oleate treated NCMs caused lipotoxicity. Here we demonstrate that a major difference between non-toxic unsaturated fatty acids and toxic saturated fatty acids is there ability to stimulate or inhibit fatty acid oxidation, respectively. This has important implications for diabetic cardiomyopathy since diabetic hearts consistently exhibit elevated lipid accumulation. - Highlights: • Palmitate had a slower clearance rate from NCMs than oleate. • Palmitate caused a significant decrease in fatty acid oxidation in cardiomyocytes. • Impaired FAO was not due to loss of Cpt1b protein or mitochondrial integrity. • Enhancing FAO attenuated palmitate mediated lipotoxicity. • Impairing FAO caused lipotoxicity by non-toxic oleate.« less

Comparative Agronomic Performance and Reaction to Fusarium wilt of Lens culinaris × L. orientalis and L. culinaris × L. ervoides derivatives

PubMed Central

Singh, Mohar; Rana, Jai C.; Singh, Badal; Kumar, Sandeep; Saxena, Deep R.; Saxena, Ashok; Rizvi, Aqeel H.; Sarker, Ashutosh

2017-01-01

The development of transgressive phenotype in the segregating populations has been speculated to contribute to niche divergence of hybrid lineages, which occurs most frequently at larger genetic distances. Wild Lens species are considered to be more resistant against major biotic and abiotic stresses than that of the cultivated species. In the present study, we assessed the comparative agronomic performance of lentil (Lens culinaris subsp. culinaris) inter-sub-specific (L. culinaris subsp. orientalis) and interspecific (L. ervoides) derivatives, also discussed its probable basis of occurrence. The F3, F4, and F5 inter sub-specific and interspecific populations of ILL8006 × ILWL62 and ILL10829 × ILWL30, respectively revealed a substantial range of variation for majority of agro-morphological traits as reflected by the range, mean and coefficient of variation. A high level of fruitful heterosis was also observed in F3 and F4 progeny for important traits of interest. Phenotypic coefficient of variation (PCV) was higher in magnitude than genotypic coefficient of variation (GCV) in all generations for several quantitative characters. The results showed high heritability estimates for majority of traits in conjunction with low to high genetic advance in F3 and F4 generations. Further, F5 progeny of ILL10829 × ILWL30, manifested resistant disease reaction for fifteen recombinant inbred lines (RILs) against (Fusarium oxysporum f. sp. lentis (Vasd. Srin.) Gord.). The multilocation agronomic evaluation of both crosses showed better results for earliness, desirable seed yield and Fusarium wilt resistance under two agro-ecological regions of north-western India. These better performing recombinants of ILL8006 × ILWL62 and ILL10829 × ILWL30 can be advanced for further genetic improvement and developing high yielding disease resistant cultivars of lentil. PMID:28751897

The association between the pulse pressure gradient at the cranio-cervical junction derived from phase-contrast magnetic resonance imaging and invasively measured pulsatile intracranial pressure in symptomatic patients with Chiari malformation type 1.

PubMed

Frič, Radek; Lindstrøm, Erika Kristina; Ringstad, Geir Andre; Mardal, Kent-André; Eide, Per Kristian

2016-12-01

In symptomatic Chiari malformation type 1 (CMI), impaired intracranial compliance (ICC) is associated with an increased cranio-spinal pulsatile pressure gradient. Phase-contrast magnetic resonance imaging (MRI) represents a non-invasive modality for the assessment of the pulse pressure gradient at the cranio-cervical junction (CCJ). We wished to explore how the MRI-derived pulse pressure gradient (MRI-dP) compares with invasively measured pulsatile intracranial pressure (ICP) in CMI, and with healthy controls. From phase-contrast MRI of CMI patients and healthy controls, we computed cerebrospinal fluid (CSF) flow velocities and MRI-dP at the CCJ. We assessed bidirectional flow and compared the flow between the anterior and the posterior subarachnoid space at the CCJ. We computed total intracranial volume (ICV), ventricular CSF volume (VV), and posterior cranial fossa volume (PCFV). We analyzed the static and pulsatile ICP scores from overnight monitoring in CMI patients. Five CMI patients and four healthy subjects were included. The CMI group had a significantly larger extent of tonsillar ectopia, smaller PCFV, and a smaller area of CSF in the FM. The pulsatile ICP (mean ICP wave amplitude, MWA) was abnormally increased in 4/5 CMI patients and correlated positively with MRI-dP. However, the MRI-dP as well as the CSF flow velocities did not differ significantly between CMI and healthy subjects. Moreover, bidirectional flow was observed in both CMI as well as healthy subjects, with no significant difference. In symptomatic CMI patients, we found a significant association between the pulse pressure gradient at the CCJ derived from phase-contrast MRI and the pulsatile ICP (MWA) measured invasively. However, the MRI-dP was close to identical in CMI patients and healthy subjects. Moreover, the CSF flow velocities at the CCJ and the occurrence of bidirectional flow were not different in CMI patients and healthy individuals. Further studies are required to determine the diagnostic role of phase-contrast MRI in CMI patients.

Comparison of Intravitreal Bevacizumab, Intravitreal Ranibizumab and Laser Photocoagulation for Treatment of Type 1 Retinopathy of Prematurity in Turkish Preterm Children.

PubMed

Kabataş, Emrah Utku; Kurtul, Bengi Ece; Altıaylık Özer, Pınar; Kabataş, Naciye

2017-07-01

To evaluate effectiveness of treatment modalities, major complications and refractive errors in children who were treated with intravitreal bevacizumab (IVB), intravitreal ranibizumab (IVR) or laser photocoagulation (LP) for type 1 retinopathy of prematurity (ROP). Premature infants who underwent IVB monotherapy (Group 1), IVR monotherapy (Group 2) or LP (Group 3) for type 1 ROP and infants with spontaneously regressed ROP (Group 4) were included for the study. Major complications, recurrence rate, recurrence time, total retinal vascularization time and refractive errors at 18 months of corrected age (CA) were determined. Groups 1, 2, 3 and 4 included 24 eyes of 12 patients, 12 eyes of six patients, 72 eyes of 36 patients and 148 eyes of 74 patients, respectively. Recurrence of the disease occurred in two eyes of one patient in Group 1 at 52 weeks of postmenstrual age (PMA) and two eyes of one patient at 48 weeks of PMA in Group 2. In Group 3, disease did not regress after the first treatment in 10 eyes of five patients. The mean vascularization time in Group 1 was 73 ± 10.1 weeks of PMA and 61.8 ± 6.6 weeks of PMA in Group 2 (p = 0.027). Macular ectopia was seen in two eyes of one patient and exudative retinal detachment (ERD) occurred in two eyes of one patient in Group 3. Mean spherical equivalent was 1.49 ± 3.04 diopters (D) in Group 1, -1.79 ± 2.87D in Group 2, -1.27 ± 2.8 D in Group 3 and 1.52 ± 1.07 D in Group 4 at 18 months of CA. There was no significant difference in astigmatism values in all groups. IVB, IVR and LP are options that can successfully treat ROP. Myopia was observed to be the main refractive error in all treatment groups. Vascularization of the retina was completed later in the IVB group than in the IVR group.

Syntaxin-4 mediates exocytosis of pre-docked and newcomer insulin granules underlying biphasic glucose-stimulated insulin secretion in human pancreatic beta cells.

PubMed

Xie, Li; Zhu, Dan; Dolai, Subhankar; Liang, Tao; Qin, Tairan; Kang, Youhou; Xie, Huanli; Huang, Ya-Chi; Gaisano, Herbert Y

2015-06-01

Of the four exocytotic syntaxins (Syns), much is now known about the role of Syn-1A (pre-docked secretory granules [SGs]) and Syn-3 (newcomer SGs) in insulin exocytosis. Some work was reported on Syn-4's role in biphasic glucose-stimulated insulin secretion (GSIS), but its precise role in insulin SG exocytosis remains unclear. In this paper we examine this role in human beta cells. Endogenous function of Syn-4 in human islets was assessed by knocking down its expression with lentiviral single hairpin RNA (lenti-shRNA)-RFP. Biphasic GSIS was determined by islet perifusion assay. Single-cell analysis of exocytosis of red fluorescent protein (RFP)-positive beta cells (exhibiting near-total depletion of Syn-4) was by patch clamp capacitance measurements (Cm) and total internal reflection fluorescence microscopy (TIRFM), the latter to further assess single SG behaviour. Co-immunoprecipitations were conducted on INS-1 cells to assess exocytotic complexes. Syn-4 knockdown (KD) of 77% in human islets caused a concomitant reduction in cognate Munc18c expression (46%) without affecting expression of other exocytotic proteins; this resulted in reduction of GSIS in the first phase (by 42%) and the second phase (by 40%). Cm of RFP-tagged Syn-4-KD beta cells showed severe inhibition in the readily releasable pool (by 71%) and mobilisation from reserve pools (by 63%). TIRFM showed that Syn-4-KD-induced inhibition of first-phase GSIS was attributed to reduction in exocytosis of both pre-docked and newcomer SGs (which undergo minimal residence or docking time at the plasma membrane before fusion). Second-phase inhibition was attributed to reduction in newcomer SGs. Stx-4 co-immunoprecipitated Munc18c, VAMP2 and VAMP8, suggesting that these exocytotic complexes may be involved in exocytosis of pre-docked and newcomer SGs. Syn-4 is involved in distinct molecular machineries that influence exocytosis of both pre-docked and newcomer SGs in a manner functionally redundant to Syn-1A and Syn-3, respectively; this underlies Syn-4's role in mediating portions of first-phase and second-phase GSIS.

UMG Lenti: Novel Lentiviral Vectors for Efficient Transgene- and Reporter Gene Expression in Human Early Hematopoietic Progenitors

PubMed Central

Chiarella, Emanuela; Carrà, Giovanna; Scicchitano, Stefania; Codispoti, Bruna; Mega, Tiziana; Lupia, Michela; Pelaggi, Daniela; Marafioti, Maria G.; Aloisio, Annamaria; Giordano, Marco; Nappo, Giovanna; Spoleti, Cristina B.; Grillone, Teresa; Giovannone, Emilia D.; Spina, Raffaella; Bernaudo, Francesca; Moore, Malcolm A. S.; Bond, Heather M.; Mesuraca, Maria; Morrone, Giovanni

2014-01-01

Lentiviral vectors are widely used to investigate the biological properties of regulatory proteins and/or of leukaemia-associated oncogenes by stably enforcing their expression in hematopoietic stem and progenitor cells. In these studies it is critical to be able to monitor and/or sort the infected cells, typically via fluorescent proteins encoded by the modified viral genome. The most popular strategy to ensure co-expression of transgene and reporter gene is to insert between these cDNAs an IRES element, thus generating bi-cistronic mRNAs whose transcription is driven by a single promoter. However, while the product of the gene located upstream of the IRES is generally abundantly expressed, the translation of the downstream cDNA (typically encoding the reporter protein) is often inconsistent, which hinders the detection and the isolation of transduced cells. To overcome these limitations, we developed novel lentiviral dual-promoter vectors (named UMG-LV5 and –LV6) where transgene expression is driven by the potent UBC promoter and that of the reporter protein, EGFP, by the minimal regulatory element of the WASP gene. These vectors, harboring two distinct transgenes, were tested in a variety of human haematopoietic cell lines as well as in primary human CD34+ cells in comparison with the FUIGW vector that contains the expression cassette UBC-transgene-IRES-EGFP. In these experiments both UMG-LV5 and UMG–LV6 yielded moderately lower transgene expression than FUIGW, but dramatically higher levels of EGFP, thereby allowing the easy distinction between transduced and non-transduced cells. An additional construct was produced, in which the cDNA encoding the reporter protein is upstream, and the transgene downstream of the IRES sequence. This vector, named UMG-LV11, proved able to promote abundant expression of both transgene product and EGFP in all cells tested. The UMG-LVs represent therefore useful vectors for gene transfer-based studies in hematopoietic stem and progenitor cells, as well as in non-hematopoietic cells. PMID:25502183

microRNA 126 inhibits the transition of endothelial progenitor cells to mesenchymal cells via the PIK3R2-PI3K/Akt signalling pathway.

PubMed

Zhang, Junfeng; Zhang, Zongqi; Zhang, David Y; Zhu, Jianbing; Zhang, Tiantian; Wang, Changqian

2013-01-01

Endothelial progenitor cells (EPCs) are capable of proliferating and differentiating into mature endothelial cells, and they have been considered as potential candidates for coronary heart disease therapy. However, the transition of EPCs to mesenchymal cells is not fully understood. This study aimed to explore the role of microRNA 126 (miR-126) in the endothelial-to-mesenchymal transition (EndMT) induced by transforming growth factor beta 1 (TGFβ1). EndMT of rat bone marrow-derived EPCs was induced by TGFβ1 (5 ng/mL) for 7 days. miR-126 expression was depressed in the process of EPC EndMT. The luciferase reporter assay showed that the PI3K regulatory subunit p85 beta (PIK3R2) was a direct target of miR-126 in EPCs. Overexpression of miR-126 by a lentiviral vector (lenti-miR-126) was found to downregulate the mRNA expression of mesenchymal cell markers (α-SMA, sm22-a, and myocardin) and to maintain the mRNA expression of progenitor cell markers (CD34, CD133). In the cellular process of EndMT, there was an increase in the protein expression of PIK3R2 and the nuclear transcription factors FoxO3 and Smad4; PI3K and phosphor-Akt expression decreased, a change that was reversed markedly by overexpression of miR-126. Furthermore, knockdown of PIK3R2 gene expression level showed reversed morphological changes of the EPCs treated with TGFβ1, thereby giving the evidence that PIK3R2 is the target gene of miR-126 during EndMT process. These results show that miR-126 targets PIK3R2 to inhibit EPC EndMT and that this process involves regulation of the PI3K/Akt signalling pathway. miR-126 has the potential to be used as a biomarker for the early diagnosis of intimal hyperplasia in cardiovascular disease and can even be a therapeutic tool for treating cardiovascular diseases mediated by the EndMT process.

CD147 Required for Corneal Endothelial Lactate Transport

PubMed Central

Li, Shimin; Nguyen, Tracy T.; Bonanno, Joseph A.

2014-01-01

Purpose. CD147/basigin is a chaperone for lactate:H+ cotransporters (monocarboxylate transporters) MCT1 and MCT4. We tested the hypothesis that MCT1 and -4 in corneal endothelium contribute to lactate efflux from stroma to anterior chamber and that silencing CD147 expression would cause corneal edema. Methods. CD147 was silenced via small interfering ribonucleic acid (siRNA) transfection of rabbit corneas ex vivo and anterior chamber lenti-small hairpin RNA (shRNA) pseudovirus in vivo. CD147 and MCT expression was examined by Western blot, RT-PCR, and immunofluorescence. Functional effects were examined by measuring lactate-induced cell acidification, corneal lactate efflux, [lactate], central cornea thickness (CCT), and Azopt (a carbonic anhydrase inhibitor) sensitivity. Results. In ex vivo corneas, 100 nM CD147 siRNA reduced CD147, MCT1, and MCT4 expression by 85%, 79%, and 73%, respectively, while MCT2 expression was unaffected. CD147 siRNA decreased lactate efflux from 3.9 ± 0.81 to 1.5 ± 0.37 nmol/min, increased corneal [lactate] from 19.28 ± 7.15 to 56.73 ± 8.97 nmol/mg, acidified endothelial cells (pHi = 6.83 ± 0.07 vs. 7.19 ± 0.09 in control), and slowed basolateral lactate-induced acidification from 0.0034 ± 0.0005 to 0.0012 ± 0.0005 pH/s, whereas apical acidification was unchanged. In vivo, CD147 shRNA increased CCT by 28.1 ± 0.9 μm at 28 days; Azopt increased CCT to 24.4 ± 3.12 vs. 12.0 ± 0.48 μm in control, and corneal [lactate] was 47.63 ± 6.29 nmol/mg in shCD147 corneas and 17.82 ± 4.93 nmol/mg in paired controls. Conclusions. CD147 is required for the expression of MCT1 and MCT4 in the corneal endothelium. Silencing CD147 slows lactate efflux, resulting in stromal lactate accumulation and corneal edema, consistent with lactate efflux as a significant component of the corneal endothelial pump. PMID:24970254

CD147 required for corneal endothelial lactate transport.

PubMed

Li, Shimin; Nguyen, Tracy T; Bonanno, Joseph A

2014-06-26

CD147/basigin is a chaperone for lactate:H(+) cotransporters (monocarboxylate transporters) MCT1 and MCT4. We tested the hypothesis that MCT1 and -4 in corneal endothelium contribute to lactate efflux from stroma to anterior chamber and that silencing CD147 expression would cause corneal edema. CD147 was silenced via small interfering ribonucleic acid (siRNA) transfection of rabbit corneas ex vivo and anterior chamber lenti-small hairpin RNA (shRNA) pseudovirus in vivo. CD147 and MCT expression was examined by Western blot, RT-PCR, and immunofluorescence. Functional effects were examined by measuring lactate-induced cell acidification, corneal lactate efflux, [lactate], central cornea thickness (CCT), and Azopt (a carbonic anhydrase inhibitor) sensitivity. In ex vivo corneas, 100 nM CD147 siRNA reduced CD147, MCT1, and MCT4 expression by 85%, 79%, and 73%, respectively, while MCT2 expression was unaffected. CD147 siRNA decreased lactate efflux from 3.9 ± 0.81 to 1.5 ± 0.37 nmol/min, increased corneal [lactate] from 19.28 ± 7.15 to 56.73 ± 8.97 nmol/mg, acidified endothelial cells (pHi = 6.83 ± 0.07 vs. 7.19 ± 0.09 in control), and slowed basolateral lactate-induced acidification from 0.0034 ± 0.0005 to 0.0012 ± 0.0005 pH/s, whereas apical acidification was unchanged. In vivo, CD147 shRNA increased CCT by 28.1 ± 0.9 μm at 28 days; Azopt increased CCT to 24.4 ± 3.12 vs. 12.0 ± 0.48 μm in control, and corneal [lactate] was 47.63 ± 6.29 nmol/mg in shCD147 corneas and 17.82 ± 4.93 nmol/mg in paired controls. CD147 is required for the expression of MCT1 and MCT4 in the corneal endothelium. Silencing CD147 slows lactate efflux, resulting in stromal lactate accumulation and corneal edema, consistent with lactate efflux as a significant component of the corneal endothelial pump. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Decreased miR-199 augments visceral pain in patients with IBS through translational upregulation of TRPV1.

PubMed

Zhou, QiQi; Yang, Liuqing; Larson, Scott; Basra, Sapreet; Merwat, Shehzad; Tan, Alai; Croce, Carlo; Verne, G Nicholas

2016-05-01

Many patients with irritable bowel syndrome IBS not only have abdominal pain but also may suffer from visceral hypersensitivity and heighted visceral nociception. Moreover, IBS has few effective therapeutic agents and mechanisms of disease are unclear. Our goals were to (i) identify microRNA (miRNA) expression, signalling and targets in human colon (controls; patients with IBS); (ii) verify in vitro, IBS-associated changes in miRNAs, especially miR-199, which is complementary to the transient receptor potential vanilloid type 1 (TRPV1) gene; and (iii) determine whether modulating the expression of miRNAs in vivo, especially miR-199, reverses associated changes and pathological hallmarks of visceral hypersensitivity via TRPV1 signalling. We evaluated 45 patients with diarrhoea-predominant IBS (IBS-D) and 40 controls with (1) visceral pain severity score and (2) colonoscopy with biopsies. miRNA expression was evaluated in human colon following miRNA array analysis. Luciferase assays were done to confirm relationships between miR-199 and TRPV1 expression. A rat model of visceral hypersensitivity was used to study miR-199 and its target gene (TRPV1) expression in dorsal root ganglion (DRG) and colon in vivo. Gut miR-199a/b expression in IBS-D was significantly decreased, which correlated directly with both increased visceral pain scores and TRPV1 expression. In vivo upregulation of miR-199a by intraperitoneal injection of lenti-miR-199a precursors decreased visceral hypersensitivity via diminished TRPV1 signalling. Decreased colonic miR-199a/b correlates with visceral pain in patients with IBS-D. Similarly, reduced miR-199a expression in rat DRG and colon tissue is associated with heightened visceral hypersensitivity. In vivo upregulation of miR-199a decreases visceral pain via inhibition of TRPV1 signalling. Thus, miR-199 precursors may be promising therapeutic candidates for the treatment in patients with visceral pain. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Etiological evaluation of primary congenital hypothyroidism cases.

PubMed

Bezen, Diğdem; Dilek, Emine; Torun, Neşe; Tütüncüler, Filiz

2017-06-01

Primary congenital hypothyroidism is frequently seen endocrine disorder and one of the preventable cause of mental retardation. Aim of study was to evaluate the frequency of permanent/transient hypothyrodism, and to detect underlying reason to identfy any marker which carries potential to discriminate permanent/transient form. Forty eight cases older than 3 years of age, diagnosed as primary congenital hypothyroidism and started thyroxin therapy in newborn-period, and followed up between January 2007-June 2013 were included in the study. Thyroid hormon levels were evaluated and thyroid ultrasonography was performed in cases who are at the end of their 3 years of age, after 6 weeks of thyroxine free period. Thyroid sintigraphy was performed if serum thyroid-stimulating hormone was high (≥ 5 mIU/mL) and perchlorate discharge test was performed if uptake was normal or increased on sintigraphy. Cases with thyroid-stimulating hormone levels ≥ 5 mIU/mL were defined as permanent primary congenital hypothyroidism group and as transient primary congenital hypothyroidism group with normal thyroid hormones during 6 months. The mean age was 3.8±0.7 years. Mean diagnosis age was 16.6±6.5 days and 14 cases (29.2%) were diagnosed by screening program of Ministry of Health. There were 23 cases (14F, 9M) in permanent primary congenital hypothyroidism group and 12 (52.2%) of them were dysgenesis (8 hypoplasia, 4 ectopia), and 11 (47.8%) dyshormonogenesis. In transient primary congenital hypothyroidism group, there were 25 cases (17M, 8F). The mean thyroid-stimulating hormone levels at diagnosis were similar in two groups. The mean thyroxin dose in permanent primary congenital hypothyroidism group was significantly higher than transient group at the time of thyroxin cessation (2.1±0.7, 1.5±0.5 mg/kg/d, respectively, p=0.004). Thyroxin dose ≥1.6 mcg/kg/d was 72% sensitive and 69.6% specific for predicting permenant primary congenital hypothyroidism. Transient primary congenital hypothyroidism is more frequent than expected and found often in males in the primary congenital hypothyroidism cases, started thyroxin therapy in neonatal period. While fT4, thyroid-stimulating hormone, Tg levels at diagnosis do not predict transient/permenant primary congenital hypothyroidism, thyroxin dose before the therapy cessation at the age of 3 may make the distinction between transient/permenant primary congenital hypothyroidism.

Clinical evidence for cervical myelopathy due to Chiari malformation and spinal stenosis in a non-randomized group of patients with the diagnosis of fibromyalgia.

PubMed

Heffez, Dan S; Ross, Ruth E; Shade-Zeldow, Yvonne; Kostas, Konstantinos; Shah, Sagar; Gottschalk, Robert; Elias, Dean A; Shepard, Alan; Leurgans, Sue E; Moore, Charity G

2004-10-01

While patients with fibromyalgia report symptoms consistent with cervical myelopathy, a detailed neurological evaluation is not routine. We sought to determine if patients with fibromyalgia manifest objective neurological signs of cervical myelopathy. Two hundred and seventy patients, 18 years and older, who carried the diagnosis of fibromyalgia but who had no previously recognized neurological disease underwent detailed clinical neurological and neuroradiological evaluation for the prevalence of objective evidence of cervical myelopathy and radiological evidence of cerebellar tonsillar herniation (Chiari 1 malformation) or cervical spinal canal stenosis. Patients were primarily women (87%), of mean age 44 years, who had been symptomatic for 8 years (standard deviation, 6.3 years). The predominant complaints were neck/back pain (95%), fatigue (95%), exertional fatigue (96%), cognitive impairment (92%), instability of gait (85%), grip weakness (83%), paresthesiae (80%), dizziness (71%) and numbness (69%). Eighty-eight percent of patients reported worsening symptoms with neck extension. The neurological examination was consistent with cervical myelopathy: upper thoracic spinothalamic sensory level (83%), hyperreflexia (64%), inversion of the radial periosteal reflex (57%), positive Romberg sign (28%), ankle clonus (25%), positive Hoffman sign (26%), impaired tandem walk (23%), dysmetria (15%) and dysdiadochokinesia (13%). MRI and contrast-enhanced CT imaging of the cervical spine revealed stenosis. The mean antero-posterior (AP) spinal canal diameter at C2/3, C3/4, C4/5, C5/6, C6/7 and C7/T1 was 13.5 mm, 11.8 mm, 11.5 mm, 10.4 mm, 11.3 mm and 14.5 mm respectively, (CT images). In 46% of patients, the AP spinal diameter at C5/6 measured 10 mm, or less, with the neck positioned in mild extension, i.e., clinically significant spinal canal stenosis. MRI of the brain revealed tonsillar ectopia >5 mm in 20% of patients (mean=7.1+/-1.8 mm), i.e., Chiari 1 malformation. CONCLUSION. Our findings indicate that some patients who carry the diagnosis of fibromyalgia have both signs and symptoms consistent with cervical myelopathy, most likely resulting from spinal cord compression. We recommend detailed neurological evaluation of patients with fibromyalgia in order to exclude cervical myelopathy, a potentially treatable condition.

Identification of phlebotomine sand fly blood meals by real-time PCR.

PubMed

Sales, Kamila Gaudêncio da Silva; Costa, Pietra Lemos; de Morais, Rayana Carla Silva; Otranto, Domenico; Brandão-Filho, Sinval Pinto; Cavalcanti, Milena de Paiva; Dantas-Torres, Filipe

2015-04-16

Phlebotomine sand flies are blood-feeding insects of great medical and veterinary significance acting as vectors of Leishmania parasites. Studying the blood-feeding pattern of these insects may help in the understanding of their interactions with potential reservoir hosts of Leishmania parasites. In this study, we developed real time PCR assays for the identification of sand fly blood meal. Six pairs of primers were designed based on cytochrome b gene sequences available in GenBank of the following potential hosts: dog, cat, horse, chicken, black rat, and human. Firstly, SYBR Green-based real time PCR assays were conducted using a standard curve with eight different concentrations (i.e., 10 ng, 1 ng, 100 pg, 10 pg, 1 pg, 100 fg, 10 fg and 1 fg per 2 μl) of DNA samples extracted from EDTA blood samples from each target animal. Then, DNA samples extracted from field-collected engorged female sand flies belonging to three species (i.e., Lutzomyia longipalpis, L. migonei and L. lenti) were tested by the protocols standardized herein. Additionally, female sand flies were experimentally fed on a black rat (Rattus rattus) and used for evaluating the time course of the detection of the protocol targeting this species. The protocols performed well with detection limits of 10 pg to 100 fg. Field-collected female sand flies were fed on blood from humans (73%), chickens (23%), dogs (22%), horses (15%), black rats (11%) and cats (2%). Interestingly, 76.1% of the L. longipalpis females were positive for human blood. In total, 48% of the tested females were fed on single sources, 31% on two and 12% on three. The analysis of the time course showed that the real time PCR protocol targeting the black rat DNA was able to detect small amounts of the host DNA up to 5 days after the blood meal. The real time PCR assays standardized herein successfully detected small amounts of host DNA in female sand flies fed on different vertebrate species and, specifically for the black rats, up to 5 days after the blood meal. These assays represent promising tools for the identification of blood meal in field-collected female sand flies.

Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia.

