An Exploration of Latent Structure in Observational Huntington’s Disease Studies

PubMed Central

Ghosh, Soumya; Sun, Zhaonan; Li, Ying; Cheng, Yu; Mohan, Amrita; Sampaio, Cristina; Hu, Jianying

2017-01-01

Huntington’s disease (HD) is a monogenic neurodegenerative disorder characterized by the progressive decay of motor and cognitive abilities accompanied by psychiatric episodes. Tracking and modeling the progression of the multi-faceted clinical symptoms of HD is a challenging problem that has important implications for staging of HD patients and the development of improved enrollment criteria for future HD studies and trials. In this paper, we describe the first steps towards this goal. We begin by curating data from four recent observational HD studies, each containing a diverse collection of clinical assessments. The resulting dataset is unprecedented in size and contains data from 19,269 study participants. By analyzing this large dataset, we are able to discover hidden low dimensional structure in the data that correlates well with surrogate measures of HD progression. The discovered structures are promising candidates for future consumption by downstream statistical HD progression models. PMID:28815114

Less contribution of mast cells to the progression of renal fibrosis in Rat kidneys with chronic renal failure.

PubMed

Baba, Asuka; Tachi, Masahiro; Ejima, Yutaka; Endo, Yasuhiro; Toyama, Hiroaki; Saito, Kazutomo; Abe, Nozomu; Yamauchi, Masanori; Miura, Chieko; Kazama, Itsuro

2017-02-01

Chronic renal failure (CRF) is histopathologically characterized by tubulointerstitial fibrosis in addition to glomerulosclerosis. Although mast cells are known to infiltrate into the kidneys with chronic inflammation, we know little about their contribution to the pathogenesis of renal fibrosis associated with CRF. The aim of this study was to reveal the involvement of mast cells in the progression of renal fibrosis in CRF. Using a rat model with CRF resulting from 5/6 nephrectomy, we examined the histopathological features of the kidneys and the infiltration of mast cells into the renal interstitium. By treating the rats with a potent mast cell stabilizer, tranilast, we also examined the involvement of mast cells in the progression of renal fibrosis associated with CRF. The CRF rat kidneys were characterized by the wide staining of collagen III and increased number of myofibroblasts, indicating the progression of renal fibrosis. Compared to T-lymphocytes or macrophages, the number of tryptase-positive mast cells was much smaller within the fibrotic kidneys and they did not proliferate in situ. The mRNA expression of mast cell-derived fibroblast-activating factors was not increased in the renal cortex isolated from CRF rat kidneys. Treatment with tranilast did not suppress the progression of renal fibrosis, nor did it ameliorate the progression of glomerulosclerosis and the interstitial proliferation of inflammatory leukocytes. This study demonstrated for the first time that mast cells are neither increased nor activated in the fibrotic kidneys of CRF rats. Compared to T-lymphocytes or macrophages that proliferate in situ within the fibrotic kidneys, mast cells were less likely to contribute to the progression of renal fibrosis associated with CRF. © 2016 Asian Pacific Society of Nephrology.

Progressing towards the Implementation of the Tennessee Model for Comprehensive School Counseling Programs: A Study of School Counselor Priorities and Practices

ERIC Educational Resources Information Center

Cobb, Nicole Adrienne

2011-01-01

The profession of school counseling is rapidly changing from one often characterized by indirect local administrative accountability to one characterized by accountability for student outcomes. School counseling leadership has led a movement for role transformation (ASCA, 2003; 2005; Education Trust, 2007) that has initiated significant changes in…

(Photosynthesis in intact plants)

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

Not Available

Progress in the two years since the last renewal application has been excellent. We have made substantial contributions on both main fronts of the projects, and are particularly happy with the progress of our research on intact plants. The approach of basing our field work on a sound foundation of laboratory studies has enabled is to use methods which provide unambiguous assays of well characterized reactions. We have also made excellent progress in several laboratory studies which will have direct applications in future field work, and have introduced to the laboratory a range of molecular genetics techniques which will allowmore » us to explore new options in the attempt to understand function at the level of molecular structure.« less

A Novel Use of Three-dimensional High-frequency Ultrasonography for Early Pregnancy Characterization in the Mouse.

PubMed

Peavey, Mary C; Reynolds, Corey L; Szwarc, Maria M; Gibbons, William E; Valdes, Cecilia T; DeMayo, Francesco J; Lydon, John P

2017-10-24

High-frequency ultrasonography (HFUS) is a common method to non-invasively monitor the real-time development of the human fetus in utero. The mouse is routinely used as an in vivo model to study embryo implantation and pregnancy progression. Unfortunately, such murine studies require pregnancy interruption to enable follow-up phenotypic analysis. To address this issue, we used three-dimensional (3-D) reconstruction of HFUS imaging data for early detection and characterization of murine embryo implantation sites and their individual developmental progression in utero. Combining HFUS imaging with 3-D reconstruction and modeling, we were able to accurately quantify embryo implantation site number as well as monitor developmental progression in pregnant C57BL6J/129S mice from 5.5 days post coitus (d.p.c.) through to 9.5 d.p.c. with the use of a transducer. Measurements included: number, location, and volume of implantation sites as well as inter-implantation site spacing; embryo viability was assessed by cardiac activity monitoring. In the immediate post-implantation period (5.5 to 8.5 d.p.c.), 3-D reconstruction of the gravid uterus in both mesh and solid overlay format enabled visual representation of the developing pregnancies within each uterine horn. As genetically engineered mice continue to be used to characterize female reproductive phenotypes derived from uterine dysfunction, this method offers a new approach to detect, quantify, and characterize early implantation events in vivo. This novel use of 3-D HFUS imaging demonstrates the ability to successfully detect, visualize, and characterize embryo-implantation sites during early murine pregnancy in a non-invasive manner. The technology offers a significant improvement over current methods, which rely on the interruption of pregnancies for gross tissue and histopathologic characterization. Here we use a video and text format to describe how to successfully perform ultrasounds of early murine pregnancy to generate reliable and reproducible data with reconstruction of the uterine form in mesh and solid 3-D images.

Recent advances in studies on milk oligosaccharides of cows and other domestic farm animals.

PubMed

Urashima, Tadasu; Taufik, Epi; Fukuda, Kenji; Asakuma, Sadaki

2013-01-01

Human mature milk and colostrum contain 12-13 g/L and 22-24 g/L of milk oligosaccharides respectively, and the structures of least 115 human milk oligosaccharides (HMOs) have been characterized to date. By way of comparison, bovine colostrum collected immediately post partum contains only around 1 g/L of oligosaccharides, and this concentration rapidly decreases after 48 h. It was recently recognized that HMOs have several biological functions, and this study area has become very active, as illustrated by a recent symposium, but it appears that advances in studies on the milk oligosaccharides of domestic farm animals, including cows, have been rather slow compared with those on HMOs. Nevertheless, studies on bovine milk oligosaccharides (BMOs) have progressed recently, especially in regard to structural characterization, with the development of methods termed glycomics. This review is concerned with recent progress in studies on the milk oligosaccharides of domestic farm animals, especially of BMOs and bovine glycoproteins, and it discusses the possibility of industrial utilization in the near future.

Comparative phylogeography of oceanic archipelagos: Hotspots for inferences of evolutionary process

PubMed Central

Shaw, Kerry L.; Gillespie, Rosemary G.

2016-01-01

Remote island archipelagos offer superb opportunities to study the evolution of community assembly because of their relatively young and simple communities where speciation contributes to the origin and evolution of community structure. There is great potential for common phylogeographic patterns among remote archipelagos that originate through hotspot volcanism, particularly when the islands formed are spatially isolated and linearly arranged. The progression rule is characterized by a phylogeographic concordance between island age and lineage age in a species radiation. Progression is most likely to arise when a species radiation begins on an older island before the emergence of younger islands of a hotspot archipelago. In the simplest form of progression, colonization of younger islands as they emerge and offer appropriate habitat, is coincident with cladogenesis. In this paper, we review recent discoveries of the progression rule on seven hotspot archipelagos. We then discuss advantages that progression offers to the study of community assembly, and insights that community dynamics may offer toward understanding the evolution of progression. We describe results from two compelling cases of progression where the mosaic genome may offer insights into contrasting demographic histories that shed light on mechanisms of speciation and progression on remote archipelagos. PMID:27432948

A Learning Progression for Elementary Students' Functional Thinking

ERIC Educational Resources Information Center

Stephens, Ana C.; Fonger, Nicole; Strachota, Susanne; Isler, Isil; Blanton, Maria; Knuth, Eric; Murphy Gardiner, Angela

2017-01-01

In this article we advance characterizations of and supports for elementary students' progress in generalizing and representing functional relationships as part of a comprehensive approach to early algebra. Our learning progressions approach to early algebra research involves the coordination of a curricular framework and progression, an…

Does hypervascularity of liver metastases as detected on MRI predict disease progression in breast cancer patients?

PubMed

Braga, Larissa; Semelka, Richard C; Pietrobon, Ricardo; Martin, Diego; de Barros, Nestor; Guller, Ulrich

2004-05-01

The aim of our study was to evaluate the association of the vascularity of liver metastases, as characterized by MRI, and disease progression in breast cancer patients. Sixteen breast cancer patients with liver metastases who underwent MRI before and after systemic therapy were retrospectively identified. On the basis of comparison of each MRI examination with the previous examination, disease status of the patients was classified as complete response, partial response, stable disease, or progressive disease. Liver metastases were characterized as hyper- or hypovascular on the basis of the degree of enhancement in the arterial, portal, and interstitial phases of imaging after administration of a contrast agent. Fisher's exact test and ordinal logistic regression models, including the type of systemic therapy, presence of multiple metastases, and hormone receptor status, were used to estimate the unadjusted and risk-adjusted association between the presence of hypervascular liver metastases and disease progression. All patients in our sample (n = 16) were women and most (12/16, 75%) were white. Their median age was 51.5 years. In unadjusted analyses, the association between the presence of hypervascular liver metastases and disease progression was statistically significant (p < 0.0001). In multiple logistic regression analyses, hypervascular liver metastases were found to be an independent predictor of disease progression. Patients with hypervascular liver lesions were 20.5 times more likely to experience disease progression than patients without hypervascular metastases (odds ratio, 20.5; 95% confidence interval, 5.1-83.5; p < 0.0001). Our analysis provides suggestive evidence that disease progression can be predicted through MRI assessment of the vascularity of liver metastases in patients with breast cancer.

Uncertainty and Variability in Physiologically-Based Pharmacokinetic (PBPK) Models: Key Issues and Case Studies (Final Report)

EPA Science Inventory

EPA announced the availability of the final report, Uncertainty and Variability in Physiologically-Based Pharmacokinetic (PBPK) Models: Key Issues and Case Studies. This report summarizes some of the recent progress in characterizing uncertainty and variability in physi...

Advances on the constitutive characterization of composites via multiaxial robotic testing and design optimization

Treesearch

John G. Michopoulos; John Hermanson; Athanasios Iliopoulos

2014-01-01

The research areas of mutiaxial robotic testing and design optimization have been recently utilized for the purpose of data-driven constitutive characterization of anisotropic material systems. This effort has been enabled by both the progress in the areas of computers and information in engineering as well as the progress in computational automation. Although our...

Biophysics of cancer progression and high-throughput mechanical characterization of biomaterials

NASA Astrophysics Data System (ADS)

Osborne, Lukas Dylan

Cancer metastasis involves a series of events known as the metastatic cascade. In this complex progression, cancer cells detach from the primary tumor, invade the surrounding stromal space, transmigrate the vascular system, and establish secondary tumors at distal sites. Specific mechanical phenotypes are likely adopted to enable cells to successfully navigate the mechanical environments encountered during metastasis. To examine the role of cell mechanics in cancer progression, I employed force-consistent biophysical and biochemical assays to characterize the mechanistic links between stiffness, stiffness response and cell invasion during the epithelial to mesenchymal transition (EMT). EMT is an essential physiological process, whose abnormal reactivation has been implicated in the detachment of cancer cells from epithelial tissue and their subsequent invasion into stromal tissue. I demonstrate that epithelial-state cells respond to force by evoking a stiffening response, and that after EMT, mesenchymal-state cells have reduced stiffness but also lose the ability to increase their stiffness in response to force. Using loss and gain of function studies, two proteins are established as functional connections between attenuated stiffness and stiffness response and the increased invasion capacity acquired after EMT. To enable larger scale assays to more fully explore the connection between biomechanics and cancer, I discuss the development of an automated array high throughput (AHT) microscope. The AHT system is shown to implement passive microbead rheology to accurately characterize the mechanical properties of biomaterials. Compared to manually performed mechanical characterizations, the AHT system executes experiments in two orders of magnitude less time. Finally, I use the AHT microscope to study the effect of gain of function oncogenic molecules on cell stiffness. I find evidence that our assay can identify alterations in cell stiffness due to constitutive activation of cancer pathways.

Effect of acarbose to delay progression of carotid intima-media thickness in early diabetes.

PubMed

Patel, Y R; Kirkman, M S; Considine, R V; Hannon, T S; Mather, K J

2013-10-01

The anti-diabetic agent acarbose reduces postprandial glucose excursions. We have evaluated the effect of randomized treatment with acarbose on the progression of carotid intima-media thickness (IMT) in early diabetes. The Early Diabetes Intervention Program was a randomized trial of acarbose versus placebo in 219 participants with early diabetes characterized by glucose values over 11.1 mmol/L 2 h after a 75 g oral glucose load and a mean HbA1c of 6.3%. IMT was measured at baseline and yearly. Follow-up was discontinued if participants progressed to the study glucose endpoints; IMT readings were available for a median of 2 years, with 72 subjects followed for 5 years. Progressive increases in IMT were seen in both treatment groups, but progression was reduced in participants randomized to acarbose (p = 0.047). In age, sex and smoking-adjusted analyses, IMT progression was associated with greater fasting and oral glucose tolerance test-excursion glucose, fasting insulin, cholesterol and glycated low-density lipoprotein concentrations. IMT progression was reduced with study-related changes in weight, insulin and non-esterified fatty acids; these features were more strongly associated with reduced IMT progression than acarbose treatment. Despite strong associations of baseline glycemia with IMT progression, study-related changes in glucose were not important determinants of IMT progression. Acarbose can delay progression of carotid intima-media thickness in early diabetes defined by an oral glucose tolerance test. Glucose, weight, insulin and lipids contributed to risk of progression but reductions in glycemia were not major determinants of reduced rate of IMT progression. Vascular benefits of acarbose may be independent of its glycemic effects. Copyright © 2013 John Wiley & Sons, Ltd.

[Pathogenetic and Prognostic Role of Growth Factors in the Development of Chronic Heart Failure].

PubMed

Teplyakov, A T; Berezikova, E N; Shilov, S N; Efremova, A V; Pustovetova, M G; Popova, A A; Grakova, E V; Torim, Y Y; Safronov, I D; Andriyanova, A V

2017-10-01

To study the role of growth factors ((vascular endothelial growth factor (VEGF), platelet derived growth factor AB (PDGF-AB) and basic fibroblast growth factor (FGF-basic)) in the development and progression of chronic heart failure (CHF) in patients with ishcemic heart disease (IHD). We included in this study 94 patients with CHF. The control group comprised 32 persons. Blood serum levels of growth factors were determined at baseline and after 12 months of observation by enzyme-linked immunosorbent assay. VEGF, PDGF-AB and FGF-basic play an important role in the pathogenesis and progression of heart failure in patients with IHD, determining the increased risk of adverse cardiovascular events in this pathology. Serum activity of growth factors characterizes the severity and course of CHF: with disease progression levels of VEGF and FGF-basic decrease and PDGF-AB concentration increases. Initial low level of VEGF expression regardless of the sex of the patient's sex, significantly low level of FGF-basic and significantly high PDGF-AB in men characterizes unfavorable course of CHF. A correlation has been established between blood serum levels of VEGF, PDGF-AB and FGF-basic and severity and course of CHF.

Kinetics and cellular sources of cathelicidin during the course of experimental latent tuberculous infection and progressive pulmonary tuberculosis.

PubMed

Castañeda-Delgado, J; Hernández-Pando, R; Serrano, C J; Aguilar-León, D; León-Contreras, J; Rivas-Santiago, C; Méndez, R; González-Curiel, I; Enciso-Moreno, A; Rivas-Santiago, B

2010-09-01

In spite of advances in immunology on mycobacterial infection, there are few studies on the role of anti-microbial peptides in tuberculosis. The cathelin-related anti-microbial peptide (CRAMP) is the only cathelicidin isolated from mice. In this work we investigated the cellular sources and the production kinetics of this molecule during experimental tuberculosis, using two well-characterized models of latent or chronic infection and progressive disease. The lung of non-infected control mice expressed CRAMP at very low levels. In both models of experimental tuberculosis the main cells immunolabelled for CRAMP were bronchial epithelial cells, macrophages and pneumocytes types II and I. After intratracheal infection with a high bacilli dose (H37Rv strain) in Balb/c mice to produce progressive disease, a high CRAMP gene expression was induced showing three peaks: very early after 1 day of infection, at day 21 when the peak of protective immunity in this model is raised, and at day 28 when the progressive phase starts and the immunoelectronmicroscopy study showed intense immunolabelling in the cell wall and cytoplasm of intracellular bacilli, as well as in cytoplasmic vacuoles. Interestingly, at day 60 post-infection, when advanced progressive disease is well established, characterized by high bacillary loads and extensive tissue damage, CRAMP gene expression decreased but strong CRAMP immunostaining was detected in vacuolated macrophages filled with bacilli. Thus, cathelicidin is highly produced during experimental pulmonary tuberculosis from diverse cellular sources and could have significant participation in its pathogenesis. © 2010 British Society for Immunology.

Gilles de la Tourette Syndrome: A Case Study.

ERIC Educational Resources Information Center

Hallenberg, Harvey

1997-01-01

Describes a Montessori teacher's experience with a sufferer of Tourette's syndrome, a dysfunction characterized by motor and vocal tics. Studies the progress over a school year, including work on academic skills utilizing the Montessori method and behavior. Shares research, successes, and failures in trying to reach the child. (SD)

Making Sense by Measuring Arcs: A Teaching Experiment in Angle Measure

ERIC Educational Resources Information Center

Moore, Kevin C.

2013-01-01

I discuss a teaching experiment that sought to characterize precalculus students' angle measure understandings. The study's findings indicate that the students initially conceived angle measures in terms of geometric objects. As the study progressed, the students formed more robust understandings of degree and radian measures by constructing an…

Dyscirculatory encephalopathy in Chernobyl disaster clean-up workers (a 20-year study).

PubMed

Podsonnaya, I V; Shumakher, G I; Golovin, V A

2010-05-01

Results obtained over 20-years of following 536 Chernobyl clean-up workers and 436 control subjects are presented. Dyscirculatory encephalopathy developed more frequently in persons exposed to radiation at age 30 years. As compared with the control group, workers were characterized by early onset of disease, faster progression, stable symptomatology for 5-6 years, and further progression of disease in the form of autonomic dysfunction, psycho-organic syndrome, and epilepsy. Major strokes were also more common in clean-up workers.

Effects of Acarbose to Delay Progression of Carotid Intima-Media Thickness in Early Diabetes

PubMed Central

Patel, YR; Kirkman, MS; Considine, RV; Hannon, TS; Mather, KJ

2014-01-01

Background The antidiabetic agent acarbose reduces postprandial glucose excursions. We have evaluated the effect of randomized treatment with acarbose on the progression of carotid intima-media thickness (IMT) in early diabetes. Methods The Early Diabetes Intervention Program (EDIP) was a randomized trial of acarbose versus placebo, in 219 participants with early diabetes characterized by glucose values over 11.1 mmol/L 2 hours after a 75g oral glucose load, and mean HbA1c 6.3%. IMT was measured at baseline and yearly. Follow-up was discontinued if participants progressed to the study glucose endpoints; IMT readings were available for a median of 2 years, with 72 subjects followed for 5 years. Results Progressive increases in IMT were seen in both treatment groups, but this was reduced in participants randomized to acarbose (p=0.047). In age, sex and smoking-adjusted analyses IMT progression was associated with greater fasting and OGTT-excursion glucose, fasting insulin, cholesterol, and glycated LDL concentrations. IMT progression was reduced with study-related changes in weight, insulin, and nonesterified fatty acids; these features were more strongly associated with reduced IMT progression than acarbose treatment. Despite strong associations of baseline glycemia with IMT progression, study-related changes in glucose were not important determinants of IMT progression. Conclusions Acarbose can delay progression of carotid intima-media thickness in early diabetes defined by an oral glucose tolerance test. Glucose, weight, insulin and lipids contributed to risk of progression but reductions in glycemia were not major determinants of reduced rate of IMT progression. Vascular benefits of acarbose may be independent of its glycemic effects. PMID:23908125

10 CFR 60.18 - Review of site characterization activities. 2

Code of Federal Regulations, 2011 CFR

2011-01-01

... developed, and on the progress of waste form and waste package research and development. The semiannual... of site characterization will be established. Other topics related to site characterization shall...

10 CFR 60.18 - Review of site characterization activities. 2

Code of Federal Regulations, 2012 CFR

2012-01-01

... developed, and on the progress of waste form and waste package research and development. The semiannual... of site characterization will be established. Other topics related to site characterization shall...

10 CFR 60.18 - Review of site characterization activities. 2

Code of Federal Regulations, 2013 CFR

2013-01-01

... developed, and on the progress of waste form and waste package research and development. The semiannual... of site characterization will be established. Other topics related to site characterization shall...

10 CFR 60.18 - Review of site characterization activities. 2

Code of Federal Regulations, 2014 CFR

2014-01-01

... developed, and on the progress of waste form and waste package research and development. The semiannual... of site characterization will be established. Other topics related to site characterization shall...

Recent Progress in Using Advanced Characterization and Modeling Approaches to Study Radiation Effects in Oxide Ceramics

DOE PAGES

Bai, Xian-Ming

2014-10-23

I serve as a Guest Editor for the Nuclear Materials Committee of the TMS Structural Materials Division, and coordinated the topic ‘‘Radiation Effects in Oxide Ceramics and Novel LWR Fuels" for JOM in the December 2014 issue. I selected five articles related this topic. These articles talk about some recent progress of using advanced experimental and modeling tools to study radiation effects in oxide ceramics at atomistic scale and mesoscale. In this guest editor commentary article, I summarize the novel aspects of these papers and also provide some suggestions for future research directions.

Identification of a prospective early motor progression cluster of Parkinson's disease: Data from the PPMI study.

PubMed

Vavougios, George D; Doskas, Triantafyllos; Kormas, Constantinos; Krogfelt, Karen A; Zarogiannis, Sotirios G; Stefanis, Leonidas

2018-04-15

The aim of our study is to phenotype PD motor progression, and to detect whether serum, cerebrospinal fluid (CSF), neuroimaging biomarkers and neuropsychological measures characterize PD motor progression phenotypes. We defined motor progression as a difference of at least one point in the Hoehn & Yahr (H&Y) scale between the baseline (Visit 0, V0), 12 months (Visit 04, V04) and 36 months (Visit 08, V08) milestones of the Progression Markers Initiative (PPMI) study. H&Y progression events were recorded at each milestone in order to be used as cluster analysis variables, in order to produce progression phenotypes. Subsequently, cross-cluster comparisons prior to and following (pairwise) propensity score matching were performed in order to assess phenotype - defining characteristics. Four progression clusters where identified: SPPD: Secondarily Progressive PD, H&Y progression between V04 and V08; EPPD: Early Progressive PD. H&Y progression between V0 and V04; NPPD: Non Progressive PD, no H&Y progression; MIPD: Minimally Improving PD, i.e. Minimal H&Y improvement H&Y progression between V04 and V08;. Independent Samples Mann Whitney U tests determined CSF aSyn (p = 0.006, adj p-value = 0.036. I) and Semantic Animal fluency T-score (SFT, p = 0.003, adjusted p-value = 0.016.) as statistically significant cross-cluster characteristics. Following Propensity Score Matching, SFT, Hopkins Verbal Learning Test (Retention/Recall), Serum IGF1, CSF aSyn, DaT-SPECT binding ratios (SBRs) and the Benton Judgement of Line Orientation Test (BJLOT) were determined as statistically significant predictors of cluster differentiation (p < 0.05). SFT, Serum IGF1, CSF aSyn and DaT-SPECT-derived, basal ganglia Striatal Binding Ratios warrant further investigation as possible motor progression biomarkers. Copyright © 2018 Elsevier B.V. All rights reserved.

Sleep characteristics and progression of coronary artery calcification: Results from the Heinz Nixdorf Recall cohort study.

PubMed

Kowall, Bernd; Lehmann, Nils; Mahabadi, Amir-Abbas; Lehnich, Anna-Therese; Moebus, Susanne; Budde, Thomas; Seibel, Rainer; Grönemeyer, Dietrich; Erbel, Raimund; Jöckel, Karl-Heinz; Stang, Andreas

2018-04-01

Sleep characteristics are associated with incident cardiovascular diseases (CVD), but there is a lack of studies on the association between sleep characteristics and incidence/progression of coronary artery calcification (CAC). In the Heinz Nixdorf Recall Study, a population-based cohort study in Germany, CAC was assessed by electron-beam tomography at baseline and at 5-year follow-up. In an analysis set of 3043 subjects (age at baseline 45-74 years; 47% men), we fitted logistic and linear regression models to assess associations between self-rated sleep characteristics (nocturnal and total sleep duration; napping; various sleep disorders) and CAC incidence/CAC progression. Progression was measured as 5-year progression factor, as categories of absolute CAC change, and additionally characterized as rapid or slow compared to an extrapolation of baseline CAC values. We observed barely any association between sleep characteristics and CAC progression regardless of the chosen statistical approach; associations between sleep and CAC incidence were slightly larger, e.g., the geometric mean of the 5-year CAC progression factor was 6.8% (95% confidence interval: -9.5; 25.9) larger for ≤5 h, 2.9% (-7.3; 14.3) larger for 5.1-6.9 h and 7.1% (-2.4; 15.7) smaller for ≥7.5 h total sleep compared to 7- <7.5 h total sleep. For subjects with any regular sleep disorder, the geometric mean of the 5-year CAC progression was 3.5% (-4.7; 11.2) smaller compared to subjects without any regular sleep disorder. In this German cohort study, sleep characteristics were barely associated with CAC progression. Copyright © 2018 Elsevier B.V. All rights reserved.

Estimation of fatigue life using electromechanical impedance technique

NASA Astrophysics Data System (ADS)

Lim, Yee Yan; Soh, Chee Kiong

2010-04-01

Fatigue induced damage is often progressive and gradual in nature. Structures subjected to large number of fatigue load cycles will encounter the process of progressive crack initiation, propagation and finally fracture. Monitoring of structural health, especially for the critical components, is therefore essential for early detection of potential harmful crack. Recent advent of smart materials such as piezo-impedance transducer adopting the electromechanical impedance (EMI) technique and wave propagation technique are well proven to be effective in incipient damage detection and characterization. Exceptional advantages such as autonomous, real-time and online, remote monitoring may provide a cost-effective alternative to the conventional structural health monitoring (SHM) techniques. In this study, the main focus is to investigate the feasibility of characterizing a propagating fatigue crack in a structure using the EMI technique as well as estimating its remaining fatigue life using the linear elastic fracture mechanics (LEFM) approach. Uniaxial cyclic tensile load is applied on a lab-sized aluminum beam up to failure. Progressive shift in admittance signatures measured by the piezo-impedance transducer (PZT patch) corresponding to increase of loading cycles reflects effectiveness of the EMI technique in tracing the process of fatigue damage progression. With the use of LEFM, prediction of the remaining life of the structure at different cycles of loading is possible.