PubMed

Thompson, Alexis A; Walters, Mark C; Kwiatkowski, Janet; Rasko, John E J; Ribeil, Jean-Antoine; Hongeng, Suradej; Magrin, Elisa; Schiller, Gary J; Payen, Emmanuel; Semeraro, Michaela; Moshous, Despina; Lefrere, Francois; Puy, Hervé; Bourget, Philippe; Magnani, Alessandra; Caccavelli, Laure; Diana, Jean-Sébastien; Suarez, Felipe; Monpoux, Fabrice; Brousse, Valentine; Poirot, Catherine; Brouzes, Chantal; Meritet, Jean-François; Pondarré, Corinne; Beuzard, Yves; Chrétien, Stany; Lefebvre, Thibaud; Teachey, David T; Anurathapan, Usanarat; Ho, P Joy; von Kalle, Christof; Kletzel, Morris; Vichinsky, Elliott; Soni, Sandeep; Veres, Gabor; Negre, Olivier; Ross, Robert W; Davidson, David; Petrusich, Alexandria; Sandler, Laura; Asmal, Mohammed; Hermine, Olivier; De Montalembert, Mariane; Hacein-Bey-Abina, Salima; Blanche, Stéphane; Leboulch, Philippe; Cavazzana, Marina

2018-04-19

Donor availability and transplantation-related risks limit the broad use of allogeneic hematopoietic-cell transplantation in patients with transfusion-dependent β-thalassemia. After previously establishing that lentiviral transfer of a marked β-globin (β A-T87Q ) gene could substitute for long-term red-cell transfusions in a patient with β-thalassemia, we wanted to evaluate the safety and efficacy of such gene therapy in patients with transfusion-dependent β-thalassemia. In two phase 1-2 studies, we obtained mobilized autologous CD34+ cells from 22 patients (12 to 35 years of age) with transfusion-dependent β-thalassemia and transduced the cells ex vivo with LentiGlobin BB305 vector, which encodes adult hemoglobin (HbA) with a T87Q amino acid substitution (HbA T87Q ). The cells were then reinfused after the patients had undergone myeloablative busulfan conditioning. We subsequently monitored adverse events, vector integration, and levels of replication-competent lentivirus. Efficacy assessments included levels of total hemoglobin and HbA T87Q , transfusion requirements, and average vector copy number. At a median of 26 months (range, 15 to 42) after infusion of the gene-modified cells, all but 1 of the 13 patients who had a non-β 0 /β 0 genotype had stopped receiving red-cell transfusions; the levels of HbA T87Q ranged from 3.4 to 10.0 g per deciliter, and the levels of total hemoglobin ranged from 8.2 to 13.7 g per deciliter. Correction of biologic markers of dyserythropoiesis was achieved in evaluated patients with hemoglobin levels near normal ranges. In 9 patients with a β 0 /β 0 genotype or two copies of the IVS1-110 mutation, the median annualized transfusion volume was decreased by 73%, and red-cell transfusions were discontinued in 3 patients. Treatment-related adverse events were typical of those associated with autologous stem-cell transplantation. No clonal dominance related to vector integration was observed. Gene therapy with autologous CD34+ cells transduced with the BB305 vector reduced or eliminated the need for long-term red-cell transfusions in 22 patients with severe β-thalassemia without serious adverse events related to the drug product. (Funded by Bluebird Bio and others; HGB-204 and HGB-205 ClinicalTrials.gov numbers, NCT01745120 and NCT02151526 .).

Virus-mediated swapping of zolpidem-insensitive with zolpidem-sensitive GABA(A) receptors in cortical pyramidal cells.

PubMed

Sumegi, Mate; Fukazawa, Yugo; Matsui, Ko; Lorincz, Andrea; Eyre, Mark D; Nusser, Zoltan; Shigemoto, Ryuichi

2012-04-01

Recently developed pharmacogenetic and optogenetic approaches, with their own advantages and disadvantages, have become indispensable tools in modern neuroscience. Here, we employed a previously described knock-in mouse line (GABA(A)Rγ2(77I)lox) in which the γ2 subunit of the GABA(A) receptor (GABA(A)R) was mutated to become zolpidem insensitive (γ2(77I)) and used viral vectors to swap γ2(77I) with wild-type, zolpidem-sensitive γ2 subunits (γ2(77F)). The verification of unaltered density and subcellular distribution of the virally introduced γ2 subunits requires their selective labelling. For this we generated six N- and six C-terminal-tagged γ2 subunits, with which cortical cultures of GABA(A)Rγ2(−/−) mice were transduced using lentiviruses. We found that the N-terminal AU1 tag resulted in excellent immunodetection and unimpaired synaptic localization. Unaltered kinetic properties of the AU1-tagged γ2 ((AU1)γ2(77F)) channels were demonstrated with whole-cell patch-clamp recordings of spontaneous IPSCs from cultured cells. Next, we carried out stereotaxic injections of lenti- and adeno-associated viruses containing Cre-recombinase and the (AU1)γ2(77F) subunit (Cre-2A-(AU1)γ2(77F)) into the neocortex of GABA(A)Rγ2(77I)lox mice. Light microscopic immunofluorescence and electron microscopic freeze-fracture replica immunogold labelling demonstrated the efficient immunodetection of the AU1 tag and the normal enrichment of the (AU1)γ2(77F) subunits in perisomatic GABAergic synapses. In line with this,miniature and action potential-evoked IPSCs whole-cell recorded from transduced cells had unaltered amplitudes, kinetics and restored zolpidem sensitivity. Our results obtained with a wide range of structural and functional verification methods reveal unaltered subcellular distributions and functional properties of γ2(77I) and (AU1)γ2(77F) GABA(A)Rs in cortical pyramidal cells. This transgenic–viral pharmacogenetic approach has the advantage that it does not require any extrinsic protein that might endow some unforeseen alterations of the genetically modified cells. In addition, this virus-based approach opens up the possibility of modifying multiple cell types in distinct brain regions and performing alternative recombination-based intersectional genetic manipulations.

Glymphatic distribution of CSF-derived apoE into brain is isoform specific and suppressed during sleep deprivation.

PubMed

Achariyar, Thiyagaragan M; Li, Baoman; Peng, Weiguo; Verghese, Philip B; Shi, Yang; McConnell, Evan; Benraiss, Abdellatif; Kasper, Tristan; Song, Wei; Takano, Takahiro; Holtzman, David M; Nedergaard, Maiken; Deane, Rashid

2016-12-08

Apolipoprotein E (apoE) is a major carrier of cholesterol and essential for synaptic plasticity. In brain, it's expressed by many cells but highly expressed by the choroid plexus and the predominant apolipoprotein in cerebrospinal fluid (CSF). The role of apoE in the CSF is unclear. Recently, the glymphatic system was described as a clearance system whereby CSF and ISF (interstitial fluid) is exchanged via the peri-arterial space and convective flow of ISF clearance is mediated by aquaporin 4 (AQP4), a water channel. We reasoned that this system also serves to distribute essential molecules in CSF into brain. The aim was to establish whether apoE in CSF, secreted by the choroid plexus, is distributed into brain, and whether this distribution pattern was altered by sleep deprivation. We used fluorescently labeled lipidated apoE isoforms, lenti-apoE3 delivered to the choroid plexus, immunohistochemistry to map apoE brain distribution, immunolabeled cells and proteins in brain, Western blot analysis and ELISA to determine apoE levels and radiolabeled molecules to quantify CSF inflow into brain and brain clearance in mice. Data were statistically analyzed using ANOVA or Student's t- test. We show that the glymphatic fluid transporting system contributes to the delivery of choroid plexus/CSF-derived human apoE to neurons. CSF-delivered human apoE entered brain via the perivascular space of penetrating arteries and flows radially around arteries, but not veins, in an isoform specific manner (apoE2 > apoE3 > apoE4). Flow of apoE around arteries was facilitated by AQP4, a characteristic feature of the glymphatic system. ApoE3, delivered by lentivirus to the choroid plexus and ependymal layer but not to the parenchymal cells, was present in the CSF, penetrating arteries and neurons. The inflow of CSF, which contains apoE, into brain and its clearance from the interstitium were severely suppressed by sleep deprivation compared to the sleep state. Thus, choroid plexus/CSF provides an additional source of apoE and the glymphatic fluid transporting system delivers it to brain via the periarterial space. By implication, failure in this essential physiological role of the glymphatic fluid flow and ISF clearance may also contribute to apoE isoform-specific disorders in the long term.

Etiological evaluation of primary congenital hypothyroidism cases

PubMed Central

Bezen, Diğdem; Dilek, Emine; Torun, Neşe; Tütüncüler, Filiz

2017-01-01

Aim Primary congenital hypothyroidism is frequently seen endocrine disorder and one of the preventable cause of mental retardation. Aim of study was to evaluate the frequency of permanent/transient hypothyrodism, and to detect underlying reason to identfy any marker which carries potential to discriminate permanent/transient form. Material and Methods Forty eight cases older than 3 years of age, diagnosed as primary congenital hypothyroidism and started thyroxin therapy in newborn-period, and followed up between January 2007–June 2013 were included in the study. Thyroid hormon levels were evaluated and thyroid ultrasonography was performed in cases who are at the end of their 3 years of age, after 6 weeks of thyroxine free period. Thyroid sintigraphy was performed if serum thyroid-stimulating hormone was high (≥ 5 mIU/mL) and perchlorate discharge test was performed if uptake was normal or increased on sintigraphy. Cases with thyroid-stimulating hormone levels ≥ 5 mIU/mL were defined as permanent primary congenital hypothyroidism group and as transient primary congenital hypothyroidism group with normal thyroid hormones during 6 months. Results The mean age was 3.8±0.7 years. Mean diagnosis age was 16.6±6.5 days and 14 cases (29.2%) were diagnosed by screening program of Ministry of Health. There were 23 cases (14F, 9M) in permanent primary congenital hypothyroidism group and 12 (52.2%) of them were dysgenesis (8 hypoplasia, 4 ectopia), and 11 (47.8%) dyshormonogenesis. In transient primary congenital hypothyroidism group, there were 25 cases (17M, 8F). The mean thyroid-stimulating hormone levels at diagnosis were similar in two groups. The mean thyroxin dose in permanent primary congenital hypothyroidism group was significantly higher than transient group at the time of thyroxin cessation (2.1±0.7, 1.5±0.5 mg/kg/d, respectively, p=0.004). Thyroxin dose ≥1.6 mcg/kg/d was 72% sensitive and 69.6% specific for predicting permenant primary congenital hypothyroidism. Conclusions Transient primary congenital hypothyroidism is more frequent than expected and found often in males in the primary congenital hypothyroidism cases, started thyroxin therapy in neonatal period. While fT4, thyroid-stimulating hormone, Tg levels at diagnosis do not predict transient/permenant primary congenital hypothyroidism, thyroxin dose before the therapy cessation at the age of 3 may make the distinction between transient/permenant primary congenital hypothyroidism. PMID:28747839

Protein p16 as a marker of dysplastic and neoplastic alterations in cervical epithelial cells

PubMed Central

Volgareva, Galina; Zavalishina, Larisa; Andreeva, Yulia; Frank, Georgy; Krutikova, Ella; Golovina, Darya; Bliev, Alexander; Spitkovsky, Dimitry; Ermilova, Valeriya; Kisseljov, Fjodor

2004-01-01

Background Cervical carcinomas are second most frequent type of women cancer. Success in diagnostics of this disease is due to the use of Pap-test (cytological smear analysis). However Pap-test gives significant portion of both false-positive and false-negative conclusions. Amendments of the diagnostic procedure are desirable. Aetiological role of papillomaviruses in cervical cancer is established while the role of cellular gene alterations in the course of tumor progression is less clear. Several research groups including us have recently named the protein p16INK4a as a possible diagnostic marker of cervical cancer. To evaluate whether the specificity of p16INK4a expression in dysplastic and neoplastic cervical epithelium is sufficient for such application we undertook a broader immunochistochemical registration of this protein with a highly p16INK4a-specific monoclonal antibody. Methods Paraffin-embedded samples of diagnostic biopsies and surgical materials were used. Control group included vaginal smears of healthy women and biopsy samples from patients with cervical ectopia. We examined 197 samples in total. Monoclonal antibody E6H4 (MTM Laboratories, Germany) was used. Results In control samples we did not find any p16INK4a-positive cells. Overexpression of p16INK4a was detected in samples of cervical dysplasia (CINs) and carcinomas. The portion of p16INK4a-positive samples increased in the row: CIN I – CIN II – CIN III – invasive carcinoma. For all stages the samples were found to be heterogeneous with respect to p16INK4a-expression. Every third of CINs III and one invasive squamous cell carcinoma (out of 21 analyzed) were negative. Conclusions Overexpression of the protein p16INK4a is typical for dysplastic and neoplastic epithelium of cervix uteri. However p16INK4a-negative CINs and carcinomas do exist. All stages of CINs and carcinomas analyzed are heterogeneous with respect to p16INK4a expression. So p16INK4a-negativity is not a sufficient reason to exclude a patient from the high risk group. As far as normal cervical epithelium is p16INK4a-negative and the ratio p16INK4a-positive/ p16INK4a-negative samples increases at the advanced stages application of immunohisto-/cytochemical test for p16INK4a may be regarded as a supplementary test for early diagnostics of cervical cancer. PMID:15339339

The effects of Kiaa0319 knockdown on cortical and subcortical anatomy in male rats

PubMed Central

Szalkowski, Caitlin E.; Fiondella, Christopher F.; Truong, Dongnhu T.; Rosen, Glenn D.; LoTurco, Joseph J.; Fitch, Roslyn H.

2012-01-01

Developmental dyslexia is a disorder characterized by a specific deficit in reading despite adequate overall intelligence and educational resources. The neurological substrate underlying these significant behavioral impairments is not known. Studies of post mortem brain tissue from male and female dyslexic individuals revealed focal disruptions of neuronal migration concentrated in the left hemisphere, along with aberrant symmetry of the right and left the planum temporale, and changes in cell size distribution within the medial geniculate nucleus of the thalamus (Galaburda et al., 1985; Humphreys et al., 1990). More recent neuroimaging studies have identified several changes in the brains of dyslexic individuals, including regional changes in gray matter, changes in white matter, and changes in patterns of functional activation. In a further effort to elucidate the etiology of dyslexia, epidemiological and genetic studies have identified several candidate dyslexia susceptibility genes. Some recent work has investigated associations between some of these genetic variants and structural changes in the brain. Variants of one candidate dyslexia susceptibility gene, KIAA0319, have been linked to morphological changes in the cerebellum and functional activational changes in the superior temporal sulcus (Jamadar et al., 2011; Pinel et al., 2012). Animal models have been used to create a knockdown of Kiaa0319 (the rodent homolog of the human gene) via in utero RNA interference in order to study the gene’s effects on brain development and behavior. Studies using this animal model have demonstrated that knocking down the gene leads to focal disruptions of neuronal migration in the form of ectopias and heterotopias, similar to those observed in the brains of human dyslexics. However, further changes to the structure of the brain have not been studied following this genetic disruption. The current study sought to determine the effects of embryonic Kiaa0319 knockdown on volume of the cortex and hippocampus, as well as midsagittal area of the corpus callosum in male rats. Results demonstrate that Kiaa0319 knockdown did not change the volume of the cortex or hippocampus, but did result in a significant reduction in the midsagittal area of the corpus callosum. Taken in the context of previous reports of behavioral deficits following Kiaa0319 knockdown (Szalkowski et al., 2012), and reports that reductions of corpus callosum size are related to processing deficits in humans (Paul et al., 2011), these results suggest that Kiaa0319 has a specific involvement in neural systems important for temporal processing. PMID:23220223

77 FR 76604 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-28

... currently approved collection. Title: Form 5304-SIMPLE; Form 5305-SIMPLE; Notice 98-4. Abstract: Forms 5304-SIMPLE and 5035-SIMPLE are used by an employer to permit employees to make salary reduction contributions to a savings incentive match plan (SIMPLE IRA) described in Code section 408(p). These forms are not...

Simple Kidney Cysts

MedlinePlus

... Solitary Kidney Your Kidneys & How They Work Simple Kidney Cysts What are simple kidney cysts? Simple kidney cysts are abnormal, fluid-filled ... that form in the kidneys. What are the kidneys and what do they do? The kidneys are ...

Simple Rules, Not So Simple: The Use of International Ovarian Tumor Analysis (IOTA) Terminology and Simple Rules in Inexperienced Hands in a Prospective Multicenter Cohort Study.

PubMed

Meys, Evelyne; Rutten, Iris; Kruitwagen, Roy; Slangen, Brigitte; Lambrechts, Sandrina; Mertens, Helen; Nolting, Ernst; Boskamp, Dieuwke; Van Gorp, Toon

2017-12-01

 To analyze how well untrained examiners - without experience in the use of International Ovarian Tumor Analysis (IOTA) terminology or simple ultrasound-based rules (simple rules) - are able to apply IOTA terminology and simple rules and to assess the level of agreement between non-experts and an expert.  This prospective multicenter cohort study enrolled women with ovarian masses. Ultrasound was performed by non-expert examiners and an expert. Ultrasound features were recorded using IOTA nomenclature, and used for classifying the mass by simple rules. Interobserver agreement was evaluated with Fleiss' kappa and percentage agreement between observers.  50 consecutive women were included. We observed 46 discrepancies in the description of ovarian masses when non-experts utilized IOTA terminology. Tumor type was misclassified often (n = 22), resulting in poor interobserver agreement between the non-experts and the expert (kappa = 0.39, 95 %-CI 0.244 - 0.529, percentage of agreement = 52.0 %). Misinterpretation of simple rules by non-experts was observed 57 times, resulting in an erroneous diagnosis in 15 patients (30 %). The agreement for classifying the mass as benign, malignant or inconclusive by simple rules was only moderate between the non-experts and the expert (kappa = 0.50, 95 %-CI 0.300 - 0.704, percentage of agreement = 70.0 %). The level of agreement for all 10 simple rules features varied greatly (kappa index range: -0.08 - 0.74, percentage of agreement 66 - 94 %).  Although simple rules are useful to distinguish benign from malignant adnexal masses, they are not that simple for untrained examiners. Training with both IOTA terminology and simple rules is necessary before simple rules can be introduced into guidelines and daily clinical practice. © Georg Thieme Verlag KG Stuttgart · New York.

Pseudo-simple heteroclinic cycles in R4

NASA Astrophysics Data System (ADS)

Chossat, Pascal; Lohse, Alexander; Podvigina, Olga

2018-06-01

We study pseudo-simple heteroclinic cycles for a Γ-equivariant system in R4 with finite Γ ⊂ O(4) , and their nearby dynamics. In particular, in a first step towards a full classification - analogous to that which exists already for the class of simple cycles - we identify all finite subgroups of O(4) admitting pseudo-simple cycles. To this end we introduce a constructive method to build equivariant dynamical systems possessing a robust heteroclinic cycle. Extending a previous study we also investigate the existence of periodic orbits close to a pseudo-simple cycle, which depends on the symmetry groups of equilibria in the cycle. Moreover, we identify subgroups Γ ⊂ O(4) , Γ ⊄ SO(4) , admitting fragmentarily asymptotically stable pseudo-simple heteroclinic cycles. (It has been previously shown that for Γ ⊂ SO(4) pseudo-simple cycles generically are completely unstable.) Finally, we study a generalized heteroclinic cycle, which involves a pseudo-simple cycle as a subset.

Simple projects guidebook : federal-aid procedure for simple projects

DOT National Transportation Integrated Search

2002-06-01

Experience has shown that a simple project generally 1) does not have any right-of-way involvement and 2) has a Programmatic Categorical Exclusion or Categorical Exclusion environmental determination. Page 7 outlines the definition of simple projects...

Triple-loaded single-anchor stitch configurations: an analysis of cyclically loaded suture-tendon interface security.

PubMed

Coons, David A; Barber, F Alan; Herbert, Morley A

2006-11-01

This study evaluated the strength and suture-tendon interface security of different suture configurations from triple-suture-loaded anchors. A juvenile bovine infraspinatus tendon was detached and repaired by use of 4 different suture combinations from 2 suture anchors: 3 simple sutures in each anchor (ThreeVo anchor; Linvatec, Largo, FL); 2 peripheral simple stitches and 1 central horizontal mattress suture passed deeper into the tendon, creating a larger footprint (bigfoot-print anchor); 2 peripheral simple stitches with 1 central horizontal mattress stitch passed through the same holes as the simple sutures (stitch-of-Burns); and 2 simple stitches (TwoVo anchor; Linvatec). The constructs were cyclically loaded between 10 N and 180 N for 3,500 cycles and then destructively tested. The number of cycles required to create a 5-mm gap and a 10-mm gap and the ultimate load to failure and failure mode were recorded. The ThreeVo anchor was strongest and most resistant to cyclic loading (P < .01). The TwoVo anchor was least resistant to cyclic loading. The stitch-of-Burns anchor was more resistant to cyclic loading than both the bigfoot-print anchor and the TwoVo anchor (P < .03). The ThreeVo, stitch-of-Burns, and TwoVo anchors were stronger than the bigfoot-print anchor (P < .05). Three simple sutures in an anchor hold better than two simple sutures. Three simple sutures provide superior suture-tendon security than combinations of one mattress and two simple stitches subjected to cyclic loading. A central mattress stitch placed more medially than two peripheral simple stitches (bigfoot-print anchor) configured to enlarge the tendon-suture footprint was not as resistant to cyclic loading or destructive testing as three simple stitches (ThreeVo anchor). Placing a central mattress stitch more medially than 2 peripheral simple stitches to enlarge the tendon-suture footprint was not as resistant to cyclic loading or destructive testing as 3 simple stitches.

77 FR 63925 - Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-17

..., Savings Incentive Match Plan for Employees of Small Employers (SIMPLE)--Not for Use With a Designated Financial Institution; Form 5305-SIMPLE, Savings Incentive Match Plan for Employees of Small Employers (SIMPLE)--for Use With a Designated Financial Institution; Notice 98-4, Simple IRA Plan Guidance. DATES...

Canonical Representations of the Simple Map

NASA Astrophysics Data System (ADS)

Kerwin, Olivia; Punjabi, Alkesh; Ali, Halima; Boozer, Allen

2007-11-01

The simple map is the simplest map that has the topology of a divertor tokamak. The simple map has three canonical representations: (i) toroidal flux and poloidal angle (ψ,θ) as canonical coordinates, (ii) the physical variables (R,Z) or (X,Y) as canonical coordinates, and (iii) the action-angle (J,ζ) or magnetic variables (ψ,θ) as canonical coordinates. We give the derivation of the simple map in the (X,Y) representation. The simple map in this representation has been studied extensively (Ref. 1 and references therein). We calculate the magnetic coordinates for the simple map, construct the simple map in magnetic coordinates, and calculate generic topological effects of magnetic perturbations in divertor tokamaks using the map. We also construct the simple map in (ψ,θ) representation. Preliminary results of these studies will be presented. This work is supported by US DOE OFES DE-FG02-01ER54624 and DE-FG02-04ER54793. [1] A. Punjabi, H. Ali, T. Evans, and A. Boozer, Phys Lett A 364 140--145 (2007).

Study on shear properties of coral sand under cyclic simple shear condition

NASA Astrophysics Data System (ADS)

Ji, Wendong; Zhang, Yuting; Jin, Yafei

2018-05-01

In recent years, the ocean development in our country urgently needs to be accelerated. The construction of artificial coral reefs has become an important development direction. In this paper, experimental studies of simple shear and cyclic simple shear of coral sand are carried out, and the shear properties and particle breakage of coral sand are analyzed. The results show that the coral sand samples show an overall shear failure in the simple shear test, which is more accurate and effective for studying the particle breakage. The shear displacement corresponding to the peak shear stress of the simple shear test is significantly larger than that corresponding to the peak shear stress of the direct shear test. The degree of particle breakage caused by the simple shear test is significantly related to the normal stress level. The particle breakage of coral sand after the cyclic simple shear test obviously increases compared with that of the simple shear test, and universal particle breakage occurs within the whole particle size range. The increasing of the cycle-index under cyclic simple shear test results in continuous compacting of the sample, so that the envelope curve of peak shearing force increases with the accumulated shear displacement.

SIMPLE: An Introduction.

ERIC Educational Resources Information Center

Endres, Frank L.

Symbolic Interactive Matrix Processing Language (SIMPLE) is a conversational matrix-oriented source language suited to a batch or a time-sharing environment. The two modes of operation of SIMPLE are conversational mode and programing mode. This program uses a TAURUS time-sharing system and cathode ray terminals or teletypes. SIMPLE performs all…

76 FR 17718 - Simple Alternatives, LLC and The RBB Fund, Inc.; Notice of Application

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-30

... SECURITIES AND EXCHANGE COMMISSION [Investment Company Act Release No. 29616; 812-13801] Simple... approval and would grant relief from certain disclosure requirements. Applicants: Simple Alternatives, LLC (``Simple Alternatives'') and The RBB Fund, Inc. (the ``Company''). Filing Dates: The application was filed...

76 FR 56263 - Titles II and XVI: Documenting and Evaluating Disability in Young Adults

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-12

... carrying out simple instructions and work procedures during a school-sponsored work experience; Difficulty... instructions; Make simple work-related judgments typically required for unskilled work; Respond appropriately... ability to hear and understand simple oral messages, including instructions, and to communicate simple...

Management system of simple rental flats study based on technical aspect and health in Medan city

NASA Astrophysics Data System (ADS)

Novrial; Indra Cahaya, S.

2018-03-01

Medan city is a metropolis city in Sumatera that has slums area. Simple rental flats have been built to overcome the problem. However the preliminary survey result showed that the physical and non-physical environment management of simple rent flats is very bad. This study conducted in 3 simple rent flats. It has observed the simple rent flats environment and has interviewed occupants and related agencies. Results of conducted research showed the occupant’s characteristics based on the largest percentage are Javanese; last education is senior high with self-employed work with average income Rp 1,000,000 – Rp 2,500,000. Waste retribution submitted to their cleanliness except for Amplas simple rent flats, their waste management system does not manage properly and the garbage littered. The number of family members of Wisma Labuhan and Amplas simple rent flats exceeds the regulation number of occupants, so it is crowded and noisy. Physical conditions of Amplas simple rent flats are bad, septic tank is full and are not vacuumed. Clean water sources derived from wells and artesian wll are vulnerable to be contaminated by pollutants such as leachate and bad quality water. It is necessary to improve the physical, basic sanitation, and guidance for the simple rent flats occupants to the management system of Simple Rent Flats.

Simple yet Hidden Counterexamples in Undergraduate Real Analysis

ERIC Educational Resources Information Center

Shipman, Barbara A.; Shipman, Patrick D.

2013-01-01

We study situations in introductory analysis in which students affirmed false statements as true, despite simple counterexamples that they easily recognized afterwards. The study draws attention to how simple counterexamples can become hidden in plain sight, even in an active learning atmosphere where students proposed simple (as well as more…

5 CFR 1315.17 - Formulas.

Code of Federal Regulations, 2010 CFR

2010-01-01

...) Daily simple interest formula. (1) To calculate daily simple interest the following formula may be used... a payment is due on April 1 and the payment is not made until April 11, a simple interest... equation calculates simple interest on any additional days beyond a monthly increment. (3) For example, if...

8 CFR 293.3 - Simple interest table.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Simple interest table. 293.3 Section 293.3 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY IMMIGRATION REGULATIONS DEPOSIT OF AND INTEREST ON CASH RECEIVED TO SECURE IMMIGRATION BONDS § 293.3 Simple interest table. Following is a simple interest...

SIMPL Systems, or: Can We Design Cryptographic Hardware without Secret Key Information?

NASA Astrophysics Data System (ADS)

Rührmair, Ulrich

This paper discusses a new cryptographic primitive termed SIMPL system. Roughly speaking, a SIMPL system is a special type of Physical Unclonable Function (PUF) which possesses a binary description that allows its (slow) public simulation and prediction. Besides this public key like functionality, SIMPL systems have another advantage: No secret information is, or needs to be, contained in SIMPL systems in order to enable cryptographic protocols - neither in the form of a standard binary key, nor as secret information hidden in random, analog features, as it is the case for PUFs. The cryptographic security of SIMPLs instead rests on (i) a physical assumption on their unclonability, and (ii) a computational assumption regarding the complexity of simulating their output. This novel property makes SIMPL systems potentially immune against many known hardware and software attacks, including malware, side channel, invasive, or modeling attacks.

Is simple nephrectomy truly simple? Comparison with the radical alternative.

PubMed

Connolly, S S; O'Brien, M Frank; Kunni, I M; Phelan, E; Conroy, R; Thornhill, J A; Grainger, R

2011-03-01

The Oxford English dictionary defines the term "simple" as "easily done" and "uncomplicated". We tested the validity of this terminology in relation to open nephrectomy surgery. Retrospective review of 215 patients undergoing open, simple (n = 89) or radical (n = 126) nephrectomy in a single university-affiliated institution between 1998 and 2002. Operative time (OT), estimated blood loss (EBL), operative complications (OC) and length of stay in hospital (LOS) were analysed. Statistical analysis employed Fisher's exact test and Stata Release 8.2. Simple nephrectomy was associated with shorter OT (mean 126 vs. 144 min; p = 0.002), reduced EBL (mean 729 vs. 859 cc; p = 0.472), lower OC (9 vs. 17%; 0.087), and more brief LOS (mean 6 vs. 8 days; p < 0.001). All parameters suggest favourable outcome for the simple nephrectomy group, supporting the use of this terminology. This implies "simple" nephrectomies are truly easier to perform with less complication than their radical counterpart.

Simple Levelized Cost of Energy (LCOE) Calculator Documentation | Energy

Science.gov Websites

Analysis | NREL Simple Levelized Cost of Energy (LCOE) Calculator Documentation Simple Levelized Cost of Energy (LCOE) Calculator Documentation Transparent Cost Database Button This is a simple : 1). Cost and Performance Adjust the sliders to suitable values for each of the cost and performance

The Role of Diffusion-Weighted Magnetic Resonance Imaging in the Differential Diagnosis of Simple and Hydatid Cysts of the Liver.

PubMed

Aksoy, S; Erdil, I; Hocaoglu, E; Inci, E; Adas, G T; Kemik, O; Turkay, R

2018-02-01

The present study indicates that simple and hydatid cysts in liver are a common health problem in Turkey. The aim of the study is to differentiate different types of hydatid cysts from simple cysts by using diffusion-weighted images. In total, 37 hydatid cysts and 36 simple cysts in the liver were diagnosed. We retrospectively reviewed the medical records of the patients who had both ultrasonography and magnetic resonance imaging. We measured apparent diffusion coefficient (ADC) values of all the cysts and then compared the findings. There was no statistically meaningful difference between the ADC values of simple cysts and type 1 hydatid cysts. However, for the other types of hydatid cysts, it is possible to differentiate hydatid cysts from simple cysts using the ADC values. Although in our study we cannot differentiate between type I hydatid cysts and simple cysts in the liver, diffusion-weighted images are very useful to differentiate different types of hydatid cysts from simple cysts using the ADC values.

Change in hippocampal theta activity with transfer from simple discrimination tasks to a simultaneous feature-negative task

PubMed Central

Sakimoto, Yuya; Sakata, Shogo

2014-01-01

It was showed that solving a simple discrimination task (A+, B−) and a simultaneous feature-negative (FN) task (A+, AB−) used the hippocampal-independent strategy. Recently, we showed that the number of sessions required for a rat to completely learn a task differed between the FN and simple discrimination tasks, and there was a difference in hippocampal theta activity between these tasks. These results suggested that solving the FN task relied on a different strategy than the simple discrimination task. In this study, we provided supportive evidence that solving the FN and simple discrimination tasks involved different strategies by examining changes in performance and hippocampal theta activity in the FN task after transfer from the simple discrimination task (A+, B− → A+, AB−). The results of this study showed that performance on the FN task was impaired and there was a difference in hippocampal theta activity between the simple discrimination task and FN task. Thus, we concluded that solving the FN task uses a different strategy than the simple discrimination task. PMID:24917797

Analysis of pre-service physics teacher skills designing simple physics experiments based technology

NASA Astrophysics Data System (ADS)

Susilawati; Huda, C.; Kurniawan, W.; Masturi; Khoiri, N.

2018-03-01

Pre-service physics teacher skill in designing simple experiment set is very important in adding understanding of student concept and practicing scientific skill in laboratory. This study describes the skills of physics students in designing simple experiments based technologicall. The experimental design stages include simple tool design and sensor modification. The research method used is descriptive method with the number of research samples 25 students and 5 variations of simple physics experimental design. Based on the results of interviews and observations obtained the results of pre-service physics teacher skill analysis in designing simple experimental physics charged technology is good. Based on observation result, pre-service physics teacher skill in designing simple experiment is good while modification and sensor application are still not good. This suggests that pre-service physics teacher still need a lot of practice and do experiments in designing physics experiments using sensor modifications. Based on the interview result, it is found that students have high enough motivation to perform laboratory activities actively and students have high curiosity to be skilled at making simple practicum tool for physics experiment.

IOTA simple rules in differentiating between benign and malignant ovarian tumors.

PubMed

Tantipalakorn, Charuwan; Wanapirak, Chanane; Khunamornpong, Surapan; Sukpan, Kornkanok; Tongsong, Theera

2014-01-01

To evaluate the diagnostic performance of IOTA simple rules in differentiating between benign and malignant ovarian tumors. A study of diagnostic performance was conducted on women scheduled for elective surgery due to ovarian masses between March 2007 and March 2012. All patients underwent ultrasound examination for IOTA simple rules within 24 hours of surgery. All examinations were performed by the authors, who had no any clinical information of the patients, to differentiate between benign and malignant adnexal masses using IOTA simple rules. Gold standard diagnosis was based on pathological or operative findings. A total of 398 adnexal masses, in 376 women, were available for analysis. Of them, the IOTA simple rules could be applied in 319 (80.1%) including 212 (66.5%) benign tumors and 107 (33.6%) malignant tumors. The simple rules yielded inconclusive results in 79 (19.9%) masses. In the 319 masses for which the IOTA simple rules could be applied, sensitivity was 82.9% and specificity 95.3%. The IOTA simple rules have high diagnostic performance in differentiating between benign and malignant adnexal masses. Nevertheless, inconclusive results are relatively common.

Enhancement of orientation gradients during simple shear deformation by application of simple compression

NASA Astrophysics Data System (ADS)

Jahedi, Mohammad; Ardeljan, Milan; Beyerlein, Irene J.; Paydar, Mohammad Hossein; Knezevic, Marko

2015-06-01

We use a multi-scale, polycrystal plasticity micromechanics model to study the development of orientation gradients within crystals deforming by slip. At the largest scale, the model is a full-field crystal plasticity finite element model with explicit 3D grain structures created by DREAM.3D, and at the finest scale, at each integration point, slip is governed by a dislocation density based hardening law. For deformed polycrystals, the model predicts intra-granular misorientation distributions that follow well the scaling law seen experimentally by Hughes et al., Acta Mater. 45(1), 105-112 (1997), independent of strain level and deformation mode. We reveal that the application of a simple compression step prior to simple shearing significantly enhances the development of intra-granular misorientations compared to simple shearing alone for the same amount of total strain. We rationalize that the changes in crystallographic orientation and shape evolution when going from simple compression to simple shearing increase the local heterogeneity in slip, leading to the boost in intra-granular misorientation development. In addition, the analysis finds that simple compression introduces additional crystal orientations that are prone to developing intra-granular misorientations, which also help to increase intra-granular misorientations. Many metal working techniques for refining grain sizes involve a preliminary or concurrent application of compression with severe simple shearing. Our finding reveals that a pre-compression deformation step can, in fact, serve as another processing variable for improving the rate of grain refinement during the simple shearing of polycrystalline metals.

Evaluating Lexical Coverage in Simple English Wikipedia Articles: A Corpus-Driven Study

ERIC Educational Resources Information Center

Hendry, Clinton; Sheepy, Emily

2017-01-01

Simple English Wikipedia is a user-contributed online encyclopedia intended for young readers and readers whose first language is not English. We compiled a corpus of the entirety of Simple English Wikipedia as of June 20th, 2017. We used lexical frequency profiling tools to investigate the vocabulary size needed to comprehend Simple English…

Item Selection, Evaluation, and Simple Structure in Personality Data

PubMed Central

Pettersson, Erik; Turkheimer, Eric

2010-01-01

We report an investigation of the genesis and interpretation of simple structure in personality data using two very different self-reported data sets. The first consists of a set of relatively unselected lexical descriptors, whereas the second is based on responses to a carefully constructed instrument. In both data sets, we explore the degree of simple structure by comparing factor solutions to solutions from simulated data constructed to have either strong or weak simple structure. The analysis demonstrates that there is little evidence of simple structure in the unselected items, and a moderate degree among the selected items. In both instruments, however, much of the simple structure that could be observed originated in a strong dimension of positive vs. negative evaluation. PMID:20694168

Airtightness the simple(CS) way

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

Andrews, S.

Builders who might buck against such time consuming air sealing methods as polyethylene wrap and the airtight drywall approach (ADA) may respond better to current strategies. One such method, called SimpleCS, has proven especially effective. SimpleCS, pronounced simplex, stands for simple caulk and seal. A modification of the ADA, SimpleCS is an air-sealing management tool, a simplified systems approach to building tight homes. The system address the crucial question of when and by whom various air sealing steps should be done. It avoids the problems that often occur when later contractors cut open polyethylene wrap to drill holes in themore » drywall. The author describes how SimpleCS works, and the cost and training involved.« less

[Comparison of four MICS intraocular lenses regarding their rates of neodymium:YAG laser capsulotomy].

PubMed

Spyridaki, M; Höh, H

2010-03-01

The aim of this study was to evaluate the incidence of posterior capsule opacification up to 50 months following 1.7-mm bimanual MICS-cataract surgery. Bimanual MICS cataract surgery was performed in 197 eyes (135 patients) via two 1.7-mm corneal incisions. Four MICS acrylic foldable IOLs were implanted: AcriSmart 48S-5, n = 54 (Acritec GmbH, Hennigsdorf, now AT.Smart 48S Carl-Zeiss-Meditec, AG, Jena, Germany), ThinLens UltraChoice 1.0, n = 53 (Technomed GmbH, Baesweiler, Germany), AcriFlex 46, n = 41 und AcriFlex 48 CSE, n = 7 (Acrimed GmbH, Berlin, now: Lentis L-303, Oculentis GmbH, Berlin, Germany) and CareFlex, n = 43 (w2o Medizintechnik AG, Bruchsal, Germany). Statistical analysis was performed using the Kaplan-Meier technique. High levels of completeness of follow-up rates were: ThinLens 96%, CareFlex 100%, AcriSmart 93%, AcriFlex 92%. The capsulotomy rate was 43.13% for ThinLens within a mean/max. follow-up period of 801/1131 days, 34.88% for CareFlex (565/872 days), 40% for AcriSmart (988/1506 days) and 15.91% for AcriFlex (728/975 days). By limiting the follow-up period to a comparable maximum of 850 days for all four IOLs, our capsulotomy rates were as follows: ThinLens 33.33%, CareFlex 32.56 %, AcriSmart 20.0% and AcriFlex 11.36%. MICS IOLs have higher capsulotomy rates than hydrophobic acrylic lenses and sharp-edged silicone lenses. In literature comparisons MICS-IOLs do not exceed the variance levels of capsulotomy rates of PMMA, hydrophilic acrylic and silicone lenses without sharp edges. Cases of decentration or luxation of MICS-IOLs following Neodym:YAG laser capsulotomy were not detected. Capsulotomy frequency with the CareFlex was statistically significantly higher in comparison to the AcriSmart (Log Rank Mantel Cox Test, p = 0.007) and AcriFlex (log rank Mantel Cox test, p = 0.002). Capsulotomy rates observed varied for the four MICS-IOL-types tested. The posterior capsule opacification frequency of the two best MICS-IOLs (AcriFlex, AcriSmart) did not exceed the higher variance levels of posterior capsule opacification rates of the round-edged "conventional" non-MICS IOLs of PMMA, silicone or hydrophilic acryl material. Sharp-edged silicone or hydrophobic acrylic "conventional" lenses have shown lower posterior capsule opacification rates. Georg Thieme Verlag KG Stuttgart, New York.

Inverse kinematic solution for near-simple robots and its application to robot calibration

NASA Technical Reports Server (NTRS)

Hayati, Samad A.; Roston, Gerald P.

1986-01-01

This paper provides an inverse kinematic solution for a class of robot manipulators called near-simple manipulators. The kinematics of these manipulators differ from those of simple-robots by small parameter variations. Although most robots are by design simple, in practice, due to manufacturing tolerances, every robot is near-simple. The method in this paper gives an approximate inverse kinematics solution for real time applications based on the nominal solution for these robots. The validity of the results are tested both by a simulation study and by applying the algorithm to a PUMA robot.

Simple and Double Alfven Waves: Hamiltonian Aspects

NASA Astrophysics Data System (ADS)

Webb, G. M.; Zank, G. P.; Hu, Q.; le Roux, J. A.; Dasgupta, B.

2011-12-01

We discuss the nature of simple and double Alfvén waves. Simple waves depend on a single phase variable \\varphi, but double waves depend on two independent phase variables \\varphi1 and \\varphi2. The phase variables depend on the space and time coordinates x and t. Simple and double Alfvén waves have the same integrals, namely, the entropy, density, magnetic pressure, and group velocity (the sum of the Alfvén and fluid velocities) are constant throughout the flow. We present examples of both simple and double Alfvén waves, and discuss Hamiltonian formulations of the waves.

Synaptic Basis for Differential Orientation Selectivity between Complex and Simple Cells in Mouse Visual Cortex

PubMed Central

Li, Ya-tang; Liu, Bao-hua; Chou, Xiao-lin; Zhang, Li I.

2015-01-01

In the primary visual cortex (V1), orientation-selective neurons can be categorized into simple and complex cells primarily based on their receptive field (RF) structures. In mouse V1, although previous studies have examined the excitatory/inhibitory interplay underlying orientation selectivity (OS) of simple cells, the synaptic bases for that of complex cells have remained obscure. Here, by combining in vivo loose-patch and whole-cell recordings, we found that complex cells, identified by their overlapping on/off subfields, had significantly weaker OS than simple cells at both spiking and subthreshold membrane potential response levels. Voltage-clamp recordings further revealed that although excitatory inputs to complex and simple cells exhibited a similar degree of OS, inhibition in complex cells was more narrowly tuned than excitation, whereas in simple cells inhibition was more broadly tuned than excitation. The differential inhibitory tuning can primarily account for the difference in OS between complex and simple cells. Interestingly, the differential synaptic tuning correlated well with the spatial organization of synaptic input: the inhibitory visual RF in complex cells was more elongated in shape than its excitatory counterpart and also was more elongated than that in simple cells. Together, our results demonstrate that OS of complex and simple cells is differentially shaped by cortical inhibition based on its orientation tuning profile relative to excitation, which is contributed at least partially by the spatial organization of RFs of presynaptic inhibitory neurons. SIGNIFICANCE STATEMENT Simple and complex cells, two classes of principal neurons in the primary visual cortex (V1), are generally thought to be equally selective for orientation. In mouse V1, we report that complex cells, identified by their overlapping on/off subfields, has significantly weaker orientation selectivity (OS) than simple cells. This can be primarily attributed to the differential tuning selectivity of inhibitory synaptic input: inhibition in complex cells is more narrowly tuned than excitation, whereas in simple cells inhibition is more broadly tuned than excitation. In addition, there is a good correlation between inhibitory tuning selectivity and the spatial organization of inhibitory inputs. These complex and simple cells with differential degree of OS may provide functionally distinct signals to different downstream targets. PMID:26245969

Synaptic Basis for Differential Orientation Selectivity between Complex and Simple Cells in Mouse Visual Cortex.

PubMed

Li, Ya-tang; Liu, Bao-hua; Chou, Xiao-lin; Zhang, Li I; Tao, Huizhong W

2015-08-05

In the primary visual cortex (V1), orientation-selective neurons can be categorized into simple and complex cells primarily based on their receptive field (RF) structures. In mouse V1, although previous studies have examined the excitatory/inhibitory interplay underlying orientation selectivity (OS) of simple cells, the synaptic bases for that of complex cells have remained obscure. Here, by combining in vivo loose-patch and whole-cell recordings, we found that complex cells, identified by their overlapping on/off subfields, had significantly weaker OS than simple cells at both spiking and subthreshold membrane potential response levels. Voltage-clamp recordings further revealed that although excitatory inputs to complex and simple cells exhibited a similar degree of OS, inhibition in complex cells was more narrowly tuned than excitation, whereas in simple cells inhibition was more broadly tuned than excitation. The differential inhibitory tuning can primarily account for the difference in OS between complex and simple cells. Interestingly, the differential synaptic tuning correlated well with the spatial organization of synaptic input: the inhibitory visual RF in complex cells was more elongated in shape than its excitatory counterpart and also was more elongated than that in simple cells. Together, our results demonstrate that OS of complex and simple cells is differentially shaped by cortical inhibition based on its orientation tuning profile relative to excitation, which is contributed at least partially by the spatial organization of RFs of presynaptic inhibitory neurons. Simple and complex cells, two classes of principal neurons in the primary visual cortex (V1), are generally thought to be equally selective for orientation. In mouse V1, we report that complex cells, identified by their overlapping on/off subfields, has significantly weaker orientation selectivity (OS) than simple cells. This can be primarily attributed to the differential tuning selectivity of inhibitory synaptic input: inhibition in complex cells is more narrowly tuned than excitation, whereas in simple cells inhibition is more broadly tuned than excitation. In addition, there is a good correlation between inhibitory tuning selectivity and the spatial organization of inhibitory inputs. These complex and simple cells with differential degree of OS may provide functionally distinct signals to different downstream targets. Copyright © 2015 the authors 0270-6474/15/3511081-13$15.00/0.

Enabling People with Developmental Disabilities to Actively Follow Simple Instructions and Perform Designated Occupational Activities According to Simple Instructions with Battery-Free Wireless Mice by Controlling Environmental Stimulation

ERIC Educational Resources Information Center

Shih, Ching-Hsiang; Chang, Man-Ling

2012-01-01

This study extended Battery-free wireless mouse functionality to assess whether two people with developmental disabilities would be able to actively perform designated simple occupational activities according to simple instructions by controlling their favorite environmental stimulation using Battery-free wireless mice with a newly developed…

26 CFR 19.3-1 - Interest on certain deferred payments; interest rate for use in determining whether there is...

Code of Federal Regulations, 2010 CFR

2010-04-01

... annum simple interest shall be used. As an illustration of the meaning of simple interest, if a contract provides for payments of $6,000 in 3 equal installments of $2,000 plus 4 percent per annum simple interest... provides for discounting payments at a 4 percent per annum simple interest rate, shall be used for...

Management of Simple Clavicle Fractures by Primary Care Physicians.

PubMed

Stepanyan, Hayk; Gendelberg, David; Hennrikus, William

2017-05-01

The clavicle is the most commonly fractured bone. Children with simple fractures are often referred to orthopedic surgeons by primary care physician to ensure adequate care. The objective of this study was to show that simple clavicle fractures have excellent outcomes and are within the scope of primary care physician's practice. We performed a retrospective chart review of 16 adolescents with simple clavicle fractures treated with a sling. Primary outcomes were bony union, pain, and function. The patients with simple clavicle fractures had excellent outcomes with no complications or complaints of pain or restriction of their activities of daily living. The outcomes are similar whether treated by an orthopedic surgeon or a primary care physician. The cost to society and the patient is less when the primary care physician manages the fracture. Therefore, primary care physicians should manage simple clavicle fractures.

Combinational Reasoning of Quantitative Fuzzy Topological Relations for Simple Fuzzy Regions

PubMed Central

Liu, Bo; Li, Dajun; Xia, Yuanping; Ruan, Jian; Xu, Lili; Wu, Huanyi

2015-01-01

In recent years, formalization and reasoning of topological relations have become a hot topic as a means to generate knowledge about the relations between spatial objects at the conceptual and geometrical levels. These mechanisms have been widely used in spatial data query, spatial data mining, evaluation of equivalence and similarity in a spatial scene, as well as for consistency assessment of the topological relations of multi-resolution spatial databases. The concept of computational fuzzy topological space is applied to simple fuzzy regions to efficiently and more accurately solve fuzzy topological relations. Thus, extending the existing research and improving upon the previous work, this paper presents a new method to describe fuzzy topological relations between simple spatial regions in Geographic Information Sciences (GIS) and Artificial Intelligence (AI). Firstly, we propose a new definition for simple fuzzy line segments and simple fuzzy regions based on the computational fuzzy topology. And then, based on the new definitions, we also propose a new combinational reasoning method to compute the topological relations between simple fuzzy regions, moreover, this study has discovered that there are (1) 23 different topological relations between a simple crisp region and a simple fuzzy region; (2) 152 different topological relations between two simple fuzzy regions. In the end, we have discussed some examples to demonstrate the validity of the new method, through comparisons with existing fuzzy models, we showed that the proposed method can compute more than the existing models, as it is more expressive than the existing fuzzy models. PMID:25775452

Mutation of SIMPLE in Charcot–Marie–Tooth 1C alters production of exosomes

PubMed Central

Zhu, Hong; Guariglia, Sara; Yu, Raymond Y. L.; Li, Wenjing; Brancho, Deborah; Peinado, Hector; Lyden, David; Salzer, James; Bennett, Craig; Chow, Chi-Wing

2013-01-01

Charcot–Marie–Tooth (CMT) disease is an inherited neurological disorder. Mutations in the small integral membrane protein of the lysosome/late endosome (SIMPLE) account for the rare autosomal-dominant demyelination in CMT1C patients. Understanding the molecular basis of CMT1C pathogenesis is impeded, in part, by perplexity about the role of SIMPLE, which is expressed in multiple cell types. Here we show that SIMPLE resides within the intraluminal vesicles of multivesicular bodies (MVBs) and inside exosomes, which are nanovesicles secreted extracellularly. Targeting of SIMPLE to exosomes is modulated by positive and negative regulatory motifs. We also find that expression of SIMPLE increases the number of exosomes and secretion of exosome proteins. We engineer a point mutation on the SIMPLE allele and generate a physiological mouse model that expresses CMT1C-mutated SIMPLE at the endogenous level. We find that CMT1C mouse primary embryonic fibroblasts show decreased number of exosomes and reduced secretion of exosome proteins, in part due to improper formation of MVBs. CMT1C patient B cells and CMT1C mouse primary Schwann cells show similar defects. Together the data indicate that SIMPLE regulates the production of exosomes by modulating the formation of MVBs. Dysregulated endosomal trafficking and changes in the landscape of exosome-mediated intercellular communications may place an overwhelming burden on the nervous system and account for CMT1C molecular pathogenesis. PMID:23576546

IOTA Simple Rules in Differentiating between Benign and Malignant Adnexal Masses by Non-expert Examiners.

PubMed

Tinnangwattana, Dangcheewan; Vichak-Ururote, Linlada; Tontivuthikul, Paponrad; Charoenratana, Cholaros; Lerthiranwong, Thitikarn; Tongsong, Theera

2015-01-01

To evaluate the diagnostic performance of IOTA simple rules in predicting malignant adnexal tumors by non-expert examiners. Five obstetric/gynecologic residents, who had never performed gynecologic ultrasound examination by themselves before, were trained for IOTA simple rules by an experienced examiner. One trained resident performed ultrasound examinations including IOTA simple rules on 100 women, who were scheduled for surgery due to ovarian masses, within 24 hours of surgery. The gold standard diagnosis was based on pathological or operative findings. The five-trained residents performed IOTA simple rules on 30 patients for evaluation of inter-observer variability. A total of 100 patients underwent ultrasound examination for the IOTA simple rules. Of them, IOTA simple rules could be applied in 94 (94%) masses including 71 (71.0%) benign masses and 29 (29.0%) malignant masses. The diagnostic performance of IOTA simple rules showed sensitivity of 89.3% (95%CI, 77.8%; 100.7%), specificity 83.3% (95%CI, 74.3%; 92.3%). Inter-observer variability was analyzed using Cohen's kappa coefficient. Kappa indices of the four pairs of raters are 0.713-0.884 (0.722, 0.827, 0.713, and 0.884). IOTA simple rules have high diagnostic performance in discriminating adnexal masses even when are applied by non-expert sonographers, though a training course may be required. Nevertheless, they should be further tested by a greater number of general practitioners before widely use.

Congenital renal anomalies in cloacal exstrophy: Is there a difference?

PubMed

Suson, K D; Inouye, B; Carl, A; Gearhart, J P

2016-08-01

Cloacal exstrophy (CE) is the most severe manifestation of the epispadias-exstrophy spectrum. Previous studies have indicated an increased rate of renal anomalies in children with classic bladder exstrophy (CBE). Given the increased severity of the CE defect, it was hypothesized that there would be an even greater incidence among these children. The primary objective was to characterize renal anatomy in CE patients. Two secondary objectives were to compare these renal anatomic findings in male and female patients, and female patients with and without Müllerian anomalies. An Institutional Review Board-approved retrospective review of 75 patients from an institutional exstrophy database. Data points included: age at analysis, sex, and renal and Müllerian anatomy. Abnormal renal anatomy was defined as a solitary kidney, malrotation, renal ectopia, congenital cysts, duplication, and/or proven obstruction. Abnormal Müllerian anatomy was defined as uterine or vaginal duplication, obstruction, and/or absence. The Summary Table presents demographic data and renal anomalies. Males were more likely to have renal anomalies. Müllerian anomalies were present in 65.7% of female patients. Girls with abnormal Müllerian anatomy were 10 times more likely to have renal anomalies than those with normal Müllerian anatomy (95% CI 1.1-91.4, P = 0.027). Patients with CE had a much higher rate of renal anomalies than that reported for CBE. Males and females with Müllerian anomalies were at greater risk than females with normal uterine structures. Mesonephric and Müllerian duct interaction is required for uterine structures to develop normally. It has been proposed that women with both Müllerian and renal anomalies be classified separately from other uterine malformations on an embryonic basis. In these patients, an absent or dysfunctional mesonephric duct has been implicated as potentially causal. This provided an embryonic explanation for uterine anomalies in female CE patients. There were also clinical implications. Women with renal agenesis and uterine anomalies were more likely to have endometriosis than those with isolated uterine anomalies, but were also more likely to have successful pregnancies. Males may have had an analogous condition with renal agenesis and seminal vesicle cysts. Future research into long-term kidney function in this population, uterine function, and possible male sexual duct malformation is warranted. Congenital renal anomalies occurred frequently in children with CE. They were more common in boys than in girls. Girls with abnormal Müllerian anatomy were more likely to have anomalous renal development. Mesonephric duct dysfunction may be embyologically responsible for both renal and Müllerian maldevelopment. Copyright © 2016 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Stability of simple/complex classification with contrast and extraclassical receptive field modulation in macaque V1

PubMed Central

Henry, Christopher A.

2013-01-01

A key property of neurons in primary visual cortex (V1) is the distinction between simple and complex cells. Recent reports in cat visual cortex indicate the categorization of simple and complex can change depending on stimulus conditions. We investigated the stability of the simple/complex classification with changes in drive produced by either contrast or modulation by the extraclassical receptive field (eCRF). These two conditions were reported to increase the proportion of simple cells in cat cortex. The ratio of the modulation depth of the response (F1) to the elevation of response (F0) to a drifting grating (F1/F0 ratio) was used as the measure of simple/complex. The majority of V1 complex cells remained classified as complex with decreasing contrast. Near contrast threshold, an equal proportion of simple and complex cells changed their classification. The F1/F0 ratio was stable between optimal and large stimulus areas even for those neurons that showed strong eCRF suppression. There was no discernible overall effect of surrounding spatial context on the F1/F0 ratio. Simple/complex cell classification is relatively stable across a range of stimulus drives, produced by either contrast or eCRF suppression. PMID:23303859

Successful aspiration and ethanol sclerosis of a large, symptomatic, simple liver cyst: Case presentation and review of the literature

PubMed Central

Blonski, Wojciech C; Campbell, Mical S; Faust, Thomas; Metz, David C

2006-01-01

Simple liver cysts are congenital with a prevalence of 2.5%-4.25%. Imaging, whether by US, CT or MRI, is accurate in distinguishing simple cysts from other etiologies, including parasitic, neoplastic, duct-related, and traumatic cysts. Symptomatic simple liver cysts are rare, and the true frequency of symptoms is not known. Symptomatic simple liver cysts are predominantly large (> 4 cm), right-sided, and more common in women and older patients. The vast majority of simple hepatic cysts require no treatment or follow-up, though large cysts (> 4 cm) may be followed initially with serial imaging to ensure stability. Attribution of symptoms to a large simple cyst should be undertaken with caution, after alternative diagnoses have been excluded. Aspiration may be performed to test whether symptoms are due to the cyst; however, cyst recurrence should be expected. Limited experience with both laparoscopic deroofing and aspiration, followed by instillation of a sclerosing agent has demonstrated promising results for the treatment of symptomatic cysts. Here, we describe a patient with a large, symptomatic, simple liver cyst who experienced complete resolution of symptoms following cyst drainage and alcohol ablation, and we present a comprehensive review of the literature. PMID:16718826

Migraines: Simple Steps to Head Off the Pain

MedlinePlus

Migraines: Simple steps to head off the pain Migraines cause pain as real as the pain of ... Healthy habits and simple nonmedical remedies sometimes stop migraines before they start. By Mayo Clinic Staff Medication ...

Simple, Internally Adjustable Valve

NASA Technical Reports Server (NTRS)

Burley, Richard K.

1990-01-01

Valve containing simple in-line, adjustable, flow-control orifice made from ordinary plumbing fitting and two allen setscrews. Construction of valve requires only simple drilling, tapping, and grinding. Orifice installed in existing fitting, avoiding changes in rest of plumbing.

Simple-MSSM: a simple and efficient method for simultaneous multi-site saturation mutagenesis.

PubMed

Cheng, Feng; Xu, Jian-Miao; Xiang, Chao; Liu, Zhi-Qiang; Zhao, Li-Qing; Zheng, Yu-Guo

2017-04-01

To develop a practically simple and robust multi-site saturation mutagenesis (MSSM) method that enables simultaneously recombination of amino acid positions for focused mutant library generation. A general restriction enzyme-free and ligase-free MSSM method (Simple-MSSM) based on prolonged overlap extension PCR (POE-PCR) and Simple Cloning techniques. As a proof of principle of Simple-MSSM, the gene of eGFP (enhanced green fluorescent protein) was used as a template gene for simultaneous mutagenesis of five codons. Forty-eight randomly selected clones were sequenced. Sequencing revealed that all the 48 clones showed at least one mutant codon (mutation efficiency = 100%), and 46 out of the 48 clones had mutations at all the five codons. The obtained diversities at these five codons are 27, 24, 26, 26 and 22, respectively, which correspond to 84, 75, 81, 81, 69% of the theoretical diversity offered by NNK-degeneration (32 codons; NNK, K = T or G). The enzyme-free Simple-MSSM method can simultaneously and efficiently saturate five codons within one day, and therefore avoid missing interactions between residues in interacting amino acid networks.

Creating Simple Admin Tools Using Info*Engine and Java

NASA Technical Reports Server (NTRS)

Jones, Corey; Kapatos, Dennis; Skradski, Cory; Felkins, J. D.

2012-01-01

PTC has provided a simple way to dynamically interact with Windchill using Info*Engine. This presentation will describe how to create a simple Info*Engine Tasks capable of saving Windchill 10.0 administration of tedious work.