[Pure progressive amnesia, isolated for 16 years with focal hippocampus atrophy].

PubMed

Richard-Mornas, A; Foyatier-Michel, N; Thomas-Antérion, C

2011-01-01

Pure progressive amnesia is a rare and unusual syndrome involving long preservation of autonomy and absence of progression in other cognitive domains. We report a case which remained quiescent for 16 years characterized by severe isolated episodic amnesia and preservation of spatial, semantic and implicit memory and autonomy. MRI revealed bilateral focal atrophy of the hippocampus. This specific pattern of impairment differs from other types of amnesic syndromes. It is important to identify this kind of amnesia because of its specific course. Studying the topography of the brain lesions may contribute to a better understanding of the neural systems involved in declarative memory. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Spousal Recollections of Early Signs of Primary Progressive Aphasia

ERIC Educational Resources Information Center

Pozzebon, Margaret; Douglas, Jacinta; Ames, David

2018-01-01

Background: Although primary progressive aphasia (PPA) is characterized by progressive loss of language and communication skills, knowledge about the earliest emerging signs announcing the onset of this condition is limited. Aims: To explore spousal recollections regarding the earliest signs of PPA and to compare the nature of the earliest…

Gene mapping of the Usher syndromes.

PubMed

Kimberling, W; Smith, R J

1992-10-01

USH is an autosomal recessive group of diseases characterized by auditory impairment and visual loss owing to RP. Two common types of USH are known, types I and II. USH type I is characterized by a congenital severe to profound hearing impairment, absent vestibular function, and a progressive pigmentary retinopathy. Persons with type I do not find hearing aids useful, have delayed motor development, and experience progressive night blindness and peripheral visual loss, which usually begins in their second decade. USH type II is characterized by a congenital moderate to severe hearing loss with a down-sloping audiogram, normal vestibular function, and a progressive pigmentary retinopathy. Persons with USH2 find hearing aids beneficial, have normal psychomotor development, and experience progressive night blindness and peripheral visual loss, which usually begins in their third decade. Vestibular dysfunction is the best distinguishing hallmark to differentiate USH type I from type II. One USH type II gene (called USH2) has been assigned to chromosome 1q. One USH type I gene has been tentatively assigned to chromosome 14q. There are other USH genes that have not yet been localized.

Responsive copolymers for enhanced petroleum recovery. Quarterly technical progress report, June 23--September 21, 1994

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

McCormick, C.; Hester, R.

Summaries are given on the technical progress on three tasks of this project. Monomer and polymer synthesis discusses the preparation of 1(7-aminoheptyloxymethyl)naphthalene and poly(maleic anhydride-alt-ethyl vinyl ether). Task 2, Characterization of molecular structure, discusses terpolymer solution preparation, UV analysis, fluorescence analysis, low angle laser light scattering, and viscometry. The paper discusses the effects of hydrophobic groups, the effect of pH, the effect of electrolyte addition, and photophysical studies. Task 3, Solution properties, describes the factorial experimental design for characterizing polymer solutions by light scattering, the light scattering test model, orthogonal factorial test design, linear regression in coded space, confidence levelmore » for coded space test mode coefficients, coefficients of the real space test model, and surface analysis of the model equations.« less

Fine Grained Chaos in AdS2 Gravity

NASA Astrophysics Data System (ADS)

Haehl, Felix M.; Rozali, Moshe

2018-03-01

Quantum chaos can be characterized by an exponential growth of the thermal out-of-time-order four-point function up to a scrambling time u^*. We discuss generalizations of this statement for certain higher-point correlation functions. For concreteness, we study the Schwarzian theory of a one-dimensional time reparametrization mode, which describes two-dimensional anti-de Sitter space (AdS2 ) gravity and the low-energy dynamics of the Sachdev-Ye-Kitaev model. We identify a particular set of 2 k -point functions, characterized as being both "maximally braided" and "k -out of time order," which exhibit exponential growth until progressively longer time scales u^*(k)˜(k -1 )u^*. We suggest an interpretation as scrambling of increasingly fine grained measures of quantum information, which correspondingly take progressively longer time to reach their thermal values.

Fine Grained Chaos in AdS_{2} Gravity.

PubMed

Haehl, Felix M; Rozali, Moshe

2018-03-23

Quantum chaos can be characterized by an exponential growth of the thermal out-of-time-order four-point function up to a scrambling time u[over ^]_{*}. We discuss generalizations of this statement for certain higher-point correlation functions. For concreteness, we study the Schwarzian theory of a one-dimensional time reparametrization mode, which describes two-dimensional anti-de Sitter space (AdS_{2}) gravity and the low-energy dynamics of the Sachdev-Ye-Kitaev model. We identify a particular set of 2k-point functions, characterized as being both "maximally braided" and "k-out of time order," which exhibit exponential growth until progressively longer time scales u[over ^]_{*}^{(k)}∼(k-1)u[over ^]_{*}. We suggest an interpretation as scrambling of increasingly fine grained measures of quantum information, which correspondingly take progressively longer time to reach their thermal values.

What Is the End of Life Period? Trajectories and Characterization Based on Primary Caregiver Reports.

PubMed

Cohen-Mansfield, Jiska; Cohen, Rinat; Skornick-Bouchbinder, Michal; Brill, Shai

2018-04-17

As the population lives longer, end of life (EOL) is emerging as a distinct life phase, about which there is still limited understanding. Characterizing this important period is vital for clarifying issues regarding trajectory and decline at EOL and for health service planning on an institutional, communal, and societal level. In this article, we aim to characterize the EOL period, examining the duration and number of EOL stages, as well as functional, attitudinal, and emotional trajectories. In this cross-sectional study, 70 primary caregivers of deceased persons were interviewed. Standardized rates of functional, attitudinal, and emotional change across the EOL period were calculated. Frequencies were compared using the McNemar statistical test. EOL period was found to have a median length of 3.25 years, and an average of approximately three progressive stages. The duration of EOL stages tended to decrease as death approached. Unexpected events (eg new medical diagnosis/accident) served as the precipitating event for the EOL period for approximately half of the deceased persons, and changes in existing conditions (eg health status/cognitive state) were also reported to precipitate EOL for a similar proportion. Reports of functionality across stages found the steepest decline in the "physical" domain and the most moderate decline in the "social" domain. With each stage, positive indicators, such as "will to live," showed a progressive decline, whereas negative indicators, including "suffering" and "dependence level," progressively increased. Results help characterize EOL trajectories and should inform care planning and decision making at various levels. In addition, they suggest a methodology for better understanding EOL.

Progression of language decline and cortical atrophy in subtypes of primary progressive aphasia.

PubMed

Rogalski, E; Cobia, D; Harrison, T M; Wieneke, C; Weintraub, S; Mesulam, M-M

2011-05-24

To examine the longitudinal course of primary progressive aphasia (PPA) over a 2-year period and to offer quantitative ranges of expected change that could be used to guide the design and evaluation of therapeutic intervention trials. Regional changes of cortical thickness and whole-brain cortical volume loss as well as neuropsychological language performance were assessed at baseline and 2 years later in 13 rigorously characterized patients who fulfilled research criteria for logopenic, agrammatic, and semantic PPA subtypes (6 PPA-L, 3 PPA-G, and 4 PPA-S). There was substantial progression of clinical deficits and cortical atrophy over 2 years. Neuropsychological language performance patterns lost the sharp distinctions that differentiated one PPA variant from another. Nonetheless, the subtype-specific differential impairment of word comprehension vs grammatical processing was largely maintained. Peak atrophy sites spread beyond the initial distinctive locations that characterized each of the 3 subtypes and displayed a more convergent distribution encompassing all 3 major components of the language network: the inferior frontal gyrus, the temporoparietal junction, and lateral temporal cortex. Despite the progression, overall peak atrophy remained lateralized to the left hemisphere. The results suggest that the unique features, which sharply differentiate the PPA variants at the early to middle stages, may lose their distinctiveness as the degeneration becomes more severe. Given the substantial atrophy over 2 years, PPA clinical trials may require fewer patients and shorter study durations than Alzheimer disease trials to detect significant therapeutic effects.

Progression of language decline and cortical atrophy in subtypes of primary progressive aphasia

PubMed Central

Cobia, D.; Harrison, T.M.; Wieneke, C.; Weintraub, S.; Mesulam, M.-M.

2011-01-01

Objectives: To examine the longitudinal course of primary progressive aphasia (PPA) over a 2-year period and to offer quantitative ranges of expected change that could be used to guide the design and evaluation of therapeutic intervention trials. Methods: Regional changes of cortical thickness and whole-brain cortical volume loss as well as neuropsychological language performance were assessed at baseline and 2 years later in 13 rigorously characterized patients who fulfilled research criteria for logopenic, agrammatic, and semantic PPA subtypes (6 PPA-L, 3 PPA-G, and 4 PPA-S). Results: There was substantial progression of clinical deficits and cortical atrophy over 2 years. Neuropsychological language performance patterns lost the sharp distinctions that differentiated one PPA variant from another. Nonetheless, the subtype-specific differential impairment of word comprehension vs grammatical processing was largely maintained. Peak atrophy sites spread beyond the initial distinctive locations that characterized each of the 3 subtypes and displayed a more convergent distribution encompassing all 3 major components of the language network: the inferior frontal gyrus, the temporoparietal junction, and lateral temporal cortex. Despite the progression, overall peak atrophy remained lateralized to the left hemisphere. Conclusions: The results suggest that the unique features, which sharply differentiate the PPA variants at the early to middle stages, may lose their distinctiveness as the degeneration becomes more severe. Given the substantial atrophy over 2 years, PPA clinical trials may require fewer patients and shorter study durations than Alzheimer disease trials to detect significant therapeutic effects. PMID:21606451

Subtypes of depressive symptoms and inflammatory biomarkers: An exploratory study on a sample of HIV-positive patients

PubMed Central

Pala, A. Norcini; Steca, P.; Bagrodia, R.; Helpman, L.; Colangeli, V.; Viale, P.; Wainberg, M.L.

2017-01-01

Depressive symptoms cause major impairment and may accelerate HIV progression despite the use of antiretroviral medication. The somatic symptoms criteria for HIV infection and depression partially overlap, which can make differential diagnosis challenging. Because of chronic inflammation caused by HIV infection, HIV-positive patients may develop somatic and affective-cognitive symptoms of depression. Inflammation-related depression is primarily characterized with severe somatic symptoms such as fatigue and sleep disturbance. This study sought to explore the patterns of somatic and cognitive-affective depressive symptoms that characterize HIV-positive patients. Our specific aims were (1) to identify subtypes of depressive symptoms in a sample of HIV-positive patients; and (2) to test the subtypes’ difference on inflammatory and HIV disease progression biomarkers. HIV-positive men and women (N = 102) with and without depressive symptoms were randomly selected from an Italian HIV clinic. Depressive symptoms (PHQ-9), viral load (VL), CD4+, Il-6, TNF-α, and monocytes were assessed. The three subtypes formed using Latent Class Analysis (LCA) identified patients with (1) severe cognitive-affective and somatic depressive symptoms; (2) severe/moderate somatic symptoms; and (3) absent or low depressive symptoms. The subtype with severe/moderate somatic symptoms was characterized with elevated levels of Il-6 and monocytes. No difference on HIV progression biomarkers was found. The subtypes of depressive symptoms might help differentiating depressive symptoms from HIV- and inflammatory-related somatic symptoms. When present, cognitive-affective and/or somatic symptoms cause significant impairment to patients’ lives and thus warrant further assessment and treatment. PMID:26883521

Subtypes of depressive symptoms and inflammatory biomarkers: An exploratory study on a sample of HIV-positive patients.

PubMed

Norcini Pala, A; Steca, P; Bagrodia, R; Helpman, L; Colangeli, V; Viale, P; Wainberg, M L

2016-08-01

Depressive symptoms cause major impairment and may accelerate HIV progression despite the use of antiretroviral medication. The somatic symptoms criteria for HIV infection and depression partially overlap, which can make differential diagnosis challenging. Because of chronic inflammation caused by HIV infection, HIV-positive patients may develop somatic and affective-cognitive symptoms of depression. Inflammation-related depression is primarily characterized with severe somatic symptoms such as fatigue and sleep disturbance. This study sought to explore the patterns of somatic and cognitive-affective depressive symptoms that characterize HIV-positive patients. Our specific aims were (1) to identify subtypes of depressive symptoms in a sample of HIV-positive patients; and (2) to test the subtypes' difference on inflammatory and HIV disease progression biomarkers. HIV-positive men and women (N=102) with and without depressive symptoms were randomly selected from an Italian HIV clinic. Depressive symptoms (PHQ-9), viral load (VL), CD4+, Il-6, TNF-α, and monocytes were assessed. The three subtypes formed using Latent Class Analysis (LCA) identified patients with (1) severe cognitive-affective and somatic depressive symptoms; (2) severe/moderate somatic symptoms; and (3) absent or low depressive symptoms. The subtype with severe/moderate somatic symptoms was characterized with elevated levels of Il-6 and monocytes. No difference on HIV progression biomarkers was found. The subtypes of depressive symptoms might help differentiating depressive symptoms from HIV- and inflammatory-related somatic symptoms. When present, cognitive-affective and/or somatic symptoms cause significant impairment to patients' lives and thus warrant further assessment and treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

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

Ruzic, David

The Thermoelectric-Driven Liquid-Metal Plasma-Facing Structures (TELS) project was able to establish the experimental conditions necessary for flowing liquid metal surfaces in order to be utilized as surfaces facing fusion relevant energetic plasma flux. The work has also addressed additional developments along with progressing along the timeline detailed in the proposal. A no-cost extension was requested to conduct other relevant experiment- specifically regarding the characterization droplet ejection during energetic plasma flux impact. A specially designed trench module, which could accommodate trenches with different aspect ratios was fabricated and installed in the TELS setup and plasma gun experiments were performed. Droplet ejectionmore » was characterized using high speed image acquisition and also surface mounted probes were used to characterize the plasma. The Gantt chart below had been provided with the original proposal, indicating the tasks to be performed in the third year of funding. These tasks are listed above in the progress report outline, and their progress status is detailed below.« less

Mitochondrial transfer RNA(Phe) mutation associated with a progressive neurodegenerative disorder characterized by psychiatric disturbance, dementia, and akinesia-rigidity.

PubMed

Young, Tim M; Blakely, Emma L; Swalwell, Helen; Carter, Janet E; Kartsounis, Luke D; O'Donovan, Dominic G; Turnbull, Douglass M; Taylor, Robert W; de Silva, Rajith N

2010-11-01

Mitochondrial diseases are characterized by wide phenotypic and genetic variability, but presentations in adults with akinetic rigidity and hyperkinetic movement disorders are rare. To describe clinically a subject with progressive neurodegeneration characterized by psychosis, dementia, and akinesia-rigidity, and to associate this phenotype with a novel mitochondrial transfer RNA(Phe) (tRNA(Phe)) (MTTF) mutation. Case description and detailed laboratory investigations of a 57-year-old woman at a university teaching hospital and a specialist mitochondrial diagnostic laboratory. Histopathological findings indicated that an underlying mitochondrial abnormality was responsible for the subject's progressive neurological disorder, with mitochondrial genome sequencing revealing a novel m.586G>A MTTF mutation. The clinical phenotypes associated with mitochondrial disorders may include akinesia-rigidity and psychosis. Our findings further broaden the spectrum of neurological disease associated with mitochondrial tRNA(Phe) mutations.

Development of Si(1-x)Ge(x) technology for microwave sensing applications

NASA Technical Reports Server (NTRS)

Mena, Rafael A.; Taub, Susan R.; Alterovitz, Samuel A.; Young, Paul E.; Simons, Rainee N.; Rosenfeld, David

1993-01-01

The progress for the first year of the work done under the Director's Discretionary Fund (DDF) research project entitled, 'Development of Si(1-x)Ge(x) Technology for Microwave Sensing Applications.' This project includes basic material characterization studies of silicon-germanium (SiGe), device processing on both silicon (Si) and SiGe substrates, and microwave characterization of transmission lines on silicon substrates. The material characterization studies consisted of ellipsometric and magneto-transport measurements and theoretical calculations of the SiGe band-structure. The device fabrication efforts consisted of establishing SiGe device processing capabilities in the Lewis cleanroom. The characterization of microwave transmission lines included studying the losses of various coplanar transmission lines and the development of transitions on silicon. Each part of the project is discussed individually and the findings for each part are presented. Future directions are also discussed.

Methodology for Characterizing Trends | Cancer Trends Progress Report

Cancer.gov

The Cancer Trends Progress Report, first issued in 2001, summarizes our nation's advances against cancer in relation to Healthy People targets set forth by the Department of Health and Human Services.

DNA linkage studies of degenerative retinal diseases.

PubMed

Daiger, S P; Heckenlively, J R; Lewis, R A; Pelias, M Z

1987-01-01

DNA linkage studies of human genetic diseases have led to rapid characterization of a number of otherwise intractable disease loci. Detection of a linked DNA marker, the first step in "reverse genetics", has permitted cloning of the genes for Duchenne muscular dystrophy, retinoblastoma and chronic granulomatosis disease, among others. Thus, the case for applying these techniques to retinitis pigmentosa and related diseases, and the urgency in capitalizing on molecular developments, is justified and compelling. The first major success regarding RP was in demonstrating linkage of the DNA marker DXS7 (L1.28) to XRP. For autosomal forms of the disease, conventional linkage studies have provided tentative evidence for linkage of ADRP to the Rh blood group on chromosome lp and for linkage of Usher's syndrome to Gc and 4q. These provisional assignments are, at least, an important starting point for DNA analysis. The Support Program for DNA Linkage Studies of Degenerative Retinal Diseases was established to provide access for the scientific community to appropriate families, using the resources of the Human Genetic Mutant Cell Repository to prepare, store and distribute lymphoblast lines. To date, two extensive, well-characterized families are included in the program: the autosomal dominant RP family UCLA-RP01, and the Usher's syndrome families LSU-US01. It is highly likely that rapid progress will be made in mapping and characterizing the inherited retinal dystrophies. We believe the support program will facilitate this progress.

Common Progress Monitoring Omissions: Planning and Practice. Progress Monitoring Brief #1

ERIC Educational Resources Information Center

National Center on Response to Intervention, 2013

2013-01-01

Progress monitoring, one of the essential components of Response to Intervention (RTI), is characterized by repeated measurement of academic performance that is conducted at least monthly. The process may be used to assess students' academic performance over time, to quantify student rates of improvement or responsiveness to instruction, and to…

Common Progress Monitoring Omissions: Reporting Information to Parents. Progress Monitoring Brief #4

ERIC Educational Resources Information Center

National Center on Response to Intervention, 2013

2013-01-01

Progress monitoring, one of the essential components of Response to Intervention (RTI), is characterized by repeated measurement of academic performance that is conducted at least monthly. The process may be used to assess students' academic performance over time, to quantify student rates of improvement or responsiveness to instruction, and to…

Stem cells in prostate cancer initiation and progression

PubMed Central

Lawson, Devon A.; Witte, Owen N.

2007-01-01

Peter Nowell and David Hungerford’s discovery of the Philadelphia chromosome facilitated many critical studies that have led to a paradigm shift in our understanding of cancer as a disease of stem cells. This Review focuses on the application of these concepts to investigation of the role of stem cells in prostate cancer initiation and progression. Major strides in the development of in vitro and in vivo assays have enabled identification and characterization of prostate stem cells as well as functional evaluation of the tumorigenic effects of prostate cancer–related genetic alterations. PMID:17671638

Learning of speckle statistics for in vivo and noninvasive characterization of cutaneous wound regions using laser speckle contrast imaging.

PubMed

Basak, Kausik; Dey, Goutam; Mahadevappa, Manjunatha; Mandal, Mahitosh; Sheet, Debdoot; Dutta, Pranab Kumar

2016-09-01

Laser speckle contrast imaging (LSCI) provides a noninvasive and cost effective solution for in vivo monitoring of blood flow. So far, most of the researches consider changes in speckle pattern (i.e. correlation time of speckle intensity fluctuation), account for relative change in blood flow during abnormal conditions. This paper introduces an application of LSCI for monitoring wound progression and characterization of cutaneous wound regions on mice model. Speckle images are captured on a tumor wound region at mice leg in periodic interval. Initially, raw speckle images are converted to their corresponding contrast images. Functional characterization begins with first segmenting the affected area using k-means clustering, taking wavelet energies in a local region as feature set. In the next stage, different regions in wound bed are clustered based on progressive and non-progressive nature of tissue properties. Changes in contrast due to heterogeneity in tissue structure and functionality are modeled using LSCI speckle statistics. Final characterization is achieved through supervised learning of these speckle statistics using support vector machine. On cross evaluation with mice model experiment, the proposed approach classifies the progressive and non-progressive wound regions with an average sensitivity of 96.18%, 97.62% and average specificity of 97.24%, 96.42% respectively. The clinical information yield with this approach is validated with the conventional immunohistochemistry result of wound to justify the ability of LSCI for in vivo, noninvasive and periodic assessment of wounds. Copyright © 2016 Elsevier Inc. All rights reserved.

Detection and Characterization of Circulating Tumor Associated Cells in Metastatic Breast Cancer.

PubMed

Mu, Zhaomei; Benali-Furet, Naoual; Uzan, Georges; Znaty, Anaëlle; Ye, Zhong; Paolillo, Carmela; Wang, Chun; Austin, Laura; Rossi, Giovanna; Fortina, Paolo; Yang, Hushan; Cristofanilli, Massimo

2016-09-30

The availability of blood-based diagnostic testing using a non-invasive technique holds promise for real-time monitoring of disease progression and treatment selection. Circulating tumor cells (CTCs) have been used as a prognostic biomarker for the metastatic breast cancer (MBC). The molecular characterization of CTCs is fundamental to the phenotypic identification of malignant cells and description of the relevant genetic alterations that may change according to disease progression and therapy resistance. However, the molecular characterization of CTCs remains a challenge because of the rarity and heterogeneity of CTCs and technological difficulties in the enrichment, isolation and molecular characterization of CTCs. In this pilot study, we evaluated circulating tumor associated cells in one blood draw by size exclusion technology and cytological analysis. Among 30 prospectively enrolled MBC patients, CTCs, circulating tumor cell clusters (CTC clusters), CTCs of epithelial-mesenchymal transition (EMT) and cancer associated macrophage-like cells (CAMLs) were detected and analyzed. For molecular characterization of CTCs, size-exclusion method for CTC enrichment was tested in combination with DEPArray™ technology, which allows the recovery of single CTCs or pools of CTCs as a pure CTC sample for mutation analysis. Genomic mutations of TP53 and ESR1 were analyzed by targeted sequencing on isolated 7 CTCs from a patient with MBC. The results of genomic analysis showed heterozygous TP53 R248W mutation from one single CTC and pools of three CTCs, and homozygous TP53 R248W mutation from one single CTC and pools of two CTCs. Wild-type ESR1 was detected in the same isolated CTCs. The results of this study reveal that size-exclusion method can be used to enrich and identify circulating tumor associated cells, and enriched CTCs were characterized for genetic alterations in MBC patients, respectively.

Characterization of an immortalized human vaginal epithelial cell line.

PubMed

Rajan, N; Pruden, D L; Kaznari, H; Cao, Q; Anderson, B E; Duncan, J L; Schaeffer, A J

2000-02-01

Adherence of type 1 piliated Escherichia coli to vaginal mucosa plays a major role in the pathogenesis of ascending urinary tract infections (UTIs) in women. Progress in understanding the mechanism of adherence to the vaginal surface could be enhanced by the utilization of well-characterized vaginal epithelial cells. The objective of this study was to immortalize vaginal epithelial cells and study their bacterial adherence properties. Primary vaginal cells were obtained from a normal post-menopausal woman, immortalized by infection with E6/E7 genes from human papillomavirus 16 (HPV 16) and cultured in serum free keratinocyte growth factor medium. Positive immunostaining with a pool of antibodies to cytokeratins 1, 5, 10 and 14 (K1, K5, K10 and K14) and to K13 confirmed the epithelial origin of these cells. The immortalized cells showed binding of type 1 piliated E. coli in a pili specific and mannose sensitive manner. This model system should facilitate studies on the interaction of pathogens with vaginal mucosal cells, an essential step in the progression of ascending UTIs in women.

A study of the discrepant QSO X-ray luminosity function from the HEAO-2 data archive

NASA Technical Reports Server (NTRS)

Margon, B.

1984-01-01

An in-progress investigation aimed at characterizing the X-ray luminosity of very faint QSOs is described. More than 100 faint, previously uncataloged QSOs which lie in areas imaged in X rays at very high sensitivity were discovered.

A heritable symbiont and host-associated factors shape fungal endophyte communities across spatial scales

USDA-ARS?s Scientific Manuscript database

Microbial ecologists are intensely interested in the processes governing microbial community assembly, progress has been limited by a lack of studies that span multiple geographical scales and levels of biological organization. High throughput sequencing was used to characterize foliar fungal endoph...

Impact analysis of composite aircraft structures

NASA Technical Reports Server (NTRS)

Pifko, Allan B.; Kushner, Alan S.

1993-01-01

The impact analysis of composite aircraft structures is discussed. Topics discussed include: background remarks on aircraft crashworthiness; comments on modeling strategies for crashworthiness simulation; initial study of simulation of progressive failure of an aircraft component constructed of composite material; and research direction in composite characterization for impact analysis.

Predictors of Recurrence, Progression, and Retreatment in Basilar Tip Aneurysms: A Location-Controlled Analysis.

PubMed

Abecassis, Isaac Josh; Sen, Rajeev D; Barber, Jason; Shetty, Rakshith; Kelly, Cory M; Ghodke, Basavaraj V; Hallam, Danial K; Levitt, Michael R; Kim, Louis J; Sekhar, Laligam N

2018-06-14

Endovascular treatment of intracranial aneurysms is associated with higher rates of recurrence and retreatment, though contemporary rates and risk factors for basilar tip aneurysms (BTAs) are less well-described. To characterize progression, retreatement, and retreated progression of BTAs treated with microsurgical or endovascular interventions. We retrospectively reviewed records for 141 consecutive BTA patients. We included 158 anterior communicating artery (ACoA) and 118 middle cerebral artery (MCA) aneurysms as controls. Univariate and multivariate analyses were used to calculate rates of progression (recurrence of previously obliterated aneurysms and progression of known residual aneurysm dome or neck), retreatment, and retreated progression. Kaplan-Meier analysis was used to characterize 24-mo event rates for primary outcome prediction. Of 141 BTA patients, 62.4% were ruptured and 37.6% were unruptured. Average radiographical follow-up was 33 mo. Among ruptured aneurysms treated with clipping, there were 2 rehemorrhages due to recurrence (6.1%), and none in any other cohorts. Overall rates of progression (28.9%), retreatment (28.9%), and retreated progression (24.7%) were not significantly different between surgical and endovascular subgroups, though ruptured aneurysms had higher event rates. Multivariate modeling confirmed rupture status (P = .003, hazard ratio = 0.14) and aneurysm dome width (P = .005, hazard ratio = 1.23) as independent predictors of progression requiring retreatment. In a separate multivariate analysis with ACoA and MCA aneurysms, basilar tip location was an independent predictor of progression, retreatment, and retreated progression. BTAs have higher rates of progression and retreated progression than other aneurysm locations, independent of treatment modality. Rupture status and dome width are risk factors for progression requiring retreatment.

Genome-wide Association Study Implicates PARD3B-based AIDS Restriction

PubMed Central

Nelson, George W.; Lautenberger, James A.; Chinn, Leslie; McIntosh, Carl; Johnson, Randall C.; Sezgin, Efe; Kessing, Bailey; Malasky, Michael; Hendrickson, Sher L.; Pontius, Joan; Tang, Minzhong; An, Ping; Winkler, Cheryl A.; Limou, Sophie; Le Clerc, Sigrid; Delaneau, Olivier; Zagury, Jean-François; Schuitemaker, Hanneke; van Manen, Daniëlle; Bream, Jay H.; Gomperts, Edward D.; Buchbinder, Susan; Goedert, James J.; Kirk, Gregory D.; O'Brien, Stephen J.

2011-01-01

Background. Host genetic variation influences human immunodeficiency virus (HIV) infection and progression to AIDS. Here we used clinically well-characterized subjects from 5 pretreatment HIV/AIDS cohorts for a genome-wide association study to identify gene associations with rate of AIDS progression. Methods.  European American HIV seroconverters (n = 755) were interrogated for single-nucleotide polymorphisms (SNPs) (n = 700,022) associated with progression to AIDS 1987 (Cox proportional hazards regression analysis, co-dominant model). Results.  Association with slower progression was observed for SNPs in the gene PARD3B. One of these, rs11884476, reached genome-wide significance (relative hazard = 0.3; P =3. 370 × 10−9) after statistical correction for 700,022 SNPs and contributes 4.52% of the overall variance in AIDS progression in this study. Nine of the top-ranked SNPs define a PARD3B haplotype that also displays significant association with progression to AIDS (hazard ratio, 0.3; P = 3.220 × 10−8). One of these SNPs, rs10185378, is a predicted exonic splicing enhancer; significant alteration in the expression profile of PARD3B splicing transcripts was observed in B cell lines with alternate rs10185378 genotypes. This SNP was typed in European cohorts of rapid progressors and was found to be protective for AIDS 1993 definition (odds ratio, 0.43, P = .025). Conclusions. These observations suggest a potential unsuspected pathway of host genetic influence on the dynamics of AIDS progression. PMID:21502085

Calculating stage duration statistics in multistage diseases.

PubMed

Komarova, Natalia L; Thalhauser, Craig J

2011-01-01

Many human diseases are characterized by multiple stages of progression. While the typical sequence of disease progression can be identified, there may be large individual variations among patients. Identifying mean stage durations and their variations is critical for statistical hypothesis testing needed to determine if treatment is having a significant effect on the progression, or if a new therapy is showing a delay of progression through a multistage disease. In this paper we focus on two methods for extracting stage duration statistics from longitudinal datasets: an extension of the linear regression technique, and a counting algorithm. Both are non-iterative, non-parametric and computationally cheap methods, which makes them invaluable tools for studying the epidemiology of diseases, with a goal of identifying different patterns of progression by using bioinformatics methodologies. Here we show that the regression method performs well for calculating the mean stage durations under a wide variety of assumptions, however, its generalization to variance calculations fails under realistic assumptions about the data collection procedure. On the other hand, the counting method yields reliable estimations for both means and variances of stage durations. Applications to Alzheimer disease progression are discussed.

Fukushima Daiichi Unit 1 Accident Progression Uncertainty Analysis and Implications for Decommissioning of Fukushima Reactors - Volume I.

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

Gauntt, Randall O.; Mattie, Patrick D.

Sandia National Laboratories (SNL) has conducted an uncertainty analysis (UA) on the Fukushima Daiichi unit (1F1) accident progression with the MELCOR code. The model used was developed for a previous accident reconstruction investigation jointly sponsored by the US Department of Energy (DOE) and Nuclear Regulatory Commission (NRC). That study focused on reconstructing the accident progressions, as postulated by the limited plant data. This work was focused evaluation of uncertainty in core damage progression behavior and its effect on key figures-of-merit (e.g., hydrogen production, reactor damage state, fraction of intact fuel, vessel lower head failure). The primary intent of this studymore » was to characterize the range of predicted damage states in the 1F1 reactor considering state of knowledge uncertainties associated with MELCOR modeling of core damage progression and to generate information that may be useful in informing the decommissioning activities that will be employed to defuel the damaged reactors at the Fukushima Daiichi Nuclear Power Plant. Additionally, core damage progression variability inherent in MELCOR modeling numerics is investigated.« less

Combined application of imaging techniques for the characterization and authentication of ancient weapons

NASA Astrophysics Data System (ADS)

Salvemini, Filomena; Grazzi, Francesco; Kardjilov, Nikolay; Wieder, Frank; Manke, Ingo; Edge, David; Williams, Alan; Zoppi, Marco

2017-05-01

Non-invasive experimental methods play an important role in the field of cultural heritage. Benefiting from the technical progress in recent years, neutron imaging has been demonstrated to complement effectively studies based on surface analysis, allowing for a non-invasive characterization of the whole three-dimensional volume. This study focuses on a kris and a kanjar, two weapons from ancient Asia, to show the potential of the combined use of X-ray and neutron imaging techniques for the characterisation of the manufacturing methods and the authentication of objects of cultural and historical interest.

Effects of Malignant Melanoma Initiating Cells on T-Cell Activation

PubMed Central

Schatton, Tobias; Schütte, Ute; Frank, Markus H.

2016-01-01

Although human malignant melanoma is a highly immunogenic cancer, both the endogenous antitumor immune response and melanoma immunotherapy often fail to control neoplastic progression. Accordingly, characterizing melanoma cell subsets capable of evading antitumor immunity could unravel optimized treatment strategies that might reduce morbidity and mortality from melanoma. By virtue of their preferential capacity to modulate antitumor immune responses and drive inexorable tumor growth and progression, malignant melanoma-initiating cells (MMICs) warrant closer investigation to further elucidate the cellular and molecular mechanisms underlying melanoma immune evasion and immunotherapy resistance. Here we describe methodologies that enable the characterization of immunoregulatory effects of purified MMICs versus melanoma bulk populations in coculture with syngeneic or allogeneic lymphocytes, using [3H] thymidine incorporation, enzyme-linked immunosorbent spot (ELISPOT), or ELISA assays. These assays were traditionally developed to analyze alloimmune processes and we successfully adapted them for the study of tumor-mediated immunomodulatory functions. PMID:26786883

Characterization of Damage Progression in SCS-6/timetal 21S (0)4 Under Thermomechanical Fatigue Loadings

NASA Technical Reports Server (NTRS)

Castelli, Michael G.

1994-01-01

A detailed experimental investigation was performed at a single maximum cyclic stress (sigma max) level to physically characterize the progression of thermomechanical fatigue (lW) damage in continuously reinforced (0 deg) SCS-6/Timetal 21S, a titanium matrix composite. In-phase (IP) and out of-phase (OP) loadings were investigated at sigma max = 1000 MPa with a temperature cycle from 150 to 6500 C. Damage progression, in terms of macroscopic property degradation, was experimentally quantified through an advanced TMF test methodology which incorporates explicit measurements of the isothermal static moduli at the TMF temperature extremes and the coefficient of thermal expansion (CTE) as functions of the TMF cycles. Detailed characterization of the physical damage progression at the microstructural level was performed by interrupting multiple TMF tests at various stages of mechanical property degradation and analyzing the microstructure through extensive destructive metallography. Further, the extent of damage was also quantified through residual static strength measurements. Results indicated that damage initiation occurred very early in cyclic life (N less than 0.1Nf) for both the IP and OP TMF loadings. IP TMF damage was found to be dominated by fiber breakage with a physical damage progression in the microstructure which was difficult to quantify. OP TMF loadings produced matrix cracking exclusively associated with surface initiations. Here, damage progression was easily distinguished in terms of both the number of cracks and their relative inward progressions toward the outer fiber rows with increased cycling. The point at which the leading cracks reached the outer fiber rows (when localized fiber/matrix de-bonding and matrix crack bridging occurred) appeared to be reflected in the macroscopic property degradation curves.

Hearing loss in Usher syndrome type II is nonprogressive.

PubMed

Reisser, Christoph F V; Kimberling, William J; Otterstedde, Christian R

2002-12-01

Usher syndrome is an autosomal recessive disorder characterized by sensorineural hearing loss and progressive visual loss secondary to retinitis pigmentosa. In the literature, a possible progression of the moderate to severe hearing loss in Usher syndrome type II (Usher II) is controversial. We studied the development of the hearing loss of 125 patients with a clinical diagnosis of Usher syndrome type II intraindividually and interindividually by repeatedly performing complete audiological and neuro-otologic examinations. Our data show a very characteristic slope of the hearing curve in all Usher II patients and no clinically relevant progression of the hearing loss over up to 17 years. The subjective impression of a deterioration of the communicative abilities of Usher II patients must therefore be attributed to the progressive visual loss. The patients should be reassured that changes in their hearing abilities are unlikely and should be provided with optimally fitted modern hearing aids.

Hierarchical kernel mixture models for the prediction of AIDS disease progression using HIV structural gp120 profiles

PubMed Central

2010-01-01

Changes to the glycosylation profile on HIV gp120 can influence viral pathogenesis and alter AIDS disease progression. The characterization of glycosylation differences at the sequence level is inadequate as the placement of carbohydrates is structurally complex. However, no structural framework is available to date for the study of HIV disease progression. In this study, we propose a novel machine-learning based framework for the prediction of AIDS disease progression in three stages (RP, SP, and LTNP) using the HIV structural gp120 profile. This new intelligent framework proves to be accurate and provides an important benchmark for predicting AIDS disease progression computationally. The model is trained using a novel HIV gp120 glycosylation structural profile to detect possible stages of AIDS disease progression for the target sequences of HIV+ individuals. The performance of the proposed model was compared to seven existing different machine-learning models on newly proposed gp120-Benchmark_1 dataset in terms of error-rate (MSE), accuracy (CCI), stability (STD), and complexity (TBM). The novel framework showed better predictive performance with 67.82% CCI, 30.21 MSE, 0.8 STD, and 2.62 TBM on the three stages of AIDS disease progression of 50 HIV+ individuals. This framework is an invaluable bioinformatics tool that will be useful to the clinical assessment of viral pathogenesis. PMID:21143806

Modelling gene expression profiles related to prostate tumor progression using binary states

PubMed Central

2013-01-01

Background Cancer is a complex disease commonly characterized by the disrupted activity of several cancer-related genes such as oncogenes and tumor-suppressor genes. Previous studies suggest that the process of tumor progression to malignancy is dynamic and can be traced by changes in gene expression. Despite the enormous efforts made for differential expression detection and biomarker discovery, few methods have been designed to model the gene expression level to tumor stage during malignancy progression. Such models could help us understand the dynamics and simplify or reveal the complexity of tumor progression. Methods We have modeled an on-off state of gene activation per sample then per stage to select gene expression profiles associated to tumor progression. The selection is guided by statistical significance of profiles based on random permutated datasets. Results We show that our method identifies expected profiles corresponding to oncogenes and tumor suppressor genes in a prostate tumor progression dataset. Comparisons with other methods support our findings and indicate that a considerable proportion of significant profiles is not found by other statistical tests commonly used to detect differential expression between tumor stages nor found by other tailored methods. Ontology and pathway analysis concurred with these findings. Conclusions Results suggest that our methodology may be a valuable tool to study tumor malignancy progression, which might reveal novel cancer therapies. PMID:23721350

Genomic and Epigenomic Alterations in Cancer.

PubMed

Chakravarthi, Balabhadrapatruni V S K; Nepal, Saroj; Varambally, Sooryanarayana

2016-07-01

Multiple genetic and epigenetic events characterize tumor progression and define the identity of the tumors. Advances in high-throughput technologies, like gene expression profiling, next-generation sequencing, proteomics, and metabolomics, have enabled detailed molecular characterization of various tumors. The integration and analyses of these high-throughput data have unraveled many novel molecular aberrations and network alterations in tumors. These molecular alterations include multiple cancer-driving mutations, gene fusions, amplification, deletion, and post-translational modifications, among others. Many of these genomic events are being used in cancer diagnosis, whereas others are therapeutically targeted with small-molecule inhibitors. Multiple genes/enzymes that play a role in DNA and histone modifications are also altered in various cancers, changing the epigenomic landscape during cancer initiation and progression. Apart from protein-coding genes, studies are uncovering the critical regulatory roles played by noncoding RNAs and noncoding regions of the genome during cancer progression. Many of these genomic and epigenetic events function in tandem to drive tumor development and metastasis. Concurrent advances in genome-modulating technologies, like gene silencing and genome editing, are providing ability to understand in detail the process of cancer initiation, progression, and signaling as well as opening up avenues for therapeutic targeting. In this review, we discuss some of the recent advances in cancer genomic and epigenomic research. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Descriptions of Improvisational Thinking by Developing Jazz Improvisers

ERIC Educational Resources Information Center

Norgaard, Martin

2017-01-01

Research investigating improvisational skill development in adolescent learners is scant. In this study interviews with developing jazz improvisers are used to characterize the skill-building process. The findings were considered in light of two views of skill learning. In one view, students progress through several discrete levels, while in a…

Progress in industrial holography in France

NASA Astrophysics Data System (ADS)

Smigielski, Paul

1992-01-01

Industrial applications of holography in France are briefly reviewed. Particular attention is given to nondestructive testing of helicopter blades at Aerospatiale Central Laboratory, the use of holography at Renault for car-engine vibration study, vibration characterization of turbo-jet engine components at SNECMA, and vibration analysis of plates in an industrial hemodynamic tunnel.

GENERATION AND CHARACTERIZATION OF FOUR DILUTIONS OF DIESEL ENGINE EXHAUST FOR A SUBCHRONIC INHALATION STUDY. (R826442)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

Electron-Transfer/Higher-Energy Collision Dissociation (EThcD)-Enabled Intact Glycopeptide/Glycoproteome Characterization

NASA Astrophysics Data System (ADS)

Yu, Qing; Wang, Bowen; Chen, Zhengwei; Urabe, Go; Glover, Matthew S.; Shi, Xudong; Guo, Lian-Wang; Kent, K. Craig; Li, Lingjun

2017-09-01

Protein glycosylation, one of the most heterogeneous post-translational modifications, can play a major role in cellular signal transduction and disease progression. Traditional mass spectrometry (MS)-based large-scale glycoprotein sequencing studies heavily rely on identifying enzymatically released glycans and their original peptide backbone separately, as there is no efficient fragmentation method to produce unbiased glycan and peptide product ions simultaneously in a single spectrum, and that can be conveniently applied to high throughput glycoproteome characterization, especially for N-glycopeptides, which can have much more branched glycan side chains than relatively less complex O-linked glycans. In this study, a redefined electron-transfer/higher-energy collision dissociation (EThcD) fragmentation scheme is applied to incorporate both glycan and peptide fragments in one single spectrum, enabling complete information to be gathered and great microheterogeneity details to be revealed. Fetuin was first utilized to prove the applicability with 19 glycopeptides and corresponding five glycosylation sites identified. Subsequent experiments tested its utility for human plasma N-glycoproteins. Large-scale studies explored N-glycoproteomics in rat carotid arteries over the course of restenosis progression to investigate the potential role of glycosylation. The integrated fragmentation scheme provides a powerful tool for the analysis of intact N-glycopeptides and N-glycoproteomics. We also anticipate this approach can be readily applied to large-scale O-glycoproteome characterization. [Figure not available: see fulltext.

Recent Seismicity in Texas and Research Design and Progress of the TexNet-CISR Collaboration

NASA Astrophysics Data System (ADS)

Hennings, P.; Savvaidis, A.; Rathje, E.; Olson, J. E.; DeShon, H. R.; Datta-Gupta, A.; Eichhubl, P.; Nicot, J. P.; Kahlor, L. A.

2017-12-01

The recent increase in the rate of seismicity in Texas has prompted the establishment of an interdisciplinary, interinstitutional collaboration led by the Texas Bureau of Economic Geology which includes the TexNet Seismic Monitoring and Research project as funded by The State of Texas (roughly 2/3rds of our funding) and the industry-funded Center for Integrated Seismicity Research (CISR) (1/3 of funding). TexNet is monitoring and cataloging seismicity across Texas using a new backbone seismic network, investigating site-specific earthquake sequences by deploying temporary seismic monitoring stations, and conducting reservoir modeling studies. CISR expands TexNet research into the interdisciplinary realm to more thoroughly study the factors that contribute to seismicity, characterize the associated hazard and risk, develop strategies for mitigation and management, and develop methods of effective communication for all stakeholders. The TexNet-CISR research portfolio has 6 themes: seismicity monitoring, seismology, geologic and hydrologic description, geomechanics and reservoir modeling, seismic hazard and risk assessment, and seismic risk social science. Twenty+ specific research projects span and connect these themes. We will provide a synopsis of research progress including recent seismicity trends in Texas; Fort Worth Basin integrated studies including geological modeling and fault characterization, fluid injection data syntheses, and reservoir and geomechanical modeling; regional ground shaking characterization and mapping, infrastructure vulnerability assessment; and social science topics of public perception and information seeking behavior.

Utility of behavioral versus cognitive measures in differentiating between subtypes of frontotemporal lobar degeneration and Alzheimer's disease.

PubMed

Heidler-Gary, Jennifer; Gottesman, Rebecca; Newhart, Melissa; Chang, Shannon; Ken, Lynda; Hillis, Argye E

2007-01-01

We hypothesized that a modified version of the Frontal Behavioral Inventory (FBI-mod), along with a few cognitive tests, would be clinically useful in distinguishing between clinically defined Alzheimer's disease (AD) and subtypes of frontotemporal lobar degeneration (FTLD): frontotemporal dementia (dysexecutive type), progressive nonfluent aphasia, and semantic dementia. We studied 80 patients who were diagnosed with AD (n = 30) or FTLD (n = 50), on the basis of a comprehensive neuropsychological battery, imaging, neurological examination, and history. We found significant between-group differences on the FBI-mod, two subtests of the Rey Auditory Verbal Learning Test (verbal learning and delayed recall), and the Trail Making Test Part B (one measure of 'executive functioning'). AD was characterized by relatively severe impairment in verbal learning, delayed recall, and executive functioning, with relatively normal scores on the FBI-mod. Frontotemporal dementia was characterized by relatively severe impairment on the FBI-mod and executive functioning in the absence of severe impairment in verbal learning and recall. Progressive nonfluent aphasia was characterized by severe impairment in executive functioning with relatively normal scores on verbal learning and recall and FBI-mod. Finally, semantic dementia was characterized by relatively severe deficits in delayed recall, but relatively normal performance on new learning, executive functioning, and on FBI-mod. Discriminant function analysis confirmed that the FBI-mod, in conjunction with the Rey Auditory Verbal Learning Test, and the Trail Making Test Part B categorized the majority of patients as subtypes of FTLD or AD in the same way as a full neuropsychological battery, neurological examination, complete history, and imaging. These tests may be useful for efficient clinical diagnosis, although progressive nonfluent aphasia and semantic dementia are likely to be best distinguished by language tests not included in standard neuropsychological test batteries.

Megabladder mouse model of congenital obstructive nephropathy: genetic etiology and renal adaptation.

PubMed

McHugh, Kirk M

2014-04-01

Congenital obstructive nephropathy remains one of the leading causes of chronic renal failure in children. The direct link between obstructed urine flow and abnormal renal development and subsequent dysfunction represents a central paradigm of urogenital pathogenesis that has far-reaching clinical implications. Even so, a number of diagnostic, prognostic, and therapeutic quandaries still exist in the management of congenital obstructive nephropathy. Studies in our laboratory have characterized a unique mutant mouse line that develops in utero megabladder, variable hydronephrosis, and progressive renal failure. Megabladder mice represent a valuable functional model for the study of congenital obstructive nephropathy. Recent studies have begun to shed light on the genetic etiology of mgb (-/-) mice as well as the molecular pathways controlling disease progression in these animals.

10 CFR 60.18 - Review of site characterization activities. 2

Code of Federal Regulations, 2010 CFR

2010-01-01

... IN GEOLOGIC REPOSITORIES Licenses Preapplication Review § 60.18 Review of site characterization... its progress in developing the design of a geologic repository operations area appropriate for the...

Ultrastructural characterization of primary cilia in pathologically characterized human glioblastoma multiforme (GBM) tumors.

PubMed

Moser, Joanna J; Fritzler, Marvin J; Rattner, Jerome B

2014-01-01

Primary cilia are non-motile sensory cytoplasmic organelles that are involved in cell cycle progression. Ultrastructurally, the primary cilium region is complex, with normal ciliogenesis progressing through five distinct morphological stages in human astrocytes. Defects in early stages of ciliogenesis are key features of astrocytoma/glioblastoma cell lines and provided the impetus for the current study which describes the morphology of primary cilia in molecularly characterized human glioblastoma multiforme (GBM) tumors. Seven surgically resected human GBM tissue samples were molecularly characterized according to IDH1/2 mutation status, EGFR amplification status and MGMT promoter methylation status and were examined for primary cilia expression and structure using indirect immunofluorescence and electron microscopy. We report for the first time that primary cilia are disrupted in the early stages of ciliogenesis in human GBM tumors. We confirm that immature primary cilia and basal bodies/centrioles have aberrant ciliogenesis characteristics including absent paired vesicles, misshaped/swollen vesicular hats, abnormal configuration of distal appendages, and discontinuity of centriole microtubular blades. Additionally, the transition zone plate is able to form in the absence of paired vesicles on the distal end of the basal body and when a cilium progresses beyond the early stages of ciliogenesis, it has electron dense material clumped along the transition zone and a darkening of the microtubules at the proximal end of the cilium. Primary cilia play a role in a variety of human cancers. Previously primary cilia structure was perturbed in cultured cell lines derived from astrocytomas/glioblastomas; however there was always some question as to whether these findings were a cell culture phenomena. In this study we confirm that disruptions in ciliogenesis at early stages do occur in GBM tumors and that these ultrastructural findings bear resemblance to those previously observed in cell cultures. This is the first study to demonstrate that defects in cilia expression and function are a true hallmark of GBM tumors and correlate with their unrestrained growth. A review of the current ultrastructural profiles in the literature provides suggestions as to the best possible candidate protein that underlies defects in the early stages of ciliogenesis within GBM tumors.

Characterization of the Tumor Microenvironment and Tumor–Stroma Interaction by Non-invasive Preclinical Imaging

PubMed Central

Ramamonjisoa, Nirilanto; Ackerstaff, Ellen

2017-01-01

Tumors are often characterized by hypoxia, vascular abnormalities, low extracellular pH, increased interstitial fluid pressure, altered choline-phospholipid metabolism, and aerobic glycolysis (Warburg effect). The impact of these tumor characteristics has been investigated extensively in the context of tumor development, progression, and treatment response, resulting in a number of non-invasive imaging biomarkers. More recent evidence suggests that cancer cells undergo metabolic reprograming, beyond aerobic glycolysis, in the course of tumor development and progression. The resulting altered metabolic content in tumors has the ability to affect cell signaling and block cellular differentiation. Additional emerging evidence reveals that the interaction between tumor and stroma cells can alter tumor metabolism (leading to metabolic reprograming) as well as tumor growth and vascular features. This review will summarize previous and current preclinical, non-invasive, multimodal imaging efforts to characterize the tumor microenvironment, including its stromal components and understand tumor–stroma interaction in cancer development, progression, and treatment response. PMID:28197395

Infrared Imaging and Characterization of Exoplanets: Can we Detect Earth-Twins on a Budget?

NASA Technical Reports Server (NTRS)

Danchi, William

2010-01-01

During the past decade considerable progress has been made developing techniques that can be used to detect and characterize Earth twins in the mid- infrared (7-20 microns). The principal technique is called nulling interferometry, and it was invented by Bracewell in the late 1970's. The nulling technique is an interferometric equivalent of an optical coronagraph. At the present time most of the technological hurdles have been overcome for a space mission to be able to begin Phase A early in the next decade, and it is possible to detect and characterize Earth-twins on a mid- sized strategic mission budget ($600-800 million). I will review progress on this exciting method of planet detection in the context of recent work on the Exoplanet Community Forum and the US Decadal Survey (Astro2010), including biomarkers, technological progress, mission concepts, the theory of these instruments, and a.comparison of the discovery space of this technique with others also under consideration.

BCL2 expression in CD105 positive neoangiogenic cells and tumor progression in angioimmunoblastic T-cell lymphoma.

PubMed

Ratajczak, Philippe; Leboeuf, Christophe; Wang, Li; Brière, Josette; Loisel-Ferreira, Irmine; Thiéblemont, Catherine; Zhao, Wei-Li; Janin, Anne

2012-06-01

The angiogenic microenvironment has been known to be a component of angioimmunoblastic T-cell lymphoma since its initial characterization. We have shown that angioimmunoblastic T-cell lymphoma endothelial cells produce vascular endothelial growth factor-A (VEGFA), and participate in lymphoma progression. In squamous cell carcinoma, endothelial BCL2 expression induces a crosstalk with tumor cells through VEGFA, a major mediator of tumoral angiogenesis. In the present study, we analyzed BCL2 and VEGFA in 30 angioimmunoblastic T-cell lymphomas, using triple immunofluorescence to identify protein coexpression in well-characterized lymphoma cells and microenvironment neoangiogenic endothelial cells. Using quantitative real-time PCR, we assessed mRNA expression levels in laser-microdissected endothelial and lymphoma cells. In lymphoma cells, as in endothelial cells, BCL2 and VEGFA proteins were coexpressed. BCL2 was expressed only in neoangiogenic CD34(+)CD105(+) endothelial cells. In laser-microdissected cells, mRNA studies showed a significant relationship between BCL2 and VEGFA levels in CD34(+) endothelial cells, but not in CD3(+)CD10(+)lymphoma cells, or in CD34(+) endothelial cells from lymph node hyperplasia. Further study showed that, in AITL, BCL2 mRNA levels in CD34(+)CD105(+) neoangiogenic endothelial cells also correlated with microvessel density, International Prognostic Index, Ann Arbor stage, bone marrow involvement and elevated LDH. BCL2 expression by CD105(+) neoangiogenic endothelial cells is related to tumor progression in angioimmunoblastic T-cell lymphoma.

Progress in vacuum susceptibilities and their applications to the chiral phase transition of QCD

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

Cui, Zhu-Fang, E-mail: phycui@nju.edu.cn; State Key Laboratory of Theoretical Physics, Institute of Theoretical Physics, CAS, Beijing, 100190; Hou, Feng-Yao

2015-07-15

The QCD vacuum condensates and various vacuum susceptibilities are all important parameters which characterize the nonperturbative properties of the QCD vacuum. In the QCD sum rules external field formula, various QCD vacuum susceptibilities play important roles in determining the properties of hadrons. In this paper, we review the recent progress in studies of vacuum susceptibilities together with their applications to the chiral phase transition of QCD. The results of the tensor, the vector, the axial–vector, the scalar, and the pseudo-scalar vacuum susceptibilities are shown in detail in the framework of Dyson–Schwinger equations.