A Simple, Low Overhead Data Compression Algorithm for Converting Lossy Compression Processes to Lossless

DTIC Science & Technology

1993-12-01

0~0 S* NAVAL POSTGRADUATE SCHOOL Monterey, California DTIC ELECTE THESIS S APR 11 1994DU A SIMPLE, LOW OVERHEAD DATA COMPRESSION ALGORITHM FOR...A SIMPLE. LOW OVERHEAD DATA COMPRESSION ALGORITHM FOR CONVERTING LOSSY COMPRESSION PROCESSES TO LOSSLESS. 6. AUTHOR(S) Abbott, Walter D., III 7...Approved for public release; distribution is unlimited. A Simple, Low Overhead Data Compression Algorithm for Converting Lossy Processes to Lossless by

Simple animal models for amyotrophic lateral sclerosis drug discovery.

PubMed

Patten, Shunmoogum A; Parker, J Alex; Wen, Xiao-Yan; Drapeau, Pierre

2016-08-01

Simple animal models have enabled great progress in uncovering the disease mechanisms of amyotrophic lateral sclerosis (ALS) and are helping in the selection of therapeutic compounds through chemical genetic approaches. Within this article, the authors provide a concise overview of simple model organisms, C. elegans, Drosophila and zebrafish, which have been employed to study ALS and discuss their value to ALS drug discovery. In particular, the authors focus on innovative chemical screens that have established simple organisms as important models for ALS drug discovery. There are several advantages of using simple animal model organisms to accelerate drug discovery for ALS. It is the authors' particular belief that the amenability of simple animal models to various genetic manipulations, the availability of a wide range of transgenic strains for labelling motoneurons and other cell types, combined with live imaging and chemical screens should allow for new detailed studies elucidating early pathological processes in ALS and subsequent drug and target discovery.

Changes in Purkinje cell simple spike encoding of reach kinematics during adaption to a mechanical perturbation.

PubMed

Hewitt, Angela L; Popa, Laurentiu S; Ebner, Timothy J

2015-01-21

The cerebellum is essential in motor learning. At the cellular level, changes occur in both the simple spike and complex spike firing of Purkinje cells. Because simple spike discharge reflects the main output of the cerebellar cortex, changes in simple spike firing likely reflect the contribution of the cerebellum to the adapted behavior. Therefore, we investigated in Rhesus monkeys how the representation of arm kinematics in Purkinje cell simple spike discharge changed during adaptation to mechanical perturbations of reach movements. Monkeys rapidly adapted to a novel assistive or resistive perturbation along the direction of the reach. Adaptation consisted of matching the amplitude and timing of the perturbation to minimize its effect on the reach. In a majority of Purkinje cells, simple spike firing recorded before and during adaptation demonstrated significant changes in position, velocity, and acceleration sensitivity. The timing of the simple spike representations change within individual cells, including shifts in predictive versus feedback signals. At the population level, feedback-based encoding of position increases early in learning and velocity decreases. Both timing changes reverse later in learning. The complex spike discharge was only weakly modulated by the perturbations, demonstrating that the changes in simple spike firing can be independent of climbing fiber input. In summary, we observed extensive alterations in individual Purkinje cell encoding of reach kinematics, although the movements were nearly identical in the baseline and adapted states. Therefore, adaption to mechanical perturbation of a reaching movement is accompanied by widespread modifications in the simple spike encoding. Copyright © 2015 the authors 0270-6474/15/351106-19$15.00/0.

Changes in Purkinje Cell Simple Spike Encoding of Reach Kinematics during Adaption to a Mechanical Perturbation

PubMed Central

Hewitt, Angela L.; Popa, Laurentiu S.

2015-01-01

The cerebellum is essential in motor learning. At the cellular level, changes occur in both the simple spike and complex spike firing of Purkinje cells. Because simple spike discharge reflects the main output of the cerebellar cortex, changes in simple spike firing likely reflect the contribution of the cerebellum to the adapted behavior. Therefore, we investigated in Rhesus monkeys how the representation of arm kinematics in Purkinje cell simple spike discharge changed during adaptation to mechanical perturbations of reach movements. Monkeys rapidly adapted to a novel assistive or resistive perturbation along the direction of the reach. Adaptation consisted of matching the amplitude and timing of the perturbation to minimize its effect on the reach. In a majority of Purkinje cells, simple spike firing recorded before and during adaptation demonstrated significant changes in position, velocity, and acceleration sensitivity. The timing of the simple spike representations change within individual cells, including shifts in predictive versus feedback signals. At the population level, feedback-based encoding of position increases early in learning and velocity decreases. Both timing changes reverse later in learning. The complex spike discharge was only weakly modulated by the perturbations, demonstrating that the changes in simple spike firing can be independent of climbing fiber input. In summary, we observed extensive alterations in individual Purkinje cell encoding of reach kinematics, although the movements were nearly identical in the baseline and adapted states. Therefore, adaption to mechanical perturbation of a reaching movement is accompanied by widespread modifications in the simple spike encoding. PMID:25609626

Behavior related pauses in simple spike activity of mouse Purkinje cells are linked to spike rate modulation

PubMed Central

Cao, Ying; Maran, Selva K.; Dhamala, Mukesh; Jaeger, Dieter; Heck, Detlef H.

2012-01-01

Purkinje cells (PCs) in the mammalian cerebellum express high frequency spontaneous activity with average spike rates between 30 and 200 Hz. Cerebellar nuclear (CN) neurons receive converging input from many PCs resulting in a continuous barrage of inhibitory inputs. It has been hypothesized that pauses in PC activity trigger increases in CN spiking activity. A prediction derived from this hypothesis is that pauses in PC simple spike activity represent relevant behavioral or sensory events. Here we asked whether pauses in the simple spike activity of PCs related to either fluid licking or respiration, play a special role in representing information about behavior. Both behaviors are widely represented in cerebellar PC simple spike activity. We recorded PC activity in the vermis and lobus simplex of head fixed mice while monitoring licking and respiratory behavior. Using cross correlation and Granger causality analysis we examined whether short ISIs had a different temporal relation to behavior than long ISIs or pauses. Behavior related simple spike pauses occurred during low-rate simple spike activity in both licking and breathing related PCs. Granger causality analysis revealed causal relationships between simple spike pauses and behavior. However, the same results were obtained from an analysis of surrogate spike trains with gamma ISI distributions constructed to match rate modulations of behavior related Purkinje cells. Our results therefore suggest that the occurrence of pauses in simple spike activity does not represent additional information about behavioral or sensory events that goes beyond the simple spike rate modulations. PMID:22723707

Using a Modified Simple Pendulum to Find the Variations in the Value of “g”

NASA Astrophysics Data System (ADS)

Arnold, Jonathan P.; Efthimiou, C.

2007-05-01

The simple pendulum is one of the most known and studied system of Newtonian Mechanics. It also provides one of the most elegant and simple devices to measure the acceleration of gravity at any location. In this presentation we will revisit the problem of measuring the acceleration of gravity using a simple pendulum and will present a modification to the standard technique that increases the accuracy of the measurement.

Simple Map in Action-Angle Coordinates.

NASA Astrophysics Data System (ADS)

Kerwin, Olivia; Punjabi, Alkesh; Ali, Halima

2008-04-01

The simple map is the simplest map that has the topology of a divertor tokamak. The simple map has three canonical representations: (i) the natural coordinates - toroidal magnetic flux and poloidal angle (ψ,θ), (ii) the physical coordinates - the physical variables (R,Z) or (X,Y), and (iii) the action-angle coordinates - (J,θ) or magnetic coordinates (ψ, θ). All three are canonical coordinates for field lines. The simple map in the (X,Y) representation has been studied extensively ^1, 2. Here we analytically calculate the action-angle coordinates and safety factor q for the simple map. We construct the equilibrium generating function for the simple map in action-angle coordinates. We derive the simple map in action-angle representation, and calculate the stochastic broadening of the ideal separatrix due to topological noise in action-angle representation. We also show how the geometric effects such as elongation, the height, and width of the ideal separatrix surface can be investigated using a slight modification of the simple map in action-angle representation. This work is supported by the following grants US Department of Energy - OFES DE-FG02-01ER54624 and DE-FG02-04ER54793 and National Science Foundation - HRD-0630372 and 0411394. [1] A. Punjabi, H. Ali, T. Evans, and A. Boozer, Phys Lett A, 364 140-145 (2007). [2] A. Punjabi, A. Verma, and A. Boozer, Phys.Rev. Lett. 69, 3322 (1992).

The dynamic relationship between cerebellar Purkinje cell simple spikes and the spikelet number of complex spikes

PubMed Central

Burroughs, Amelia; Wise, Andrew K.; Xiao, Jianqiang; Houghton, Conor; Tang, Tianyu; Suh, Colleen Y.; Lang, Eric J.

2016-01-01

Key points Purkinje cells are the sole output of the cerebellar cortex and fire two distinct types of action potential: simple spikes and complex spikes.Previous studies have mainly considered complex spikes as unitary events, even though the waveform is composed of varying numbers of spikelets.The extent to which differences in spikelet number affect simple spike activity (and vice versa) remains unclear.We found that complex spikes with greater numbers of spikelets are preceded by higher simple spike firing rates but, following the complex spike, simple spikes are reduced in a manner that is graded with spikelet number.This dynamic interaction has important implications for cerebellar information processing, and suggests that complex spike spikelet number may maintain Purkinje cells within their operational range. Abstract Purkinje cells are central to cerebellar function because they form the sole output of the cerebellar cortex. They exhibit two distinct types of action potential: simple spikes and complex spikes. It is widely accepted that interaction between these two types of impulse is central to cerebellar cortical information processing. Previous investigations of the interactions between simple spikes and complex spikes have mainly considered complex spikes as unitary events. However, complex spikes are composed of an initial large spike followed by a number of secondary components, termed spikelets. The number of spikelets within individual complex spikes is highly variable and the extent to which differences in complex spike spikelet number affects simple spike activity (and vice versa) remains poorly understood. In anaesthetized adult rats, we have found that Purkinje cells recorded from the posterior lobe vermis and hemisphere have high simple spike firing frequencies that precede complex spikes with greater numbers of spikelets. This finding was also evident in a small sample of Purkinje cells recorded from the posterior lobe hemisphere in awake cats. In addition, complex spikes with a greater number of spikelets were associated with a subsequent reduction in simple spike firing rate. We therefore suggest that one important function of spikelets is the modulation of Purkinje cell simple spike firing frequency, which has implications for controlling cerebellar cortical output and motor learning. PMID:27265808

Influence of dose rate on the induction of simple and complex chromosome exchanges by gamma rays.

PubMed

Loucas, Bradford D; Eberle, Richard; Bailey, Susan M; Cornforth, Michael N

2004-10-01

Single-color painting of whole chromosomes, or protocols in which only a few chromosomes are distinctively painted, will always fail to detect a proportion of complex exchanges because they frequently produce pseudosimple painting patterns that are indistinguishable from those produced by bona fide simple exchanges. When 24-color multi-fluor FISH (mFISH) was employed for the purpose of distinguishing (truly) simple from pseudosimple exchanges, it was confirmed that the acute low-LET radiation dose-response relationship for simple exchanges lacked significant upward curvature. This result has been interpreted to indicate that the formation of simple exchanges requires only one chromosome locus be damaged (e.g. broken) by radiation to initiate an exchange-not two, as classical cytogenetic theory maintains. Because a one-lesion mechanism implies single-track action, it follows that the production of simple exchanges should not be influenced by changes in dose rate. To examine this prediction, we irradiated noncycling primary human fibroblasts with graded doses of (137)Cs gamma rays at an acute dose rate of 1.10 Gy/min and compared, using mFISH, the yield of simple exchanges to that observed after exposure to the same radiation delivered at a chronic dose rate of 0.08 cGy/min. The shape of the dose response was found to be quasi-linear for both dose rates, but, counter to providing support for a one-lesion mechanism, the yield of simple aberrations was greatly reduced by protracted exposure. Although chronic doses were delivered at rates low enough to produce damage exclusively by single-track action, this did not altogether eliminate the formation of complex aberrations, an analysis of which leads to the conclusion that a single track of low-LET radiation is capable of inducing complex exchanges requiring up to four proximate breaks for their formation. For acute exposures, the ratio of simple reciprocal translocations to simple dicentrics was near unity.

Efficient hybrid white organic light-emitting diodes for application of triplet harvesting with simple structure

NASA Astrophysics Data System (ADS)

Hwang, Kyo Min; Lee, Song Eun; Lee, Sungkyu; Yoo, Han Kyu; Baek, Hyun Jung; Kim, Young Kwan; Kim, Jwajin; Yoon, Seung Soo

2016-08-01

In this study, we fabricated hybrid white organic light-emitting diodes (WOLEDs) based on triplet harvesting with a simple structure. All the hole transporting material and host in the emitting layer (EML) of devices utilized the same material N,N'-di-1-naphthalenyl-N,N'-diphenyl [1,1':4',1″:4″,1‴-quaterphenyl]-4,4‴-diamine (4P-NPD), which is known to be blue fluorescent material. Simple hybrid WOLEDs were fabricated with blue fluorescent, green and red phosphorescent materials. We investigated the effect of triplet harvesting (TH) by an exciton generation zone on simple hybrid WOLEDs. The simple hybrid WOLEDs characteristically had a dominant hole mobility, so an exciton generation zone was expected in the EML. Additionally, the optimal the thickness of the hole transporting layer and electron transporting layer was fabricated a simple hybrid WOLEDs. The simple hybrid WOLED exhibits a maximum luminous efficiency of 29.3 cd/A and a maximum external quantum efficiency of 11.2%. The Commission Internationale de l'Éclairage (International Commission on Illumination) coordinates were (0.45, 0.43) at about 10,000 cd/m2.

Dense simple plasmas as high-temperature liquid simple metals

NASA Technical Reports Server (NTRS)

Perrot, F.

1990-01-01

The thermodynamic properties of dense plasmas considered as high-temperature liquid metals are studied. An attempt is made to show that the neutral pseudoatom picture of liquid simple metals may be extended for describing plasmas in ranges of densities and temperatures where their electronic structure remains 'simple'. The primary features of the model when applied to plasmas include the temperature-dependent self-consistent calculation of the electron charge density and the determination of a density and temperature-dependent ionization state.

A Simple System for the Early Detection of Breast Cancer

DTIC Science & Technology

2016-07-01

AWARD NUMBER: W81XWH-14-1-0231 TITLE: A Simple System for Early Detection of Breast Cancer PRINCIPAL INVESTIGATOR: Stephen Johnston CONTRACTING...ADDRESS. 1. REPORT DATE July 2016 2. REPORT TYPE Annual 3. DATES COVERED 1Jul2015 - 30Jun2016 4. TITLE AND SUBTITLE A Simple System for the Early...Form 298 (Rev. 8-98) Prescribed by ANSI Std. Z39.18 W81XWH-14-1-0231 Abstract: We invented the immunosignature technology (IMS) as a simple , universal

Mi Quinto Libro de Maquinas Simples: El Plano Inclinado. Escuela Intermedia Grados 7, 8 y 9 (My Fifth Book of Simple Machines: The Inclined Plane. Intermediate School Grades 7, 8, and 9).

ERIC Educational Resources Information Center

Alvarado, Patricio R.; Montalvo, Luis

This is the fifth book in a five-book physical science series on simple machines. The books are designed for Spanish-speaking junior high school students. This volume explains the principles and some of the uses of inclined planes, as they appear in simple machines, by suggesting experiments and posing questions concerning drawings in the book…

The Krylov accelerated SIMPLE(R) method for flow problems in industrial furnaces

NASA Astrophysics Data System (ADS)

Vuik, C.; Saghir, A.; Boerstoel, G. P.

2000-08-01

Numerical modeling of the melting and combustion process is an important tool in gaining understanding of the physical and chemical phenomena that occur in a gas- or oil-fired glass-melting furnace. The incompressible Navier-Stokes equations are used to model the gas flow in the furnace. The discrete Navier-Stokes equations are solved by the SIMPLE(R) pressure-correction method. In these applications, many SIMPLE(R) iterations are necessary to obtain an accurate solution. In this paper, Krylov accelerated versions are proposed: GCR-SIMPLE(R). The properties of these methods are investigated for a simple two-dimensional flow. Thereafter, the efficiencies of the methods are compared for three-dimensional flows in industrial glass-melting furnaces. Copyright

Simple shear of deformable square objects

NASA Astrophysics Data System (ADS)

Treagus, Susan H.; Lan, Labao

2003-12-01

Finite element models of square objects in a contrasting matrix in simple shear show that the objects deform to a variety of shapes. For a range of viscosity contrasts, we catalogue the changing shapes and orientations of objects in progressive simple shear. At moderate simple shear ( γ=1.5), the shapes are virtually indistinguishable from those in equivalent pure shear models with the same bulk strain ( RS=4), examined in a previous study. In theory, differences would be expected, especially for very stiff objects or at very large strain. In all our simple shear models, relatively competent square objects become asymmetric barrel shapes with concave shortened edges, similar to some types of boudin. Incompetent objects develop shapes surprisingly similar to mica fish described in mylonites.

Comparison of rigorous and simple vibrational models for the CO2 gasdynamic laser

NASA Technical Reports Server (NTRS)

Monson, D. J.

1977-01-01

The accuracy of a simple vibrational model for computing the gain in a CO2 gasdynamic laser is assessed by comparing results computed from it with results computed from a rigorous vibrational model. The simple model is that of Anderson et al. (1971), in which the vibrational kinetics are modeled by grouping the nonequilibrium vibrational degrees of freedom into two modes, to each of which there corresponds an equation describing vibrational relaxation. The two models agree fairly well in the computed gain at low temperatures, but the simple model predicts too high a gain at the higher temperatures of current interest. The sources of error contributing to the overestimation given by the simple model are determined by examining the simplified relaxation equations.

Simple and Effective Algorithms: Computer-Adaptive Testing.

ERIC Educational Resources Information Center

Linacre, John Michael

Computer-adaptive testing (CAT) allows improved security, greater scoring accuracy, shorter testing periods, quicker availability of results, and reduced guessing and other undesirable test behavior. Simple approaches can be applied by the classroom teacher, or other content specialist, who possesses simple computer equipment and elementary…

A Simple Laboratory Exercise Illustrating Active Transport in Yeast Cells.

ERIC Educational Resources Information Center

Stambuk, Boris U.

2000-01-01

Describes a simple laboratory activity illustrating the chemiosmotic principles of active transport in yeast cells. Demonstrates the energy coupling mechanism of active a-glucoside uptake by Saccaromyces cerevisiae cells with a colorimetric transport assay using very simple equipment. (Contains 22 references.) (Author/YDS)

Using "Tracker" to Prove the Simple Harmonic Motion Equation

ERIC Educational Resources Information Center

Kinchin, John

2016-01-01

Simple harmonic motion (SHM) is a common topic for many students to study. Using the free, though versatile, motion tracking software; "Tracker", we can extend the students experience and show that the general equation for SHM does lead to the correct period of a simple pendulum.

Secondary School Students' Misconceptions about Simple Electric Circuits

ERIC Educational Resources Information Center

Küçüközer, Hüseyin; Kocakülah, Sabri

2007-01-01

The aim of this study is to reveal secondary school students' misconceptions about simple electric circuits and to define whether specific misconceptions peculiar to Turkish students exist within those identified. Data were obtained with a conceptual understanding test for simple electric circuits and semi-structured interviews. Conceptual…

20 CFR 725.608 - Interest.

Code of Federal Regulations, 2010 CFR

2010-04-01

... simple annual interest, computed from the date on which the benefits were due. The interest shall be... payment of retroactive benefits, the beneficiary shall also be entitled to simple annual interest on such... entitled to simple annual interest computed from the date upon which the beneficiary's right to additional...

A SIMPLE METHOD FOR THE EXTRACTION AND QUANTIFICATION OF PHOTOPIGMENTS FROM SYMBIODINIUM SPP.

EPA Science Inventory

John E. Rogers and Dragoslav Marcovich. Submitted. Simple Method for the Extraction and Quantification of Photopigments from Symbiodinium spp.. Limnol. Oceanogr. Methods. 19 p. (ERL,GB 1192).

We have developed a simple, mild extraction procedure using methanol which, when...

A simple bias correction in linear regression for quantitative trait association under two-tail extreme selection.

PubMed

Kwan, Johnny S H; Kung, Annie W C; Sham, Pak C

2011-09-01

Selective genotyping can increase power in quantitative trait association. One example of selective genotyping is two-tail extreme selection, but simple linear regression analysis gives a biased genetic effect estimate. Here, we present a simple correction for the bias.

Two Methods for Teaching Simple Visual Discriminations to Learners with Severe Disabilities

ERIC Educational Resources Information Center

Graff, Richard B.; Green, Gina

2004-01-01

Simple discriminations are involved in many functional skills; additionally, they are components of conditional discriminations (identity and arbitrary matching-to-sample), which are involved in a wide array of other important performances. Many individuals with severe disabilities have difficulty acquiring simple discriminations with standard…

47 CFR 52.36 - Standard data fields for simple port order processing.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 3 2012-10-01 2012-10-01 false Standard data fields for simple port order... CARRIER SERVICES (CONTINUED) NUMBERING Number Portability § 52.36 Standard data fields for simple port order processing. (a) A telecommunications carrier may require only the data described in paragraphs (b...

Modeling Age-Related Differences in Immediate Memory Using SIMPLE

ERIC Educational Resources Information Center

Surprenant, Aimee M.; Neath, Ian; Brown, Gordon D. A.

2006-01-01

In the SIMPLE model (Scale Invariant Memory and Perceptual Learning), performance on memory tasks is determined by the locations of items in multidimensional space, and better performance is associated with having fewer close neighbors. Unlike most previous simulations with SIMPLE, the ones reported here used measured, rather than assumed,…

Two-way ANOVA Problems with Simple Numbers.

ERIC Educational Resources Information Center

Read, K. L. Q.; Shihab, L. H.

1998-01-01

Describes how to construct simple numerical examples in two-way ANOVAs, specifically randomized blocks, balanced two-way layouts, and Latin squares. Indicates that working through simple numerical problems is helpful to students meeting a technique for the first time and should be followed by computer-based analysis of larger, real datasets when…

Simple scaling of cooperation in donor-recipient games.

PubMed

Berger, Ulrich

2009-09-01

We present a simple argument which proves a general version of the scaling phenomenon recently observed in donor-recipient games by Tanimoto [Tanimoto, J., 2009. A simple scaling of the effectiveness of supporting mutual cooperation in donor-recipient games by various reciprocity mechanisms. BioSystems 96, 29-34].

Simple Numerical Analysis of Longboard Speedometer Data

ERIC Educational Resources Information Center

Hare, Jonathan

2013-01-01

Simple numerical data analysis is described, using a standard spreadsheet program, to determine distance, velocity (speed) and acceleration from voltage data generated by a skateboard/longboard speedometer (Hare 2012 "Phys. Educ." 47 409-17). This simple analysis is an introduction to data processing including scaling data as well as…

75 FR 57719 - Federal Acquisition Regulation; TINA Interest Calculations

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-22

... the term ``simple interest'' as the requirement for calculating interest for TINA cost impacts with.... Revising the date of the clause; and b. Removing from paragraph (e)(1) ``Simple interest'' and adding...) ``Simple interest'' and adding ``Interest compounded daily, as required by 26 U.S.C. 6622,'' in its place...

15 CFR 921.13 - Management plan and environmental impact statement development.

Code of Federal Regulations, 2010 CFR

2010-01-01

... simple property interest (e.g., conservation easement), fee simple property acquisition, or a combination... simple options) to establish adequate long-term state control; an estimate of the fair market value of any property interest—which is proposed for acquisition; a schedule estimating the time required to...

7 CFR 3550.58 - Ownership requirements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... requirements. After the loan is closed, the borrower must have an acceptable interest in the property as evidenced by one of the following. (a) Fee-simple ownership. Acceptable fee-simple ownership is evidenced by a fully marketable title with a deed vesting a fee-simple interest in the property to the borrower...

12 CFR 226.24 - Advertising.

Code of Federal Regulations, 2010 CFR

2010-01-01

.... If an advertisement for credit secured by a dwelling states a simple annual rate of interest and more than one simple annual rate of interest will apply over the term of the advertised loan, the advertisement shall disclose in a clear and conspicuous manner: (A) Each simple annual rate of interest that...

Simple Experiments for Teaching Air Pressure

ERIC Educational Resources Information Center

Shamsipour, Gholamreza

2006-01-01

Everyone who teaches physics knows very well that sometimes a simple device or experiment can help to make a concept clear. In this paper, inspired by "The Jumping Pencil" by Martin Gardner, I will discuss a simple demonstration device that can be used to start the study of air pressure.

Closure of colostomy.

PubMed Central

Beck, P H; Conklin, H B

1975-01-01

We analyzed the records of 77 cases of loop colostomy closure in Vietnam War Casualties. All records were complete from the date of injury to discharge following colostomy closure. Simple of the loop colostomy was performed in 44 patients and resection of the stoma and reanastomosis of bowel segments was performed in 33 patients. Average operating time for simple closure of the loop was 70 minutes compared to 115 minutes for resection and anastomosis. Nasogastric suction was used less frequently and for a shorter time with simple loop closure. The total postoperative complication rate was 9% with simple loop closure as compared to 24% for resection and anastomosis. Simple closure of the loop described in this report is technically easier and as safe as resection of the stoma and reanastomosis. Images Fig. 1. PMID:1094967

[Analysis on the accuracy of simple selection method of Fengshi (GB 31)].

PubMed

Li, Zhixing; Zhang, Haihua; Li, Suhe

2015-12-01

To explore the accuracy of simple selection method of Fengshi (GB 31). Through the study of the ancient and modern data,the analysis and integration of the acupuncture books,the comparison of the locations of Fengshi (GB 31) by doctors from all dynasties and the integration of modern anatomia, the modern simple selection method of Fengshi (GB 31) is definite, which is the same as the traditional way. It is believed that the simple selec tion method is in accord with the human-oriented thought of TCM. Treatment by acupoints should be based on the emerging nature and the individual difference of patients. Also, it is proposed that Fengshi (GB 31) should be located through the integration between the simple method and body surface anatomical mark.

The dynamic relationship between cerebellar Purkinje cell simple spikes and the spikelet number of complex spikes.

PubMed

Burroughs, Amelia; Wise, Andrew K; Xiao, Jianqiang; Houghton, Conor; Tang, Tianyu; Suh, Colleen Y; Lang, Eric J; Apps, Richard; Cerminara, Nadia L

2017-01-01

Purkinje cells are the sole output of the cerebellar cortex and fire two distinct types of action potential: simple spikes and complex spikes. Previous studies have mainly considered complex spikes as unitary events, even though the waveform is composed of varying numbers of spikelets. The extent to which differences in spikelet number affect simple spike activity (and vice versa) remains unclear. We found that complex spikes with greater numbers of spikelets are preceded by higher simple spike firing rates but, following the complex spike, simple spikes are reduced in a manner that is graded with spikelet number. This dynamic interaction has important implications for cerebellar information processing, and suggests that complex spike spikelet number may maintain Purkinje cells within their operational range. Purkinje cells are central to cerebellar function because they form the sole output of the cerebellar cortex. They exhibit two distinct types of action potential: simple spikes and complex spikes. It is widely accepted that interaction between these two types of impulse is central to cerebellar cortical information processing. Previous investigations of the interactions between simple spikes and complex spikes have mainly considered complex spikes as unitary events. However, complex spikes are composed of an initial large spike followed by a number of secondary components, termed spikelets. The number of spikelets within individual complex spikes is highly variable and the extent to which differences in complex spike spikelet number affects simple spike activity (and vice versa) remains poorly understood. In anaesthetized adult rats, we have found that Purkinje cells recorded from the posterior lobe vermis and hemisphere have high simple spike firing frequencies that precede complex spikes with greater numbers of spikelets. This finding was also evident in a small sample of Purkinje cells recorded from the posterior lobe hemisphere in awake cats. In addition, complex spikes with a greater number of spikelets were associated with a subsequent reduction in simple spike firing rate. We therefore suggest that one important function of spikelets is the modulation of Purkinje cell simple spike firing frequency, which has implications for controlling cerebellar cortical output and motor learning. © 2016 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.

The prevalence of incidental simple ovarian cysts >or= 3 cm detected by transvaginal sonography in early pregnancy.

PubMed

Glanc, Phyllis; Brofman, Nicole; Salem, Shia; Kornecki, Anat; Abrams, Jason; Farine, Dan

2007-06-01

To determine the prevalence of simple ovarian cysts of >or= 3 cm diameter detected by transvaginal sonography (TVS) in a population of asymptomatic women in early pregnancy. We conducted a retrospective review of 10,830 consecutive women presenting prior to 14 weeks' gestational age (GA) for early dating TVS. The records of all women with simple cysts >or= 3 cm in diameter were included. The study population was divided into five groups by GA: >or= 6 weeks; 6.1-8 weeks; 8.1-10 weeks; 10.1-12 weeks; and 12.1-14 weeks. A simple cyst >or= 3 cm in diameter was present in 4.9% of women at >or= 6 weeks' gestation, in 5.1% between 6.1 and 8 weeks, in 5.3% between 8.1 and 10 weeks, in 3.2% between 10.1. and 12 weeks, and in 1.5% between 12 and 14 weeks. Overall, a simple cyst >or= 3 cm was present in 516 women (4.8%). Prior to 10 weeks, 5.1% had simple cysts >or= 3 cm, dropping to 2.7% after 10 weeks, a statistically significant decrease (P<0.0001). Between 10.1 weeks and 12 weeks, the prevalence dropped to 3.2%, and then to 1.5% in the 12.1-14 week group. This investigation provides reference data on the prevalence of detecting simple ovarian cysts >or= 3 cm by TVS in an asymptomatic early pregnancy population. A progressive decline in the frequency of detecting simple ovarian cysts >or= 3 cm begins after 10 weeks' gestational age.