Recent Progress in the Study of Topological Semimetals

NASA Astrophysics Data System (ADS)

Bernevig, Andrei; Weng, Hongming; Fang, Zhong; Dai, Xi

2018-04-01

The topological semimetal is a new, theoretically predicted and experimentally discovered, topological state of matter. In one of its several realizations, the topological semimetal hosts Weyl fermions, elusive particles predicted more than 85 years ago, sought after in high-energy experiments, but only recently found in a condensed-matter setting. In the present review, we catalogue the most recent progress in this fast-developing research field. We give special attention to topological invariants and the material realization of three different types of topological semimetal. We also discuss various photo emission, transport and optical experimental observables that characterize the appearance of topological semimetal phases.

Progressive damage, fracture predictions and post mortem correlations for fiber composites

NASA Technical Reports Server (NTRS)

1985-01-01

Lewis Research Center is involved in the development of computational mechanics methods for predicting the structural behavior and response of composite structures. In conjunction with the analytical methods development, experimental programs including post failure examination are conducted to study various factors affecting composite fracture such as laminate thickness effects, ply configuration, and notch sensitivity. Results indicate that the analytical capabilities incorporated in the CODSTRAN computer code are effective in predicting the progressive damage and fracture of composite structures. In addition, the results being generated are establishing a data base which will aid in the characterization of composite fracture.

Otolith Dysfunction Alters Exploratory Movement in Mice

PubMed Central

Blankenship, Philip A.; Cherep, Lucia A.; Donaldson, Tia N.; Brockman, Sarah N.; Trainer, Alexandria D.; Yoder, Ryan M.; Wallace, Douglas G.

2017-01-01

The organization of rodent exploratory behavior appears to depend on self-movement cue processing. As of yet, however, no studies have directly examined the vestibular system’s contribution to the organization of exploratory movement. The current study sequentially segmented open field behavior into progressions and stops in order to characterize differences in movement organization between control and otoconia-deficient tilted mice under conditions with and without access to visual cues. Under completely dark conditions, tilted mice exhibited similar distance traveled and stop times overall, but had significantly more circuitous progressions, larger changes in heading between progressions, and less stable clustering of home bases, relative to control mice. In light conditions, control and tilted mice were similar on all measures except for the change in heading between progressions. This pattern of results is consistent with otoconia-deficient tilted mice using visual cues to compensate for impaired self-movement cue processing. This work provides the first empirical evidence that signals from the otolithic organs mediate the organization of exploratory behavior, based on a novel assessment of spatial orientation. PMID:28235587

Yucca Mountain Biological Resources Monitoring Program. Progress report, January 1994--December 1994

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

NONE

1995-07-01

The US Department of Energy (DOE) is required by the Nuclear Waste Policy Act of 1982 (as amended in 1987) to study and characterize the suitability of Yucca Mountain as a potential geological repository for high-level nuclear waste. During site characterization, the DOE will conduct a variety of geotechnical, geochemical, geological, and hydrological studies to determine the suitability of Yucca Mountain as a potential repository. To ensure that site characterization activities do not adversely affect the environment at Yucca Mountain, a program has been implemented to monitor and mitigate potential impacts and ensure activities comply with applicable environmental regulations. Thismore » report describes the activities and accomplishments of EG and G Energy Measurements, Inc. (EG and G/EM) from January 1994 through December 1994 for six program areas within the Terrestrial Ecosystem component of the environmental program for the Yucca Mountain Site Characterization Project (YMP): Site Characterization Effects, Desert Tortoises (Gopherus agassizii), Habitat Reclamation, Monitoring and Mitigation, Radiological Monitoring, and Biological Support.« less

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

Martin, Christopher Blake

A new particle decaying to a pair of vector bosons was discovered in 2012 by the ATLAS and CMS experiments at the Large Hadron Collider. In the wake of this discovery a rush of measurements was made to characterize this particle. The fourlepton final state has been instrumental in both the discovery and characterization of this new particle. With only about 20 events seen in the resonance peak at 125 GeV the CMS experiment has been able to make considerable progress in characterizing the Higgs-like boson using the wealth of information in this final state in concert with other decaymore » modes. In addition to the search for this new boson we present three recent results in the study of the Higgs-like boson properties: studies of the production mode, total width, and spin-parity quantum numbers.« less

Characterization of Retinal Disease Progression in a 1-Year Longitudinal Study of Eyes With Mild Nonproliferative Retinopathy in Diabetes Type 2.

PubMed

Ribeiro, Luisa; Bandello, Francesco; Tejerina, Amparo Navea; Vujosevic, Stela; Varano, Monica; Egan, Catherine; Sivaprasad, Sobha; Menon, Geeta; Massin, Pascale; Verbraak, Frank D; Lund-Andersen, Henrik; Martinez, Jose P; Jürgens, Ignasi; Smets, Erica; Coriat, Caroline; Wiedemann, Peter; Ágoas, Victor; Querques, Giuseppe; Holz, Frank G; Nunes, Sandrina; Neves, Catarina; Cunha-Vaz, José

2015-08-01

To identify eyes of patients with diabetes type 2 that show progression of retinal disease within a 1-year period using noninvasive techniques. Three hundred seventy-four type 2 diabetic patients with mild nonproliferative diabetic retinopathy (Early Treatment Diabetic Retinopathy Study [ETDRS] level 20 or 35) were included in a 12-month prospective observational study to identify retinopathy progression. Four visits were scheduled at 0, 3, 6, and 12 months. Microaneurysm (MA) activity using the RetmarkerDR and retinal thickness using spectral-domain optical coherence tomography (SD-OCT) were assessed by a central reading center at all visits and ETDRS severity level in the first and last visits. Three hundred thirty-one eyes/patients completed the study. Microaneurysm formation rate greater than or equal to 2 was present in 68.1% of the eyes and MA turnover greater than or equal to 6 in 54.0% at month 6. Higher MA turnover values were registered in eyes that showed progression in ETDRS severity level (P < 0.03). There were also significant correlations between increased microaneurysm activity and increases in retinal thickness. Spectral-domain OCT identified clinical macular edema in 24 eyes/patients (6.7%) and subclinical macular edema in 104 eyes/patients (28.9%) at baseline. Progression of retinal thickening was registered in eyes that had either subclinical or clinical macular edema at baseline. Changes in MA activity measured with RetmarkerDR and in central retinal thickness in eyes with mild nonproliferative diabetic retinopathy and diabetes type 2 are able to identify eyes at risk of progression. These eyes/patients should be selected for inclusion in future clinical trials of drugs targeted to prevent diabetic retinopathy progression to vision-threatening complications. (ClinicalTrials.gov number, NCT01145599.)

Risk factors for predicting visual field progression in Chinese patients with primary open-angle glaucoma: A retrospective study.

PubMed

Hung, Kuo-Hsuan; Cheng, Ching-Yu; Liu, Catherine Jui-Ling

2015-07-01

Glaucoma is a leading cause of irreversible blindness worldwide. It is characterized by progressive deterioration of the visual field (VF) that results in a complete loss of vision. This study aimed to determine the risk factors associated with VF progression in Chinese patients with primary open-angle glaucoma (POAG). We reviewed the charts of POAG patients who visited our clinic between July 2009 and June 2010. We included patients with five or more reliable VF tests using the Humphrey Field Analyzer (Humphrey Instruments, San Leandro, CA, USA) during a period of at least 2 years. The scoring system of the Collaborative Initial Glaucoma Treatment Study (CIGTS) was used to code the VF. Progression was defined as an increasing score ≥3, compared to the averaged baseline data. Univariate and multivariate logistic regression analyses were performed to identify the risk factors of VF progression. There were 92 patients (representing 92 eyes) with an average of 8.9 reliable VFs over a mean follow up of 5.4 years. Multivariate logistic regression showed that eyes with more VF tests [odds ratio (OR) = 1.500, p < 0.010] and either increased peak intraocular pressure (IOP) (OR = 1.235, p = 0.044) or a wide IOP range (OR = 1.165, p = 0.041) favored VF progression. High myopia (less than -6.0 D) was not a risk factor (OR = 1.289, p = 0.698) for VF progression in this study. In addition to a greater number of VF tests, Chinese patients with treated POAG who experienced a high peak IOP or a wide range of IOP during follow up were more likely to have VF deterioration. Copyright © 2015. Published by Elsevier Taiwan.

Intellectual Ability and Executive Function in Pediatric Moyamoya Vasculopathy

ERIC Educational Resources Information Center

Williams, Tricia S.; Westmacott, Robyn; Dlamini, Nomazulu; Granite, Leeor; Dirks, Peter; Askalan, Rand; MacGregor, Daune; Moharir, Mahendranath; Deveber, Gabrielle

2012-01-01

Aim: Moyamoya vasculopathy is characterized by progressive stenosis of the major arteries of the Circle of Willis, resulting in compromised cerebral blood flow and increased risk of stroke. The objectives of the current study were to examine intellectual and executive functioning of children with moyamoya and to evaluate the impact of moyamoya…

America's Middle Schools: Practices and Progress. A 25 Year Perspective.

ERIC Educational Resources Information Center

McEwin, C. Kenneth; And Others

The 1990s will likely be a watershed period for middle level education, as the real challenges surrounding making "second level" changes replace the euphoria that accompanied early growth of the middle school movement. Yet, zealousness still characterizes reform efforts at the middle level. This study, the most comprehensive ever…

Education Policy Research in the Big Data Era: Methodological Frontiers, Misconceptions, and Challenges

ERIC Educational Resources Information Center

Wang, Yinying

2017-01-01

Despite abundant data and increasing data availability brought by technological advances, there has been very limited education policy studies that have capitalized on big data--characterized by large volume, wide variety, and high velocity. Drawing on the recent progress of using big data in public policy and computational social science…

Systems for Program Change in Teacher Education. Teacher Education Forum; Volume 3, Number 18.

ERIC Educational Resources Information Center

Beckner, Weldon E.; Medley, Gene W.

Current trends in teacher education are characterized by programs designed to emphasize approaches to learning which are competency based, field centered, and individualized. Presently few colleges and universitites have progressed very far in the development and implementation of these innovative teacher education programs. This study presents…

MR-1 blocks the megakaryocytic differentiation and transition of CML from chronic phase to blast crisis through MEK dephosphorylation

PubMed Central

Zhao, W; He, H; Ren, K; Li, B; Zhang, H; Lin, Y; Shao, R-g

2013-01-01

Chronic myelogenous leukemia (CML) evolves from a chronic phase characterized by the Philadelphia chromosome as the sole genetic abnormality and the accumulation of mature cells in peripheral blood into blast crisis, which is characterized by the rapid expansion of myeloid- or lymphoid-differentiation-arrested blast cells. Although ample studies have been conducted on the disease progress mechanisms, the underlying molecular mechanisms of the malignant phenotype transition are still unclear. In this study, we have shown that myofibrillogenesis regulator-1 (MR-1) was overexpressed in blast crisis patients and leukemic cells, but there was little trace expressed in healthy individuals and in most patients in CML chronic phase. MR-1 could inhibit the differentiation of myeloid cells into megakaryocytic lineages and accelerate cell proliferation. The molecular mechanism responsible for these effects was the interaction of MR-1 with MEK, which blocked the MEK/ERK signaling pathway by dephosphorylating MEK. Our results provide compelling and important evidence that MR-1 might act as a diagnostic marker and potential target of CML progression from chronic phase to blast crisis. PMID:23542180

Characterizing the motivational orientation of students in higher education: a naturalistic study in three Hong Kong universities.

PubMed

Kember, David; Hong, Celina; Ho, Amber

2008-06-01

Consideration of motivation in higher education has often been drawn upon theories and research that were based upon school or workplace studies. This paper reports an open naturalistic study to better characterize the motivational orientation of students in higher education. Open semi-structured individual interviews were conducted with 36 students from three universities in Hong Kong. The analysis used an exploratory grounded theory approach. Motivation was characterized as a framework with six continua with positive and negative poles. On enrolment, students had positions on the six facets of motivation, which shifted as they progressed through their degree, according to perceptions of their teaching and learning environment. The positive poles of the six continua were given labels: compliance, individual goal setting, interest, career, sense of belonging and university lifestyle. The formulation of motivational orientation is consistent with contemporary social cognitive theories of motivation in that it has been characterized as a multifaceted phenomenon, with students expressing context-dependent multiple motives.

Lonomia obliqua venom: In vivo effects and molecular aspects associated with the hemorrhagic syndrome.

PubMed

Pinto, Antônio F M; Berger, Markus; Reck, José; Terra, Renata M S; Guimarães, Jorge A

2010-12-15

Caterpillar envenomation has been an emergent health issue. Lonomia obliqua is a medically important animal that causes a hemorrhagic syndrome that can progress to acute renal failure, intracranial hemorrhage and death. In the past few years the molecular characterization of L. obliqua venom in addition to experimental models has provided fundamental information to the understanding of the envenomation syndrome. Herein studies from several authors which characterized the complex toxic-pharmacological actions of whole venom are reviewed. Copyright © 2010 Elsevier Ltd. All rights reserved.

Attenuated-Signal Plaque Progression Predicts Long-Term Mortality After Heart Transplantation: IVUS Assessment of Cardiac Allograft Vasculopathy.

PubMed

Okada, Kozo; Fearon, William F; Luikart, Helen; Kitahara, Hideki; Otagiri, Kyuhachi; Tanaka, Shigemitsu; Kimura, Takumi; Yock, Paul G; Fitzgerald, Peter J; Yeung, Alan C; Valantine, Hannah A; Khush, Kiran K; Honda, Yasuhiro

2016-07-26

Although cardiac allograft vasculopathy (CAV) is typically characterized by diffuse coronary intimal thickening with pathological vessel remodeling, plaque instability may also play an important role in CAV. Previous studies of native coronary atherosclerosis have demonstrated associations between attenuated-signal plaque (ASP), plaque instability, and adverse clinical events. This study's aim was to characterize the association between ASP and long-term mortality post-heart transplantation. In 105 heart transplant recipients, serial (baseline and 1-year post-transplant) intravascular ultrasound was performed in the first 50 mm of the left anterior descending artery. The ASP score was calculated by grading the measured angle of attenuation from grades 0 to 4 (specifically, 0°, 1° to 90°, 91° to 180°, 181° to 270°, and >270°) at 1-mm intervals. The primary endpoint was all-cause death or retransplantation. At 1-year post-transplant, 10.5% of patients demonstrated ASP progression (newly developed or increased ASP). Patients with ASP progression had a higher incidence of acute cellular rejection during the first year (63.6% vs. 22.3%; p = 0.006) and tendency for greater intimal growth (percent intimal volume: 9.2 ± 9.3% vs. 4.4 ± 5.3%; p = 0.07) than those without. Over a median follow-up of 4.6 years, there was a significantly lower event-free survival rate in patients with ASP progression at 1-year post-transplant compared with those without. In contrast, maximum intimal thickness did not predict long-term mortality. ASP progression appears to reflect chronic inflammation related to acute cellular rejection and is an independent predictor of long-term mortality after heart transplantation. Serial assessments of plaque instability may enhance identification of high-risk patients who may benefit from closer follow-up and targeted medical therapies. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

[Cytogenetics, cytogenomics and cancer].

PubMed

Bernheim, Alain

2002-02-01

Chromosomal study in malignancy has demonstrated the pivotal role of somatic chromosomal rearrangements in oncogenesis and tumoral progression. Structural or quantitative these abnormalities can now be studied in great details with the various Fish techniques, including CGH on chromosomes or in a near future on micro arrays. The multistep pattern of most solid tumors is characterized and their genomic abnormalities more and more used for the diagnosis and the prognosis.

Progress in the characterization of diamond thin films prepared by a laser plasma discharge

NASA Astrophysics Data System (ADS)

Davanloo, F.; Juengerman, E. M.; Jander, D. R.; Lee, T. J.; Collins, C. B.

Progress in the characterization of diamond thin films produced by a unique laser plasma discharge source at practical growth rates of 0.7 micron/hr is reported. Optical properties, mass densities, and electrical resistivities of deposited films are given and their relationship to the power density of the laser at the graphite target is discussed. Examination of films with scanning tunneling microscopy show the clear prevalence of the structure recently predicted by Angus et al. (1990) in which sp3 clusters are bonded together with the carbon polytypes.

A far-infrared spatial/spectral Fourier interferometry laboratory-based testbed instrument

NASA Astrophysics Data System (ADS)

Spencer, Locke D.; Naylor, David A.; Scott, Jeremy P.; Weiler, Vince F.; MacCrimmon, Roderick K.; Sitwell, Geoffrey R. H.; Ade, Peter A. R.

2016-07-01

We describe the current status, including preliminary design, characterization efforts, and recent progress, in the development of a spatial/spectral double Fourier laboratory-based interferometer testbed instrument within the Astronomical Instrumentation Group (AIG) laboratories at the University of Lethbridge, Canada (UL). Supported by CRC, CFI, and NSERC grants, this instrument development will provide laboratory demonstration of spatial-spectral interferometry with a concentration of furthering progress in areas including the development of spatial/spectral interferometry observation, data processing, characterization, and analysis techniques in the Far-Infrared (FIR) region of the electromagnetic spectrum.

Investigating the Evolution of Progressive Die Wear on Uncoated Dp1180 Steel in Production Environment

NASA Astrophysics Data System (ADS)

Wu, W.; Zhou, D. J.; Adamski, D. J.; Young, D.; Wang, Y. W.

2017-09-01

A study of die wear was performed using an uncoated dual phase, 1,180 MPa ultimate tensile strength steel (DP1180) in a progressive die. The objectives of the current study are to evaluate the die durability of various tooling materials and coatings for forming operations on uncoated DP1180 steel and update OEM’s die standards based on the experimental results in the real production environment. In total, 100,800 hits were performed in manufacturing production conditions, where 33 die inserts with the combination of 10 die materials and 9 coatings were investigated. The die inserts were evaluated for surface wear using scanning electron microscopy and characterized in terms of die material and/or coating defects, failure mode, failure initiation and propagation. Surface roughness of the formed parts was characterized using a WYKO NT110 machine. The analytical analysis of the die inserts and formed parts, combined with the failure mode and service life, provide a basis for die material and coating selection for forming AHSS components. The conclusions of this study will guide the selection of die material and coatings for high-volume production of AHSS components.

Characterization of naïve, memory and effector T cells in progressive multiple sclerosis.

PubMed

Nielsen, Birgitte Romme; Ratzer, Rikke; Börnsen, Lars; von Essen, Marina Rode; Christensen, Jeppe Romme; Sellebjerg, Finn

2017-09-15

We characterized naïve, central memory (CM), effector memory (EM) and terminally differentiated effector memory (TEMRA) CD4 + and CD8 + T cells and their expression of CD49d and CD26 in peripheral blood in patients with multiple sclerosis (MS) and healthy controls. CD26 + CD28 + CD4 + TEMRA T cells were increased in all subtypes of MS, and CD26 + CD28 + CD8 + TEMRA T cells were increased in relapsing-remitting and secondary progressive MS. Conversely, in progressive MS, CD49d + CM T cells were decreased and natalizumab increased the circulating number of all six subsets but reduced the frequency of most subsets expressing CD49d and CD26. Copyright © 2017 Elsevier B.V. All rights reserved.

Modifications of the mouse bone marrow microenvironment favor angiogenesis and correlate with disease progression from asymptomatic to symptomatic multiple myeloma

PubMed Central

Calcinotto, Arianna; Ponzoni, Maurilio; Ria, Roberto; Grioni, Matteo; Cattaneo, Elena; Villa, Isabella; Sabrina Bertilaccio, Maria Teresa; Chesi, Marta; Rubinacci, Alessandro; Tonon, Giovanni; Bergsagel, P Leif; Vacca, Angelo; Bellone, Matteo

2015-01-01

While multiple myeloma (MM) is almost invariably preceded by asymptomatic monoclonal gammopathy of undetermined significance (MGUS) and/or smoldering MM (SMM), the alterations of the bone marrow (BM) microenvironment that establish progression to symptomatic disease are circumstantial. Here we show that in Vk*MYC mice harboring oncogene-driven plasma cell proliferative disorder, disease appearance associated with substantial modifications of the BM microenvironment, including a progressive accumulation of both CD8+ and CD4+ T cells with a dominant T helper type 1 (Th1) response. Progression from asymptomatic to symptomatic MM was characterized by further BM accrual of T cells with reduced Th1 and persistently increased Th2 cytokine production, which associated with accumulation of CD206+Tie2+ macrophages, and increased pro-angiogenic cytokines and microvessel density (MVD). Notably, MVD was also increased at diagnosis in the BM of MGUS and SMM patients that subsequently progressed to MM when compared with MGUS and SMM that remained quiescent. These findings suggest a multistep pathogenic process in MM, in which the immune system may contribute to angiogenesis and disease progression. They also suggest initiating a large multicenter study to investigate MVD in asymptomatic patients as prognostic factor for the progression and outcome of this disease. PMID:26155424

Cumulative mtDNA damage and mutations contribute to the progressive loss of RGCs in a rat model of glaucoma

PubMed Central

Nickerson, John M.; Gao, Feng-juan; Sun, Zhongmou; Chen, Xin-ya; Zhang, Shu-jie; Gao, Feng; Chen, Jun-yi; Luo, Yi; Wang, Yan; Sun, Xing-huai

2015-01-01

Glaucoma is a chronic neurodegenerative disease characterized by the progressive loss of retinal ganglion cells (RGCs). Mitochondrial DNA (mtDNA) alterations have been documented as a key component of many neurodegenerative disorders. However, whether mtDNA alterations contribute to the progressive loss of RGCs and the mechanism whereby this phenomenon could occur are poorly understood. We investigated mtDNA alterations in RGCs using a rat model of chronic intraocular hypertension and explored the mechanisms underlying progressive RGC loss. We demonstrate that the mtDNA damage and mutations triggered by intraocular pressure (IOP) elevation are initiating, crucial events in a cascade leading to progressive RGC loss. Damage to and mutation of mtDNA, mitochondrial dysfunction, reduced levels of mtDNA repair/replication enzymes, and elevated reactive oxygen species form a positive feedback loop that produces irreversible mtDNA damage and mutation and contributes to progressive RGC loss, which occurs even after a return to normal IOP. Furthermore, we demonstrate that mtDNA damage and mutations increase the vulnerability of RGCs to elevated IOP and glutamate levels, which are among the most common glaucoma insults. This study suggests that therapeutic approaches that target mtDNA maintenance and repair and that promote energy production may prevent the progressive death of RGCs. PMID:25478814

The Potential Biomarkers to Identify the Development of Steatosis in Hyperuricemia

PubMed Central

He, Xiaojuan; Lu, Cheng; He, Bing; Niu, Xuyan; Xiao, Cheng; Xu, Gang; Bian, Zhaoxiang; Zu, Xianpeng; Zhang, Ge; Zhang, Weidong; Lu, Aiping

2016-01-01

Hyperuricemia (HU) often progresses to combine with non-alcoholic fatty liver disease (NAFLD) in the clinical scenario, which further exacerbates metabolic disorders; early detection of biomarkers, if obtained during the HU progression, may be beneficial for preventing its combination with NAFLD. This study aimed to decipher the biomarkers and mechanisms of the development of steatosis in HU. Four groups of subjects undergoing health screening, including healthy subjects, subjects with HU, subjects with HU combined with NAFLD (HU+NAFLD) and subjects with HU initially and then with HU+NAFLD one year later (HU→HU+NAFLD), were recruited in this study. The metabolic profiles of all subjects’ serum were analyzed by liquid chromatography quadruple time-of-flight mass spectrometry. The metabolomic data from subjects with HU and HU+NAFLD were compared, and the biomarkers for the progression from HU to HU+NAFLD were predicted. The metabolomic data from HU→HU+NAFLD subjects were collected for further verification. The results showed that the progression was associated with disturbances of phospholipase metabolism, purine nucleotide degradation and Liver X receptor/retinoic X receptor activation as characterized by up-regulated phosphatidic acid, cholesterol ester (18:0) and down-regulated inosine. These metabolic alterations may be at least partially responsible for the development of steatosis in HU. This study provides a new paradigm for better understanding and further prevention of disease progression. PMID:26890003

Myth and Reality in Hydrogeological Site Characterization at DD and R Sites

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

Rubin, Yoram

2008-01-15

The science of hydrogeological site characterization has made significant progress over the last twenty years. Progress has been made in modeling of flow and transport in the heterogeneous subsurface, in understanding of the complex patterns of geological heterogeneity and in measurement technologies. Modeling of uncertainty has also advanced significantly, in recognition of the inherent limitations of subsurface characterization. Much less progress has been made in transforming this progress into practice, where characterization is determined to a large extent by regulations. Environmental regulations have not progressed as much as the science, for example, in recognizing uncertainty. As such, practitioners are lessmore » inclined to adopt advanced, science-based solutions, this opening the door for myths and conflicts. Myths develop where the science base is perceived to be weak, whereas conflicts arise in the face of a disconnect between the science and the regulations. Myths translate to ad-hoc solutions and misplaced empiricism, as well as to unjustified reliance on field experience, to the detriment of D and DR. This paper explores the roots for this situation and identifies ideas that may help in bridging the gap between research and applications. A rational approach for DD and R is needed that will encourage innovation in site characterization, reduce costs and accelerate completion. Such an approach needs to include several elements. DD and R regulations need to recognize the various aspects of uncertainty inherent to site characterization, and as such, should be formulated using probabilistic concepts. One of the immediate benefits will be in allowing a gradual approach for data acquisition in DD and R sites: decisions can be made even under the most severe data limitations, and can be modified as additional data become available. The definition of risk is another major element. There is no universal definition of risk or of a methodology to define risk. Different sites justify different definitions, depending on many environmental, economical and social factors. Despite the lack of consensus, it seems that a good place to start is in fact to recognize that there is a room for all these factors, and a need to balance between them. As experience is gained, through research and discussions among DD and R stakeholders, this may become less of a challenge. Regulations need to recognize the possibility of developing alternative, site-specific characterization strategies based on the various length and time scales that define specific environmental problems, including length scales of heterogeneity, source dimensions and distance to environmental targets. For example, point and distributed sources justify different characterization strategies. Development of problem- or site-specific strategies will create the context for defining innovative efficient DD and R strategies. Innovation in characterization can will also follow from recognizing the specific physiological aspects of the toxins and the related uncertainty. This will open the door for improving risk characterization not only from the hydrologic perspective, but also form the physiologic one.« less

Laser ablation/ionization characterization of solids: Second interim progress report of the strategic environmental research development program

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

Hess, W.P.; Bushaw, B.A.; McCarthy, M.I.