Strategy as simple rules.

PubMed

Eisenhardt, K M; Sull, D N

2001-01-01

The success of Yahoo!, eBay, Enron, and other companies that have become adept at morphing to meet the demands of changing markets can't be explained using traditional thinking about competitive strategy. These companies have succeeded by pursuing constantly evolving strategies in market spaces that were considered unattractive according to traditional measures. In this article--the third in an HBR series by Kathleen Eisenhardt and Donald Sull on strategy in the new economy--the authors ask, what are the sources of competitive advantage in high-velocity markets? The secret, they say, is strategy as simple rules. The companies know that the greatest opportunities for competitive advantage lie in market confusion, but they recognize the need for a few crucial strategic processes and a few simple rules. In traditional strategy, advantage comes from exploiting resources or stable market positions. In strategy as simple rules, advantage comes from successfully seizing fleeting opportunities. Key strategic processes, such as product innovation, partnering, or spinout creation, place the company where the flow of opportunities is greatest. Simple rules then provide the guidelines within which managers can pursue such opportunities. Simple rules, which grow out of experience, fall into five broad categories: how- to rules, boundary conditions, priority rules, timing rules, and exit rules. Companies with simple-rules strategies must follow the rules religiously and avoid the temptation to change them too frequently. A consistent strategy helps managers sort through opportunities and gain short-term advantage by exploiting the attractive ones. In stable markets, managers rely on complicated strategies built on detailed predictions of the future. But when business is complicated, strategy should be simple.

Chemical Kinetics, Heat Transfer, and Sensor Dynamics Revisited in a Simple Experiment

ERIC Educational Resources Information Center

Sad, Maria E.; Sad, Mario R.; Castro, Alberto A.; Garetto, Teresita F.

2008-01-01

A simple experiment about thermal effects in chemical reactors is described, which can be used to illustrate chemical reactor models, the determination and validation of their parameters, and some simple principles of heat transfer and sensor dynamics. It is based in the exothermic reaction between aqueous solutions of sodium thiosulfate and…

A Simple "Tubeless" Telescope

ERIC Educational Resources Information Center

Straulino, S.; Bonechi, L.

2010-01-01

Two lenses make it possible to create a simple telescope with quite large magnification. The set-up is very simple and can be reproduced in schools, provided the laboratory has a range of lenses with different focal lengths. In this article, the authors adopt the Keplerian configuration, which is composed of two converging lenses. This instrument,…

Study Guide: Seven Simple Secrets

ERIC Educational Resources Information Center

Satterfield, Nancy; Breaux, Annette; Whitaker, Todd

2007-01-01

This study guide has been developed to accompany the "Seven Simple Secrets" book written by Dr. Todd Whitaker and Annette Breaux. "Seven Simple Secrets" focuses on those attributes that have been found to help teachers be their absolute best in their daily challenges of teaching and improving student learning. The study guide is divided into the…

Learn about Physical Science: Simple Machines. [CD-ROM].

ERIC Educational Resources Information Center

2000

This CD-ROM, designed for students in grades K-2, explores the world of simple machines. It allows students to delve into the mechanical world and learn the ways in which simple machines make work easier. Animated demonstrations are provided of the lever, pulley, wheel, screw, wedge, and inclined plane. Activities include practical matching and…

Fun with Physics in the Elementary School.

ERIC Educational Resources Information Center

Ediger, Marlow

Primary grade pupils can become fascinated with simple machines. This paper suggests that teachers have simple machines in the classroom for a unit of study. It proposes some guidelines to create a unit of study for six simple machines that include the fulcrum, inclined plane, pulley, wheel and axle, wedge, and screw. Friction, gravity, force, and…

10 CFR 436.23 - Estimated simple payback time.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Methodology and Procedures for Life Cycle Cost Analyses § 436.23 Estimated simple payback time. The estimated simple payback time is the number of years required for the cumulative value of energy or water cost savings less future non-fuel or non-water costs to equal the investment costs of the building energy or...

7 CFR 4280.115 - Construction planning and performing development.

Code of Federal Regulations, 2010 CFR

2010-01-01

... projects as applicable. For contracts of $200,000 or less, the simple contract method, as specified in... warranty documents. (e) Simple contract method. The simple contract method may be used for small projects... Agency and may be used only if they are customarily used in the area and protect the interest of the...

Everyday Engineering: What Makes a Bic Click?

ERIC Educational Resources Information Center

Moyer, Richard; Everett, Susan

2009-01-01

The ballpoint pen is an ideal example of simple engineering that we use everyday. But is it really so simple? The ballpoint pen is a remarkable combination of technology and science. Its operation uses several scientific principles related to chemistry and physics, such as properties of liquids and simple machines. They represent significant…

47 CFR 52.36 - Standard data fields for simple port order processing.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 3 2010-10-01 2010-10-01 false Standard data fields for simple port order processing. 52.36 Section 52.36 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) NUMBERING Number Portability § 52.36 Standard data fields for simple port order processing. (a) A telecommunications...

10 CFR 436.23 - Estimated simple payback time.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Methodology and Procedures for Life Cycle Cost Analyses § 436.23 Estimated simple payback time. The estimated simple payback time is the number of years required for the cumulative value of energy or water cost savings less future non-fuel or non-water costs to equal the investment costs of the building energy or...

10 CFR 436.23 - Estimated simple payback time.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Methodology and Procedures for Life Cycle Cost Analyses § 436.23 Estimated simple payback time. The estimated simple payback time is the number of years required for the cumulative value of energy or water cost savings less future non-fuel or non-water costs to equal the investment costs of the building energy or...

10 CFR 436.23 - Estimated simple payback time.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Methodology and Procedures for Life Cycle Cost Analyses § 436.23 Estimated simple payback time. The estimated simple payback time is the number of years required for the cumulative value of energy or water cost savings less future non-fuel or non-water costs to equal the investment costs of the building energy or...

10 CFR 436.23 - Estimated simple payback time.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Methodology and Procedures for Life Cycle Cost Analyses § 436.23 Estimated simple payback time. The estimated simple payback time is the number of years required for the cumulative value of energy or water cost savings less future non-fuel or non-water costs to equal the investment costs of the building energy or...

Science 101: Q--What Is the Physics behind Simple Machines?

ERIC Educational Resources Information Center

Robertson, Bill

2013-01-01

Bill Robertson thinks that questioning the physics behind simple machines is a great idea because when he encounters the subject of simple machines in textbooks, activities, and classrooms, he seldom encounters, a scientific explanation of how they work. Instead, what one often sees is a discussion of load, effort, fulcrum, actual mechanical…

26 CFR 1.401(k)-4 - SIMPLE 401(k) plan requirements.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 26 Internal Revenue 5 2012-04-01 2011-04-01 true SIMPLE 401(k) plan requirements. 1.401(k)-4 Section 1.401(k)-4 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED...(k)-4 SIMPLE 401(k) plan requirements. (a) General rule. A cash or deferred arrangement satisfies the...

26 CFR 1.401(k)-4 - SIMPLE 401(k) plan requirements.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 26 Internal Revenue 5 2014-04-01 2014-04-01 false SIMPLE 401(k) plan requirements. 1.401(k)-4 Section 1.401(k)-4 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED...(k)-4 SIMPLE 401(k) plan requirements. (a) General rule. A cash or deferred arrangement satisfies the...

26 CFR 1.401(k)-4 - SIMPLE 401(k) plan requirements.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 26 Internal Revenue 5 2011-04-01 2011-04-01 false SIMPLE 401(k) plan requirements. 1.401(k)-4 Section 1.401(k)-4 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED...(k)-4 SIMPLE 401(k) plan requirements. (a) General rule. A cash or deferred arrangement satisfies the...

26 CFR 1.401(k)-4 - SIMPLE 401(k) plan requirements.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 26 Internal Revenue 5 2013-04-01 2013-04-01 false SIMPLE 401(k) plan requirements. 1.401(k)-4 Section 1.401(k)-4 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED...(k)-4 SIMPLE 401(k) plan requirements. (a) General rule. A cash or deferred arrangement satisfies the...

24 CFR 201.24 - Security requirements.

Code of Federal Regulations, 2010 CFR

2010-04-01

... borrower and all other owners in fee simple. (ii) If the borrower is a lessee, the borrower and all owners in fee simple must execute the mortgage or deed of trust. If the borrower is purchasing the property under a land installment contract, the borrower, all owners in fee simple, and all intervening contract...

15 CFR 921.21 - Initial acquisition and development awards.

Code of Federal Regulations, 2010 CFR

2010-01-01

.... (a) Assistance is provided to aid the recipient prior to designation in: (1) Acquiring a fee simple or less-than-fee simple real property interest in land and water areas to be included in the Reserve... documentation underlying less-then-fee-simple interests acquired in whole or part with Federal funds. (g...

A Simple Demonstration of Atomic and Molecular Orbitals Using Circular Magnets

ERIC Educational Resources Information Center

Chakraborty, Maharudra; Mukhopadhyay, Subrata; Das, Ranendu Sekhar

2014-01-01

A quite simple and inexpensive technique is described here to represent the approximate shapes of atomic orbitals and the molecular orbitals formed by them following the principles of the linear combination of atomic orbitals (LCAO) method. Molecular orbitals of a few simple molecules can also be pictorially represented. Instructors can employ the…

THE MATHEMATICAL ANALYSIS OF A SIMPLE DUEL

DTIC Science & Technology

The principles and techniques of simple Markov processes are used to analyze a simple duel to determine the limiting state probabilities (i.e., the...probabilities of occurrence of the various possible outcomes of the duel ). The duel is one in which A fires at B at a rate of r sub A shots per minute

Early Prediction of Reading Comprehension within the Simple View Framework

ERIC Educational Resources Information Center

Catts, Hugh W.; Herrera, Sarah; Nielsen, Diane Corcoran; Bridges, Mindy Sittner

2015-01-01

The simple view of reading proposes that reading comprehension is the product of word reading and language comprehension. In this study, we used the simple view framework to examine the early prediction of reading comprehension abilities. Using multiple measures for all constructs, we assessed word reading precursors (i.e., letter knowledge,…

Operator Priming and Generalization of Practice in Adults' Simple Arithmetic

ERIC Educational Resources Information Center

Chen, Yalin; Campbell, Jamie I. D.

2016-01-01

There is a renewed debate about whether educated adults solve simple addition problems (e.g., 2 + 3) by direct fact retrieval or by fast, automatic counting-based procedures. Recent research testing adults' simple addition and multiplication showed that a 150-ms preview of the operator (+ or ×) facilitated addition, but not multiplication,…

Simple Machine Junk Cars

ERIC Educational Resources Information Center

Herald, Christine

2010-01-01

During the month of May, the author's eighth-grade physical science students study the six simple machines through hands-on activities, reading assignments, videos, and notes. At the end of the month, they can easily identify the six types of simple machine: inclined plane, wheel and axle, pulley, screw, wedge, and lever. To conclude this unit,…

No Generalization of Practice for Nonzero Simple Addition

ERIC Educational Resources Information Center

Campbell, Jamie I. D.; Beech, Leah C.

2014-01-01

Several types of converging evidence have suggested recently that skilled adults solve very simple addition problems (e.g., 2 + 1, 4 + 2) using a fast, unconscious counting algorithm. These results stand in opposition to the long-held assumption in the cognitive arithmetic literature that such simple addition problems normally are solved by fact…

Marks, Spaces and Boundaries: Punctuation (and Other Effects) in the Typography of Dictionaries

ERIC Educational Resources Information Center

Luna, Paul

2011-01-01

Dictionary compilers and designers use punctuation to structure and clarify entries and to encode information. Dictionaries with a relatively simple structure can have simple typography and simple punctuation; as dictionaries grew more complex, and encountered the space constraints of the printed page, complex encoding systems were developed,…

Interpretation of styles of simple stations in Korea

NASA Astrophysics Data System (ADS)

Hwang, Minhye; Shin, Yekyeong

2018-06-01

The purpose of this paper is to apply stylistic interpretation through the exterior of simple stations in Korea. Simple Station is a kind of railway stations. It was installed when there were not a lot of passengers and it was not necessary to operate the station at a high cost. It has minimal functions such as a waiting room, an office, an operating room, and toilets and was built between the 1910s and the 1960s. The form of the building is as simple as the name of "Simple Station". That is why the reading its style is easy and obvious. But it is also difficult to interpret because of the lack of stylistic evidences. Nevertheless, in the relationship between the station and the station tree, the concept of the Picturesque and Palladian Style are found. But it is still hard to distinguish whether the whole building style is Western or Japanese. Simple Station is one of the things that Japan has built as Western Culture in Korea during the Japanese colonial era, so it is natural that its style of form is complex.

Contribution of strategy use to performance on complex and simple span tasks.

PubMed

Bailey, Heather; Dunlosky, John; Kane, Michael J

2011-04-01

Simple and complex span tasks are widely thought to measure related but separable memory constructs. Recently, however, research has demonstrated that simple and complex span tasks may tap, in part, the same construct because both similarly predict performance on measures of fluid intelligence (Gf) when the number of items retrieved from secondary memory (SM) is equated (Unsworth & Engle, Journal of Memory and Language 54:68-80 2006). Two studies (n = 105 and n = 152) evaluated whether retrieval from SM is influenced by individual differences in the use of encoding strategies during span tasks. Results demonstrated that, after equating the number of items retrieved from SM, simple and complex span performance similarly predicted Gf performance, but rates of effective strategy use did not mediate the span-Gf relationships. Moreover, at the level of individual differences, effective strategy use was more highly related to complex span performance than to simple span performance. Thus, even though individual differences in effective strategy use influenced span performance on trials that required retrieval from SM, strategic behavior at encoding cannot account for the similarities between simple and complex span tasks.

Nanoscale simple-fluid behavior under steady shear.

PubMed

Yong, Xin; Zhang, Lucy T

2012-05-01

In this study, we use two nonequilibrium molecular dynamics algorithms, boundary-driven shear and homogeneous shear, to explore the rheology and flow properties of a simple fluid undergoing steady simple shear. The two distinct algorithms are designed to elucidate the influences of nanoscale confinement. The results of rheological material functions, i.e., viscosity and normal pressure differences, show consistent Newtonian behaviors at low shear rates from both systems. The comparison validates that confinements of the order of 10 nm are not strong enough to deviate the simple fluid behaviors from the continuum hydrodynamics. The non-Newtonian phenomena of the simple fluid are further investigated by the homogeneous shear simulations with much higher shear rates. We observe the "string phase" at high shear rates by applying both profile-biased and profile-unbiased thermostats. Contrary to other findings where the string phase is found to be an artifact of the thermostats, we perform a thorough analysis of the fluid microstructures formed due to shear, which shows that it is possible to have a string phase and second shear thinning for dense simple fluids.

A simple dynamic engine model for use in a real-time aircraft simulation with thrust vectoring

NASA Technical Reports Server (NTRS)

Johnson, Steven A.

1990-01-01

A simple dynamic engine model was developed at the NASA Ames Research Center, Dryden Flight Research Facility, for use in thrust vectoring control law development and real-time aircraft simulation. The simple dynamic engine model of the F404-GE-400 engine (General Electric, Lynn, Massachusetts) operates within the aircraft simulator. It was developed using tabular data generated from a complete nonlinear dynamic engine model supplied by the manufacturer. Engine dynamics were simulated using a throttle rate limiter and low-pass filter. Included is a description of a method to account for axial thrust loss resulting from thrust vectoring. In addition, the development of the simple dynamic engine model and its incorporation into the F-18 high alpha research vehicle (HARV) thrust vectoring simulation. The simple dynamic engine model was evaluated at Mach 0.2, 35,000 ft altitude and at Mach 0.7, 35,000 ft altitude. The simple dynamic engine model is within 3 percent of the steady state response, and within 25 percent of the transient response of the complete nonlinear dynamic engine model.

Creating Simple Windchill Admin Tools Using Info*Engine

NASA Technical Reports Server (NTRS)

Jones, Corey; Kapatos, Dennis; Skradski, Cory

2012-01-01

Being a Windchill administrator often requires performing simple yet repetitive tasks on large sets of objects. These can include renaming, deleting, checking in, undoing checkout, and much more. This is especially true during a migration. Fortunately, PTC has provided a simple way to dynamically interact with Windchill using Info*Engine. This presentation will describe how to create simple Info*Engine tasks capable of saving Windchill 10.0 administrators hours of tedious work. It will also show how these tasks can be combined and displayed on a simple JSP page that acts as a "Windchill Administrator Dashboard/Toolbox". The attendee will learn some valuable tasks Info*Engine capable of performing. The attendee will gain a basic understanding of how to perform and implement Info*Engine tasks. The attendee will learn what's involved in creating a JSP page that displays Info*Engine tasks

From simple desires to ordinary beliefs: the early development of everyday psychology.

PubMed

Wellman, H M; Woolley, J D

1990-06-01

We provide evidence for the claim that before young children construe human action in terms of beliefs and desires they understand action only in terms of simple desires. This type of naive psychology--a simple desire psychology--constitutes a coherent understanding of human action, but it differs from the belief--desire psychology of slightly older children and adults. In this paper we characterize what we mean by a simple desire psychology and report two experiments. In Experiment 1 we demonstrate that 2-year-old can predict actions and reactions related to simple desires. In Experiment 2 we demonstrate that many 2-year-old pass desire reasoning tasks while at the same time failing belief reasoning tasks that are passed by slightly older children, and that are as comparable as possible to the desire tasks they pass with ease.

Simple versus complex degenerative mitral valve disease.

PubMed

Javadikasgari, Hoda; Mihaljevic, Tomislav; Suri, Rakesh M; Svensson, Lars G; Navia, Jose L; Wang, Robert Z; Tappuni, Bassman; Lowry, Ashley M; McCurry, Kenneth R; Blackstone, Eugene H; Desai, Milind Y; Mick, Stephanie L; Gillinov, A Marc

2018-07-01

At a center where surgeons favor mitral valve (MV) repair for all subsets of leaflet prolapse, we compared results of patients undergoing repair for simple versus complex degenerative MV disease. From January 1985 to January 2016, 6153 patients underwent primary isolated MV repair for degenerative disease, 3101 patients underwent primary isolated MV repair for simple disease (posterior prolapse), and 3052 patients underwent primary isolated MV repair for complex disease (anterior or bileaflet prolapse), based on preoperative echocardiographic images. Logistic regression analysis was used to generate propensity scores for risk-adjusted comparisons (n = 2065 matched pairs). Durability was assessed by longitudinal recurrence of mitral regurgitation and reoperation. Compared with patients with simple disease, those undergoing repair of complex pathology were more likely to be younger and female (both P values < .0001) but with similar symptoms (P = .3). The most common repair technique was ring/band annuloplasty (3055/99% simple vs 3000/98% complex; P = .5), followed by leaflet resection (2802/90% simple vs 2249/74% complex; P < .0001). Among propensity-matched patients, recurrence of severe mitral regurgitation 10 years after repair was 6.2% for simple pathology versus 11% for complex pathology (P = .007), reoperation at 18 years was 6.3% for simple pathology versus 11% for complex pathology, and 20-year survival was 62% for simple pathology versus 61% for complex pathology (P = .6). Early surgical intervention has become more common in patients with degenerative MV disease, regardless of valve prolapse complexity or symptom status. Valve repair was associated with similarly low operative risk and time-related survival but less durability in complex disease. Lifelong annual echocardiographic surveillance after MV repair is recommended, particularly in patients with complex disease. Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Double simple-harmonic-oscillator formulation of the thermal equilibrium of a fluid interacting with a coherent source of phonons

NASA Technical Reports Server (NTRS)

Defacio, B.; Vannevel, Alan; Brander, O.

1993-01-01

A formulation is given for a collection of phonons (sound) in a fluid at a non-zero temperature which uses the simple harmonic oscillator twice; one to give a stochastic thermal 'noise' process and the other which generates a coherent Glauber state of phonons. Simple thermodynamic observables are calculated and the acoustic two point function, 'contrast' is presented. The role of 'coherence' in an equilibrium system is clarified by these results and the simple harmonic oscillator is a key structure in both the formulation and the calculations.

Conjectures on the relations of linking and causality in causally simple spacetimes

NASA Astrophysics Data System (ADS)

Chernov, Vladimir

2018-05-01

We formulate the generalization of the Legendrian Low conjecture of Natario and Tod (proved by Nemirovski and myself before) to the case of causally simple spacetimes. We prove a weakened version of the corresponding statement. In all known examples, a causally simple spacetime can be conformally embedded as an open subset into some globally hyperbolic and the space of light rays in is an open submanifold of the space of light rays in . If this is always the case, this provides an approach to solving the conjectures relating causality and linking in causally simple spacetimes.

Simple solutions for relativistic generalizations of the Child-Langmuir law and the Langmuir-Blodgett law

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

Zhang Yongpeng; Northwest Institute of Nuclear Technology, P.O. Box 69-13, Xi'an 710024; Liu Guozhi

In this paper, the Child-Langmuir law and Langmuir-Blodgett law are generalized to the relativistic regime by a simple method. Two classical laws suitable for the nonrelativistic regime are modified to simple approximate expressions applicable for calculating the space-charge-limited currents of one-dimensional steady-state planar diodes and coaxial diodes under the relativistic regime. The simple approximate expressions, extending the Child-Langmuir law and Langmuir-Blodgett law to fit the full range of voltage, have small relative errors less than 1% for one-dimensional planar diodes and less than 5% for coaxial diodes.

Generalized Lotka—Volterra systems connected with simple Lie algebras

NASA Astrophysics Data System (ADS)

Charalambides, Stelios A.; Damianou, Pantelis A.; Evripidou, Charalambos A.

2015-06-01

We devise a new method for producing Hamiltonian systems by constructing the corresponding Lax pairs. This is achieved by considering a larger subset of the positive roots than the simple roots of the root system of a simple Lie algebra. We classify all subsets of the positive roots of the root system of type An for which the corresponding Hamiltonian systems are transformed, via a simple change of variables, to Lotka-Volterra systems. For some special cases of subsets of the positive roots of the root system of type An, we produce new integrable Hamiltonian systems.

Composition of the cellular infiltrate in patients with simple and complex appendicitis.

PubMed

Gorter, Ramon R; Wassenaar, Emma C E; de Boer, Onno J; Bakx, Roel; Roelofs, Joris J T H; Bunders, Madeleine J; van Heurn, L W Ernst; Heij, Hugo A

2017-06-15

It is now well established that there are two types of appendicitis: simple (nonperforating) and complex (perforating). This study evaluates differences in the composition of the immune cellular infiltrate in children with simple and complex appendicitis. A total of 47 consecutive children undergoing appendectomy for acute appendicitis between January 2011 and December 2012 were included. Intraoperative criteria were used to identify patients with either simple or complex appendicitis and were confirmed histopathologically. Immune histochemical techniques were used to identify immune cell markers in the appendiceal specimens. Digital imaging analysis was performed using Image J. In the specimens of patients with complex appendicitis, significantly more myeloperoxidase positive cells (neutrophils) (8.7% versus 1.2%, P < 0.001) were detected compared to patients with a simple appendicitis. In contrast, fewer CD8+ T cells (0.4% versus 1.3%, P = 0.016), CD20 + cells (2.9% versus 9.0%, P = 0.027), and CD21 + cells (0.2% versus 0.6%, P = 0.028) were present in tissue from patients with complex compared to simple appendicitis. The increase in proinflammatory innate cells and decrease of adaptive cells in patients with complex appendicitis suggest potential aggravating processes in complex appendicitis. Further research into the underlying mechanisms may identify novel biomarkers to be able to differentiate simple and complex appendicitis. Copyright © 2017 Elsevier Inc. All rights reserved.

Fast algorithms for transforming back and forth between a signed permutation and its equivalent simple permutation.

PubMed

Gog, Simon; Bader, Martin

2008-10-01

The problem of sorting signed permutations by reversals is a well-studied problem in computational biology. The first polynomial time algorithm was presented by Hannenhalli and Pevzner in 1995. The algorithm was improved several times, and nowadays the most efficient algorithm has a subquadratic running time. Simple permutations played an important role in the development of these algorithms. Although the latest result of Tannier et al. does not require simple permutations, the preliminary version of their algorithm as well as the first polynomial time algorithm of Hannenhalli and Pevzner use the structure of simple permutations. More precisely, the latter algorithms require a precomputation that transforms a permutation into an equivalent simple permutation. To the best of our knowledge, all published algorithms for this transformation have at least a quadratic running time. For further investigations on genome rearrangement problems, the existence of a fast algorithm for the transformation could be crucial. Another important task is the back transformation, i.e. if we have a sorting on the simple permutation, transform it into a sorting on the original permutation. Again, the naive approach results in an algorithm with quadratic running time. In this paper, we present a linear time algorithm for transforming a permutation into an equivalent simple permutation, and an O(n log n) algorithm for the back transformation of the sorting sequence.

Pre-Service and In-Service Physics Teachers' Ideas about Simple Electric Circuits

ERIC Educational Resources Information Center

Kucukozer, Huseyin; Demirci, Neset

2008-01-01

The aim of the study is to determine pre-service and high school physics teachers' ideas about simple electric circuits. In this study, a test containing eight questions related to simple electric circuits was given to the pre-service physics teachers (32 subjects) that had graduated from Balikesir University, Necatibey Faculty of Education, the…

Misconceptions of Mexican Teachers in the Solution of Simple Pendulum

ERIC Educational Resources Information Center

Garcia Trujillo, Luis Antonio; Ramirez Díaz, Mario H.; Rodriguez Castillo, Mario

2013-01-01

Solving the position of a simple pendulum at any time is apparently one of the most simple and basic problems to solve in high school and college physics courses. However, because of this apparent simplicity, teachers and physics texts often assume that the solution is immediate without pausing to reflect on the problem formulation or verifying…

Visual Short-Term Memory for Complex Objects in 6- and 8-Month-Old Infants

ERIC Educational Resources Information Center

Kwon, Mee-Kyoung; Luck, Steven J.; Oakes, Lisa M.

2014-01-01

Infants' visual short-term memory (VSTM) for simple objects undergoes dramatic development: Six-month-old infants can store in VSTM information about only a simple object presented in isolation, whereas 8-month-old infants can store information about simple objects presented in multiple-item arrays. This study extended this work to examine…

Symmetrical polyhedra (simple crystal forms) as orbits of noncrystallographic point symmetry groups

NASA Astrophysics Data System (ADS)

Ovsetsina, T. I.; Chuprunov, E. V.

2017-09-01

Simple crystal forms are analyzed as the orbits of noncrystallographic point symmetry groups on a set of smooth or structured ("hatched") planes of crystal space. Polyhedra with symmetrically equivalent faces, obtained using noncrystallographic point symmetry groups, are considered. All possible versions of simple forms for all noncrystallographic groups are listed in a unified table.

Bell's Theorem and Einstein's "Spooky Actions" from a Simple Thought Experiment

ERIC Educational Resources Information Center

Kuttner, Fred; Rosenblum, Bruce

2010-01-01

In 1964 John Bell proved a theorem allowing the experimental test of whether what Einstein derided as "spooky actions at a distance" actually exist. We will see that they "do". Bell's theorem can be displayed with a simple, nonmathematical thought experiment suitable for a physics course at "any" level. And a simple, semi-classical derivation of…

Patterns of Response Times and Response Choices to Science Questions: The Influence of Relative Processing Time

ERIC Educational Resources Information Center

Heckler, Andrew F.; Scaife, Thomas M.

2015-01-01

We report on five experiments investigating response choices and response times to simple science questions that evoke student "misconceptions," and we construct a simple model to explain the patterns of response choices. Physics students were asked to compare a physical quantity represented by the slope, such as speed, on simple physics…

The Fluid Foil: The Seventh Simple Machine

ERIC Educational Resources Information Center

Mitts, Charles R.

2012-01-01

A simple machine does one of two things: create a mechanical advantage (lever) or change the direction of an applied force (pulley). Fluid foils are unique among simple machines because they not only change the direction of an applied force (wheel and axle); they convert fluid energy into mechanical energy (wind and Kaplan turbines) or vice versa,…

Measuring Drag Force in Newtonian Liquids

ERIC Educational Resources Information Center

Mawhinney, Matthew T.; O'Donnell, Mary Kate; Fingerut, Jonathan; Habdas, Piotr

2012-01-01

The experiments described in this paper have two goals. The first goal is to show how students can perform simple but fundamental measurements of objects moving through simple liquids (such as water, oil, or honey). In doing so, students can verify Stokes' law, which governs the motion of spheres through simple liquids, and see how it fails at…

CMOS Active-Pixel Image Sensor With Simple Floating Gates

NASA Technical Reports Server (NTRS)

Fossum, Eric R.; Nakamura, Junichi; Kemeny, Sabrina E.