1996-10-01

The Department of Energy is undertaking the enormous task of remediating defense wastes and environmental insults which have occurred over 50 years of nuclear weapons production. It is abundantly clear that significant technology advances are needed to characterize, process, and store highly radioactive waste and to remediate contaminated zones. In addition to the processing and waste form issues, analytical technologies needed for the characterization of solids, and for monitoring storage tanks and contaminated sites do not exist or are currently expensive labor-intensive tasks. This report describes progress in developing sensitive, rapid, and widely applicable laser-based mass spectrometry techniques for analysismore » of mixed chemical wastes and contaminated soils.« less

Clinical trials in progressive multiple sclerosis: lessons learned and future perspectives

PubMed Central

Ontaneda, Daniel; Fox, Robert J.; Chataway, Jeremy

2015-01-01

Progressive multiple sclerosis is characterized by the gradual accrual of disability independent of relapses and can occur with disease onset (primary progressive) or preceded by a relapsing disease course (secondary progressive). An effective disease modifying treatment for progressive multiple sclerosis has not been identified, and the results of clinical trials to date have been generally disappointing. Ongoing advances in our understanding of pathogenesis, identification of novel targets for neuro-protection, and improved outcome measures have the potential to lead to effective treatments for progressive multiple sclerosis. In this review lessons learned from previous clinical trials and perspectives from current trials in progressive multiple sclerosis are summarized. Promising clinical, imaging, and biological markers will also be reviewed, along with novel clinical trial designs. PMID:25772899

Genetic Approaches to Study Meiosis and Meiosis-Specific Gene Expression in Saccharomyces cerevisiae.

PubMed

Kassir, Yona; Stuart, David T

2017-01-01

The budding yeast Saccharomyces cerevisiae has a long history as a model organism for studies of meiosis and the cell cycle. The popularity of this yeast as a model is in large part due to the variety of genetic and cytological approaches that can be effectively performed with the cells. Cultures of the cells can be induced to synchronously progress through meiosis and sporulation allowing large-scale gene expression and biochemical studies to be performed. Additionally, the spore tetrads resulting from meiosis make it possible to characterize the haploid products of meiosis allowing investigation of meiotic recombination and chromosome segregation. Here we describe genetic methods for analysis progression of S. cerevisiae through meiosis and sporulation with an emphasis on strategies for the genetic analysis of regulators of meiosis-specific genes.

Role for transforming growth factor-beta1 in alport renal disease progression.

PubMed

Sayers, R; Kalluri, R; Rodgers, K D; Shield, C F; Meehan, D T; Cosgrove, D

1999-11-01

Alport syndrome results from mutations in either the alpha3(IV), alpha4(IV), or alpha5(IV) collagen genes. The disease is characterized by a progressive glomerulonephritis usually associated with a high-frequency sensorineural hearing loss. A mouse model for an autosomal form of Alport syndrome [collagen alpha3(IV) knockout] was produced and characterized. In this study, the model was exploited to demonstrate a potential role for transforming growth factor-beta1 (TGF-beta1) in Alport renal disease pathogenesis. Kidneys from normal and Alport mice, taken at different stages during the course of renal disease progression, were analyzed by Northern blot, in situ hybridization, and immunohistology for expression of TGF-beta1 and components of the extracellular matrix. Normal and Alport human kidney was examined for TGF-beta1 expression using RNase protection. The mRNAs encoding TGF-beta1 (in both mouse and human), entactin, fibronectin, and the collagen alpha1(IV) and alpha2(IV) chains were significantly induced in total kidney as a function of Alport renal disease progression. The induction of these specific mRNAs was observed in the glomerular podocytes of animals with advanced disease. Type IV collagen, laminin-1, and fibronectin were markedly elevated in the tubulointerstitium at 10 weeks, but not at 6 weeks, suggesting that elevated expression of specific mRNAs on Northern blots reflects events associated with tubulointerstitial fibrosis. The concomitant accumulation of mRNAs encoding TGF-beta1 and extracellular matrix components in the podocytes of diseased kidneys may reflect key events in Alport renal disease progression. These data suggest a role for TGF-beta1 in both glomerular and tubulointerstitial damage associated with Alport syndrome.

Developing Carbon Nanotube Standards at NASA

NASA Technical Reports Server (NTRS)

Nikolaev, Pasha; Arepalli, Sivaram; Sosa, Edward; Gorelik, Olga; Yowell, Leonard

2007-01-01

Single wall carbon nanotubes (SWCNTs) are currently being produced and processed by several methods. Many researchers are continuously modifying existing methods and developing new methods to incorporate carbon nanotubes into other materials and utilize the phenomenal properties of SWCNTs. These applications require availability of SWCNTs with known properties and there is a need to characterize these materials in a consistent manner. In order to monitor such progress, it is critical to establish a means by which to define the quality of SWCNT material and develop characterization standards to evaluate of nanotube quality across the board. Such characterization standards should be applicable to as-produced materials as well as processed SWCNT materials. In order to address this issue, NASA Johnson Space Center has developed a protocol for purity and dispersion characterization of SWCNTs (Ref.1). The NASA JSC group is currently working with NIST, ANSI and ISO to establish purity and dispersion standards for SWCNT material. A practice guide for nanotube characterization is being developed in cooperation with NIST (Ref.2). Furthermore, work is in progress to incorporate additional characterization methods for electrical, mechanical, thermal, optical and other properties of SWCNTs.

Developing Carbon Nanotube Standards at NASA

NASA Technical Reports Server (NTRS)

Nikolaev, Pasha; Arepalli, Sivaram; Sosa, Edward; Gorelik, Olga; Yowell, Leonard

2007-01-01

Single wall carbon nanotubes (SWCNTs) are currently being produced and processed by several methods. Many researchers are continuously modifying existing methods and developing new methods to incorporate carbon nanotubes into other materials and utilize the phenomenal properties of SWCNTs. These applications require availability of SWCNTs with known properties and there is a need to characterize these materials in a consistent manner. In order to monitor such progress, it is critical to establish a means by which to define the quality of SWCNT material and develop characterization standards to evaluate of nanotube quality across the board. Such characterization standards should be applicable to as-produced materials as well as processed SWCNT materials. In order to address this issue, NASA Johnson Space Center has developed a protocol for purity and dispersion characterization of SWCNTs. The NASA JSC group is currently working with NIST, ANSI and ISO to establish purity and dispersion standards for SWCNT material. A practice guide for nanotube characterization is being developed in cooperation with NIST. Furthermore, work is in progress to incorporate additional characterization methods for electrical, mechanical, thermal, optical and other properties of SWCNTs.

A Further Characterization of Empirical Research Related to Learning Outcome Achievement in Remote and Virtual Science Labs

NASA Astrophysics Data System (ADS)

Brinson, James R.

2017-10-01

This paper further characterizes recently reviewed literature related to student learning outcome achievement in non-traditional (virtual and remote) versus traditional (hands-on) science labs, as well as factors to consider when evaluating the state and progress of research in this field as a whole. Current research is characterized according to (1) participant nationality and culture, (2) participant education level, (3) participant demography, (4) scientific discipline, and (5) research methodology, which could provide avenues for further research and useful dialog regarding the measurement and interpretation of data related to student learning outcome achievement in, and thus the efficacy of, non-traditional versus traditional science labs. Current research is also characterized by (6) research publication media and (7) availability of non-traditional labs used, which demonstrate some of the obstacles to progress and consensus in this research field.

Coupled Harmonic Bases for Longitudinal Characterization of Brain Networks

PubMed Central

Hwang, Seong Jae; Adluru, Nagesh; Collins, Maxwell D.; Ravi, Sathya N.; Bendlin, Barbara B.; Johnson, Sterling C.; Singh, Vikas

2016-01-01

There is a great deal of interest in using large scale brain imaging studies to understand how brain connectivity evolves over time for an individual and how it varies over different levels/quantiles of cognitive function. To do so, one typically performs so-called tractography procedures on diffusion MR brain images and derives measures of brain connectivity expressed as graphs. The nodes correspond to distinct brain regions and the edges encode the strength of the connection. The scientific interest is in characterizing the evolution of these graphs over time or from healthy individuals to diseased. We pose this important question in terms of the Laplacian of the connectivity graphs derived from various longitudinal or disease time points — quantifying its progression is then expressed in terms of coupling the harmonic bases of a full set of Laplacians. We derive a coupled system of generalized eigenvalue problems (and corresponding numerical optimization schemes) whose solution helps characterize the full life cycle of brain connectivity evolution in a given dataset. Finally, we show a set of results on a diffusion MR imaging dataset of middle aged people at risk for Alzheimer’s disease (AD), who are cognitively healthy. In such asymptomatic adults, we find that a framework for characterizing brain connectivity evolution provides the ability to predict cognitive scores for individual subjects, and for estimating the progression of participant’s brain connectivity into the future. PMID:27812274

Molecular mapping of chromosomes 17 and X. Progress report

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

Barker, D.F.

1991-01-15

Progress toward the construction of high density genetic maps of chromosomes 17 and X has been made by isolating and characterizing a relatively large set of polymorphic probes for each chromosome and using these probes to construct genetic maps. We have mapped the same polymorphic probes against a series of chromosome breakpoints on X and 17. The probes could be assigned to over 30 physical intervals on the X chromosome and 7 intervals on 17. In many cases, this process resulted in improved characterization of the relative locations of the breakpoints with respect to each other and the definition ofmore » new physical intervals. The strategy for isolation of the polymorphic clones utilized chromosome specific libraries of 1--15 kb segments from each of the two chromosomes. From these libraries, clones were screened for those detecting restriction fragment length polymorphisms. The markers were further characterized, the chromosomal assignments confirmed and in most cases segments of the original probes were subcloned into plasmids to produce probes with improved signal to noise ratios for use in the genetic marker studies. The linkage studies utilize the CEPH reference families and other well-characterized families in our collection which have been used for genetic disease linkage work. Preliminary maps and maps of portions of specific regions of 17 and X are provided. We have nearly completed a map of the 1 megabase Mycoplasma arthritidis genome by applying these techniques to a lambda phage library of its genome. We have found bit mapping to be an efficient means to organize a contiguous set of overlapping@ clones from a larger genome.« less

Cellular and molecular characterization of gametogenic progression in ex vivo cultured prepuberal mouse testes.

PubMed

Isoler-Alcaraz, J; Fernández-Pérez, D; Larriba, E; Del Mazo, J

2017-10-18

Recently, an effective testis culture method using a gas-liquid interphase, capable of differentiate male germ cells from neonatal spermatogonia to spermatozoa has been developed. Nevertheless, this methodology needs deep analyses that allow future experimental approaches in basic, pathologic and/or reprotoxicologic studies. Because of this, we characterized at cellular and molecular levels the entire in vitro spermatogenic progression, in order to understand and evaluate the characteristics that define the spermatogenic process in ex vivo cultured testes compared to the in vivo development. Testicular explants of CD1 mice aged 6 and 10 days post-partum were respectively cultured during 55 and 89 days. Cytological and molecular approaches were performed, analyzing germ cell proportion at different time culture points, meiotic markers immunodetecting synaptonemal complex protein SYCP3 by immunocytochemistry and the relative expression of different marker genes along the differentiation process by Reverse Transcription - quantitative Polymerase Chain Reaction. In addition, microRNA and piwi-interactingRNA profiles were also evaluated by Next Generation Sequencing and bioinformatic approaches. The method promoted and maintained the spermatogenic process during 89 days. At a cytological level we detected spermatogenic development delays of cultured explants compared to the natural in vivo process. The expression of different spermatogenic stages gene markers correlated with the proportion of different cell types detected in the cytological preparations. In vitro progression analysis of the different spermatogenic cell types, from both 6.5 dpp and 10.5 dpp testes explants, has revealed a relative delay in relation to in vivo process. The expression of the genes studied as biomarkers correlates with the cytologically and functional detected progression and differential expression identified in vivo. After a first analysis of deep sequencing data it has been observed that as long as cultures progress, the proportion of microRNAs declined respect to piwi-interactingRNAs levels that increased, showing a similar propensity than which happens in in vivo spermatogenesis. Our study allows to improve and potentially to control the ex vivo spermatogenesis development, opening new perspectives in the reproductive biology fields including male fertility.

Neuropsychological and brain volume differences in patients with left- and right-beginning corticobasal syndrome.

PubMed

Jütten, Kerstin; Pieperhoff, Peter; Südmeyer, Martin; Schleicher, Axel; Ferrea, Stefano; Caspers, Svenja; Zilles, Karl; Schnitzler, Alfons; Amunts, Katrin; Lux, Silke

2014-01-01

Corticobasal Syndrome (CBS) is a rare neurodegenerative syndrome characterized by unilaterally beginning frontoparietal and basal ganglia atrophy. The study aimed to prove the hypothesis that there are differences in hemispheric susceptibility to disease-related changes. Two groups of CBS patients with symptoms starting either on the left or right body side were investigated. Groups consisted of four patients each and were matched for sex, age and disease duration. Patient groups and a group of eight healthy age-matched controls were analyzed using deformation field morphometry and neuropsychological testing. To further characterize individual disease progression regarding brain atrophy and neuropsychological performance, two female, disease duration-matched patients differing in initially impaired body side were followed over six months. A distinct pattern of neural atrophy and neuropsychological performance was revealed for both CBS: Patients with initial right-sided impairment (r-CBS) revealed atrophy predominantly in frontoparietal areas and showed, except from apraxia, no other cognitive deficits. In contrast, patients with impairment of the left body side (l-CBS) revealed more widespread atrophy, extending from frontoparietal to orbitofrontal and temporal regions; and apraxia, perceptional and memory deficits could be found. A similar pattern of morphological and neuropsychological differences was found for the individual disease progression in l-CBS and r-CBS single cases. For similar durations of disease, volumetric grey matter loss related to CBS pathology appeared earlier and progressed faster in l-CBS than in r-CBS. Cognitive impairment in r-CBS was characterized by apraxia, and additional memory and perceptional deficits for l-CBS.

High frequency of brain metastases after adjuvant therapy for high-risk melanoma.

PubMed

Samlowski, Wolfram E; Moon, James; Witter, Merle; Atkins, Michael B; Kirkwood, John M; Othus, Megan; Ribas, Antoni; Sondak, Vernon K; Flaherty, Lawrence E

2017-11-01

The incidence of CNS progression in patients with high-risk regional melanoma (stages IIIAN2a-IIIC) is not well characterized. Data from the S0008 trial provided an opportunity to examine the role of CNS progression in treatment failure and survival. All patients were surgically staged. Following wide excision and full regional lymphadenectomy, patients were randomized to receive adjuvant biochemotherapy (BCT) or high-dose interferon alfa-2B (HDI). CNS progression was retrospectively identified from data forms. Survival was measured from date of CNS progression. A total of 402 eligible patients were included in the analysis (BCT: 199, HDI: 203). Median follow-up (if alive) was over 7 years (range: 1 month to 11 years). The site of initial progression was identifiable in 80% of relapsing patients. CNS progression was a component of systemic melanoma relapse in 59/402 patients (15% overall). In 34/402 patients (9%) CNS progression represented the initial site of treatment failure. CNS progression was a component of initial progression in 27% of all patients whose melanoma relapsed (59/221). The risk of CNS progression was highest within 3 years of randomization. The difference in CNS progression rates between treatment arms was not significant (BCT = 25, HDI = 34, P = 0.24). Lymph node macrometastases strongly associated with CNS progression (P = 0.001), while ulceration and head and neck primaries were not significant predictors. This retrospective analysis of the S0008 trial identified a high brain metastasis rate (15%) in regionally advanced melanoma patients. Further studies are needed to establish whether screening plus earlier treatment would improve survival following CNS progression. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Autosomal recessive progressive myoclonus epilepsy due to impaired ceramide synthesis.

PubMed

Ferlazzo, Edoardo; Striano, Pasquale; Italiano, Domenico; Calarese, Tiziana; Gasparini, Sara; Vanni, Nicola; Fruscione, Floriana; Genton, Pierre; Zara, Federico

2016-09-01

Autosomal recessive progressive myoclonus epilepsy due to impaired ceramide synthesis is an extremely rare condition, so far reported in a single family of Algerian origin presenting an unusual, severe form of progressive myoclonus epilepsy characterized by myoclonus, generalized tonic-clonic seizures and moderate to severe cognitive impairment, with probable autosomal recessive inheritance. Disease onset was between 6 and 16 years of age. Genetic study allowed to identify a homozygous nonsynonymous mutation in CERS1, the gene encoding ceramide synthase 1, a transmembrane protein of the endoplasmic reticulum (ER), catalyzes the biosynthesis of C18-ceramides. The mutation decreased C18-ceramide levels. In addition, downregulation of CerS1 in neuroblastoma cell line showed activation of ER stress response and induction of proapoptotic pathways. This observation demonstrates that impairment of ceramide biosynthesis underlies neurodegeneration in humans.

Basic mechanisms in intracranial large-artery atherosclerosis: advances and challenges.

PubMed

Arenillas, Juan F; Alvarez-Sabín, José

2005-01-01

Intracranial large-artery atherosclerosis is a major cause of ischemic stroke worldwide. Patients affected by this disease are at a high risk of suffering recurrent ischemic events despite antithrombotic therapy. Progression and a greater extent of intracranial atherosclerosis imply a higher risk for recurrence. Studies performed by our group in patients with symptomatic intracranial large-artery atherosclerosis have shown that: (1) C-reactive protein predicts its progression and recurrence, suggesting that inflammation may play a deleterious role in this condition; (2) a high level of the anti-angiogenic endostatin is also associated with a progressive and recurrent intracranial atherosclerosis, which might support a beneficial role for angiogenesis in this group of patients; and (3) elevated lipoprotein(a) concentration and diabetes mellitus characterize those patients with a higher number of intracranial stenoses. 2005 S. Karger AG, Basel

Coherent X-ray diffraction imaging and characterization of strain in silicon-on-insulator nanostructures

DOE PAGES

Xiong, Gang; Moutanabbir, Oussama; Reiche, Manfred; ...

2014-12-06

Coherent X-ray diffraction imaging (CDI) has emerged in the last decade as a promising high resolution lens-less imaging approach for the characterization of various samples. It has made significant technical progress through developments in source, algorithm and imaging methodologies thus enabling important scientific breakthroughs in a broad range of disciplines. In this report, we will introduce the principles of forward scattering CDI and Bragg geometry CDI (BCDI), with an emphasis on the latter. BCDI exploits the ultra-high sensitivity of the diffraction pattern to the distortions of crystalline lattice. Its ability of imaging strain on the nanometer scale in three dimensionsmore » is highly novel. In this study, we will present the latest progress on the application of BCDI in investigating the strain relaxation behavior in nanoscale patterned strained silicon-on-insulator (sSOI) materials, aiming to understand and engineer strain for the design and implementation of new generation semiconductor devices.« less

Circulating Tumor Cells (CTCs): Emerging Technologies for Detection, Diagnosis and Treatment

NASA Astrophysics Data System (ADS)

McCarty, Owen

2010-03-01

Circulating tumor cell enumeration and characterization have the potential of providing real-time access to epithelial cancers in patients. This fluid phase biopsy of solid phase tumors is crucial to the development of quantitative diagnostic aiding personalized medicine. Cancer is a highly heterogeneous disease over space and time. Our goal is to generate a mechanistic, yet comprehensive view of both the `FORCE-journey' of a cancer cell during the metastatic phase, and a `TIME-journey' of the disease as it progresses. The approach will correlate the `FORCE' and `TIME' journey with both the bio-clinical aspects and the genomics of this complex problem. Presented will be results from a case study in lung cancer patients for which CTC analysis is compared with clinical progression. Morphologic and molecular characterization at the single cell level will be discussed in the context of the data set and in the context of individual patient management. Preliminary data will be shown to guide a future research agenda to investigate the fluid phase of solid tumors.

[Enclosed environments and health].

PubMed

Maroni, M; Barbieri, F

1989-01-01

Problems related to Indoor Air Quality are subject of study since about twenty years. New architectural criteria, new building materials and increasing demands of energy saving have progressively changed residences, offices and all non-industrial indoor environments. This paper present a review of the IAQ-related issues from sources characterization, to pollutant assessment and definition of effects on human health.

Mesothelial Cell Autoantibodies Induce Collagen Deposition in vitro & Using a Case Study to Introduce Undergraduates to Bioinformatics

ERIC Educational Resources Information Center

Serve, Kinta M.

2013-01-01

Part I. Pleural fibrosis, a non-malignant, asbestos-related respiratory disease characterized by excessive collagen deposition, is progressive, debilitating, and potentially fatal. Disease severity may be influenced by the type of asbestos fiber inhaled, with Libby amphibole (LA) a seemingly more potent mediator of pleural fibrosis than chrysotile…

Revitalization of a forward genetic screen identifies three new regulators of fungal secondary metabolism in the genus Aspergillus

Treesearch

Brandon T. Pfannenstiel; Xixi Zhao; Jennifer Wortman; Philipp Wiemann; Kurt Throckmorton; Joseph E. Spraker; Alexandra A. Soukup; Xingyu Luo; Daniel L. Lindner; Fang Yun Lim; Benjamin P. Knox; Brian Haas; Gregory J. Fischer; Tsokyi Choera; Robert A. E. Butchko; Jin-Woo Bok; Katharyn J. Affeldt; Nancy P. Keller; Jonathan M. Palmer; B. Gillian Turgeon

2017-01-01

The study of aflatoxin in Aspergillus spp. has garnered the attention of many researchers due to aflatoxin's carcinogenic properties and frequency as a food and feed contaminant. Significant progress has been made by utilizing the model organism Aspergillus nidulans to characterize the regulation of sterigmatocystin (ST),...

Improvements in Limb Kinetic Apraxia by Repetition of a Newly Designed Facilitation Exercise in a Patient with Corticobasal Degeneration

ERIC Educational Resources Information Center

Kawahira, Kazumi; Noma, Tomokazu; Iiyama, Junichi; Etoh, Seiji; Ogata, Atsuko; Shimodozono, Megumi

2009-01-01

Corticobasal degeneration is a progressive neurological disorder characterized by a combination of parkinsonism and cortical dysfunction such as limb kinetic apraxia, alien limb phenomenon, and dementia. To study the effect of repetitive facilitation exercise (RFE) in a patient with corticobasal degeneration, we used a newly designed facilitation…

Characterization of Breast Cancer Progression by Analysis of Genetic Markers.

DTIC Science & Technology

1997-11-01

between D 11S922 and DllS569,16 a region that includes the D11S988-TH chromosomal segment. A study of 13 hepatoblastomas suggested a significant region of...maternal allele in hepatoblastoma . J Cancer Res Clin Oncol 1994, 120:732-736. 20. Weksberg R, Squire JA: Molecular biology of Beckwith-Wiedemann syndrome

Graphic Representation of Organs and Organ Systems: Psychological View and Developmental Patterns

ERIC Educational Resources Information Center

Bartoszeck, Amauri Betini; Machado, Danielle Zagonel; Amann-Gainotti, Merete

2011-01-01

The objective of this exploratory study is to characterize by means of drawings if the developmental patterns in the graphic representation of organ and organ systems progresses related to age of participants. Secondly, whether there is an integration of sex organs into the internal body image. The drawings representing the inside of the body in…

The efficacy of the modified Atkins diet in North Sea Progressive Myoclonus Epilepsy: an observational prospective open-label study.

PubMed

van Egmond, Martje E; Weijenberg, Amerins; van Rijn, Margreet E; Elting, Jan Willem J; Gelauff, Jeannette M; Zutt, Rodi; Sival, Deborah A; Lambrechts, Roald A; Tijssen, Marina A J; Brouwer, Oebele F; de Koning, Tom J

2017-03-07

North Sea Progressive Myoclonus Epilepsy is a rare and severe disorder caused by mutations in the GOSR2 gene. It is clinically characterized by progressive myoclonus, seizures, early-onset ataxia and areflexia. As in other progressive myoclonus epilepsies, the efficacy of antiepileptic drugs is disappointingly limited in North Sea Progressive Myoclonus Epilepsy. The ketogenic diet and the less restrictive modified Atkins diet have been proven to be effective in other drug-resistant epilepsy syndromes, including those with myoclonic seizures. Our aim was to evaluate the efficacy of the modified Atkins diet in patients with North Sea Progressive Myoclonus Epilepsy. Four North Sea Progressive Myoclonus Epilepsy patients (aged 7-20 years) participated in an observational, prospective, open-label study on the efficacy of the modified Atkins diet. Several clinical parameters were assessed at baseline and again after participants had been on the diet for 3 months. The primary outcome measure was health-related quality of life, with seizure frequency and blinded rated myoclonus severity as secondary outcome measures. Ketosis was achieved within 2 weeks and all patients completed the 3 months on the modified Atkins diet. The diet was well tolerated by all four patients. Health-related quality of life improved considerably in one patient and showed sustained improvement during long-term follow-up, despite the progressive nature of the disorder. Health-related quality of life remained broadly unchanged in the other three patients and they did not continue the diet. Seizure frequency remained stable and blinded rating of their myoclonus showed improvement, albeit modest, in all patients. This observational, prospective study shows that some North Sea Progressive Myoclonus Epilepsy patients may benefit from the modified Atkins diet with sustained health-related quality of life improvement. Not all our patients continued on the diet, but nonetheless we show that the modified Atkins diet might be considered as a possible treatment in this devastating disorder.

Immunological network signatures of cancer progression and survival

PubMed Central

2011-01-01

Background The immune contribution to cancer progression is complex and difficult to characterize. For example in tumors, immune gene expression is detected from the combination of normal, tumor and immune cells in the tumor microenvironment. Profiling the immune component of tumors may facilitate the characterization of the poorly understood roles immunity plays in cancer progression. However, the current approaches to analyze the immune component of a tumor rely on incomplete identification of immune factors. Methods To facilitate a more comprehensive approach, we created a ranked immunological relevance score for all human genes, developed using a novel strategy that combines text mining and information theory. We used this score to assign an immunological grade to gene expression profiles, and thereby quantify the immunological component of tumors. This immunological relevance score was benchmarked against existing manually curated immune resources as well as high-throughput studies. To further characterize immunological relevance for genes, the relevance score was charted against both the human interactome and cancer information, forming an expanded interactome landscape of tumor immunity. We applied this approach to expression profiles in melanomas, thus identifying and grading their immunological components, followed by identification of their associated protein interactions. Results The power of this strategy was demonstrated by the observation of early activation of the adaptive immune response and the diversity of the immune component during melanoma progression. Furthermore, the genome-wide immunological relevance score classified melanoma patient groups, whose immunological grade correlated with clinical features, such as immune phenotypes and survival. Conclusions The assignment of a ranked immunological relevance score to all human genes extends the content of existing immune gene resources and enriches our understanding of immune involvement in complex biological networks. The application of this approach to tumor immunity represents an automated systems strategy that quantifies the immunological component in complex disease. In so doing, it stratifies patients according to their immune profiles, which may lead to effective computational prognostic and clinical guides. PMID:21453479

Progressive kidney failure as the sole manifestation of extrapulmonary sarcoidosis.

PubMed

Sethi, Supreet; Relia, Nitin; Syal, Gaurav; Kaushik, Chhavi; Gokden, Neriman; Malik, Ahmad B

2013-09-01

Sarcoidosis is a chronic multisystem disorder characterized by an accumulation of T lymphocytes and mononuclear phagocytes, non-caseating epitheliod granulomas and derangement of normal tissue architecture in affected organs. Sarcoidosis can affect any organ system, however approximately 90% of patients with sarcoidosis have pulmonary, lymph node, cutaneous or ocular manifestations. Renal involvement in sarcoidosis is rare and clinically significant renal dysfunction even less common. We present a case of isolated renal sarcoidosis which manifested with progressively worsening renal function and hypercalcemia. A systematic diagnostic approach with pertinent laboratory studies, imaging and renal biopsy elucidated the diagnosis of renal sarcoidosis without any evidence of systemic involvement.

Chronic Cerebrospinal Vascular Insufficiency Is Not Associated with HLA DRB1*1501 Status in Multiple Sclerosis Patients

PubMed Central

Weinstock-Guttman, Bianca; Zivadinov, Robert; Cutter, Gary; Tamaño-Blanco, Miriam; Marr, Karen; Badgett, Darlene; Carl, Ellen; Elfadil, Makki; Kennedy, Cheryl; Benedict, Ralph H. B.; Ramanathan, Murali

2011-01-01

Background Chronic cerebrospinal venous insufficiency (CCSVI) was described as a vascular condition characterized by anomalies of veins outside the skull was reported to be associated with multiple sclerosis (MS). The objective was to assess the associations between HLA DRB1*1501 status and the occurrence of CCSVI in MS patients. Methodology/Principal Findings This study included 423 of 499 subjects enrolled in the Combined Transcranial and Extracranial Venous Doppler Evaluation (CTEVD) study. The HLA DRB1*1501 status was obtained in 268 MS patients and 155 controls by genotyping rs3135005, a SNP associated with DRB1*1501 status. All subjects underwent a clinical examination and Doppler scan of the head and neck. The frequency of CCSVI was higher (OR = 4.52, p<0.001) in the MS group 56.0% vs. 21.9% in the controls group and also higher in the progressive MS group 69.8% vs. 49.5% in the non-progressive MS group. The 51.9% frequency of HLA DRB1*1501 positivity (HLA+) in MS was higher compared (OR = 2.33, p<0.001) to 31.6% to controls. The HLA+ frequency in the non-progressive (51.6%) and progressive MS groups (52.3%) was similar. The frequency of HLA+ CCSVI+ was 40.7% in progressive MS, 27.5% in non-progressive MS and 8.4% in controls. The presence of CCSVI was independent of HLA DRB1*1501 status in MS patients. Conclusions/Significance The lack of strong associations of CCSVI with HLA DRB1*1501 suggests that the role of the underlying associations of CCSVI in MS should be interpreted with caution. Further longitudinal studies should determine whether interactions between these factors can contribute to disease progression in MS. PMID:21340025

Characterization in vitro and in vivo of progressively adriamycin-resistant B16-BL6 mouse melanoma cells.

PubMed

Ganapathi, R; Grabowski, D; Schmidt, H; Bell, D; Melia, M

1987-07-01

Adriamycin (ADR)-resistant sublines of B16-BL6 mouse melanoma selected by exposure to increasing concentrations of ADR were characterized in vitro for growth properties and in vivo for tumorigenicity and pulmonary metastases. The progressively resistant sublines adapted to grow in the presence of 0.025, 0.05, 0.1, and 0.25 microgram/ml ADR in monolayer culture were found to be 5-, 10-, 20-, and 40-fold ADR-resistant, respectively, compared to the parental sensitive cells, using a soft-agar colony assay and continuous ADR treatment for 7 days. The doubling time in monolayer culture of the parent sensitive and progressively ADR-resistant sublines of B16-BL6 melanoma cells was approximately 16-18 h. Although the colony-forming efficiency in soft agar of parental sensitive cells was only 0.5-4%, the 5-, 10-, 20-, and 40-fold ADR-resistant sublines had colony-forming efficiencies of 15, 20, 30, and 77%, respectively. Tumorigenicity in C57BL/6 mice of progressively ADR-resistant sublines was similar to parental sensitive cells following s.c. and i.p. implantation of 10(5)-10(6) tumor cells. Experimental pulmonary metastases were significantly lower in ADR-resistant sublines with progressive resistance. Additionally, unlike the parental sensitive and 5-fold ADR-resistant B16-BL6 cells, the 10-, 20-, and 40-fold ADR-resistant sublines were spontaneously nonmetastatic. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunochemical detection of P-glycoprotein revealed the presence of a Mr 170,000 plasma membrane glycoprotein in the 40-fold ADR-resistant subline and its counterpart maintained for 1 year in ADR-free medium. Results from this study suggest that progressively ADR-resistant B16-BL6 mouse melanoma cells selected in vitro demonstrate a marked increase in colony formation in soft agar and a decrease in the ability to produce pulmonary metastases, without alterations in tumorigenicity.

Development of method to characterize emissions from spray polyurethane foam insulation

EPA Science Inventory

This presentation updates symposium participants re EPA progress towards development of SPF insulation emissions characterization methods. The presentation highlights evaluation of experiments investigating emissions after application of SPF to substrates in micro chambers and i...

Tissue redox activity as a hallmark of carcinogenesis: from early to terminal stages of cancer.

PubMed

Bakalova, Rumiana; Zhelev, Zhivko; Aoki, Ichio; Saga, Tsuneo

2013-05-01

The study aimed to clarify the dynamics of tissue redox activity (TRA) in cancer progression and assess the importance of this parameter for therapeutic strategies. The experiments were carried out on brain tissues of neuroblastoma-bearing, glioma-bearing, and healthy mice. TRA was visualized in vivo by nitroxide-enhanced MRI on anesthetized animals or in vitro by electron paramagnetic resonance spectroscopy on isolated tissue specimens. Two biochemical parameters were analyzed in parallel: tissue total antioxidant capacity (TTAC) and plasma levels of matrix metalloproteinases (MMP). In the early stage of cancer, the brain tissues were characterized by a shorter-lived MRI signal than that from healthy brains (indicating a higher reducing activity for the nitroxide radical), which was accompanied by an enhancement of TTAC and MMP9 plasma levels. In the terminal stage of cancer, tissues in both hemispheres were characterized by a longer-lived MRI signal than in healthy brains (indicating a high-oxidative activity) that was accompanied by a decrease in TTAC and an increase in the MMP2/MMP9 plasma levels. Cancer progression also affected the redox potential of tissues distant from the primary tumor locus (liver and lung). Their oxidative status increased in both stages of cancer. The study shows that tissue redox balance is very sensitive to the progression of cancer and can be used as a diagnostic marker of carcinogenesis. The study also suggests that the noncancerous tissues of a cancer-bearing organism are susceptible to oxidative damage and should be considered a therapeutic target. ©2013 AACR.

A review of the application of inflammatory biomarkers in epidemiologic cancer research

PubMed Central

Brenner, Darren R.; Scherer, Dominique; Muir, Kenneth; Schildkraut, Joellen; Boffetta, Paolo; Spitz, Margaret R.; LeMarchand, Loic; Chan, Andrew T.; Goode, Ellen L.; Ulrich, Cornelia M.; Hung, Rayjean J.

2014-01-01

Inflammation is a facilitating process for multiple cancer types. It is believed to affect cancer development and progression through several etiologic pathways including increased levels of DNA adduct formation, increased angiogenesis and altered anti-apoptotic signaling. This review highlights the application of inflammatory biomarkers in epidemiologic studies and discusses the various cellular mediators of inflammation characterizing the innate immune system response to infection and chronic insult from environmental factors. Included is a review of six classes of inflammation-related biomarkers: cytokines/chemokines, immune-related effectors, acute phase proteins, reactive oxygen and nitrogen species, prostaglandins and cyclooxygenase-related factors, and mediators such as transcription factors and growth factors. For each of these biomarkers we provide a brief overview of the etiologic role in the inflammation response and how they have been related to cancer etiology and progression within the literature. We provide a discussion of the common techniques available for quantification of each marker including strengths, weaknesses and potential pitfalls. Subsequently, we highlight a few under-studied measures to characterize the inflammatory response and their potential utility in epidemiologic studies of cancer. Finally, we suggest integrative methods for future studies to apply multi-faceted approaches to examine the relationship between inflammatory markers and their roles in cancer development. PMID:24962838

A case-study in the clinical epidemiology of psoriatic arthritis: multistate models and causal arguments

PubMed Central

O'Keeffe, Aidan G; Tom, Brian D M; Farewell, Vernon T

2011-01-01

In psoriatic arthritis, permanent joint damage characterizes disease progression and represents a major debilitating aspect of the disease. Understanding the process of joint damage will assist in the treatment and disease management of patients. Multistate models provide a means to examine patterns of disease, such as symmetric joint damage. Additionally, the link between damage and the dynamic course of disease activity (represented by joint swelling and stress pain) at both the individual joint level and otherwise can be represented within a correlated multistate model framework. Correlation is reflected through the use of random effects for progressive models and robust variance estimation for non-progressive models. Such analyses, undertaken with data from a large psoriatic arthritis cohort, are discussed and the extent to which they permit causal reasoning is considered. For this, emphasis is given to the use of the Bradford Hill criteria for causation in observational studies and the concept of local (in)dependence to capture the dynamic nature of the relationships. PMID:22163372

Zolpidem in progressive supranuclear palsy.

PubMed

Dash, Sandip K

2013-01-01

Progressive supranuclear palsy (PSP) is a progressive neurodegenerative disorder, characterized by motor symptoms, postural instability, personality changes, and cognitive impairment. There is no effective treatment for this disorder. Reduced neurotransmission of GABA in the striatum and globus pallidus may contribute to the symptoms of motor and cognitive symptoms seen in PSP. Zolpidem is a GABA agonist of the benzodiazepine subreceptor BZ1. Here a nondiabetic, normotensive case of PSP is (Progressive Supranuclear Palsy) described, which showed improvement in swallowing, speech, and gaze paresis after zolpidem therapy and possible mechanism of actions are discussed. However, more trials are needed with large number of patients to confirm the effectiveness of zolpidem in progressive supranuclear palsy.

A CNGB1 Frameshift Mutation in Papillon and Phalène Dogs with Progressive Retinal Atrophy

PubMed Central

Ahonen, Saija J.; Arumilli, Meharji; Lohi, Hannes

2013-01-01

Progressive retinal degenerations are the most common causes of complete blindness both in human and in dogs. Canine progressive retinal atrophy (PRA) or degeneration resembles human retinitis pigmentosa (RP) and is characterized by a progressive loss of rod photoreceptor cells followed by a loss of cone function. The primary clinical signs are detected as vision impairment in a dim light. Although several genes have been associated with PRAs, there are still PRAs of unknown genetic cause in many breeds, including Papillons and Phalènes. We have performed a genome wide association and linkage studies in cohort of 6 affected Papillons and Phalènes and 14 healthy control dogs to map a novel PRA locus on canine chromosome 2, with a 1.9 Mb shared homozygous region in the affected dogs. Parallel exome sequencing of a trio identified an indel mutation, including a 1-bp deletion, followed by a 6-bp insertion in the CNGB1 gene. This mutation causes a frameshift and premature stop codon leading to probable nonsense mediated decay (NMD) of the CNGB1 mRNA. The mutation segregated with the disease and was confirmed in a larger cohort of 145 Papillons and Phalènes (PFisher = 1.4×10−8) with a carrier frequency of 17.2 %. This breed specific mutation was not present in 334 healthy dogs from 10 other breeds or 121 PRA affected dogs from 44 other breeds. CNGB1 is important for the photoreceptor cell function its defects have been previously associated with retinal degeneration in both human and mouse. Our study indicates that a frameshift mutation in CNGB1 is a cause of PRA in Papillons and Phalènes and establishes the breed as a large functional animal model for further characterization of retinal CNGB1 biology and possible retinal gene therapy trials. This study enables also the development of a genetic test for breeding purposes. PMID:24015210

Pretest characterization of WIPP experimental waste

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

Johnson, J.; Davis, H.; Drez, P.E.

The Waste Isolation Pilot Plant (WIPP) near Carlsbad, New Mexico, is an underground repository designed for the storage and disposal of transuranic (TRU) wastes from US Department of Energy (DOE) facilities across the country. The Performance Assessment (PA) studies for WIPP address compliance of the repository with applicable regulations, and include full-scale experiments to be performed at the WIPP site. These experiments are the bin-scale and alcove tests to be conducted by Sandia National Laboratories (SNL). Prior to conducting these experiments, the waste to be used in these tests needs to be characterized to provide data on the initial conditionsmore » for these experiments. This characterization is referred to as the Pretest Characterization of WIPP Experimental Waste, and is also expected to provide input to other programmatic efforts related to waste characterization. The purpose of this paper is to describe the pretest waste characterization activities currently in progress for the WIPP bin-scale waste, and to discuss the program plan and specific analytical protocols being developed for this characterization. The relationship between different programs and documents related to waste characterization efforts is also highlighted in this paper.« less

User Interfaces for Patient-Centered Communication of Health Status and Care Progress

ERIC Educational Resources Information Center

Wilcox-Patterson, Lauren

2013-01-01

The recent trend toward patients participating in their own healthcare has opened up numerous opportunities for computing research. This dissertation focuses on how technology can foster this participation, through user interfaces to effectively communicate personal health status and care progress to hospital patients. I first characterize the…

Toward a Theory of Reading Black Feminists' Writings.

ERIC Educational Resources Information Center

Bristow, M. B. Smith

Black feminist novelists continue to take issue with males who try to theorize about their artistic creations. Male attitudes toward black women's novels have been characterized as either apathetic, chauvinistic, or paternalistic. Black feminist writers should heed the call for collective racial progress and collective theoretical progress. The…

Precambrian perspectives.

PubMed

Goodwin, A M

1981-07-03

The Precambrian record is interpreted in terms of an evolutionary progression that moves in the direction of increasing continental stability. An early, highly mobile microplate tectonics phase progressed through a more stable, largely intracratonic, ensialic, mobile belt phase to the modern macroplate tectonics phase that involves large, rigid lithospheric plates. Various phases are characterized by distinctive crustal associations. Three controls-bulk earth heat production, crustal fractionation and cratonization, and atmospheric oxygen accumulation-are viewed as the cumulative cause of the trends and events that characterize the crust at different stages of development, from its inception approximately 4.6 billion years ago to the present.

Model-based economic evaluation in Alzheimer's disease: a review of the methods available to model Alzheimer's disease progression.

PubMed

Green, Colin; Shearer, James; Ritchie, Craig W; Zajicek, John P

2011-01-01

To consider the methods available to model Alzheimer's disease (AD) progression over time to inform on the structure and development of model-based evaluations, and the future direction of modelling methods in AD. A systematic search of the health care literature was undertaken to identify methods to model disease progression in AD. Modelling methods are presented in a descriptive review. The literature search identified 42 studies presenting methods or applications of methods to model AD progression over time. The review identified 10 general modelling frameworks available to empirically model the progression of AD as part of a model-based evaluation. Seven of these general models are statistical models predicting progression of AD using a measure of cognitive function. The main concerns with models are on model structure, around the limited characterization of disease progression, and on the use of a limited number of health states to capture events related to disease progression over time. None of the available models have been able to present a comprehensive model of the natural history of AD. Although helpful, there are serious limitations in the methods available to model progression of AD over time. Advances are needed to better model the progression of AD and the effects of the disease on peoples' lives. Recent evidence supports the need for a multivariable approach to the modelling of AD progression, and indicates that a latent variable analytic approach to characterising AD progression is a promising avenue for advances in the statistical development of modelling methods. Copyright © 2011 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Towards traceable transient pressure metrology

NASA Astrophysics Data System (ADS)

Hanson, Edward; Olson, Douglas A.; Liu, Haijun; Ahmed, Zeeshan; Douglass, Kevin O.

2018-04-01

We describe our progress in developing the infrastructure for traceable transient measurements of pressure. Towards that end, we have built and characterized a dual diaphragm shock tube that allows us to achieve shock amplitude reproducibility of approximately 2.3% for shocks with Mach speeds ranging from 1.26-1.5. In this proof-of-concept study we use our shock tube to characterize the dynamic response of photonic sensors embedded in polydimethylsiloxane (PDMS), a material of choice for soft tissue phantoms. Our results indicate that the PDMS-embedded photonic sensors response to shock evolves over a tens to hundreds of microseconds time scale making it a useful system for studying transient pressures in soft tissue.

Brain MRI abnormalities in the adult form of myotonic dystrophy type 1: A longitudinal case series study.

PubMed

Conforti, Renata; de Cristofaro, Mario; Cristofano, Adriana; Brogna, Barbara; Sardaro, Angela; Tedeschi, Gioacchino; Cirillo, Sossio; Di Costanzo, Alfonso

2016-02-01

This study aimed to verify whether brain abnormalities, previously described in patients with myotonic dystrophy type 1 (DM1) by magnetic resonance imaging (MRI), progressed over time and, if so, to characterize their progression. Thirteen DM1 patients, who had at least two MRI examinations, were retrospectively evaluated and included in the study. The mean duration (± standard deviation) of follow-up was 13.4 (±3.8) years, over a range of 7-20 years. White matter lesions (WMLs) were rated by semi-quantitative method, the signal intensity of white matter poster-superior to trigones (WMPST) by reference to standard images and brain atrophy by ventricular/brain ratio (VBR). At the end of MRI follow-up, the scores relative to lobar, temporal and periventricular WMLs, to WMPST signal intensity and to VBR were significantly increased compared to baseline, and MRI changes were more evident in some families than in others. No correlation was found between the MRI changes and age, onset, disease duration, muscular involvement, CTG repetition and follow-up duration. These results demonstrated that white matter involvement and brain atrophy were progressive in DM1 and suggested that progression rate varied from patient to patient, regardless of age, disease duration and genetic defect. © The Author(s) 2016.

Gene-Specific Demethylation as Targeted Therapy in MDS

DTIC Science & Technology

2017-07-01

SUPPLEMENTARY NOTES 14. ABSTRACT Myelodysplastic Syndromes (MDS) are a group of clonal hematopoietic disorders characterized by bone marrow failure and...clonal hematopoietic disorders characterized by bone marrow failure and risk of progression to Acute Myeloid Leukemia (AML) in approximately 30 percent

Optical Metamaterials: Design, Characterization and Applications

ERIC Educational Resources Information Center

Chaturvedi, Pratik

2009-01-01

Artificially engineered metamaterials have emerged with properties and functionalities previously unattainable in natural materials. The scientific breakthroughs made in this new class of electromagnetic materials are closely linked with progress in developing physics-driven design, novel fabrication and characterization methods. The intricate…

Initial Results from the Bloomsburg University Goniometer Laboratory

NASA Technical Reports Server (NTRS)

Shepard, M. K.

2002-01-01

The Bloomsburg University Goniometer Laboratory (B.U.G. Lab) consists of three systems for studying the photometric properties of samples. The primary system is an automated goniometer capable of measuring the entire bi-directional reflectance distribution function (BRDF) of samples. Secondary systems include a reflectance spectrometer and digital video camera with macro zoom lens for characterizing and documenting other physical properties of measured samples. Works completed or in progress include the characterization of the BRDF of calibration surfaces for the 2003 Mars Exploration Rovers (MER03), Martian analog soils including JSC-Mars-1, and tests of photometric models.

Characterization of flaws in a tube bundle mock-up for reliability studies

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

Kupperman, D.S.; Bakhtiari, S.

1997-02-01

As part of an assessment of in-service inspection of steam generator tubes, the authors will assemble a steam generator mock-up for round robin studies and use as a test bed in evaluating emerging technologies. Progress is reported on the characterization of flaws that will be part of the mock-up. Eddy current and ultrasonic techniques are being evaluated as a means to characterize the flaws in the mock-up tubes before final assembly. Twenty Inconel 600 tubes with laboratory-grown cracks, typical of those to be used in the mock-up, were provided by Pacific Northwest National Laboratory for laboratory testing. After the tubesmore » were inspected with eddy current and ultrasonic techniques, they were destructively analyzed to establish the actual depths, lengths, and profiles of the cracks. The analysis of the results will allow the best techniques to be used for characterizing the flaws in the mock-up tubes.« less

A locus at 7p14.3 predisposes to refractory celiac disease progression from celiac disease.

PubMed

Hrdlickova, Barbara; Mulder, Chris J; Malamut, Georgia; Meresse, Bertrand; Platteel, Mathieu; Kamatani, Yoichiro; Ricaño-Ponce, Isis; van Wanrooij, Roy L J; Zorro, Maria M; Jan Bonder, Marc; Gutierrez-Achury, Javier; Cellier, Christophe; Zhernakova, Alexandra; Nijeboer, Petula; Galan, Pilar; Withoff, Sebo; Lathrop, Mark; Bouma, Gerd; Xavier, Ramnik J; Jabri, Bana; Bensussan, Nadine C; Wijmenga, Cisca; Kumar, Vinod

2018-05-21

Approximately 5% of patients with celiac disease (CeD) do not respond to a gluten-free diet and progress to refractory celiac disease (RCD), a severe progression that is characterized by infiltration of intraepithelial T lymphocytes. Patients with RCD type II (RCDII) show clonal expansions of intraepithelial T lymphocytes that result in a poor prognosis and a high mortality rate through development of aggressive enteropathy-associated T-cell lymphoma. It is not known whether genetic variations play a role in severe progression of CeD to RCDII. We performed the first genome-wide association study to identify the causal genes for RCDII and the molecular pathways perturbed in RCDII. The genome-wide association study was performed in 38 Dutch patients with RCDII, and the 15 independent top-associated single nucleotide polymorphism (SNP) variants (P<5×10) were replicated in 56 independent French and Dutch patients with RCDII. After replication, SNP rs2041570 on chromosome 7 was significantly associated with progression to RCDII (P=2.37×10, odds ratio=2.36) but not with CeD susceptibility. SNP rs2041570 risk allele A was associated with lower levels of FAM188B expression in blood and small intestinal biopsies. Stratification of RCDII biopsies based on rs2041570 genotype showed differential expression of innate immune and antibacterial genes that are expressed in Paneth cells. We have identified a novel SNP associated with the severe progression of CeD to RCDII. Our data suggest that genetic susceptibility to CeD might be distinct from the progression to RCDII and suggest a role for Paneth cells in RCDII progression.

Viral Carcinogenesis Beyond Malignant Transformation: EBV in the Progression of Human Cancers

PubMed Central

Müller-Coan, Bárbara G.; Pagano, Joseph S.

2017-01-01

Cancer progression begins when malignant cells colonize adjacent sites, and it is characterized by increasing tumor heterogeneity, invasion and dissemination of cancer cells. Clinically, progression is the most relevant stage in the natural history of cancers. A given virus is usually regarded as oncogenic because of its ability to induce malignant transformation of cells. Nonetheless, oncogenic viruses may also be important for the progression of infection-associated cancers. Recently this hypothesis has been addressed because of studies on the contribution of the Epstein–Barr virus (EBV) to the aggressiveness of nasopharyngeal carcinoma (NPC). Several EBV products modulate cancer progression phenomena, such as the epithelial–mesenchymal transition, cell motility, invasiveness, angiogenesis, and metastasis. In this regard, there are compelling data about the effects of EBV latent membrane proteins (LMPs) and EBV nuclear antigens (EBNAs), as well as nontranslated viral RNAs, such as the EBV-encoded small nonpolyadenylated RNAs (EBERs) and viral microRNAs, notably EBV miR-BARTs. The available data on the mechanisms and players involved in the contribution of EBV infection to the aggressiveness of NPC are discussed in this review. Overall, this conceptual framework may be valuable for the understanding of the contribution of some infectious agents in the progression of cancers. PMID:27068530

Understanding Acyl Chain and Glycerolipid Metabolism in Plants

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

Ohlrogge, John B.

2013-11-05

Progress is reported in these areas: acyl-editing in initial eukaryotic lipid assembly in soybean seeds; identification and characterization of two Arabidopsis thaliana lysophosphatidyl acyltransferases with preference for lysophosphatidylethanolamine; and characterization and subcellular distribution of lysolipid acyl transferase activity of pea leaves.

Natural history of drusenoid pigment epithelial detachment in age-related macular degeneration: Age-Related Eye Disease Study Report No. 28.

PubMed

Cukras, Catherine; Agrón, Elvira; Klein, Michael L; Ferris, Frederick L; Chew, Emily Y; Gensler, Gary; Wong, Wai T

2010-03-01

To describe the natural history of eyes with drusenoid pigment epithelial detachments (DPEDs) associated with age-related macular degeneration (AMD). Multicenter, clinic-based, prospective cohort study. Among 4757 participants enrolled in the Age-Related Eye Disease Study (AREDS), 255 were identified as having DPED in at least 1 eye and having 5 or more years of follow-up after the initial detection of the DPED. Baseline and annual fundus photographs were evaluated for the evolution of the fundus features and the development of advanced AMD in the forms of central geographic atrophy (CGA) or neovascular (NV) AMD. Kaplan-Meier analyses of progression to advanced AMD and of moderate vision loss (> or =15 letters compared with baseline) were performed. Rate of progression to advanced AMD and change in visual acuity from baseline (in terms of mean letters lost and proportion losing > or =15 letters). A total of 311 eyes (from 255 participants) with DPED were followed for a median follow-up time of 8 years subsequent to the initial detection of a DPED. Of the 282 eyes that did not have advanced AMD at baseline, advanced AMD developed within 5 years in 119 eyes (42%) (19% progressing to CGA and 23% progressing to NV-AMD). In the remaining eyes that did not develop advanced AMD (n=163), progressive fundus changes, typified by the development of calcified drusen and pigmentary changes, were detected. Visual decline was prominent among study eyes, with approximately 40% of all eyes decreasing in visual acuity by > or =15 letters at 5 years follow-up. Mean visual acuity decreased from 76 letters ( approximately 20/30) at baseline to 61 letters ( approximately 20/60) at 5 years. Five-year decreases in mean visual acuity averaged 26 letters for eyes progressing to advanced AMD and 8 letters for non-progressing eyes. The natural history of eyes containing DPED is characterized by a high rate of progression to both CGA and NV-AMD. Among eyes not progressing to advanced AMD, progressive development of pigmentary changes and calcified drusen were observed. Decline of visual acuity is a common outcome, with or without progression to advanced forms of AMD. Copyright 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Cumulative mtDNA damage and mutations contribute to the progressive loss of RGCs in a rat model of glaucoma.

PubMed

Wu, Ji-Hong; Zhang, Sheng-Hai; Nickerson, John M; Gao, Feng-Juan; Sun, Zhongmou; Chen, Xin-Ya; Zhang, Shu-Jie; Gao, Feng; Chen, Jun-Yi; Luo, Yi; Wang, Yan; Sun, Xing-Huai

2015-02-01

Glaucoma is a chronic neurodegenerative disease characterized by the progressive loss of retinal ganglion cells (RGCs). Mitochondrial DNA (mtDNA) alterations have been documented as a key component of many neurodegenerative disorders. However, whether mtDNA alterations contribute to the progressive loss of RGCs and the mechanism whereby this phenomenon could occur are poorly understood. We investigated mtDNA alterations in RGCs using a rat model of chronic intraocular hypertension and explored the mechanisms underlying progressive RGC loss. We demonstrate that the mtDNA damage and mutations triggered by intraocular pressure (IOP) elevation are initiating, crucial events in a cascade leading to progressive RGC loss. Damage to and mutation of mtDNA, mitochondrial dysfunction, reduced levels of mtDNA repair/replication enzymes, and elevated reactive oxygen species form a positive feedback loop that produces irreversible mtDNA damage and mutation and contributes to progressive RGC loss, which occurs even after a return to normal IOP. Furthermore, we demonstrate that mtDNA damage and mutations increase the vulnerability of RGCs to elevated IOP and glutamate levels, which are among the most common glaucoma insults. This study suggests that therapeutic approaches that target mtDNA maintenance and repair and that promote energy production may prevent the progressive death of RGCs. Copyright © 2014 Elsevier Inc. All rights reserved.