1996-01-01

Experimental complementary metal-oxide/semiconductor (CMOS) active-pixel image sensor integrated circuit features simple floating-gate structure, with metal-oxide/semiconductor field-effect transistor (MOSFET) as active circuit element in each pixel. Provides flexibility of readout modes, no kTC noise, and relatively simple structure suitable for high-density arrays. Features desirable for "smart sensor" applications.

Simple Proof of Jury Test for Complex Polynomials

NASA Astrophysics Data System (ADS)

Choo, Younseok; Kim, Dongmin

Recently some attempts have been made in the literature to give simple proofs of Jury test for real polynomials. This letter presents a similar result for complex polynomials. A simple proof of Jury test for complex polynomials is provided based on the Rouché's Theorem and a single-parameter characterization of Schur stability property for complex polynomials.

The Simple View of Reading: Assessment and Intervention

ERIC Educational Resources Information Center

Roberts, Jenny A.; Scott, Kathleen A.

2006-01-01

The Simple View of Reading (P. B. Gough & W. Tunmer, 1986; W. A. Hoover & P. B. Gough, 1990) provides a 2-component model of reading. Each of these 2 components, decoding and comprehension, is necessary for normal reading to occur. The Simple View of Reading provides a relatively transparent model that can be used by professionals not only to…

26 CFR 1.401(k)-4 - SIMPLE 401(k) plan requirements.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 26 Internal Revenue 5 2010-04-01 2010-04-01 false SIMPLE 401(k) plan requirements. 1.401(k)-4 Section 1.401(k)-4 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Pension, Profit-Sharing, Stock Bonus Plans, Etc. § 1.401(k)-4 SIMPLE...

78 FR 34015 - Requests for Clarification of Use of Passcodes for Non-Simple Ports and Local Number Portability...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-06

... 13-1178] Requests for Clarification of Use of Passcodes for Non-Simple Ports and Local Number... to all ports, not just simple ports, thereby prohibiting the use of a carrier-initiated passcode for.... DATES: Comments must be filed on or before June 5, 2013. ADDRESSES: Interested parties may submit...

26 CFR 301.6621-1 - Interest rate.

Code of Federal Regulations, 2010 CFR

2010-04-01

... March 1, 1983. Such interest is computed at the rate of 12 percent per annum, simple interest from April 15, 1981, to January 31, 1982, and at the rate of 20 percent per annum, simple interest from January... December 31, 1982, to March 1, 1983. The total simple interest accrued but unpaid at the end of December 31...

78 FR 46425 - Sale and Issue of Marketable Book-Entry Treasury Bills, Notes, and Bonds

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-31

... a simple-interest money market yield computed on an actual/360 basis, subject to an appropriate... 13-week Treasury bill auction High Rate (stop out rate) converted into a simple actual/360 interest...-week Treasury bill auction High Rate that has been translated into a simple-interest money market yield...

Young Children and Turtle Graphics Programming: Generating and Debugging Simple Turtle Programs.

ERIC Educational Resources Information Center

Cuneo, Diane O.

Turtle graphics is a popular vehicle for introducing children to computer programming. Children combine simple graphic commands to get a display screen cursor (called a turtle) to draw designs on the screen. The purpose of this study was to examine young children's abilities to function in a simple computer programming environment. Four- and…

A reexamination of the use of simple concepts for predicting the shape and location of detached shock waves

NASA Technical Reports Server (NTRS)

Love, Eugene S

1957-01-01

A reexamination has been made of the use of simple concepts for predicting the shape and location of detached shock waves. The results show that simple concepts and modifications of existing methods can yield good predictions for many nose shapes and for a wide range of Mach numbers.

Acute osteomyelitis complicating a simple fracture. A case report.

PubMed

Drummond-Webb, J J; Schnaid, E

1983-11-26

Osteomyelitis complicating a simple fracture is unusual, but the reason for its rarity is unknown. We report on a 9-year-old Black boy who developed acute osteomyelitis after sustaining an acute simple fracture of the femur. The causative role of trauma in acute osteomyelitis is discussed and 'the relative resistance of healthy bone' questioned.

Reconsidering the Simple View of Reading in an Intriguing Case of Equivalent Models: Commentary on Tunmer and Chapman (2012)

ERIC Educational Resources Information Center

Wagner, Richard K.; Herrera, Sarah K.; Spencer, Mercedes; Quinn, Jamie M.

2015-01-01

Recently, Tunmer and Chapman provided an alternative model of how decoding and listening comprehension affect reading comprehension that challenges the simple view of reading. They questioned the simple view's fundamental assumption that oral language comprehension and decoding make independent contributions to reading comprehension by arguing…

Simple taper: Taper equations for the field forester

Treesearch

David R. Larsen

2017-01-01

"Simple taper" is set of linear equations that are based on stem taper rates; the intent is to provide taper equation functionality to field foresters. The equation parameters are two taper rates based on differences in diameter outside bark at two points on a tree. The simple taper equations are statistically equivalent to more complex equations. The linear...

Sunspots and Their Simple Harmonic Motion

ERIC Educational Resources Information Center

Ribeiro, C. I.

2013-01-01

In this paper an example of a simple harmonic motion, the apparent motion of sunspots due to the Sun's rotation, is described, which can be used to teach this subject to high-school students. Using real images of the Sun, students can calculate the star's rotation period with the simple harmonic motion mathematical expression.

Using Simple Linear Regression to Assess the Success of the Montreal Protocol in Reducing Atmospheric Chlorofluorocarbons

ERIC Educational Resources Information Center

Nelson, Dean

2009-01-01

Following the Guidelines for Assessment and Instruction in Statistics Education (GAISE) recommendation to use real data, an example is presented in which simple linear regression is used to evaluate the effect of the Montreal Protocol on atmospheric concentration of chlorofluorocarbons. This simple set of data, obtained from a public archive, can…

Simple and Cooperatively Built Wave Motion Demonstrator

ERIC Educational Resources Information Center

Cortel, Adolf

2006-01-01

Some designs of simple wave demonstration devices have been described in this journal and elsewhere. A new simple model can be built using only dowels, binder clips, and loops of thread. Not only can it be easily assembled, stored, or disassembled, but also all the students in a class can cooperate in its building by connecting successive pieces…

Depressive symptoms and cardiovascular health by the American Heart Association's definition in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study.

PubMed

Kronish, Ian M; Carson, April P; Davidson, Karina W; Muntner, Paul; Safford, Monika M

2012-01-01

Depressive symptoms are associated with increased incident and recurrent cardiovascular events. In 2010, the American Heart Association published the Life's Simple 7, a metric for assessing cardiovascular health as measured by 4 health behaviors (smoking, physical activity, body mass index, diet) and 3 biological measures (cholesterol, blood pressure, glucose). The association between depressive symptoms and the Life's Simple 7 has not yet been explored. Data from 20,093 participants ≥45 years of age who enrolled in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study between 2003 and 2007 and who had complete data available on Life's Simple 7 components were used for these analyses. The prevalence of ideal, intermediate, and poor health on each Life's Simple 7 component and total Life's Simple 7 scores were compared between participants with and without depressive symptoms. Depressive symptoms were measured using the 4-item Centers for Epidemiologic Studies of Depression scale. Participants with depressive symptoms were more likely to have poor levels on each of the Life's Simple 7 components other than cholesterol [adjusted prevalence ratios (95% CI): smoking 1.41 (1.29-1.55); physical activity 1.38 (1.31-1.46); body mass index 1.09 (1.04-1.15); diet 1.08 (1.06-1.10); blood pressure 1.11 (1.02-1.21); glucose 1.24 (1.09-1.41)]. There was a graded association between increasing depressive symptoms and lower total Life's Simple 7 score. Depressive symptoms are associated with worse cardiovascular health on the overall Life's Simple 7 and on individual components representing both health behaviors and biological factors.

A Randomized Study Comparing the Sniffing Position with Simple Head Extension for Glottis Visualization and Difficulty in Intubation during Direct Laryngoscopy.

PubMed

Akhtar, Mehmooda; Ali, Zulfiqar; Hassan, Nelofar; Mehdi, Saqib; Wani, Gh Mohammad; Mir, Aabid Hussain

2017-01-01

Proper positioning of the head and neck is important for an optimal laryngeal visualization. Traditionally, sniffing position (SP) is recommended to provide a superior glottic visualization, during direct laryngoscopy, enhancing the ease of intubation. Various studies in the last decade of this belief have challenged the need for sniffing position during intubation. We conducted a prospective study comparing the sniffing head position with simple head extension to study the laryngoscopic view and intubation difficulty during direct laryngoscopy. Five-hundred patients were included in this study and randomly distributed to SP or simple head extension. In the sniffing group, an incompressible head ring was placed under the head to raise its height by 7 cm from the neutral plane followed by maximal extension of the head. In the simple extension group, no headrest was placed under the head; however, maximal head extension was given at the time of laryngoscopy. Various factors as ability to mask ventilate, laryngoscopic visualization, intubation difficulty, and posture of the anesthesiologist during laryngoscopy and tracheal intubation were noted. In the incidence of difficult laryngoscopy (Cormack Grade III and IV), Intubation Difficulty Scale (IDS score) was compared between the two groups. There was no significant difference between two groups in Cormack grades. The IDS score differed significantly between sniffing group and simple extension group ( P = 0.000) with an increased difficulty during intubation in the simple head extension. Patients with simple head extension needed more lifting force, increased use of external laryngeal manipulation, and an increased use of alternate techniques during intubation when compared to SP. We conclude that compared to the simple head extension position, the SP should be used as a standard head position for intubation attempts under general anesthesia.

Humans' perceptions of animal mentality: ascriptions of thinking.

PubMed

Rasmussen, J L; Rajecki, D W; Craft, H D

1993-09-01

On rating scales, 294 students indicated whether it was reasonable to say that a dog, cat, bird, fish, and school-age child had the capacity for 12 commonplace human mental operations or experiences. Factor analysis of responses identified 2 levels of attributions, simple thinking and complex thinking. The child and all animals were credited with simple thinking, but respondents were much more likely to ascribe complex thinking to the child. (A pilot study with 8 animal-behavior professionals generally replicated these results.) Certain mental categories (e.g., emotion) were judged by students to be simple for all target types; others (e.g., conservation) were judged to be universally complex. Further factoring revealed articulate ascriptions for key mental categories. Play and imagine was seen as simple in the animals but complex for the child, but enumeration and sorting and dream were seen as simple in the child but complex for the animals.

Simple formula for the surface area of the body and a simple model for anthropometry.

PubMed

Reading, Bruce D; Freeman, Brian

2005-03-01

The body surface area (BSA) of any adult, when derived from the arithmetic mean of the different values calculated from four independent accepted formulae, can be expressed accurately in Systeme International d'Unites (SI) units by the simple equation BSA = 1/6(WH)0.5, where W is body weight in kg, H is body height in m, and BSA is in m2. This formula, which is derived in part by modeling the body as a simple solid of revolution or a prolate spheroid (i.e., a stretched ellipsoid of revolution) gives students, teachers, and clinicians a simple rule for the rapid estimation of surface area using rational units. The formula was tested independently for human subjects by using it to predict body volume and then comparing this prediction against the actual volume measured by Archimedes' principle. Copyright 2005 Wiley-Liss, Inc.

Simple Test Functions in Meshless Local Petrov-Galerkin Methods

NASA Technical Reports Server (NTRS)

Raju, Ivatury S.

2016-01-01

Two meshless local Petrov-Galerkin (MLPG) methods based on two different trial functions but that use a simple linear test function were developed for beam and column problems. These methods used generalized moving least squares (GMLS) and radial basis (RB) interpolation functions as trial functions. These two methods were tested on various patch test problems. Both methods passed the patch tests successfully. Then the methods were applied to various beam vibration problems and problems involving Euler and Beck's columns. Both methods yielded accurate solutions for all problems studied. The simple linear test function offers considerable savings in computing efforts as the domain integrals involved in the weak form are avoided. The two methods based on this simple linear test function method produced accurate results for frequencies and buckling loads. Of the two methods studied, the method with radial basis trial functions is very attractive as the method is simple, accurate, and robust.

Cross-cultural differences in meter perception.

PubMed

Kalender, Beste; Trehub, Sandra E; Schellenberg, E Glenn

2013-03-01

We examined the influence of incidental exposure to varied metrical patterns from different musical cultures on the perception of complex metrical structures from an unfamiliar musical culture. Adults who were familiar with Western music only (i.e., simple meters) and those who also had limited familiarity with non-Western music were tested on their perception of metrical organization in unfamiliar (Turkish) music with simple and complex meters. Adults who were familiar with Western music detected meter-violating changes in Turkish music with simple meter but not in Turkish music with complex meter. Adults with some exposure to non-Western music that was unmetered or metrically complex detected meter-violating changes in Turkish music with both simple and complex meters, but they performed better on patterns with a simple meter. The implication is that familiarity with varied metrical structures, including those with a non-isochronous tactus, enhances sensitivity to the metrical organization of unfamiliar music.

Hippocampal neuronal cells that accumulate α-synuclein fragments are more vulnerable to Aβ oligomer toxicity via mGluR5 – implications for dementia with Lewy bodies

PubMed Central

2014-01-01

Background In dementia with Lewy bodies (DLB) abnormal interactions between α-synuclein (α-syn) and beta amyloid (Aβ) result in selective degeneration of neurons in the neocortex, limbic system and striatum. However, factors rendering these neurons selectively vulnerable have not been fully investigated. The metabotropic glutamate receptor 5 (mGluR5) has been shown to be up regulated in DLB and might play a role as a mediator of the neurotoxic effects of Aβ and α-syn in vulnerable neuronal populations. In this context, the main objective of the present study was to investigate the role of mGluR5 as a mediator of the neurotoxic effects of α-syn and Aβ in the hippocampus. Results We generated double transgenic mice over-expressing amyloid precursor protein (APP) and α-syn under the mThy1 cassette and investigated the relationship between α-syn cleavage, Aβ, mGluR5 and neurodegeneration in the hippocampus. We found that compared to the single tg mice, the α-syn/APP tg mice displayed greater accumulation of α-syn and mGluR5 in the CA3 region of the hippocampus compared to the CA1 and other regions. This was accompanied by loss of CA3 (but not CA1) neurons in the single and α-syn/APP tg mice and greater loss of MAP 2 and synaptophysin in the CA3 in the α-syn/APP tg. mGluR5 gene transfer using a lentiviral vector into the hippocampus CA1 region resulted in greater α-syn accumulation and neurodegeneration in the single and α-syn/APP tg mice. In contrast, silencing mGluR5 with a lenti-shRNA protected neurons in the CA3 region of tg mice. In vitro, greater toxicity was observed in primary hippocampal neuronal cultures treated with Aβ oligomers and over-expressing α-syn; this effect was attenuated by down-regulating mGluR5 with an shRNA lentiviral vector. In α-syn-expressing neuronal cells lines, Aβ oligomers promoted increased intracellular calcium levels, calpain activation and α-syn cleavage resulting in caspase-3-dependent cell death. Treatment with pharmacological mGluR5 inhibitors such as 2-Methyl-6-(phenylethynyl)pyridine (MPEP) and 3-((2-Methyl-4-thiazolyl)ethynyl)pyridine (MTEP) attenuated the toxic effects of Aβ in α-syn-expressing neuronal cells. Conclusions Together, these results support the possibility that vulnerability of hippocampal neurons to α-syn and Aβ might be mediated via mGluR5. Moreover, therapeutical interventions targeting mGluR5 might have a role in DLB. PMID:24885390

The stationary sine-Gordon equation on metric graphs: Exact analytical solutions for simple topologies

NASA Astrophysics Data System (ADS)

Sabirov, K.; Rakhmanov, S.; Matrasulov, D.; Susanto, H.

2018-04-01

We consider the stationary sine-Gordon equation on metric graphs with simple topologies. Exact analytical solutions are obtained for different vertex boundary conditions. It is shown that the method can be extended for tree and other simple graph topologies. Applications of the obtained results to branched planar Josephson junctions and Josephson junctions with tricrystal boundaries are discussed.

Approximate Expressions for the Period of a Simple Pendulum Using a Taylor Series Expansion

ERIC Educational Resources Information Center

Belendez, Augusto; Arribas, Enrique; Marquez, Andres; Ortuno, Manuel; Gallego, Sergi

2011-01-01

An approximate scheme for obtaining the period of a simple pendulum for large-amplitude oscillations is analysed and discussed. When students express the exact frequency or the period of a simple pendulum as a function of the oscillation amplitude, and they are told to expand this function in a Taylor series, they always do so using the…

26 CFR 1.652(a)-1 - Simple trusts; inclusion of amounts in income of beneficiaries.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 26 Internal Revenue 8 2012-04-01 2012-04-01 false Simple trusts; inclusion of amounts in income of beneficiaries. 1.652(a)-1 Section 1.652(a)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE... Only § 1.652(a)-1 Simple trusts; inclusion of amounts in income of beneficiaries. Subject to the rules...

26 CFR 1.652(a)-1 - Simple trusts; inclusion of amounts in income of beneficiaries.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 26 Internal Revenue 8 2014-04-01 2014-04-01 false Simple trusts; inclusion of amounts in income of beneficiaries. 1.652(a)-1 Section 1.652(a)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE... Only § 1.652(a)-1 Simple trusts; inclusion of amounts in income of beneficiaries. Subject to the rules...

26 CFR 1.652(a)-1 - Simple trusts; inclusion of amounts in income of beneficiaries.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 26 Internal Revenue 8 2013-04-01 2013-04-01 false Simple trusts; inclusion of amounts in income of beneficiaries. 1.652(a)-1 Section 1.652(a)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE... Only § 1.652(a)-1 Simple trusts; inclusion of amounts in income of beneficiaries. Subject to the rules...

Effects of the Physical Laboratory versus the Virtual Laboratory in Teaching Simple Electric Circuits on Conceptual Achievement and Attitudes Towards the Subject

ERIC Educational Resources Information Center

Tekbiyik, Ahmet; Ercan, Orhan

2015-01-01

Current study examined the effects of virtual and physical laboratory practices on students' conceptual achievement in the subject of electricity and their attitudes towards simple electric circuits. Two groups (virtual and physical) selected through simple random sampling was taught with web-aided material called "Electricity in Our…

Relation of squeezed states between damped harmonic and simple harmonic oscillators

NASA Technical Reports Server (NTRS)

Um, Chung-In; Yeon, Kyu-Hwang; George, Thomas F.; Pandey, Lakshmi N.

1993-01-01

The minimum uncertainty and other relations are evaluated in the framework of the coherent states of the damped harmonic oscillator. It is shown that the coherent states of the damped harmonic oscillator are the squeezed coherent states of the simple harmonic oscillator. The unitary operator is also constructed, and this connects coherent states with damped harmonic and simple harmonic oscillators.

75 FR 6360 - Information on Surplus Land at a Military Installation Designated for Disposal: Newport Naval...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-09

... and unimproved fee-simple land, consisting of 7 acres of land and 3 acres of submerged land. The... Middletown and consists of approximately 3 acres of improved and unimproved fee simple land. In general, the... and 2, Portsmouth, RI Tank Farms 1 and 2 consist of improved and unimproved fee simple land located...

26 CFR 1.665(e)-1A - Preceding taxable year.

Code of Federal Regulations, 2010 CFR

2010-04-01

..., since the Internal Revenue Code of 1939 applies to those years. (b) Simple trusts. A taxable year of a trust during which the trust was a simple trust (that is, was subject to subpart B) for the entire year... widow W. The terms of the trust require that the income be distributed currently (i.e., it is a simple...

77 FR 50741 - Self-Regulatory Organizations; C2 Options Exchange, Incorporated; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-22

... interested persons. \\1\\ 15 U.S.C. 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's... orders'' as ``simple orders''. Investors generally refer to orders as either ``simple'' or ``complex'' and the terminology ``straight, one-sided orders'' is not as commonly-known. Since simple orders are...

Simple Estimators for the Simple Latent Class Mastery Testing Model. Twente Educational Memorandum No. 19.

ERIC Educational Resources Information Center

van der Linden, Wim J.

Latent class models for mastery testing differ from continuum models in that they do not postulate a latent mastery continuum but conceive mastery and non-mastery as two latent classes, each characterized by different probabilities of success. Several researchers use a simple latent class model that is basically a simultaneous application of the…

Comparative Recall and Precision of Simple and Expert Searches in Google Scholar and Eight Other Databases

ERIC Educational Resources Information Center

Walters, William H.

2011-01-01

This study evaluates the effectiveness of simple and expert searches in Google Scholar (GS), EconLit, GEOBASE, PAIS, POPLINE, PubMed, Social Sciences Citation Index, Social Sciences Full Text, and Sociological Abstracts. It assesses the recall and precision of 32 searches in the field of later-life migration: nine simple keyword searches and 23…

Effect of the Four-Step Learning Cycle Model on Students' Understanding of Concepts Related to Simple Harmonic Motion

ERIC Educational Resources Information Center

Madu, B. C.

2012-01-01

The study explored the efficacy of four-step (4-E) learning cycle approach on students understanding of concepts related to Simple Harmonic Motion (SHM). 124 students (63 for experimental group and 61 for control group) participated in the study. The students' views and ideas in simple Harmonic Achievement test were analyzed qualitatively. The…

Simple and Complex Memory Spans and Their Relation to Fluid Abilities: Evidence from List-Length Effects

ERIC Educational Resources Information Center

Unsworth, Nash; Engle, Randall W.

2006-01-01

Complex (working memory) span tasks have generally shown larger and more consistent correlations with higher-order cognition than have simple (or short-term memory) span tasks. The relation between verbal complex and simple verbal span tasks to fluid abilities as a function of list-length was examined. The results suggest that the simple…

26 CFR 1.652(a)-1 - Simple trusts; inclusion of amounts in income of beneficiaries.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 26 Internal Revenue 8 2011-04-01 2011-04-01 false Simple trusts; inclusion of amounts in income of beneficiaries. 1.652(a)-1 Section 1.652(a)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE... Only § 1.652(a)-1 Simple trusts; inclusion of amounts in income of beneficiaries. Subject to the rules...

A simple technique to increase profits in wood products marketing

Treesearch

George B. Harpole

1971-01-01

Mathematical models can be used to solve quickly some simple day-to-day marketing problems. This note explains how a sawmill production manager, who has an essentially fixed-capacity mill, can solve several optimization problems by using pencil and paper, a forecast of market prices, and a simple algorithm. One such problem is to maximize profits in an operating period...

When Simple Harmonic Motion Is Not that Simple: Managing Epistemological Complexity by Using Computer-Based Representations

ERIC Educational Resources Information Center

Parnafes, Orit

2010-01-01

Many real-world phenomena, even "simple" physical phenomena such as natural harmonic motion, are complex in the sense that they require coordinating multiple subtle foci of attention to get the required information when experiencing them. Moreover, for students to develop sound understanding of a concept or a phenomenon, they need to learn to get…

Combinatorial structures to modeling simple games and applications

NASA Astrophysics Data System (ADS)

Molinero, Xavier

2017-09-01

We connect three different topics: combinatorial structures, game theory and chemistry. In particular, we establish the bases to represent some simple games, defined as influence games, and molecules, defined from atoms, by using combinatorial structures. First, we characterize simple games as influence games using influence graphs. It let us to modeling simple games as combinatorial structures (from the viewpoint of structures or graphs). Second, we formally define molecules as combinations of atoms. It let us to modeling molecules as combinatorial structures (from the viewpoint of combinations). It is open to generate such combinatorial structures using some specific techniques as genetic algorithms, (meta-)heuristics algorithms and parallel programming, among others.

Delayed massive hemothorax complicating simple rib fracture associated with diaphragmatic injury.

PubMed

Chen, Chin-Li; Cheng, Yeung-Leung

2014-07-01

Traumatic hemothorax is potentially life threatening. Rib fractures are the commonest injury after chest trauma, which accounts for 10% of patients after trauma. A delayed massive hemothorax after simple rib fracture is rare. The possibility of delayed sequelae after chest trauma should be considered, and patients should be informed of this possibility. We present a case of this uncommon situation with delayed massive hemothorax caused by simple fracture of the lower ribs. Admission should be considered for close observation when presenting with fracture of the lower ribs because of the possibility of diaphragmatic injury or intra-abdominal injury, even if a simple rib fracture is found initially.

Simple arithmetic: not so simple for highly math anxious individuals.

PubMed

Chang, Hyesang; Sprute, Lisa; Maloney, Erin A; Beilock, Sian L; Berman, Marc G

2017-12-01

Fluency with simple arithmetic, typically achieved in early elementary school, is thought to be one of the building blocks of mathematical competence. Behavioral studies with adults indicate that math anxiety (feelings of tension or apprehension about math) is associated with poor performance on cognitively demanding math problems. However, it remains unclear whether there are fundamental differences in how high and low math anxious individuals approach overlearned simple arithmetic problems that are less reliant on cognitive control. The current study used functional magnetic resonance imaging to examine the neural correlates of simple arithmetic performance across high and low math anxious individuals. We implemented a partial least squares analysis, a data-driven, multivariate analysis method to measure distributed patterns of whole-brain activity associated with performance. Despite overall high simple arithmetic performance across high and low math anxious individuals, performance was differentially dependent on the fronto-parietal attentional network as a function of math anxiety. Specifically, low-compared to high-math anxious individuals perform better when they activate this network less-a potential indication of more automatic problem-solving. These findings suggest that low and high math anxious individuals approach even the most fundamental math problems differently. © The Author (2017). Published by Oxford University Press.

Sound Richness of Music Might Be Mediated by Color Perception: A PET Study.

PubMed

Satoh, Masayuki; Nagata, Ken; Tomimoto, Hidekazu

2015-01-01

We investigated the role of the fusiform cortex in music processing with the use of PET, focusing on the perception of sound richness. Musically naïve subjects listened to familiar melodies with three kinds of accompaniments: (i) an accompaniment composed of only three basic chords (chord condition), (ii) a simple accompaniment typically used in traditional music text books in elementary school (simple condition), and (iii) an accompaniment with rich and flowery sounds composed by a professional composer (complex condition). Using a PET subtraction technique, we studied changes in regional cerebral blood flow (rCBF) in simple minus chord, complex minus simple, and complex minus chord conditions. The simple minus chord, complex minus simple, and complex minus chord conditions regularly showed increases in rCBF at the posterior portion of the inferior temporal gyrus, including the LOC and fusiform gyrus. We may conclude that certain association cortices such as the LOC and the fusiform cortex may represent centers of multisensory integration, with foreground and background segregation occurring at the LOC level and the recognition of richness and floweriness of stimuli occurring in the fusiform cortex, both in terms of vision and audition.

Simple arithmetic: not so simple for highly math anxious individuals

PubMed Central

Sprute, Lisa; Maloney, Erin A; Beilock, Sian L; Berman, Marc G

2017-01-01

Abstract Fluency with simple arithmetic, typically achieved in early elementary school, is thought to be one of the building blocks of mathematical competence. Behavioral studies with adults indicate that math anxiety (feelings of tension or apprehension about math) is associated with poor performance on cognitively demanding math problems. However, it remains unclear whether there are fundamental differences in how high and low math anxious individuals approach overlearned simple arithmetic problems that are less reliant on cognitive control. The current study used functional magnetic resonance imaging to examine the neural correlates of simple arithmetic performance across high and low math anxious individuals. We implemented a partial least squares analysis, a data-driven, multivariate analysis method to measure distributed patterns of whole-brain activity associated with performance. Despite overall high simple arithmetic performance across high and low math anxious individuals, performance was differentially dependent on the fronto-parietal attentional network as a function of math anxiety. Specifically, low—compared to high—math anxious individuals perform better when they activate this network less—a potential indication of more automatic problem-solving. These findings suggest that low and high math anxious individuals approach even the most fundamental math problems differently. PMID:29140499

Simple webs of natural environment theme as a result of sharing in science teacher training

NASA Astrophysics Data System (ADS)

Tapilouw, M. C.; Firman, H.; Redjeki, S.; Chandra, D. T.

2018-03-01

Thematic learning is one type of integrated science (Biology, Physics, Chemistry and Earth Science) in Science Education. This study is concerning about simple webs of natural environment theme in science learning, as one of training material in science teacher training program. Making simple web is a goal of first step in teacher training program. Every group explain their web illustration to other group. Twenty Junior High School science teacher above one education foundation participate in science teacher training program. In order to gather simple webs, sharing method was used in this first step of science teacher training. The result of this study is five different simple web of natural environment themes. These webs represent science learning in class VII/Semester I, class VII/Semester II, Class VIII, Class IX/Semester I, Class IX/Semester II based on basic competency in National Curriculum 2013. Each group discussed web of natural environment theme based on their learning experience in real class which basic competency and subject matters are linked with natural environment theme. As a conclusion, simple webs are potential to develop in the next step of science teacher training program and to be implemented in real class.

Alfvén simple waves

NASA Astrophysics Data System (ADS)

Webb, G. M.; Zank, G. P.; Burrows, R. H.; Ratkiewicz, R. E.