The Putative Role of the Antiageing Protein Klotho in Cardiovascular and Renal Disease

PubMed Central

Maltese, Giuseppe; Karalliedde, Janaka

2012-01-01

Ageing is a multifactorial process often characterized by a progressive decline in physiological function(s). Ageing can and is often associated with an increased incidence of cardiovascular and renal disease. Klotho is a novel antiageing gene that encodes a protein with multiple pleiotropic functions including an emerging role in cardiorenal disease. Mice deficient for this gene display a phenotype of premature human ageing characterized by diffuse vascular calcification, altered calcium/phosphate metabolism, and shortened lifespan. Klotho is mainly expressed in the renal tubules but it also exists as circulating soluble form detectable in the blood, with systemic effects. Reduction in soluble Klotho has been associated with renal disease, hyperphosphataemia, increased oxidative stress, endothelial dysfunction, and diffuse vascular calcification. Conversely, overexpression of Klotho promotes cardiovascular-renal protection. The majority of the research on Klotho has been conducted in vitro and in animal studies but there is emerging data from human studies which suggest that Klotho may be a modifiable factor involved in the pathogenesis of cardiovascular and renal disease in at-risk populations. Further data is required to confirm if this novel protein can emerge as therapeutic tool that may be used to prevent or slow progression of cardiorenal disease. PMID:22121479

Progressive Assessment of Ischemic Injury to White Matter Using Diffusion Tensor Imaging: A Preliminary Study of a Macaque Model of Stroke.

PubMed

Zhang, Xiaodong; Yan, Yumei; Tong, Frank; Li, Chun-Xia; Jones, Benjamin; Wang, Silun; Meng, Yuguang; Muly, E Chris; Kempf, Doty; Howell, Leonard

2018-01-01

Previous Diffusion Tensor Imaging (DTI) studies have demonstrated the temporal evolution of stroke injury in grey matter and white matter can be characterized by DTI indices. However, it still remains not fully understood how the DTI indices of white matter are altered progressively during the hyperacute (first 6 hours) and acute stage of stroke (≤ 1 week). In the present study, DTI was employed to characterize the temporal evolution of infarction and white matter injury after stroke insult using a macaque model with permanent ischemic occlusion. Permanent middle cerebral artery (MCA) occlusion was induced in rhesus monkeys (n=4, 10-21 years old). The brain lesion was examined longitudinally with DTI during the hyperacute phase (2-6 hours, n=4), 48 hours (n=4) and 96 hours (n=3) post-occlusion. Cortical infarction was seen in all animals. The Mean Diffusivity (MD) in lesion regions decreased substantially at the first time point (2 hours post stroke) (35%, p <0.05, compared to the contralateral side) and became pseudo-normalized at 96 hours. In contrast, evident FA reduction was seen at 48 hours (39%, p <0.10) post-stroke. MD reduction in white matter bundles of the lesion area was much less than that in the grey matter during the hyper-acute phase but significant change was observed 4 hours (4.2%, p < 0.05) post stroke . Also, MD pseudonormalisation was seen at 96 hours post stroke. There was a significant correlation between the temporal changes of MD in white matter bundles and those in whole lesion areas during the entire study period. Meanwhile, no obvious fractional anisotropy (FA) changes were seen during the hyper-acute phase in either the entire infarct region or white matter bundles. Significant FA alteration was observed in entire lesion areas and injured white matter bundles 48 and 96 hours post stroke. The stroke lesion in grey matter and white matter was validated by pathological findings. The temporal evolution of ischemic injury to the grey matter and white matter from 2 to 96 hours after stroke onset was characterized using a macaque model and DTI. Progressive MD changes in white matter bundles are seen from hyperacute phase to acute phase after permanent MCA occlusion and temporally correlated with the MD changes in entire infarction regions. MD reduction in white matter bundles is mild in comparison with that in the grey matter but significant and progressive, indicating it may be useful to detect early white matter degeneration after stroke.

A Further Characterization of Empirical Research Related to Learning Outcome Achievement in Remote and Virtual Science Labs

ERIC Educational Resources Information Center

Brinson, James R.

2017-01-01

This paper further characterizes recently reviewed literature related to student learning outcome achievement in non-traditional (virtual and remote) versus traditional (hands-on) science labs, as well as factors to consider when evaluating the state and progress of research in this field as a whole. Current research is characterized according to…

RON is not a prognostic marker for resectable pancreatic cancer.

PubMed

Tactacan, Carole M; Chang, David K; Cowley, Mark J; Humphrey, Emily S; Wu, Jianmin; Gill, Anthony J; Chou, Angela; Nones, Katia; Grimmond, Sean M; Sutherland, Robert L; Biankin, Andrew V; Daly, Roger J

2012-09-07

The receptor tyrosine kinase RON exhibits increased expression during pancreatic cancer progression and promotes migration, invasion and gemcitabine resistance of pancreatic cancer cells in experimental models. However, the prognostic significance of RON expression in pancreatic cancer is unknown. RON expression was characterized in several large cohorts, including a prospective study, totaling 492 pancreatic cancer patients and relationships with patient outcome and clinico-pathologic variables were assessed. RON expression was associated with outcome in a training set, but this was not recapitulated in the validation set, nor was there any association with therapeutic responsiveness in the validation set or the prospective study. Although RON is implicated in pancreatic cancer progression in experimental models, and may constitute a therapeutic target, RON expression is not associated with prognosis or therapeutic responsiveness in resected pancreatic cancer.

Height outcome of short children with hypochondroplasia after recombinant human growth hormone treatment: a meta-analysis.

PubMed

Massart, Francesco; Miccoli, Mario; Baggiani, Angelo; Bertelloni, Silvano

2015-11-01

Hypochondroplasia (HCH) is a genetic skeletal dysplasia, characterized by rhizomelic short height (Ht) with facial dysmorphology and lumbar hyperlordosis. Albeit there are concerns that HCH children may not achieve optimal long-term outcome in response to recombinant human growth hormone (rhGH), anecdotal experiences suggested at least short-term Ht improvement. After thorough search of published studies, meta-analysis of rhGH use in HCH children was performed. In 113 HCH children, rhGH administration (median 0.25 mg/kg/week) progressively improved Ht pattern with 12 months catch-up growth (p < 0.0001). Then, Ht improvement resulted constant until 36 months (p < 0.0001), but stature remained subnormal. While bone age chronologically progressed, no serious adverse events were reported. In conclusion, our meta-analysis indicates that rhGH treatment progressively improved Ht outcome of HCH subjects.

Symptomatic Therapy and Rehabilitation in Primary Progressive Multiple Sclerosis

PubMed Central

Khan, Fary; Amatya, Bhasker; Turner-Stokes, Lynne

2011-01-01

Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating disease of the central nervous system and a major cause of chronic neurological disability in young adults. Primary progressive MS (PPMS) constitutes about 10% of cases, and is characterized by a steady decline in function with no acute attacks. The rate of deterioration from disease onset is more rapid than relapsing remitting and secondary progressive MS types. Multiple system involvement at onset and rapid early progression have a worse prognosis. PPMS can cause significant disability and impact on quality of life. Recent studies are biased in favour of relapsing remitting patients as treatment is now available for them and they are more likely to be seen at MS clinics. Since prognosis for PPMS is worse than other types of MS, the focus of rehabilitation is on managing disability and enhancing participation, and application of a “neuropalliative” approach as the disease progresses. This chapter presents the symptomatic treatment and rehabilitation for persons with MS, including PPMS. A multidisciplinary approach optimizes the intermediate and long-term medical, psychological and social outcomes in this population. Restoration and maintenance of functional independence and societal reintegration, and issues relating to quality of life are addressed in rehabilitation processes. PMID:22013521

Characterizing and controlling industrial dust: a case study in small particle measurement.

PubMed

Combes, Richard S; Warren, D Alan

2005-07-01

Instrumentation used to measure characteristics of fine particles entrained in gas or suspended in aerosols provides information needed to develop valid regulations for emission sources and to support the design of control technologies. This case study offers a brief history of "micromeritics," a term used by early researchers to describe the science of small particles, and the related invention of laboratory instruments for characterizing very fine particles. The historical view provides insights into the role that Progressive Era government agencies played in advancing esoteric science and applying this knowledge to the regulation of workplace air pollution. Micromeritics instrumentation developed in conjunction with federal research now has many commercial applications worldwide, with characterizing airborne pollutants only a minor one. However, the continuing advances in the micromeritics field provide important laboratory measurement capabilities to environmental research organizations, such as the National Institute for Occupational Safety and Health (NIOSH).

Gene expression profiling in the early phases of DMD: a constant molecular signature characterizes DMD muscle from early postnatal life throughout disease progression.

PubMed

Pescatori, Mario; Broccolini, Aldobrando; Minetti, Carlo; Bertini, Enrico; Bruno, Claudio; D'amico, Adele; Bernardini, Camilla; Mirabella, Massimiliano; Silvestri, Gabriella; Giglio, Vincenzo; Modoni, Anna; Pedemonte, Marina; Tasca, Giorgio; Galluzzi, Giuliana; Mercuri, Eugenio; Tonali, Pietro A; Ricci, Enzo

2007-04-01

Genome-wide gene expression profiling of skeletal muscle from Duchenne muscular dystrophy (DMD) patients has been used to describe muscle tissue alterations in DMD children older than 5 years. By studying the expression profile of 19 patients younger than 2 years, we describe with high resolution the gene expression signature that characterizes DMD muscle during the initial or "presymptomatic" phase of the disease. We show that in the first 2 years of the disease, DMD muscle is already set to express a distinctive gene expression pattern considerably different from the one expressed by normal, age-matched muscle. This "dystrophic" molecular signature is characterized by a coordinate induction of genes involved in the inflammatory response, extracellular matrix (ECM) remodeling and muscle regeneration, and the reduced transcription of those involved in energy metabolism. Despite the lower degree of muscle dysfunction experienced, our younger patients showed abnormal expression of most of the genes reported as differentially expressed in more advanced stages of the disease. By analyzing our patients as a time series, we provide evidence that some genes, including members of three pathways involved in morphogenetic signaling-Wnt, Notch, and BMP-are progressively induced or repressed in the natural history of DMD.

Gain Modulation by an Urgency Signal Controls the Speed–Accuracy Trade-Off in a Network Model of a Cortical Decision Circuit

PubMed Central

Standage, Dominic; You, Hongzhi; Wang, Da-Hui; Dorris, Michael C.

2011-01-01

The speed–accuracy trade-off (SAT) is ubiquitous in decision tasks. While the neural mechanisms underlying decisions are generally well characterized, the application of decision-theoretic methods to the SAT has been difficult to reconcile with experimental data suggesting that decision thresholds are inflexible. Using a network model of a cortical decision circuit, we demonstrate the SAT in a manner consistent with neural and behavioral data and with mathematical models that optimize speed and accuracy with respect to one another. In simulations of a reaction time task, we modulate the gain of the network with a signal encoding the urgency to respond. As the urgency signal builds up, the network progresses through a series of processing stages supporting noise filtering, integration of evidence, amplification of integrated evidence, and choice selection. Analysis of the network's dynamics formally characterizes this progression. Slower buildup of urgency increases accuracy by slowing down the progression. Faster buildup has the opposite effect. Because the network always progresses through the same stages, decision-selective firing rates are stereotyped at decision time. PMID:21415911

Gain modulation by an urgency signal controls the speed-accuracy trade-off in a network model of a cortical decision circuit.

PubMed

Standage, Dominic; You, Hongzhi; Wang, Da-Hui; Dorris, Michael C

2011-01-01

The speed-accuracy trade-off (SAT) is ubiquitous in decision tasks. While the neural mechanisms underlying decisions are generally well characterized, the application of decision-theoretic methods to the SAT has been difficult to reconcile with experimental data suggesting that decision thresholds are inflexible. Using a network model of a cortical decision circuit, we demonstrate the SAT in a manner consistent with neural and behavioral data and with mathematical models that optimize speed and accuracy with respect to one another. In simulations of a reaction time task, we modulate the gain of the network with a signal encoding the urgency to respond. As the urgency signal builds up, the network progresses through a series of processing stages supporting noise filtering, integration of evidence, amplification of integrated evidence, and choice selection. Analysis of the network's dynamics formally characterizes this progression. Slower buildup of urgency increases accuracy by slowing down the progression. Faster buildup has the opposite effect. Because the network always progresses through the same stages, decision-selective firing rates are stereotyped at decision time.

Kinetics of disease progression and host response in a rat model of bubonic plague.

PubMed

Sebbane, Florent; Gardner, Donald; Long, Daniel; Gowen, Brian B; Hinnebusch, B Joseph

2005-05-01

Plague, caused by the gram-negative bacterium Yersinia pestis, primarily affects rodents but is also an important zoonotic disease of humans. Bubonic plague in humans follows transmission by infected fleas and is characterized by an acute, necrotizing lymphadenitis in the regional lymph nodes that drain the intradermal flea bite site. Septicemia rapidly follows with spread to spleen, liver, and other organs. We developed a model of bubonic plague using the inbred Brown Norway strain of Rattus norvegicus to characterize the progression and kinetics of infection and the host immune response after intradermal inoculation of Y. pestis. The clinical signs and pathology in the rat closely resembled descriptions of human bubonic plague. The bacteriology; histopathology; host cellular response in infected lymph nodes, blood, and spleen; and serum cytokine levels were analyzed at various times after infection to determine the kinetics and route of disease progression and to evaluate hypothesized Y. pestis pathogenic mechanisms. Understanding disease progression in this rat infection model should facilitate further investigations into the molecular pathogenesis of bubonic plague and the immune response to Y. pestis at different stages of the disease.

Mechanistic and Technical Challenges in Studying the Human Microbiome and Cancer Epidemiology.

PubMed

Verma, Mukesh

2017-04-01

This article reviews the significance of the microbiome in cancer epidemiology, mechanistic and technical challenges in the field, and characterization of the microbiome in different tumor types to identify biomarkers of risk, progression, and prognosis. Publications on the microbiome and cancer epidemiology were reviewed to analyze sample collection and processing, microbiome taxa characterization by 16S ribosomal RNA sequencing, and microbiome metabolite characterization (metabotyping) by nuclear magnetic resonance and mass spectrometry. The analysis identified methodology types, research design, sample types, and issues in integrating data from different platforms. Aerodigestive cancer epidemiology studies conducted by different groups demonstrated the significance of microbiome information in developing approaches to improve health. Challenges exist in sample preparation and processing (eg, standardization of methods for collection and analysis). These challenges relate to technology, data integration from "omics" studies, inherent bias in primer selection during 16S ribosomal RNA sequencing, the need for large consortia with well-characterized biospecimens, cause and effect issues, resilience of microbiota to exposure events (requires longitudinal studies), and expanding studies for fungal and viral diversity (most studies used bacterial 16S ribosomal RNA sequencing for microbiota characterization). Despite these challenges, microbiome and cancer epidemiology studies are significant and may facilitate cancer risk assessment, diagnosis, and prognosis. In the future, clinical trials likely will use microbiota modifications to improve the efficacy of existing treatments.

Mechanistic and Technical Challenges in Studying the Human Microbiome and Cancer Epidemiology

PubMed Central

2016-01-01

This article reviews the significance of the microbiome in cancer epidemiology, mechanistic and technical challenges in the field, and characterization of the microbiome in different tumor types to identify biomarkers of risk, progression, and prognosis. Publications on the microbiome and cancer epidemiology were reviewed to analyze sample collection and processing, microbiome taxa characterization by 16S ribosomal RNA sequencing, and microbiome metabolite characterization (metabotyping) by nuclear magnetic resonance and mass spectrometry. The analysis identified methodology types, research design, sample types, and issues in integrating data from different platforms. Aerodigestive cancer epidemiology studies conducted by different groups demonstrated the significance of microbiome information in developing approaches to improve health. Challenges exist in sample preparation and processing (eg, standardization of methods for collection and analysis). These challenges relate to technology, data integration from “omics” studies, inherent bias in primer selection during 16S ribosomal RNA sequencing, the need for large consortia with well-characterized biospecimens, cause and effect issues, resilience of microbiota to exposure events (requires longitudinal studies), and expanding studies for fungal and viral diversity (most studies used bacterial 16S ribosomal RNA sequencing for microbiota characterization). Despite these challenges, microbiome and cancer epidemiology studies are significant and may facilitate cancer risk assessment, diagnosis, and prognosis. In the future, clinical trials likely will use microbiota modifications to improve the efficacy of existing treatments. PMID:27121074

In situ monitoring, separation, and characterization of gold nanorod transformation during seed-mediated synthesis.

PubMed

Nguyen, Thao M; Pettibone, John M; Gigault, Julien; Hackley, Vincent A

2016-03-01

The control of gold nanorod (GNR) solution-based syntheses has been hindered in part by the inability to examine and control the conversion of precursor seed populations to anisotropic materials, which have resulted in low yields of desired products and limited their commercial viability. The advantages offered by tandem separation and characterization methods utilizing asymmetric-flow field flow fractionation (A4F) are principally achieved as a result of their non-disruptive nature (minimizing artefacts), fast throughput, and in-situ analysis. With hyphenated A4F methods, resolved populations of seeds and secondary products, up to long aspect ratio rods, have been achieved and exemplify progress towards elucidating mechanistic aspects of formation and thus rational design. While there have been previously reported studies on A4F separation of GNRs, to our knowledge, this is the first published investigation of in situ GNR growth, separation, and characterization based on A4F, where its utilization in this capacity goes beyond traditional separation analysis. By using hydroquinone as the reducing agent, the conversion of the initial seed population to a distribution of products, including the GNRs, could be monitored in real time using A4F hyphenated with a diode array detector. Transmission electron microscopy confirms that the number of peaks observed during fractionation corresponds with size and shape dispersity. This proof-of-principle study introduces A4F as a technique that establishes a foundation for future mechanistic studies on the growth of GNRs from gold seeds, including conversion of the seed population to initial products, a topic highly relevant to advancing progress in nanomanufacturing.

From novice to master surgeon: improving feedback with a descriptive approach to intraoperative assessment.

PubMed

Huang, Emily; Wyles, Susannah M; Chern, Hueylan; Kim, Edward; O'Sullivan, Patricia

2016-07-01

A developmental and descriptive approach to assessing trainee intraoperative performance was explored. Semistructured interviews with 20 surgeon educators were recorded, transcribed, deidentified, and analyzed using a grounded theory approach to identify emergent themes. Two researchers independently coded the transcripts. Emergent themes were also compared to existing theories of skill acquisition. Surgeon educators characterized intraoperative surgical performance as an integrated practice of multiple skill categories and included anticipating, planning for contingencies, monitoring progress, self-efficacy, and "working knowledge." Comments concerning progression through stages, broadly characterized as "technician," "anatomist," "anticipator," "strategist," and "executive," formed a narrative about each stage of development. The developmental trajectory with narrative, descriptive profiles of surgeons working toward mastery provide a standardized vocabulary for communicating feedback, while fostering reflection on trainee progress. Viewing surgical performance as integrated practice rather than the conglomerate of isolated skills enhances authentic assessment. Copyright © 2015 Elsevier Inc. All rights reserved.

SITE CHARACTERIZATION AND MONITORING TECHNOLOGY VERIFICATION: PROGRESS AND RESULTS

EPA Science Inventory

The Site Characterization and Monitoring Technology Pilot of the U.S. Environmental Protection Agency's Environmental Technology Verification Program (ETV) has been engaged in verification activities since the fall of 1994 (U.S. EPA, 1997). The purpose of the ETV is to promote th...

Solid State Division progress report for period ending September 30, 1993

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

Green, P.H.; Hinton, L.W.

1994-08-01

This report covers research progress in the Solid State Division from April 1, 1992, to September 30, 1993. During this period, the division conducted a broad, interdisciplinary materials research program with emphasis on theoretical solid state physics, neutron scattering, synthesis and characterization of materials, ion beam and laser processing, and the structure of solids and surfaces. This research effort was enhanced by new capabilities in atomic-scale materials characterization, new emphasis on the synthesis and processing of materials, and increased partnering with industry and universities. The theoretical effort included a broad range of analytical studies, as well as a new emphasismore » on numerical simulation stimulated by advances in high-performance computing and by strong interest in related division experimental programs. Superconductivity research continued to advance on a broad front from fundamental mechanisms of high-temperature superconductivity to the development of new materials and processing techniques. The Neutron Scattering Program was characterized by a strong scientific user program and growing diversity represented by new initiatives in complex fluids and residual stress. The national emphasis on materials synthesis and processing was mirrored in division research programs in thin-film processing, surface modification, and crystal growth. Research on advanced processing techniques such as laser ablation, ion implantation, and plasma processing was complemented by strong programs in the characterization of materials and surfaces including ultrahigh resolution scanning transmission electron microscopy, atomic-resolution chemical analysis, synchrotron x-ray research, and scanning tunneling microscopy.« less

ENaC/DEG in Tumor Development and Progression

PubMed Central

Liu, Cui; Zhu, Li-Li; Xu, Si-Guang; Ji, Hong-Long; Li, Xiu-Min

2016-01-01

The epithelial Na+ channel/degenerin (ENaC/DEG) superfamily, including the acid-sensing ion channels (ASICs), is characterized by a high degree of similarity in structure but highly diverse in physiological functions. These ion channels have been shown to be important in several physiological functions of normal epithelial cells, including salt homeostasis, fluid transportation and cell mobility. There is increasing evidence suggesting that ENaC/DEG channels are critically engaged in cancer cell biology, such as proliferation, migration, invasion and apoptosis, playing a role in tumor development and progression. In this review, we will discuss recent studies showing the role of ENaC and ASIC channels in epithelial cells and its relationship to the oncogenesis. PMID:27698929

Total Ore Processing Integration and Management

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

Leslie Gertsch; Richard Gertsch

2006-01-30

This report outlines the technical progress achieved for project DE-FC26-03NT41785 (Total Ore Processing Integration and Management) during the period 01 July through 30 September of 2005. This ninth quarterly report discusses the activities of the project team during the period 1 July through 30 September 2005. Richard Gertsch's unexpected death due to natural causes while in Minnesota to work on this project has temporarily slowed progress. Statistical analysis of the Minntac Mine data set for late 2004 is continuing. Preliminary results raised several questions that could be amenable to further study. Detailed geotechnical characterization is being applied to improve themore » predictability of mill and agglomerator performance at Hibtac Mine.« less

Understanding nature of science as progressive transitions in heuristic principles

NASA Astrophysics Data System (ADS)

Niaz, Mansoor

2001-11-01

This study has the following objectives: (a) understand nature of science as progressive transitions in heuristic principles as conceptualized by Schwab (1962); (b) reformulate Smith and Scharmann's characterization of nature of science (Smith & Scharmann, 1999) in the light of evidence from history and philosophy of science; and (c) provide a rationale for the inclusion of three more characteristics of nature of science, to the original five suggested by Smith and Scharmann. It is concluded that nature of science manifests in the different topics of the science curriculum as heuristic principles. Science education, by emphasizing not only the empirical nature of science but also the underlying heuristic principles, can facilitate conceptual understanding.

Cancer Systems Biology Consortium | Informatics Technology for Cancer Research (ITCR)

Cancer.gov

Cancer is a complex disease system involving multiple molecular, genetic, and cellular events. From its early initiation through progression and metastasis, cancer can adapt and evolve as a result of both internal and external signals. These properties make cancer difficult to predict, prevent, and treat. There has been significant progress in characterizing the genetics of cancer, as well as the downstream effects on the molecular and cellular pathways that are critical for the initiation and progression of cancer.

Characterization of Drosophila Saposin-related mutants as a model for lysosomal sphingolipid storage diseases

PubMed Central

Schulze, Heike; Paradis, Marie; Gosejacob, Dominic; Papan, Cyrus; Shevchenko, Andrej; Psathaki, Olympia Ekaterina; Thielisch, Melanie; Sandhoff, Konrad

2017-01-01

ABSTRACT Sphingolipidoses are inherited diseases belonging to the class of lysosomal storage diseases (LSDs), which are characterized by the accumulation of indigestible material in the lysosome caused by specific defects in the lysosomal degradation machinery. While some LSDs can be efficiently treated by enzyme replacement therapy (ERT), this is not possible if the nervous system is affected due to the presence of the blood-brain barrier. Sphingolipidoses in particular often present as severe, untreatable forms of LSDs with massive sphingolipid and membrane accumulation in lysosomes, neurodegeneration and very short life expectancy. The digestion of intralumenal membranes within lysosomes is facilitated by lysosomal sphingolipid activator proteins (saposins), which are cleaved from a prosaposin precursor. Prosaposin mutations cause some of the severest forms of sphingolipidoses, and are associated with perinatal lethality in mice, hampering studies on disease progression. We identify the Drosophila prosaposin orthologue Saposin-related (Sap-r) as a key regulator of lysosomal lipid homeostasis in the fly. Its mutation leads to a typical spingolipidosis phenotype with an enlarged endolysosomal compartment and sphingolipid accumulation as shown by mass spectrometry and thin layer chromatography. Sap-r mutants show reduced viability with ∼50% survival to adulthood, allowing us to study progressive neurodegeneration and analyze their lipid profile in young and aged flies. Additionally, we observe a defect in sterol homeostasis with local sterol depletion at the plasma membrane. Furthermore, we find that autophagy is increased, resulting in the accumulation of mitochondria in lysosomes, concomitant with increased oxidative stress. Together, we establish Drosophila Sap-r mutants as a lysosomal storage disease model suitable for studying the age-dependent progression of lysosomal dysfunction associated with lipid accumulation and the resulting pathological signaling events. PMID:28389479

Characterizing the course of back pain after osteoporotic vertebral fracture: a hierarchical cluster analysis of a prospective cohort study.

PubMed

Toyoda, Hiromitsu; Takahashi, Shinji; Hoshino, Masatoshi; Takayama, Kazushi; Iseki, Kazumichi; Sasaoka, Ryuichi; Tsujio, Tadao; Yasuda, Hiroyuki; Sasaki, Takeharu; Kanematsu, Fumiaki; Kono, Hiroshi; Nakamura, Hiroaki

2017-09-23

This study demonstrated four distinct patterns in the course of back pain after osteoporotic vertebral fracture (OVF). Greater angular instability in the first 6 months after the baseline was one factor affecting back pain after OVF. Understanding the natural course of symptomatic acute OVF is important in deciding the optimal treatment strategy. We used latent class analysis to classify the course of back pain after OVF and identify the risk factors associated with persistent pain. This multicenter cohort study included 218 consecutive patients with ≤ 2-week-old OVFs who were enrolled at 11 institutions. Dynamic x-rays and back pain assessment with a visual analog scale (VAS) were obtained at enrollment and at 1-, 3-, and 6-month follow-ups. The VAS scores were used to characterize patient groups, using hierarchical cluster analysis. VAS for 128 patients was used for hierarchical cluster analysis. Analysis yielded four clusters representing different patterns of back pain progression. Cluster 1 patients (50.8%) had stable, mild pain. Cluster 2 patients (21.1%) started with moderate pain and progressed quickly to very low pain. Patients in cluster 3 (10.9%) had moderate pain that initially improved but worsened after 3 months. Cluster 4 patients (17.2%) had persistent severe pain. Patients in cluster 4 showed significant high baseline pain intensity, higher degree of angular instability, and higher number of previous OVFs, and tended to lack regular exercise. In contrast, patients in cluster 2 had significantly lower baseline VAS and less angular instability. We identified four distinct groups of OVF patients with different patterns of back pain progression. Understanding the course of back pain after OVF may help in its management and contribute to future treatment trials.