2011-02-01

Multi-dimensional Alfvén simple waves in magnetohydrodynamics (MHD) are investigated using Boillat's formalism. For simple wave solutions, all physical variables (the gas density, pressure, fluid velocity, entropy, and magnetic field induction in the MHD case) depend on a single phase function ϕ, which is a function of the space and time variables. The simple wave ansatz requires that the wave normal and the normal speed of the wave front depend only on the phase function ϕ. This leads to an implicit equation for the phase function and a generalization of the concept of a plane wave. We obtain examples of Alfvén simple waves, based on the right eigenvector solutions for the Alfvén mode. The Alfvén mode solutions have six integrals, namely that the entropy, density, magnetic pressure, and the group velocity (the sum of the Alfvén and fluid velocity) are constant throughout the wave. The eigenequations require that the rate of change of the magnetic induction B with ϕ throughout the wave is perpendicular to both the wave normal n and B. Methods to construct simple wave solutions based on specifying either a solution ansatz for n(ϕ) or B(ϕ) are developed.

Alfven Simple Waves

NASA Astrophysics Data System (ADS)

Webb, G. M.; Zank, G. P.; Burrows, R.

2009-12-01

Multi-dimensional Alfvén simple waves in magnetohydrodynamics (MHD) are investigated using Boillat's formalism. For simple wave solutions, all physical variables (the gas density, pressure, fluid velocity, entropy, and magnetic field induction in the MHD case) depend on a single phase function ǎrphi which is a function of the space and time variables. The simple wave ansatz requires that the wave normal and the normal speed of the wave front depend only on the phase function ǎrphi. This leads to an implicit equation for the phase function, and a generalisation of the concept of a plane wave. We obtain examples of Alfvén simple waves, based on the right eigenvector solutions for the Alfvén mode. The Alfvén mode solutions have six integrals, namely that the entropy, density, magnetic pressure and the group velocity (the sum of the Alfvén and fluid velocity) are constant throughout the wave. The eigen-equations require that the rate of change of the magnetic induction B with ǎrphi throughout the wave is perpendicular to both the wave normal n and B. Methods to construct simple wave solutions based on specifying either a solution ansatz for n(ǎrphi) or B(ǎrphi) are developed.

Sonographic Diagnosis of Tubal Cancer with IOTA Simple Rules Plus Pattern Recognition

PubMed Central

Tongsong, Theera; Wanapirak, Chanane; Tantipalakorn, Charuwan; Tinnangwattana, Dangcheewan

2017-01-01

Objective: To evaluate diagnostic performance of IOTA simple rules plus pattern recognition in predicting tubal cancer. Methods: Secondary analysis was performed on prospective database of our IOTA project. The patients recruited in the project were those who were scheduled for pelvic surgery due to adnexal masses. The patients underwent ultrasound examinations within 24 hours before surgery. On ultrasound examination, the masses were evaluated using the well-established IOTA simple rules plus pattern recognition (sausage-shaped appearance, incomplete septum, visible ipsilateral ovaries) to predict tubal cancer. The gold standard diagnosis was based on histological findings or operative findings. Results: A total of 482 patients, including 15 cases of tubal cancer, were evaluated by ultrasound preoperatively. The IOTA simple rules plus pattern recognition gave a sensitivity of 86.7% (13 in 15) and specificity of 97.4%. Sausage-shaped appearance was identified in nearly all cases (14 in 15). Incomplete septa and normal ovaries could be identified in 33.3% and 40%, respectively. Conclusion: IOTA simple rules plus pattern recognition is relatively effective in predicting tubal cancer. Thus, we propose the simple scheme in diagnosis of tubal cancer as follows. First of all, the adnexal masses are evaluated with IOTA simple rules. If the B-rules could be applied, tubal cancer is reliably excluded. If the M-rules could be applied or the result is inconclusive, careful delineation of the mass with pattern recognition should be performed. PMID:29172273

Development of fetal yawn compared with non-yawn mouth openings from 24-36 weeks gestation.

PubMed

Reissland, Nadja; Francis, Brian; Mason, James

2012-01-01

Although some research suggests that fetuses yawn, others disagree arguing that is it simple mouth opening. Furthermore there is no developmental account of fetal yawning compared with simple mouth opening. The aim of the present study was to establish in a repeated measures design the development of fetal yawning compared with simple mouth opening. Video recordings were made of the fetal face and upper torso visualized by means of 4D full frontal or facial profile ultrasound recordings. Fifteen healthy fetuses were scanned four times at 24, 28, 32 and 36 weeks gestation. Yawning was distinguished from non-yawning in terms of the length of time it took to reach the apex of the mouth stretch, with yawns being defined as more than 50% of the total time observed. To assess changes in frequency, a Poisson mixed effects model was fitted to the count of number of yawn and simple mouth opening events with age and gender as fixed effects, and person as a random effect. For both yawns and simple mouth openings a smooth varying age effect was significant. The number of yawns observed declined with age from 28 weeks gestation, whereas simple mouth openings were less frequent and the decline was observed from 24 weeks. Gender was not significant either for yawn and simple mouth openings. Yawning can be reliably distinguished from other forms of mouth opening with the potential of using yawning as an index of fetal healthy development.

Calculation of stochastic broadening due to noise and field errors in the simple map in action-angle coordinates

NASA Astrophysics Data System (ADS)

Hinton, Courtney; Punjabi, Alkesh; Ali, Halima

2008-11-01

The simple map is the simplest map that has topology of divertor tokamaks [1]. Recently, the action-angle coordinates for simple map are analytically calculated, and simple map is constructed in action-angle coordinates [2]. Action-angle coordinates for simple map can not be inverted to real space coordinates (R,Z). Because there is logarithmic singularity on the ideal separatrix, trajectories can not cross separatrix [2]. Simple map in action-angle coordinates is applied to calculate stochastic broadening due to magnetic noise and field errors. Mode numbers for noise + field errors from the DIII-D tokamak are used. Mode numbers are (m,n)=(3,1), (4,1), (6,2), (7,2), (8,2), (9,3), (10,3), (11,3), (12,3) [3]. The common amplitude δ is varied from 0.8X10-5 to 2.0X10-5. For this noise and field errors, the width of stochastic layer in simple map is calculated. This work is supported by US Department of Energy grants DE-FG02-07ER54937, DE-FG02-01ER54624 and DE-FG02-04ER54793 1. A. Punjabi, H. Ali, T. Evans, and A. Boozer, Phys. Let. A 364, 140--145 (2007). 2. O. Kerwin, A. Punjabi, and H. Ali, to appear in Physics of Plasmas. 3. A. Punjabi and H. Ali, P1.012, 35^th EPS Conference on Plasma Physics, June 9-13, 2008, Hersonissos, Crete, Greece.

Sonographic Diagnosis of Tubal Cancer with IOTA Simple Rules Plus Pattern Recognition

PubMed

Tongsong, Theera; Wanapirak, Chanane; Tantipalakorn, Charuwan; Tinnangwattana, Dangcheewan

2017-11-26

Objective: To evaluate diagnostic performance of IOTA simple rules plus pattern recognition in predicting tubal cancer. Methods: Secondary analysis was performed on prospective database of our IOTA project. The patients recruited in the project were those who were scheduled for pelvic surgery due to adnexal masses. The patients underwent ultrasound examinations within 24 hours before surgery. On ultrasound examination, the masses were evaluated using the well-established IOTA simple rules plus pattern recognition (sausage-shaped appearance, incomplete septum, visible ipsilateral ovaries) to predict tubal cancer. The gold standard diagnosis was based on histological findings or operative findings. Results: A total of 482 patients, including 15 cases of tubal cancer, were evaluated by ultrasound preoperatively. The IOTA simple rules plus pattern recognition gave a sensitivity of 86.7% (13 in 15) and specificity of 97.4%. Sausage-shaped appearance was identified in nearly all cases (14 in 15). Incomplete septa and normal ovaries could be identified in 33.3% and 40%, respectively. Conclusion: IOTA simple rules plus pattern recognition is relatively effective in predicting tubal cancer. Thus, we propose the simple scheme in diagnosis of tubal cancer as follows. First of all, the adnexal masses are evaluated with IOTA simple rules. If the B-rules could be applied, tubal cancer is reliably excluded. If the M-rules could be applied or the result is inconclusive, careful delineation of the mass with pattern recognition should be performed. Creative Commons Attribution License

Laparoscopic repair of perforated peptic ulcer: simple closure versus omentopexy.

PubMed

Lin, Being-Chuan; Liao, Chien-Hung; Wang, Shang-Yu; Hwang, Tsann-Long

2017-12-01

This report presents our experience with laparoscopic repair performed in 118 consecutive patients diagnosed with a perforated peptic ulcer (PPU). We compared the surgical outcome of simple closure with modified Cellan-Jones omentopexy and report the safety and benefit of simple closure. From January 2010 to December 2014, 118 patients with PPU underwent laparoscopic repair with simple closure (n = 27) or omentopexy (n = 91). Charts were retrospectively reviewed for demographic characteristics and outcome. The data were compared by Fisher's exact test, Mann-Whitney U test, Pearson's chi-square test, and the Kruskal-Wallis test. The results were considered statistically significant if P < 0.05. No patients died, whereas three incurred leakage. After matching, the simple closure and omentopexy groups had similarity in sex, systolic blood pressure, pulse rate, respiratory rate, Boey score, Charlson comorbidity index, Mannheim peritonitis index, and leakage. There were statistically significant differences in age, length of hospital stay, perforated size, and operating time. Comparison of the operating time in the ≤4.0 mm and 5.0-12 mm groups revealed that the simple closure took less time than omentopexy in both groups (≤4.0 mm, 76 versus 133 minutes, P < 0.0001; 5.0-12 mm, 97 versus 139.5 minutes; P = 0.006). Compared to the omentopexy, laparoscopic simple closure is a safe procedure and shortens the operating time. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

An Approximate Solution to the Equation of Motion for Large-Angle Oscillations of the Simple Pendulum with Initial Velocity

ERIC Educational Resources Information Center

Johannessen, Kim

2010-01-01

An analytic approximation of the solution to the differential equation describing the oscillations of a simple pendulum at large angles and with initial velocity is discussed. In the derivation, a sinusoidal approximation has been applied, and an analytic formula for the large-angle period of the simple pendulum is obtained, which also includes…

Enhancing Learning Objectives by Use of Simple Virtual Microscopic Slides in Cellular Physiology and Histology: Impact and Attitudes

ERIC Educational Resources Information Center

Anyanwu, Godson Emeka; Agu, Augustine Uchechukwu; Anyaehie, Ugochukwu Bond

2012-01-01

The impact and perception of students on the use of a simple, low technology-driven version of a virtual microscope in teaching and assessments in cellular physiology and histology were studied. Its impact on the time and resources of the faculty were also assessed. Simple virtual slides and conventional microscopes were used to conduct the same…

All about Simple Machines. Physical Science for Children[TM]. Schlessinger Science Library. [Videotape].

ERIC Educational Resources Information Center

2000

All kids know the word "work." But they probably don't understand that work happens whenever a force is used to move something--whether it's lifting a heavy object or playing on a see-saw. All About Simple Machines introduces kids to the concepts of forces, work and how machines are used to make work easier. Six simple machines are…

A simple agar plate preparation for effective transfer of Ureaplasma colonies onto nitrocellulose membranes for colony immunoblotting.

PubMed

Zimmerman, Carl-Ulrich R; Stiedl, Thomas; Spergser, Joachim; Rosengarten, Renate

2014-09-01

A simple method for preparing agar plates is presented, which allows an efficient transfer of Ureaplasma colonies to nitrocellulose membranes for subsequent immunological detection. This simple and reproducible procedure was used to demonstrate antigenic variation in the phase-variable mba-locus of Ureaplasma parvum serovar 3. Copyright © 2014 Elsevier B.V. All rights reserved.

26 CFR 1.652(a)-1 - Simple trusts; inclusion of amounts in income of beneficiaries.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Simple trusts; inclusion of amounts in income of beneficiaries. 1.652(a)-1 Section 1.652(a)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE....652(a)-1 Simple trusts; inclusion of amounts in income of beneficiaries. Subject to the rules in §§ 1...

Phonon scattering in nanoscale systems: lowest order expansion of the current and power expressions

NASA Astrophysics Data System (ADS)

Paulsson, Magnus; Frederiksen, Thomas; Brandbyge, Mads

2006-04-01

We use the non-equilibrium Green's function method to describe the effects of phonon scattering on the conductance of nano-scale devices. Useful and accurate approximations are developed that both provide (i) computationally simple formulas for large systems and (ii) simple analytical models. In addition, the simple models can be used to fit experimental data and provide physical parameters.

Community Involvement Manual.

DTIC Science & Technology

1979-05-01

and social problems, does not lend itself to a single or simple solution. This is why we must all be involved. For this reason we. believe that...of admission to decisionmaking. At times the implications of this relatively simple premise are not minor. Many people beginning community...involvement programs have found it extremely difficult to locate technical people able to translate technical reports into simple , every- day English. There

Simple two-electrode biosignal amplifier.

PubMed

Dobrev, D; Neycheva, T; Mudrov, N

2005-11-01

A simple, cost effective circuit for a two-electrode non-differential biopotential amplifier is proposed. It uses a 'virtual ground' transimpedance amplifier and a parallel RC network for input common mode current equalisation, while the signal input impedance preserves its high value. With this innovative interface circuit, a simple non-inverting amplifier fully emulates high CMRR differential. The amplifier equivalent CMRR (typical range from 70-100 dB) is equal to the open loop gain of the operational amplifier used in the transimpedance interface stage. The circuit has very simple structure and utilises a small number of popular components. The amplifier is intended for use in various two-electrode applications, such as Holter-type monitors, defibrillators, ECG monitors, biotelemetry devices etc.

On the (In)Validity of Tests of Simple Mediation: Threats and Solutions

PubMed Central

Pek, Jolynn; Hoyle, Rick H.

2015-01-01

Mediation analysis is a popular framework for identifying underlying mechanisms in social psychology. In the context of simple mediation, we review and discuss the implications of three facets of mediation analysis: (a) conceptualization of the relations between the variables, (b) statistical approaches, and (c) relevant elements of design. We also highlight the issue of equivalent models that are inherent in simple mediation. The extent to which results are meaningful stem directly from choices regarding these three facets of mediation analysis. We conclude by discussing how mediation analysis can be better applied to examine causal processes, highlight the limits of simple mediation, and make recommendations for better practice. PMID:26985234

Pattern of refractive errors among patients at a tertiary hospital in Kathmandu.

PubMed

Rizyal, A; Ghising, R; Shrestha, R K; Kansakar, I

2011-09-01

A hospital based cross sectional study was carried out to determine the pattern of refractive errors among patients attending the out patient department, Department of Ophthalmology, Nepal Medical College Teaching Hospital. A total of 1100 patients were evaluated, (male 43.67%; female 56.33%). Simple myopic astigmatism was the most prevalent type of refractive error accounting for 27.18% followed by simple myopia (21.66%) and compound myopic astigmatism (19.48%). Simple hypermetropia (15.03%) and mixed astigmatism (4.3%) were also noted. Simple myopia was prevalent among the younger age group in the first to third decades, whereas hypermetropia was seen in the older patients in the third to fifth decades.

Local SIMPLE multi-atlas-based segmentation applied to lung lobe detection on chest CT

NASA Astrophysics Data System (ADS)

Agarwal, M.; Hendriks, E. A.; Stoel, B. C.; Bakker, M. E.; Reiber, J. H. C.; Staring, M.

2012-02-01

For multi atlas-based segmentation approaches, a segmentation fusion scheme which considers local performance measures may be more accurate than a method which uses a global performance measure. We improve upon an existing segmentation fusion method called SIMPLE and extend it to be localized and suitable for multi-labeled segmentations. We demonstrate the algorithm performance on 23 CT scans of COPD patients using a leave-one- out experiment. Our algorithm performs significantly better (p < 0.01) than majority voting, STAPLE, and SIMPLE, with a median overlap of the fissure of 0.45, 0.48, 0.55 and 0.6 for majority voting, STAPLE, SIMPLE, and the proposed algorithm, respectively.

A comparison of simple global kinetic models for coal devolatilization with the CPD model

DOE PAGES

Richards, Andrew P.; Fletcher, Thomas H.

2016-08-01

Simulations of coal combustors and gasifiers generally cannot incorporate the complexities of advanced pyrolysis models, and hence there is interest in evaluating simpler models over ranges of temperature and heating rate that are applicable to the furnace of interest. In this paper, six different simple model forms are compared to predictions made by the Chemical Percolation Devolatilization (CPD) model. The model forms included three modified one-step models, a simple two-step model, and two new modified two-step models. These simple model forms were compared over a wide range of heating rates (5 × 10 3 to 10 6 K/s) at finalmore » temperatures up to 1600 K. Comparisons were made of total volatiles yield as a function of temperature, as well as the ultimate volatiles yield. Advantages and disadvantages for each simple model form are discussed. In conclusion, a modified two-step model with distributed activation energies seems to give the best agreement with CPD model predictions (with the fewest tunable parameters).« less

A simple structure of Cu2ZnSnS4/CdS solar cells prepared by sputtering

NASA Astrophysics Data System (ADS)

Li, Zhishan; Wang, Shurong; Ma, Xun; Yang, Min; Jiang, Zhi; Liu, Tao; Lu, Yilei; Liu, Sijia

2017-12-01

In this work, Cu2ZnSnS4 (CZTS) thin films were grown on Mo-coated Soda-lime-glass (SLG) substrates by annealing of sputtered ZnS/Sn/CuS precursors at 580 ℃ for 15 min. As a try, the CZTS solar cells were fabricated using simple structure of Mo-coated SLG/CZTS/CdS/Al and traditional structure of Mo-coated SLG/CZTS/CdS/i-ZnO/In2O3:SnO2 (ITO)/Al, respectively. The results show that the CZTS device with simple structure can achieve same level of the open circuit voltage (Voc) compared with that of traditional structure. In addition, the power conversion efficiency of 2.95% and 3.59% were obtained with simple structure and traditional structure, respectively. The CZTS solar cell with simple structure provides a promising way and an easy process to prepare high-performance CZTS thin film solar cells which is available to large-scale industrial production in the future.

Accuracy of simple urine tests for diagnosis of urinary tract infections in low-risk pregnant women.

PubMed

Feitosa, Danielle Cristina Alves; da Silva, Márcia Guimarães; de Lima Parada, Cristina Maria Garcia

2009-01-01

Anatomic and physiological alterations during pregnancy predispose pregnant women to urinary tract infections (UTI). This study aimed to identify the accuracy of the simple urine test for UTI diagnosis in low-risk pregnant women. Diagnostic test performance was conducted in Botucatu, SP, involving 230 pregnant women, between 2006 and 2008. Results showed 10% UTI prevalence. Sensitivity, specificity and accuracy of the simple urine test were 95.6%, 63.3% and 66.5%, respectively, in relation to UTI diagnoses. The analysis of positive (PPV) and negative (NPV) predictive values showed that, when a regular simple urine test was performed, the chance of UTI occurrence was small (NPV 99.2%). In view of an altered result for such a test, the possibility of UTI existence was small (PPV 22.4%). It was concluded that the accuracy of the simple urine test as a diagnostic means for UTI was low, and that performing a urine culture is essential for appropriate diagnosis.

Integrin Beta 1 Suppresses Multilayering of a Simple Epithelium

PubMed Central

Chen, Jichao; Krasnow, Mark A.

2012-01-01

Epithelia are classified as either simple, a single cell layer thick, or stratified (multilayered). Stratified epithelia arise from simple epithelia during development, and transcription factor p63 functions as a key positive regulator of epidermal stratification. Here we show that deletion of integrin beta 1 (Itgb1) in the developing mouse airway epithelium abrogates airway branching and converts this monolayer epithelium into a multilayer epithelium with more than 10 extra layers. Mutant lung epithelial cells change mitotic spindle orientation to seed outer layers, and cells in different layers become molecularly and functionally distinct, hallmarks of normal stratification. However, mutant lung epithelial cells do not activate p63 and do not switch to the stratified keratin profile of epidermal cells. These data, together with previous data implicating Itgb1 in regulation of epidermal stratification, suggest that the simple-versus-stratified developmental decision may involve not only stratification inducers like p63 but suppressors like Itgb1 that prevent simple epithelia from inappropriately activating key steps in the stratification program. PMID:23285215

Memory-Based Simple Heuristics as Attribute Substitution: Competitive Tests of Binary Choice Inference Models.

PubMed

Honda, Hidehito; Matsuka, Toshihiko; Ueda, Kazuhiro

2017-05-01

Some researchers on binary choice inference have argued that people make inferences based on simple heuristics, such as recognition, fluency, or familiarity. Others have argued that people make inferences based on available knowledge. To examine the boundary between heuristic and knowledge usage, we examine binary choice inference processes in terms of attribute substitution in heuristic use (Kahneman & Frederick, 2005). In this framework, it is predicted that people will rely on heuristic or knowledge-based inference depending on the subjective difficulty of the inference task. We conducted competitive tests of binary choice inference models representing simple heuristics (fluency and familiarity heuristics) and knowledge-based inference models. We found that a simple heuristic model (especially a familiarity heuristic model) explained inference patterns for subjectively difficult inference tasks, and that a knowledge-based inference model explained subjectively easy inference tasks. These results were consistent with the predictions of the attribute substitution framework. Issues on usage of simple heuristics and psychological processes are discussed. Copyright © 2016 Cognitive Science Society, Inc.

Compressive Hyperspectral Imaging and Anomaly Detection

DTIC Science & Technology

2010-02-01

Level Set Systems 1058 Embury Street Pacific Palisades , CA 90272 8. PERFORMING ORGANIZATION REPORT NUMBER 1A-2010 9. SPONSORING/MONITORING...were obtained from a simple algorithm, namely, the atoms in the trained image were very similar to the simple cell receptive fields in early vision...Field, "Emergence of simple- cell receptive field properties by learning a sparse code for natural images,’" Nature 381(6583), pp. 607-609, 1996. M

Simple coupling with cosmological implications. The initial singularity and the inflationary universe

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

Saez, D.

1987-03-15

In this work the metric is coupled with a scalar field phi in a simple way. Although this coupling becomes problematic because the energy density of phi appears to be unbounded from below, it is displayed as a very simple coupling leading to a nonsingular cosmological model with an early antigravity regime. A basic study of the inflationary period and various suggestions are presented.

Method for estimating the morphological significance of simple forms of crystals from X-ray data

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

Treivus, E. B., E-mail: sbobr1@bk.ru

2010-09-15

When developing V.I. Mikheev and I.I. Shafranovskii's method for estimating the morphological significance of faces of different simple forms from X-ray reflection intensities, a way to approximately evaluate the morphological significance of simple forms on crystals from the structure amplitudes of the corresponding atomic planes is proposed. The potential for this approach is demonstrated by the examples of marcasite and zircon.

A simple assay system to monitor the potential for contamination during different stages of cryopreservation.

PubMed

Morris, G J

2009-01-01

A simple assay to monitor the potential for contamination during different steps of cryopreservation is described. The assay is based on the contamination of liquid nitrogen using crystals of sucrose hemi-heptahydrate, these are stable in liquid nitrogen, nitrogen vapour and ambient air and can be monitored by a simple assay which allows contamination risks to be evaluated in a direct, rapid manner.

Analyzing C2 Structures and Self-Synchronization with Simple Computational Models

DTIC Science & Technology

2011-06-01

16th ICCRTS “Collective C2 in Multinational Civil-Military Operations” Analyzing C2 Structures and Self- Synchronization with Simple...Self- Synchronization with Simple Computational Models 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT...models. The Kuramoto Model, though with some serious limitations, provides a representation of information flow and self- synchronization in an

A Taxonomy of Network Centric Warfare Architectures

DTIC Science & Technology

2008-01-01

mound structure emerges as a result of the termites following very simple rules, and exchanging very simple pheromone signals (Solé & Goodwin 2000...only fairly simple decisions.” For example, in far northern Australia, “magnetic termites ” build large termite mounds which are oriented north-south...and contain a complex ventilation system which controls temperature, humidity, and oxygen levels. But termite brains are too small to store a plan

Mapping Network Centric Operational Architectures to C2 and Software Architectures

DTIC Science & Technology

2007-06-01

Instead, the termite mound structure emerges as a result of the termites following very simple rules, and exchanging very simple pheromone signals...Each worker need make only fairly simple decisions.” For example, in far northern Australia, “magnetic termites ” build large termite mounds which are...oriented north-south and contain a complex ventilation system which controls temperature, humidity, and oxygen levels. But termite brains are too

Anticancer Agents Based on a New Class of Transition- State Analog Inhibitors for Serine and Cysteine Proteases

DTIC Science & Technology

1999-08-01

electrostatic repulsion between the het- eroatom and the ketone. Swain and Lupton31 have constructed a modified Hammett equation (eq 2) in which they...determined by nonlinear fit to the Michaelis-Menten equation for competitive inhibition using simple weighing. Competitive inhibition was confirmed... equation for competitive inhibition using simple weighing. Competitive inhibition was confirmed by Lineweaver - Burk analysis using simple

Low-Cost Manufacturing, Usability, and Security: An Analysis of Bluetooth Simple Pairing and Wi-Fi Protected Setup

NASA Astrophysics Data System (ADS)

Kuo, Cynthia; Walker, Jesse; Perrig, Adrian

Bluetooth Simple Pairing and Wi-Fi Protected Setup specify mechanisms for exchanging authentication credentials in wireless networks. Both Simple Pairing and Protected Setup support multiple setup mechanisms, which increases security risks and hurts the user experience. To improve the security and usability of these specifications, we suggest defining a common baseline for hardware features and a consistent, interoperable user experience across devices.

Fabricating Simple Wax Screen-Printing Paper-Based Analytical Devices to Demonstrate the Concept of Limiting Reagent in Acid- Base Reactions

ERIC Educational Resources Information Center

Namwong, Pithakpong; Jarujamrus, Purim; Amatatongchai, Maliwan; Chairam, Sanoe

2018-01-01

In this article, a low-cost, simple, and rapid fabrication of paper-based analytical devices (PADs) using a wax screen-printing method is reported here. The acid-base reaction is implemented in the simple PADs to demonstrate to students the chemistry concept of a limiting reagent. When a fixed concentration of base reacts with a gradually…

The Design of SimpleITK.

PubMed

Lowekamp, Bradley C; Chen, David T; Ibáñez, Luis; Blezek, Daniel

2013-01-01

SimpleITK is a new interface to the Insight Segmentation and Registration Toolkit (ITK) designed to facilitate rapid prototyping, education and scientific activities via high level programming languages. ITK is a templated C++ library of image processing algorithms and frameworks for biomedical and other applications, and it was designed to be generic, flexible and extensible. Initially, ITK provided a direct wrapping interface to languages such as Python and Tcl through the WrapITK system. Unlike WrapITK, which exposed ITK's complex templated interface, SimpleITK was designed to provide an easy to use and simplified interface to ITK's algorithms. It includes procedural methods, hides ITK's demand driven pipeline, and provides a template-less layer. Also SimpleITK provides practical conveniences such as binary distribution packages and overloaded operators. Our user-friendly design goals dictated a departure from the direct interface wrapping approach of WrapITK, toward a new facade class structure that only exposes the required functionality, hiding ITK's extensive template use. Internally SimpleITK utilizes a manual description of each filter with code-generation and advanced C++ meta-programming to provide the higher-level interface, bringing the capabilities of ITK to a wider audience. SimpleITK is licensed as open source software library under the Apache License Version 2.0 and more information about downloading it can be found at http://www.simpleitk.org.

Evaluation of SimpleTreat 4.0: Simulations of pharmaceutical removal in wastewater treatment plant facilities.

PubMed

Lautz, L S; Struijs, J; Nolte, T M; Breure, A M; van der Grinten, E; van de Meent, D; van Zelm, R

2017-02-01

In this study, the removal of pharmaceuticals from wastewater as predicted by SimpleTreat 4.0 was evaluated. Field data obtained from literature of 43 pharmaceuticals, measured in 51 different activated sludge WWTPs were used. Based on reported influent concentrations, the effluent concentrations were calculated with SimpleTreat 4.0 and compared to measured effluent concentrations. The model predicts effluent concentrations mostly within a factor of 10, using the specific WWTP parameters as well as SimpleTreat default parameters, while it systematically underestimates concentrations in secondary sludge. This may be caused by unexpected sorption, resulting from variability in WWTP operating conditions, and/or QSAR applicability domain mismatch and background concentrations prior to measurements. Moreover, variability in detection techniques and sampling methods can cause uncertainty in measured concentration levels. To find possible structural improvements, we also evaluated SimpleTreat 4.0 using several specific datasets with different degrees of uncertainty and variability. This evaluation verified that the most influencing parameters for water effluent predictions were biodegradation and the hydraulic retention time. Results showed that model performance is highly dependent on the nature and quality, i.e. degree of uncertainty, of the data. The default values for reactor settings in SimpleTreat result in realistic predictions. Copyright © 2016 Elsevier Ltd. All rights reserved.

SimpleBox 4.0: Improving the model while keeping it simple….

PubMed

Hollander, Anne; Schoorl, Marian; van de Meent, Dik

2016-04-01

Chemical behavior in the environment is often modeled with multimedia fate models. SimpleBox is one often-used multimedia fate model, firstly developed in 1986. Since then, two updated versions were published. Based on recent scientific developments and experience with SimpleBox 3.0, a new version of SimpleBox was developed and is made public here: SimpleBox 4.0. In this new model, eight major changes were implemented: removal of the local scale and vegetation compartments, addition of lake compartments and deep ocean compartments (including the thermohaline circulation), implementation of intermittent rain instead of drizzle and of depth dependent soil concentrations, adjustment of the partitioning behavior for organic acids and bases as well as of the value for enthalpy of vaporization. In this paper, the effects of the model changes in SimpleBox 4.0 on the predicted steady-state concentrations of chemical substances were explored for different substance groups (neutral organic substances, acids, bases, metals) in a standard emission scenario. In general, the largest differences between the predicted concentrations in the new and the old model are caused by the implementation of layered ocean compartments. Undesirable high model complexity caused by vegetation compartments and a local scale were removed to enlarge the simplicity and user friendliness of the model. Copyright © 2016 Elsevier Ltd. All rights reserved.

Does linear separability really matter? Complex visual search is explained by simple search

PubMed Central

Vighneshvel, T.; Arun, S. P.

2013-01-01

Visual search in real life involves complex displays with a target among multiple types of distracters, but in the laboratory, it is often tested using simple displays with identical distracters. Can complex search be understood in terms of simple searches? This link may not be straightforward if complex search has emergent properties. One such property is linear separability, whereby search is hard when a target cannot be separated from its distracters using a single linear boundary. However, evidence in favor of linear separability is based on testing stimulus configurations in an external parametric space that need not be related to their true perceptual representation. We therefore set out to assess whether linear separability influences complex search at all. Our null hypothesis was that complex search performance depends only on classical factors such as target-distracter similarity and distracter homogeneity, which we measured using simple searches. Across three experiments involving a variety of artificial and natural objects, differences between linearly separable and nonseparable searches were explained using target-distracter similarity and distracter heterogeneity. Further, simple searches accurately predicted complex search regardless of linear separability (r = 0.91). Our results show that complex search is explained by simple search, refuting the widely held belief that linear separability influences visual search. PMID:24029822

Calculation of stochastic broadening due to low mn magnetic perturbation in the simple map in action-angle coordinates

NASA Astrophysics Data System (ADS)

Hinton, Courtney; Punjabi, Alkesh; Ali, Halima

2009-11-01

The simple map is the simplest map that has topology of divertor tokamaks [A. Punjabi, H. Ali, T. Evans, and A. Boozer, Phys. Let. A 364, 140--145 (2007)]. Recently, the action-angle coordinates for simple map are analytically calculated, and simple map is constructed in action-angle coordinates [O. Kerwin, A. Punjabi, and H. Ali, Phys. Plasmas 15, 072504 (2008)]. Action-angle coordinates for simple map cannot be inverted to real space coordinates (R,Z). Because there is logarithmic singularity on the ideal separatrix, trajectories cannot cross separatrix [op cit]. Simple map in action-angle coordinates is applied to calculate stochastic broadening due to the low mn magnetic perturbation with mode numbers m=1, and n=±1. The width of stochastic layer near the X-point scales as 0.63 power of the amplitude δ of low mn perturbation, toroidal flux loss scales as 1.16 power of δ, and poloidal flux loss scales as 1.26 power of δ. Scaling of width deviates from Boozer-Rechester scaling by 26% [A. Boozer, and A. Rechester, Phys. Fluids 21, 682 (1978)]. This work is supported by US Department of Energy grants DE-FG02-07ER54937, DE-FG02-01ER54624 and DE-FG02-04ER54793.

Possible Explanation of the Different Temporal Behaviors of Various Classes of Sunspot Groups

NASA Astrophysics Data System (ADS)

Gao, Peng-Xin; Li, Ke-Jun; Li, Fu-Yu

2017-09-01

In order to investigate the periodicity and long-term trends of various classes of sunspot groups (SGs), we separated SGs into two categories: simple SGs (A/U ≤ 4.5, where A represents the total corrected whole spot area of the group in millionths of the solar hemisphere (msh), and U represents the total corrected umbral area of the group in msh); and complex SGs (A/U > 6.2). Based on the revised version of the Greenwich Photoheliographic Results sunspot catalogue, we investigated the periodic behaviors and long-term trends of simple and complex SGs from 1875 to 1976 using the Hilbert-Huang Transform method, and we confirm that the temporal behaviors of simple and complex SGs are quite different. Our main findings are as follows. i) For simple and complex SGs, the values of the Schwabe cycle wax and wane, following the solar activity cycle. ii) There are significant phase differences (almost antiphase) between the periodicity of 53.50 ± 3.79 years extracted from yearly simple SG numbers and the periodicity of 56.21 ± 2.92 years extracted from yearly complex SG numbers. iii) The adaptive trends of yearly simple and complex SG numbers are also quite different: for simple SGs, the values of the adaptive trend gradually increase during the time period of 1875 - 1949, then they decrease gradually from 1949 to 1976, similar to the rise and the maximum phase of a sine curve; for complex SGs, the values of the adaptive trend first slowly increase and then quickly increase, similar to the minimum and rise phase of a sine curve.

Development of Fetal Yawn Compared with Non-Yawn Mouth Openings from 24–36 Weeks Gestation

PubMed Central

Reissland, Nadja; Francis, Brian; Mason, James

2012-01-01

Background Although some research suggests that fetuses yawn, others disagree arguing that is it simple mouth opening. Furthermore there is no developmental account of fetal yawning compared with simple mouth opening. The aim of the present study was to establish in a repeated measures design the development of fetal yawning compared with simple mouth opening. Methodology/Findings Video recordings were made of the fetal face and upper torso visualized by means of 4D full frontal or facial profile ultrasound recordings. Fifteen healthy fetuses were scanned four times at 24, 28, 32 and 36 weeks gestation. Yawning was distinguished from non-yawning in terms of the length of time it took to reach the apex of the mouth stretch, with yawns being defined as more than 50% of the total time observed. To assess changes in frequency, a Poisson mixed effects model was fitted to the count of number of yawn and simple mouth opening events with age and gender as fixed effects, and person as a random effect. For both yawns and simple mouth openings a smooth varying age effect was significant. The number of yawns observed declined with age from 28 weeks gestation, whereas simple mouth openings were less frequent and the decline was observed from 24 weeks. Gender was not significant either for yawn and simple mouth openings. Conclusions/Significance Yawning can be reliably distinguished from other forms of mouth opening with the potential of using yawning as an index of fetal healthy development. PMID:23185638

Tapping to a Slow Tempo in the Presence of Simple and Complex Meters Reveals Experience-Specific Biases for Processing Music

PubMed Central

Ullal-Gupta, Sangeeta; Hannon, Erin E.; Snyder, Joel S.

2014-01-01

Musical meters vary considerably across cultures, yet relatively little is known about how culture-specific experience influences metrical processing. In Experiment 1, we compared American and Indian listeners' synchronous tapping to slow sequences. Inter-tone intervals contained silence or to-be-ignored rhythms that were designed to induce a simple meter (familiar to Americans and Indians) or a complex meter (familiar only to Indians). A subset of trials contained an abrupt switch from one rhythm to another to assess the disruptive effects of contradicting the initially implied meter. In the unfilled condition, both groups tapped earlier than the target and showed large tap-tone asynchronies (measured in relative phase). When inter-tone intervals were filled with simple-meter rhythms, American listeners tapped later than targets, but their asynchronies were smaller and declined more rapidly. Likewise, asynchronies rose sharply following a switch away from simple-meter but not from complex-meter rhythm. By contrast, Indian listeners performed similarly across all rhythm types, with asynchronies rapidly declining over the course of complex- and simple-meter trials. For these listeners, a switch from either simple or complex meter increased asynchronies. Experiment 2 tested American listeners but doubled the duration of the synchronization phase prior to (and after) the switch. Here, compared with simple meters, complex-meter rhythms elicited larger asynchronies that declined at a slower rate, however, asynchronies increased after the switch for all conditions. Our results provide evidence that ease of meter processing depends to a great extent on the amount of experience with specific meters. PMID:25075514

Japanese professional nurses spend unnecessarily long time doing nursing assistants' tasks.

PubMed

Kudo, Yasushi; Yoshimura, Emiko; Shahzad, Machiko Taruzuka; Shibuya, Akitaka; Aizawa, Yoshiharu

2012-09-01

In environments in which professional nurses do simple tasks, e.g., laundry, cleaning, and waste disposal, they cannot concentrate on technical jobs by utilizing their expertise to its fullest benefit. Particularly, in Japan, the nursing shortage is a serious problem. If professional nurses take their time to do any of these simple tasks, the tasks should be preferentially allocated to nursing assistants. Because there has been no descriptive study to investigate the amount of time Japanese professional nurses spent doing such simple tasks during their working time, their actual conditions remain unclear. Professional nurses recorded their total working time and the time they spent doing such simple tasks during the week of the survey period. The time an individual respondent spent doing one or more simple tasks during that week was summed up, as was their working time. Subsequently, the percentage of the summed time he or she spent doing any of those tasks in his or her summed working time was calculated. A total of 1,086 respondents in 19 hospitals that had 87 to 376 beds were analyzed (response rate: 53.3%). The average time (SD) that respondents spent doing those simple tasks and their total working time were 2.24 (3.35) hours and 37.48 (10.88) hours, respectively. The average percentage (SD) of the time they spent doing the simple tasks in their working time was 6.00% (8.39). Hospital administrators must decrease this percentage. Proper working environments in which professional nurses can concentrate more on their technical jobs must be created.

Simple exercise test score versus cardiac stress test for the prediction of coronary artery disease in patients with type 2 diabetes.

PubMed

Pikto-Pietkiewicz, Witold; Przewłocka, Monika; Chybowska, Barbara; Cyciwa, Alona; Pasierski, Tomasz

2014-01-01

Type 2 diabetes markedly increases the risk of coronary heart disease (CHD), and screening for CHD is suggested by the guidelines. The aim of the study was to compare the diagnostic usefulness of the simple exercise test score, incorporating the clinical data and cardiac stress test results, with the standard stress test in patients with type 2 diabetes. A total of 62 consecutive patients (aged 65.4 ±8.5 years; 32 men) with type 2 diabetes and clinical symptoms suggesting CHD underwent a stress test followed by coronary angiography. The simple score was calculated for all patients. Significant coronary stenosis was observed in 41 patients (66.1%). Stress test results were positive in 36 patients (58.1%). The mean simple score was high (65.5 ±14.3 points). A positive linear relationship was observed between the score and the prevalence of CHD (R2 = 0.19; P <0.001) as well as its severity (R² = 0.23; P <0.001). The area under the receiver-operating characteristic curve for the simple score was 0.74 (95% confidence interval [CI], 0.62-0.86). At the original cut-off value of 60 points, the score had a similar prognostic value to that of the standard stress test. However, in a multivariate analysis, only the simple score (odds ratio [OR], 1.46; 95% CI, 1.11-1.94; P <0.01 for an increase in the score by 1 point) and male sex (OR, 1.57; 95% CI, 1.24-1.98; P <0.001) remained independent predictors of CHD. In patients with type 2 diabetes, the simple score correlated with the prevalence and severity of CHD. However, the cut-off value of 60 points was inadequate in the population of diabetic patients with high risk of CHD. The simple score used instead of or together with the stress test was a better predictor of CHD than the stress test alone.

Development and validation of the SIMPLE endoscopic classification of diminutive and small colorectal polyps.

PubMed

Iacucci, Marietta; Trovato, Cristina; Daperno, Marco; Akinola, Oluseyi; Greenwald, David; Gross, Seth A; Hoffman, Arthur; Lee, Jeffrey; Lethebe, Brendan C; Lowerison, Mark; Nayor, Jennifer; Neumann, Helmut; Rath, Timo; Sanduleanu, Silvia; Sharma, Prateek; Kiesslich, Ralf; Ghosh, Subrata; Saltzman, John R

2018-03-23

Prediction of histology of small polyps facilitates colonoscopic treatment. The aims of this study were: 1) to develop a simplified polyp classification, 2) to evaluate its performance in predicting polyp histology, and 3) to evaluate the reproducibility of the classification by trainees using multiplatform endoscopic systems. In phase 1, a new simplified endoscopic classification for polyps - Simplified Identification Method for Polyp Labeling during Endoscopy (SIMPLE) - was created, using the new I-SCAN OE system (Pentax, Tokyo, Japan), by eight international experts. In phase 2, the accuracy, level of confidence, and interobserver agreement to predict polyp histology before and after training, and univariable/multivariable analysis of the endoscopic features, were performed. In phase 3, the reproducibility of SIMPLE by trainees using different endoscopy platforms was evaluated. Using the SIMPLE classification, the accuracy of experts in predicting polyps was 83 % (95 % confidence interval [CI] 77 % - 88 %) before and 94 % (95 %CI 89 % - 97 %) after training ( P   = 0.002). The sensitivity, specificity, positive predictive value, and negative predictive value after training were 97 %, 88 %, 95 %, and 91 %. The interobserver agreement of polyp diagnosis improved from 0.46 (95 %CI 0.30 - 0.64) before to 0.66 (95 %CI 0.48 - 0.82) after training. The trainees demonstrated that the SIMPLE classification is applicable across endoscopy platforms, with similar post-training accuracies for narrow-band imaging NBI classification (0.69; 95 %CI 0.64 - 0.73) and SIMPLE (0.71; 95 %CI 0.67 - 0.75). Using the I-SCAN OE system, the new SIMPLE classification demonstrated a high degree of accuracy for adenoma diagnosis, meeting the ASGE PIVI recommendations. We demonstrated that SIMPLE may be used with either I-SCAN OE or NBI. © Georg Thieme Verlag KG Stuttgart · New York.

Performance Considerations for the SIMPL Single Photon, Polarimetric, Two-Color Laser Altimeter as Applied to Measurements of Forest Canopy Structure and Composition

NASA Technical Reports Server (NTRS)

Dabney, Philip W.; Harding, David J.; Valett, Susan R.; Vasilyev, Aleksey A.; Yu, Anthony W.

2012-01-01

The Slope Imaging Multi-polarization Photon-counting Lidar (SIMPL) is a multi-beam, micropulse airborne laser altimeter that acquires active and passive polarimetric optical remote sensing measurements at visible and near-infrared wavelengths. SIMPL was developed to demonstrate advanced measurement approaches of potential benefit for improved, more efficient spaceflight laser altimeter missions. SIMPL data have been acquired for wide diversity of forest types in the summers of 2010 and 2011 in order to assess the potential of its novel capabilities for characterization of vegetation structure and composition. On each of its four beams SIMPL provides highly-resolved measurements of forest canopy structure by detecting single-photons with 15 cm ranging precision using a narrow-beam system operating at a laser repetition rate of 11 kHz. Associated with that ranging data SIMPL provides eight amplitude parameters per beam unlike the single amplitude provided by typical laser altimeters. Those eight parameters are received energy that is parallel and perpendicular to that of the plane-polarized transmit pulse at 532 nm (green) and 1064 nm (near IR), for both the active laser backscatter retro-reflectance and the passive solar bi-directional reflectance. This poster presentation will cover the instrument architecture and highlight the performance of the SIMPL instrument with examples taken from measurements for several sites with distinct canopy structures and compositions. Specific performance areas such as probability of detection, after pulsing, and dead time, will be highlighted and addressed, along with examples of their impact on the measurements and how they limit the ability to accurately model and recover the canopy properties. To assess the sensitivity of SIMPL's measurements to canopy properties an instrument model has been implemented in the FLIGHT radiative transfer code, based on Monte Carlo simulation of photon transport. SIMPL data collected in 2010 over the Smithsonian Environmental Research Center, MD are currently being modelled and compared to other remote sensing and in situ data sets. Results on the adaptation of FLIGHT to model micropulse, single'photon ranging measurements are presented elsewhere at this conference. NASA's ICESat-2 spaceflight mission, scheduled for launch in 2016, will utilize a multi-beam, micropulse, single-photon ranging measurement approach (although non-polarimetric and only at 532 nm). Insights gained from the analysis and modelling of SIMPL data will help guide preparations for that mission, including development of calibration/validation plans and algorithms for the estimation of forest biophysical parameters.

Using Simple Environmental Variables to Estimate Biomass Disturbance

DTIC Science & Technology

2014-08-01

ER D C/ CE RL T R- 14 -1 3 Optimal Allocation of Land for Training and Non-Training Uses ( OPAL ) Using Simple Environmental Variables to...Uses ( OPAL ) ERDC/CERL TR-14-13 August 2014 Using Simple Environmental Variables to Estimate Biomass Disturbance Natalie Myers, Daniel Koch...Development of the Optimal Allocation of Land for Training and Non-Training Uses ( OPAL ) Program was undertak- en to meet this need. This phase of work

Boundary condition computational procedures for inviscid, supersonic steady flow field calculations

NASA Technical Reports Server (NTRS)

Abbett, M. J.

1971-01-01

Results are given of a comparative study of numerical procedures for computing solid wall boundary points in supersonic inviscid flow calculatons. Twenty five different calculation procedures were tested on two sample problems: a simple expansion wave and a simple compression (two-dimensional steady flow). A simple calculation procedure was developed. The merits and shortcomings of the various procedures are discussed, along with complications for three-dimensional and time-dependent flows.

Simple Tidal Prism Models Revisited

NASA Astrophysics Data System (ADS)

Luketina, D.

1998-01-01

Simple tidal prism models for well-mixed estuaries have been in use for some time and are discussed in most text books on estuaries. The appeal of this model is its simplicity. However, there are several flaws in the logic behind the model. These flaws are pointed out and a more theoretically correct simple tidal prism model is derived. In doing so, it is made clear which effects can, in theory, be neglected and which can not.

Simple Ontology Format (SOFT)

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

Sorokine, Alexandre

2011-10-01

Simple Ontology Format (SOFT) library and file format specification provides a set of simple tools for developing and maintaining ontologies. The library, implemented as a perl module, supports parsing and verification of the files in SOFt format, operations with ontologies (adding, removing, or filtering of entities), and converting of ontologies into other formats. SOFT allows users to quickly create ontologies using only a basic text editor, verify it, and portray it in a graph layout system using customized styles.

Mi Segundo Libro de Maquinas Simples: Las Palancas. Escuela Intermedia Grados 7, 8 y 9 (My Second Book of Simple Machines: Levers. Intermediate School Grades 7, 8, and 9).

ERIC Educational Resources Information Center

Alvarado, Patricio R.; Montalvo, Luis

This is the second book in a five-book physical science series on simple machines. The books are designed for Spanish-speaking junior high school students. By suggesting experiments and posing questions concerning drawings in the book which illustrate the scientific principles, this book explains the workings of three types of levers. Resistance…

Crowd Sourcing Data Collection through Amazon Mechanical Turk

DTIC Science & Technology

2013-09-01

The first recognition study consisted of a Panel Study using a simple detection protocol, in which participants were presented with vignettes and, for...variability than the crowdsourcing data set, hewing more closely to the year 1 verbs of interest and simple description grammar . The DT:PS data were...Study RT: PS Recognition Task: Panel Study RT: RT Recognition Task: Round Table S3 Amazon Simple Storage Service SVPA Single Verb Present /Absent

Transportable Maps Software. Volume I.

DTIC Science & Technology

1982-07-01

being collected at the beginning or end of the routine. This allows the interaction to be followed sequentially through its steps by anyone reading the...flow is either simple sequential , simple conditional (the equivalent of ’if-then-else’), simple iteration (’DO-loop’), or the non-linear recursion...input raster images to be in the form of sequential binary files with a SEGMENTED record type. The advantage of this form is that large logical records

Vortex breakdown in simple pipe bends

NASA Astrophysics Data System (ADS)

Ault, Jesse; Shin, Sangwoo; Stone, Howard

2016-11-01

Pipe bends and elbows are one of the most common fluid mechanics elements that exists. However, despite their ubiquity and the extensive amount of research related to these common, simple geometries, unexpected complexities still remain. We show that for a range of geometries and flow conditions, these simple flows experience unexpected fluid dynamical bifurcations resembling the bubble-type vortex breakdown phenomenon. Specifically, we show with simulations and experiments that recirculation zones develop within the bends under certain conditions. As a consequence, fluid and particles can remain trapped within these structures for unexpectedly-long time scales. We also present simple techniques to mitigate this recirculation effect which can potentially have impact across industries ranging from biomedical and chemical processing to food and health sciences.

Simple process of hybrid white quantum dot/organic light-emitting diodes by using quantum dot plate and fluorescence

NASA Astrophysics Data System (ADS)

Lee, Ho Won; Lee, Ki-Heon; Lee, Jae Woo; Kim, Jong-Hoon; Yang, Heesun; Kim, Young Kwan

2015-02-01

In this work, the simple process of hybrid quantum dot (QD)/organic light-emitting diode (OLED) was proposed to apply a white illumination light by using QD plate and organic fluorescence. Conventional blue fluorescent OLEDs were firstly fabricated and then QD plates of various concentrations, which can be controlled of UV-vis absorption and photoluminescence spectrum, were attached under glass substrate of completed blue devices. The suggested process indicates that we could fabricate the white device through very simple process without any deposition of orange or red organic emitters. Therefore, this work would be demonstrated that the potential simple process for white applications can be applied and also can be extended to additional research on light applications.

User manual for two simple postscript output FORTRAN plotting routines

NASA Technical Reports Server (NTRS)

Nguyen, T. X.

1991-01-01

Graphics is one of the important tools in engineering analysis and design. However, plotting routines that generate output on high quality laser printers normally come in graphics packages, which tend to be expensive and system dependent. These factors become important for small computer systems or desktop computers, especially when only some form of a simple plotting routine is sufficient. With the Postscript language becoming popular, there are more and more Postscript laser printers now available. Simple, versatile, low cost plotting routines that can generate output on high quality laser printers are needed and standard FORTRAN language plotting routines using output in Postscript language seems logical. The purpose here is to explain two simple FORTRAN plotting routines that generate output in Postscript language.

Simple microfluidic stagnation point flow geometries

PubMed Central

Dockx, Greet; Verwijlen, Tom; Sempels, Wouter; Nagel, Mathias; Moldenaers, Paula; Hofkens, Johan; Vermant, Jan

2016-01-01

A geometrically simple flow cell is proposed to generate different types of stagnation flows, using a separation flow and small variations of the geometric parameters. Flows with high local deformation rates can be changed from purely rotational, over simple shear flow, to extensional flow in a region surrounding a stagnation point. Computational fluid dynamic calculations are used to analyse how variations of the geometrical parameters affect the flow field. These numerical calculations are compared to the experimentally obtained streamlines of different designs, which have been determined by high speed confocal microscopy. As the flow type is dictated predominantly by the geometrical parameters, such simple separating flow devices may alleviate the requirements for flow control, while offering good stability for a wide variety of flow types. PMID:27462382

A Simple Exact Error Rate Analysis for DS-CDMA with Arbitrary Pulse Shape in Flat Nakagami Fading

NASA Astrophysics Data System (ADS)

Rahman, Mohammad Azizur; Sasaki, Shigenobu; Kikuchi, Hisakazu; Harada, Hiroshi; Kato, Shuzo

A simple exact error rate analysis is presented for random binary direct sequence code division multiple access (DS-CDMA) considering a general pulse shape and flat Nakagami fading channel. First of all, a simple model is developed for the multiple access interference (MAI). Based on this, a simple exact expression of the characteristic function (CF) of MAI is developed in a straight forward manner. Finally, an exact expression of error rate is obtained following the CF method of error rate analysis. The exact error rate so obtained can be much easily evaluated as compared to the only reliable approximate error rate expression currently available, which is based on the Improved Gaussian Approximation (IGA).

Protein detection by Simple Western™ analysis.

PubMed

Harris, Valerie M

2015-01-01

Protein Simple© has taken a well-known protein detection method, the western blot, and revolutionized it. The Simple Western™ system uses capillary electrophoresis to identify and quantitate a protein of interest. Protein Simple© provides multiple detection apparatuses (Wes, Sally Sue, or Peggy Sue) that are suggested to save scientists valuable time by allowing the researcher to prepare the protein sample, load it along with necessary antibodies and substrates, and walk away. Within 3-5 h the protein will be separated by size, or charge, immuno-detection of target protein will be accurately quantitated, and results will be immediately made available. Using the Peggy Sue instrument, one study recently examined changes in MAPK signaling proteins in the sex-determining stage of gonadal development. Here the methodology is described.

Preliminary study of the effect of the turbulent flow field around complex surfaces on their acoustic characteristics

NASA Technical Reports Server (NTRS)

Olsen, W. A.; Boldman, D.

1978-01-01

Fundamental theories for noise generated by flow over surfaces exist for only a few simple configurations. The role of turbulence in noise generation by complex surfaces should be essentially the same as for simple configurations. Examination of simple-surface theories indicates that the spatial distributions of the mean velocity and turbulence properties are sufficient to define the noise emission. Measurements of these flow properties were made for a number of simple and complex surfaces. The configurations were selected because of their acoustic characteristics are quite different. The spatial distribution of the turbulent flow properties around the complex surfaces and approximate theory are used to locate and describe the noise sources, and to qualitatively explain the varied acoustic characteristics.

A simple geometrical model describing shapes of soap films suspended on two rings

NASA Astrophysics Data System (ADS)

Herrmann, Felix J.; Kilvington, Charles D.; Wildenberg, Rebekah L.; Camacho, Franco E.; Walecki, Wojciech J.; Walecki, Peter S.; Walecki, Eve S.

2016-09-01

We measured and analysed the stability of two types of soap films suspended on two rings using the simple conical frusta-based model, where we use common definition of conical frustum as a portion of a cone that lies between two parallel planes cutting it. Using frusta-based we reproduced very well-known results for catenoid surfaces with and without a central disk. We present for the first time a simple conical frusta based spreadsheet model of the soap surface. This very simple, elementary, geometrical model produces results surprisingly well matching the experimental data and known exact analytical solutions. The experiment and the spreadsheet model can be used as a powerful teaching tool for pre-calculus and geometry students.

Simple BiCMOS CCCTA design and resistorless analog function realization.

PubMed

Tangsrirat, Worapong

2014-01-01

The simple realization of the current-controlled conveyor transconductance amplifier (CCCTA) in BiCMOS technology is introduced. The proposed BiCMOS CCCTA realization is based on the use of differential pair and basic current mirror, which results in simple structure. Its characteristics, that is, parasitic resistance (R x) and current transfer (i o/i z), are also tunable electronically by external bias currents. The realized circuit is suitable for fabrication using standard 0.35 μm BiCMOS technology. Some simple and compact resistorless applications employing the proposed CCCTA as active elements are also suggested, which show that their circuit characteristics with electronic controllability are obtained. PSPICE simulation results demonstrating the circuit behaviors and confirming the theoretical analysis are performed.

Restoration of labral anatomy and biomechanics after superior labral anterior-posterior repair: comparison of mattress versus simple technique.

PubMed

Boddula, Madhav R; Adamson, Gregory J; Gupta, Akash; McGarry, Michelle H; Lee, Thay Q

2012-04-01

Both simple and mattress repair techniques have been utilized with success for type II superior labral anterior-posterior (SLAP) lesions; however, direct anatomic and biomechanical comparisons of these techniques have yet to be clearly demonstrated. For type II SLAP lesions, the mattress suture repair technique will result in greater labral height and better position on the glenoid face and exhibit stronger biomechanical characteristics, when cyclically loaded and loaded to failure through the biceps, compared with the simple suture repair technique. Controlled laboratory study. Six matched pairs of cadaveric shoulders were dissected, and a clock face was created on the glenoid from 9 o'clock (posterior) to 3 o'clock (anterior). For the intact specimen, labral height and labral distance from the glenoid edge were measured using a MicroScribe. A SLAP lesion was then created from 10 o'clock to 2 o'clock. Lesions were repaired with two 3.0-mm BioSuture-Tak anchors placed at 11 o'clock and 1 o'clock. For each pair, a mattress repair was used for one shoulder, and a simple repair was used for the contralateral shoulder. After repair, labral height and labral distance from the glenoid edge were again measured. The specimens were then cyclically loaded and loaded to failure through the biceps using an Instron machine. A paired t test was used for statistical analysis. After mattress repair, a significant increase in labral height occurred compared with intact from 2.5 ± 0.3 mm to 4.3 ± 0.3 mm at 11 o'clock (P = .013), 2.7 ± 0.5 mm to 4.2 ± 0.7 mm at 12:30 o'clock (P = .007), 3.1 ± 0.5 mm to 4.2 ± 0.7 mm at 1 o'clock (P = .006), and 2.8 ± 0.7 mm to 3.7 ± 0.8 mm at 1:30 o'clock (P = .037). There was no significant difference in labral height between the intact condition and after simple repair at any clock face position. Labral height was significantly increased in the mattress repairs compared with simple repairs at 11 o'clock (mean difference, 2.0 mm; P = .008) and 12:30 o'clock (mean difference, 1.3 mm; P = .044). Labral distance from the glenoid edge was not significantly different between techniques. No difference was observed between the mattress and simple repair techniques for all biomechanical parameters, except the simple technique had a higher load and energy absorbed at 2-mm displacement. The mattress technique created a greater labral height while maintaining similar biomechanical characteristics compared with the simple repair, with the exception of load and energy absorbed at 2-mm displacement, which was increased for the simple technique. Mattress repair for type II SLAP lesions creates a higher labral bumper compared with simple repairs, while both techniques resulted in similar biomechanical characteristics.