Hypertension and Diabetes Mellitus: Coprediction and Time Trajectories.

PubMed

Tsimihodimos, Vasilis; Gonzalez-Villalpando, Clicerio; Meigs, James B; Ferrannini, Ele

2018-03-01

Type 2 diabetes mellitus and hypertension overlap in the population. In many subjects, development of diabetes mellitus is characterized by a relatively rapid increase in plasma glucose values. Whether a similar phenomenon occurs during the development of hypertension is not known. We analyzed the pattern of blood pressure (BP) changes during the development of hypertension in patients with or without diabetes mellitus using data from the MCDS (Mexico City Diabetes Study; a population-based study of diabetes mellitus in Hispanic whites) and in the FOS (Framingham Offspring Study, a community-based study in non-Hispanic whites) during a 7-year follow-up. Diabetes mellitus at baseline was a significant predictor of incident hypertension (in FOS, odds ratio, 3.14; 95% confidence interval, 2.17-4.54) independently of sex, age, body mass index, and familial diabetes mellitus. Conversely, hypertension at baseline was an independent predictor of incident diabetes mellitus (in FOS, odds ratio, 3.33; 95% CI, 2.50-4.44). In >60% of the converters, progression from normotension to hypertension was characterized by a steep increase in BP values, averaging 20 mm Hg for systolic BP within 3.5 years (in MCDS). In comparison with the nonconverters group, hypertension and diabetes mellitus converters shared a metabolic syndrome phenotype (hyperinsulinemia, higher body mass index, waist girth, BP, heart rate and pulse pressure, and dyslipidemia). Overall, results were similar in the 2 ethnic groups. We conclude that (1) development of hypertension and diabetes mellitus track each other over time, (2) transition from normotension to hypertension is characterized by a sharp increase in BP values, and (3) insulin resistance is one common feature of both prediabetes and prehypertension and an antecedent of progression to 2 respective disease states. © 2018 American Heart Association, Inc.

Dynamics of viral hemorrhagic septicemia, viral erythrocytic necrosis and ichthyophoniasis in confined juvenile Pacific herring Clupea pallasii

USGS Publications Warehouse

Hershberger, P.; Hart, A.; Gregg, J.; Elder, N.; Winton, J.

2006-01-01

Capture of wild, juvenile herring Clupea pallasii from Puget Sound (Washington, USA) and confinement in laboratory tanks resulted in outbreaks of viral hemorrhagic septicemia (VHS), viral erythrocytic necrosis (VEN) and ichthyophoniasis; however, the timing and progression of the 3 diseases differed. The VHS epidemic occurred first, characterized by an initially low infection prevalence that increased quickly with confinement time, peaking at 93 to 98% after confinement for 6 d, then decreasing to negligible levels after 20 d. The VHS outbreak was followed by a VEN epidemic that, within 12 d of confinement, progressed from undetectable levels to 100% infection prevalence with >90% of erythrocytes demonstrating inclusions. The VEN epidemic persisted for 54 d, after which the study was terminated, and was characterized by severe blood dyscrasias including reduction of mean hematocrit from 42 to 6% and replacement of mature erythrocytes with circulating erythroblasts and ghost cells. All fish with ichthyophoniasis at capture died within the first 3 wk of confinement, probably as a result of the multiple stressors associated with capture, transport, confinement, and progression of concomitant viral diseases. The results illustrate the differences in disease ecology and possible synergistic effects of pathogens affecting marine fish and highlight the difficulty in ascribing a single causation to outbreaks of disease among populations of wild fishes. ?? Inter-Research 2006.

High-Pressure Turbulent Flame Speeds and Chemical Kinetics of Syngas Blends with and without Impurities

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

Peterson, Eric; Mathieu, Olivier; Morones, Anibal

2014-12-01

This Topical Report documents the first year of the project, from October 1, 2013 through September 30, 2014. Efforts for this project included experiments to characterize the atmospheric-pressure turbulent flame speed vessel over a range of operating conditions (fan speeds and turbulent length scales). To this end, a new LDV system was acquired and set up for the detailed characterization of the turbulence field. Much progress was made in the area of impurity kinetics, which included a numerical study of the effect of impurities such as NO2, NO, H2S, and NH3 on ignition delay times and laminar flame speeds ofmore » syngas blends at engine conditions. Experiments included a series of laminar flame speed measurements for syngas (CO/H2) blends with various levels of CH4 and C2H6 addition, and the results were compared to the chemical kinetics model of NUI Galway. Also, a final NOx kinetics mechanism including ammonia was assembled, and a journal paper was written and is now in press. Overall, three journal papers and six conference papers related to this project were published this year. Finally, much progress was made on the design of the new high-pressure turbulent flame speed facility. An overall design that includes a venting system was decided upon, and the detailed design is in progress.« less

The Aurora kinase A inhibitor TC-A2317 disrupts mitotic progression and inhibits cancer cell proliferation

PubMed Central

Min, Yoo Hong; Kim, Wootae; Kim, Ja-Eun

2016-01-01

Mitotic progression is crucial for the maintenance of chromosomal stability. A proper progression is ensured by the activities of multiple kinases. One of these enzymes, the serine/threonine kinase Aurora A, is required for proper mitosis through the regulation of centrosome and spindle assembly. In this study, we functionally characterized a newly developed Aurora kinase A inhibitor, TC-A2317. In human lung cancer cells, TC-A2317 slowed proliferation by causing aberrant formation of centrosome and microtubule spindles and prolonging the duration of mitosis. Abnormal mitotic progression led to accumulation of cells containing micronuclei or multinuclei. Furthermore, TC-A2317–treated cells underwent apoptosis, autophagy or senescence depending on cell type. In addition, TC-A2317 inactivated the spindle assembly checkpoint triggered by paclitaxel, thereby exacerbating mitotic catastrophe. Consistent with this, the expression level of Aurora A in tumors was inversely correlated with survival in lung cancer patients. Collectively, these data suggest that inhibition of Aurora kinase A using TC-A2317 is a promising target for anti-cancer therapeutics. PMID:27713168

New candidate markers of head and neck squamous cell carcinoma progression

NASA Astrophysics Data System (ADS)

Kakurina, G. V.; Kolegova, E. S.; Cheremisina, O. V.; Kulbakin, D. E.; Choinzonov, E. L.

2017-09-01

The tumor progression in head and neck squamous cell carcinoma (HNSCC) is one of the main causes of high mortality of the patients with HNSCC. The tumor progression, particularly the metastasis, is characterized by the changes in the composition, functions and structure of different proteins. We have previously shown that serum of HNSCC patients contains the proteins which regulate various cellular processes—adenylyl cyclase associated protein 1 (CAP1), protein phosphatase 1 B (PPM1B), etc. The levels of CAP1 and PPM1B were determined using the enzyme immunoassay. The results of this study show that CAP1 and PPM1B take a part in the progression of HNSCC. The levels of CAP1 and PPM1B in the tumor and in morphologically normal tissue depended on the prevalence of the tumor process. The CAP1 and PPM1B levels were significantly higher in tumor tissue of the patients with regional metastasis. Our data allow assuming the potential possibility for predicting the outcome of the HNSCC measuring the level of tissue CAP1.

Connective Tissue Mineralization in Abcc6−/− Mice, a Model for Pseudoxanthoma Elasticum

PubMed Central

Kavukcuoglu, N. Beril; Li, Qiaoli; Pleshko, Nancy; Uitto, Jouni

2012-01-01

Pseudoxanthoma elasticum (PXE) is a heritable multisystem disorder characterized by ectopic mineralization. However, the structure of the mineral deposits, their interactions with the connective tissue matrix, and the details of the progressive maturation of the mineral crystals are currently unknown. In this study, we examined the mineralization processes in Abcc6−/− mice, a model system for PXE, by energy dispersive X-ray, and Fourier transform infrared imaging spectroscopy (FT-IRIS). The results indicated that the principal components of the mineral deposits were calcium and phosphate which co-localized within the histologically demonstrable lesions determined by topographic mapping. The Ca/P ratio increased in samples with progressive mineralization reaching the value comparable to that in endochondral bone. A progressive increase in mineralization was also reflected by increased mineral-to-matrix ratio determined by FT-IRIS. Determination of the mineral phases by FT-IRIS suggested progressive maturation of the mineral deposits from amorphous calcium phosphate to hydroxyapatite. These results provide critical information of the mechanisms of mineralization in PXE, with potential pharmacologic implications. PMID:22421595

Characterization of the expression of the pro-metastatic Mena(INV) isoform during breast tumor progression.

PubMed

Oudin, Madeleine J; Hughes, Shannon K; Rohani, Nazanin; Moufarrej, Mira N; Jones, Joan G; Condeelis, John S; Lauffenburger, Douglas A; Gertler, Frank B

2016-03-01

Several functionally distinct isoforms of the actin regulatory Mena are produced by alternative splicing during tumor progression. Forced expression of the Mena(INV) isoform drives invasion, intravasation and metastasis. However, the abundance and distribution of endogenously expressed Mena(INV) within primary tumors during progression remain unknown, as most studies to date have only assessed relative mRNA levels from dissociated tumor samples. We have developed a Mena(INV) isoform-specific monoclonal antibody and used it to examine Mena(INV) expression patterns in mouse mammary and human breast tumors. Mena(INV) expression increases during tumor progression and to examine the relationship between Mena(INV) expression and markers for epithelial or mesenchymal status, stemness, stromal cell types and hypoxic regions. Further, while Mena(INV) robustly expressed in vascularized areas of the tumor, it is not confined to cells adjacent to blood vessels. Altogether, these data demonstrate the specificity and utility of the anti-Mena(INV)-isoform specific antibody, and provide the first description of endogenous Mena(INV) protein expression in mouse and human tumors.

Deep dysphasic performance in non-fluent progressive aphasia: a case study.

PubMed

Tree, J J; Perfect, T J; Hirsh, K W; Copstick, S

2001-01-01

We present a patient (PW) with non-fluent progressive aphasia, characterized by severe word finding difficulties and frequent phonemic paraphasias in spontaneous speech. It has been suggested that such patients have insufficient access to phonological information for output and cannot construct the appropriate sequence of selected phonemes for articulation. Consistent with such a proposal, we found that PW was impaired on a variety of verbal tasks that demand access to phonological representations (reading, repetition, confrontational naming and rhyme judgement); she also demonstrated poor performance on syntactic and grammatical processing tasks. However, examination of PW's repetition performance also revealed that she made semantic paraphasias and that her performance was influenced by imageability and lexical status. Her auditory-verbal short-term memory was also severely compromised. These features are consistent with 'deep dysphasia', a disorder reported in patients suffering from stroke or cerebrovascular accident, and rarely reported in the context of non-fluent progressive aphasia. PW's pattern of performance is evaluated in terms of current models of both non-fluent progressive aphasia and deep dysphasia.

Serum biomarkers in patients with ossification of the posterior longitudinal ligament (OPLL): Inflammation in OPLL.

PubMed

Kawaguchi, Yoshiharu; Nakano, Masato; Yasuda, Taketoshi; Seki, Shoji; Suzuki, Kayo; Yahara, Yasuhito; Makino, Hiroto; Kitajima, Isao; Kimura, Tomoatsu

2017-01-01

Ossification of the posterior longitudinal ligament (OPLL) is characterized by replacement of ligamentous tissue by ectopic new bone formation. OPLL causes narrowing of the spinal canal, resulting in neurological impairment. However, the pathogenesis of OPLL has not been fully elucidated. We investigated whether inflammation occurs in OPLL or not using high-sensitivity CRP (hs-CRP) in a case-control study. This study included 103 patients with OPLL in the patient group and 95 age- and sex-matched volunteers with degenerative spinal disease in the control group. Of the 103 OPLL patients, 88 patients who were available for more than 2 years follow-up were checked for OPLL progression. A blood sample was obtained and Hs-CRP, and other routine data, including total protein (TP), albumin (ALB), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), glucose (Glu), calcium (Ca), inorganic phosphate (Pi), white blood cell count (WBC), hemoglobin (Hb) and platelet (PLT), were analyzed. The data were compared between the patients with OPLL and the controls. The severity of the ossified lesions in the whole spine were evaluated by the ossification index (OS index) in patients with OPLL. The data were also compared between the patients with OPLL progression (the progression group) and the patients without OPLL progression (the non-progression group). In the results, the mean hs-CRP in the OPLL group was higher than that in the controls. The Pi in the OPLL group was lower than that in the control group. A negative correlation was found between the Pi and the OS index. The mean hs-CRP in the progression group was higher than that in the non-progression group. There was a positive correlation between the average length of the OPLL progression per year and the hs-CRP. The results may suggest the occurrence of local inflammation in OPLL and the inflammation might cause OPLL progression. These facts are important for understanding the pathology of OPLL.

U.S. Geological Survey research in radioactive waste disposal - Fiscal years 1983, 1984, and 1985

USGS Publications Warehouse

Dinwiddie, G.A.; Trask, N.J.

1986-01-01

The report summarizes progress on geologic and hydrologic research related to the disposal of radioactive wastes. The research is described according to whether it is related most directly to: (1) high-level and transuranic wastes, (2) low-level wastes, or (3) uranium mill tailings. Included is research applicable to the identification and geohydrologic characterization of waste-disposal sites, to investigations of specific sites where wastes have been stored, and to studies of regions or environments where waste-disposal sites might be located. A significant part of the activity is concerned with techniques and methods for characterizing disposal sites and studies of geologic and hydrologic processes related to the transport and (or) retention of waste radionuclides.

Seizure susceptibility in intact and ovariectomized female rats treated with the convulsant pilocarpine

PubMed Central

Scharfman, Helen E.; Goodman, Jeffrey H.; Rigoulot, Marie-Aude; Berger, Russell E.; Walling, Susan G.; Mercurio, Thomas C.; Stormes, Kerry; Maclusky, Neil J.

2008-01-01

Despite numerous neuroendocrinological studies of seizures, the influence of estrogen and progesterone on seizures and epilepsy remains unclear. This may be due to the fact that previous studies have not systematically compared distinct endocrine conditions and included all relevant controls. The goal of the present study was to conduct such a study using pilocarpine as chemoconvulsant. Thus, age and weight-matched, intact or ovariectomized rats were tested to determine incidence of status epilepticus and to study events leading to status. Intact female rats were sampled at each cycle stage (proestrus, estrus, metestrus, or diestrus 2). Convulsant was administered at the same time of day, 10:00–10:30 a.m. Statistical analysis showed that there was a significantly lower incidence of status on the morning of estrus, but differences were attenuated in older animals. Ovariectomized rats were distinct in their rapid progression to status. These results show that the incidence of status in female rats following pilocarpine injection, and the progression to pilocarpine-induced status, are influenced by reproductive state as well as age. The hormonal milieu present specifically on the morning of estrus appears to decrease susceptibility to pilocarpine-induced status, particularly at young ages. In contrast, the chronic absence of reproductive steroids that characterizes the ovariectomized rat leads to a more rapid progression to status. This dissociation between incidence vs. progression provides new insight into the influence of estrogen and progesterone on seizures. PMID:16084511

DREAM-Dependent Activation of Astrocytes in Amyotrophic Lateral Sclerosis.

PubMed

Larrodé, Pilar; Calvo, Ana Cristina; Moreno-Martínez, Laura; de la Torre, Miriam; Moreno-García, Leticia; Molina, Nora; Castiella, Tomás; Iñiguez, Cristina; Pascual, Luis Fernando; Mena, Francisco Javier Miana; Zaragoza, Pilar; Y Cajal, Santiago Ramón; Osta, Rosario

2018-01-01

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of unknown origin and characterized by a relentless loss of motor neurons that causes a progressive muscle weakness until death. Among the several pathogenic mechanisms that have been related to ALS, a dysregulation of calcium-buffering proteins in motor neurons of the brain and spinal cord can make these neurons more vulnerable to disease progression. Downstream regulatory element antagonist modulator (DREAM) is a neuronal calcium-binding protein that plays multiple roles in the nucleus and cytosol. The main aim of this study was focused on the characterization of DREAM and glial fibrillary acid protein (GFAP) in the brain and spinal cord tissues from transgenic SOD1 G93A mice and ALS patients to unravel its potential role under neurodegenerative conditions. The DREAM and GFAP levels in the spinal cord and different brain areas from transgenic SOD1 G93A mice and ALS patients were analyzed by Western blot and immunohistochemistry. Our findings suggest that the calcium-dependent excitotoxicity progressively enhanced in the CNS in ALS could modulate the multifunctional nature of DREAM, strengthening its apoptotic way of action in both motor neurons and astrocytes, which could act as an additional factor to increase neuronal damage. The direct crosstalk between astrocytes and motor neurons can become vulnerable under neurodegenerative conditions, and DREAM could act as an additional switch to enhance motor neuron loss. Together, these findings could pave the way to further study the molecular targets of DREAM to find novel therapeutic strategies to fight ALS.

Toxin Models of Mitochondrial Dysfunction in Parkinson's Disease

PubMed Central

Martinez, Terina N.

2012-01-01

Abstract Significance: Parkinson's disease (PD) is a neurodegenerative disorder characterized, in part, by the progressive and selective loss of dopaminergic neuron cell bodies within the substantia nigra pars compacta (SNpc) and the associated deficiency of the neurotransmitter dopamine (DA) in the striatum, which gives rise to the typical motor symptoms of PD. The mechanisms that contribute to the induction and progressive cell death of dopaminergic neurons in PD are multi-faceted and remain incompletely understood. Data from epidemiological studies in humans and molecular studies in genetic, as well as toxin-induced animal models of parkinsonism, indicate that mitochondrial dysfunction occurs early in the pathogenesis of both familial and idiopathic PD. In this review, we provide an overview of toxin models of mitochondrial dysfunction in experimental Parkinson's disease and discuss mitochondrial mechanisms of neurotoxicity. Recent Advances: A new toxin model using the mitochondrial toxin trichloroethylene was recently described and novel methods, such as intranasal exposure to toxins, have been explored. Additionally, recent research conducted in toxin models of parkinsonism provides an emerging emphasis on extranigral aspects of PD pathology. Critical Issues: Unfortunately, none of the existing animal models of experimental PD completely mimics the etiology, progression, and pathology of human PD. Future Directions: Continued efforts to optimize established animal models of parkinsonism, as well as the development and characterization of new animal models are essential, as there still remains a disconnect in terms of translating mechanistic observations in animal models of experimental PD into bona fide disease-modifying therapeutics for human PD patients. Antioxid. Redox Signal. 16, 920–934. PMID:21554057

Second-harmonic generation and fluorescence lifetime imaging microscopy through a rodent mammary imaging window

NASA Astrophysics Data System (ADS)

Young, Pamela A.; Nazir, Muhammad; Szulczewski, Michael J.; Keely, Patricia J.; Eliceiri, Kevin W.

2012-03-01

Tumor-Associated Collagen Signatures (TACS) have been identified that manifest in specific ways during breast tumor progression and that correspond to patient outcome. There are also compelling metabolic changes associated with carcinoma invasion and progression. We have characterized the difference in the autofluorescent properties of metabolic co-factors, NADH and FAD, between normal and carcinoma breast cell lines. Also, we have shown in vitro that increased collagen density alters metabolic genes which are associated with glycolysis and leads to a more invasive phenotype. Establishing the relationship between collagen density, cellular metabolism, and metastasis in physiologically relevant cancer models is crucial for developing cancer therapies. To study cellular metabolism with respect to collagen density in vivo, we use multiphoton fluorescence excitation microscopy (MPM) in conjunction with a rodent mammary imaging window implanted in defined mouse cancer models. These models are ideal for the study of collagen changes in vivo, allowing determination of corresponding metabolic changes in breast cancer invasion and progression. To measure cellular metabolism, we collect fluorescence lifetime (FLIM) signatures of NADH and FAD, which are known to change based on the microenvironment of the cells. Additionally, MPM systems are capable of collecting second harmonic generation (SHG) signals which are a nonlinear optical property of collagen. Therefore, MPM, SHG, and FLIM are powerful tools with great potential for characterizing key features of breast carcinoma in vivo. Below we present the current efforts of our collaborative group to develop intravital approaches based on these imaging techniques to look at defined mouse mammary models.

Analyzing Students' Learning Progressions Throughout a Teaching Sequence on Acoustic Properties of Materials with a Model-Based Inquiry Approach

NASA Astrophysics Data System (ADS)

Hernández, María Isabel; Couso, Digna; Pintó, Roser

2015-04-01

The study we have carried out aims to characterize 15- to 16-year-old students' learning progressions throughout the implementation of a teaching-learning sequence on the acoustic properties of materials. Our purpose is to better understand students' modeling processes about this topic and to identify how the instructional design and actual enactment influences students' learning progressions. This article presents the design principles which elicit the structure and types of modeling and inquiry activities designed to promote students' development of three conceptual models. Some of these activities are enhanced by the use of ICT such as sound level meters connected to data capture systems, which facilitate the measurement of the intensity level of sound emitted by a sound source and transmitted through different materials. Framing this study within the design-based research paradigm, it consists of the experimentation of the designed teaching sequence with two groups of students ( n = 29) in their science classes. The analysis of students' written productions together with classroom observations of the implementation of the teaching sequence allowed characterizing students' development of the conceptual models. Moreover, we could evidence the influence of different modeling and inquiry activities on students' development of the conceptual models, identifying those that have a major impact on students' modeling processes. Having evidenced different levels of development of each conceptual model, our results have been interpreted in terms of the attributes of each conceptual model, the distance between students' preliminary mental models and the intended conceptual models, and the instructional design and enactment.

DOE/JPL advanced thermionic technology program

NASA Technical Reports Server (NTRS)

1979-01-01

Progress made in different tasks of the advanced thermionic technology program is described. The tasks include surface and plasma investigations (surface characterization, spectroscopic plasma experiments, and converter theory); low temperature converter development (tungsten emitter, tungsten oxide collector and tungsten emitter, nickel collector); component hardware development (hot shell development); flame-fired silicon carbide converters; high temperature and advanced converter studies; postoperational diagnostics; and correlation of design interfaces.

Polymer-Carbon Nanotube Composites, A Literature Review

DTIC Science & Technology

2004-08-01

have led to improvements in product controllability, yield, and cost . Other aspects of nanotube synthesis currently under scrutiny include study of...progress in many areas of characterization and applications was initially hindered by the high cost of production, as well as the requirement of...processing the nanotubes. In recent years, the production costs have decreased dramatically as a result of the development of new, high-throughput

Structural Integrity of Water Reactor Pressure Boundary Components.

DTIC Science & Technology

1979-12-31

fatigue crack growth is also on-going. Substantial progress in all three of the areas - fatigue data generation, fractography and micromechanism... Fractographie Examinations During the past year, there have been several fractographic studies and fractographically-related research efforts which have been...in the T-L orientation were characterized by a m icrostructural texture running parallel to the macroscopic crack propagation direction (Fig. 31). This

Characterization of leukocyte subsets in buffalo (Bubalus bubalis) with cross-reactive monoclonal antibodies specific for bovine MHC class I and class II molecules and leukocyte differentiation molecules

USDA-ARS?s Scientific Manuscript database

Although buffalo (Bubalus bubalis) are a major component of the livestock industry worldwide, limited progress has been made in the study of the mechanisms regulating the immune response to pathogens and parasites affecting their health and productivity. This has been, in part, attributable to the l...

X-Linked Intellectual Disability: Unique Vulnerability of the Male Genome

ERIC Educational Resources Information Center

Stevenson, Roger E.; Schwartz, Charles E.

2009-01-01

X-linked intellectual disability (XLID) accounts for approximately 16% of males with intellectual disability (ID). This is, in part, related to the fact that males have a single X chromosome. Progress in the clinical and molecular characterization of XLID has outpaced progress in the delineation of ID due to genes on the other 22 chromosomes.…

Human Rights Education: The Promise of the Third Millennium?

ERIC Educational Resources Information Center

Baxi, Upendra

The 20th century could be characterized as the "Age of Rights." Never before has there been such progress and interest in human rights standards. To ensure this progress, human rights education (HRE) needs to look at the world history of the struggles for rights and against tyranny and injustice. The notions of HRE originated in the text…

Cognitive deficits and reduced insight in primary progressive aphasia.

PubMed

Banks, Sarah Jane; Weintraub, Sandra

2008-01-01

Primary progressive aphasia (PPA) is a form of dementia caused by frontotemporal lobar degeneration. Unlike aphasia due to stroke, in which the association between particular aphasia profiles and insight has been well characterized, this relationship has not been investigated in PPA. Reduced insight is seen in other neurological conditions, but tends to involve right hemisphere damage, whereas PPA is predominantly a left hemisphere disorder. The aim of the current study was to examine whether fluent aphasia with less meaningful speech output, associated with diminished insight in stroke, is also characteristic of PPA patients with reduced insight. Fourteen PPA patients were studied. Results indicated that reduced information content in speech and poor performance on a nonlanguage test, the Pyramids and Palm Trees test, predicted reduced insight. This study has implications for the anatomical network involved in insight and clinical implications in terms of selecting interventions appropriate for individual patients with PPA.

Cognitive Deficits and Reduced Insight in Primary Progressive Aphasia

PubMed Central

Banks, Sarah Jane; Weintraub, Sandra

2009-01-01

Primary progressive aphasia (PPA) is a form of dementia caused by frontotemporal lobar degeneration. Unlike aphasia due to stroke, in which the association between particular aphasia profiles and insight has been well characterized, this relationship has not been investigated in PPA. Reduced insight is seen in other neurological conditions, but tends to involve right hemisphere damage, whereas PPA is predominantly a left hemisphere disorder. The aim of the current study was to examine whether fluent aphasia with less meaningful speech output, associated with diminished insight in stroke, is also characteristic of PPA patients with reduced insight. Fourteen PPA patients were studied. Results indicated that reduced information content in speech and poor performance on a nonlanguage test, the Pyramids and Palm Trees test, predicted reduced insight. This study has implications for the anatomical network involved in insight and clinical implications in terms of selecting interventions appropriate for individual patients with PPA. PMID:18836134

U.S. Geological Survey research in radioactive waste disposal - Fiscal years 1986-1990

USGS Publications Warehouse

Trask, N.J.; Stevens, P.R.

1991-01-01

The report summarizes progress on geologic and hydrologic research related to the disposal of radioactive wastes. The research efforts are categorized according to whether they are related most directly to: (1) high-level wastes, (2) transuranic wastes, (3) low-level and mixed low-level and hazardous wastes, or (4) uranium mill tailings. Included is research applicable to the identification and geohydrologic characterization of waste-disposal sites, to investigations of specific sites where wastes have been stored, to development of techniques and methods for characterizing disposal sites, and to studies of geologic and hydrologic processes related to the transport and/or retention of waste radionuclides.

The spectrum of progressive derecho formation environments

NASA Astrophysics Data System (ADS)

Guastini, Corey T.

Progressive derechos are severe mesoscale convective systems that often form east of the Rocky Mountains during the warm season (May--August) and cause, by definition, straight-line wind damage along paths upwards of 400 km long. This study develops a subjective, seven-category classification scheme that spans the spectrum of progressive derecho formation environments from those dominated by robust upper-level ridges to those characterized by vigorous upper-level troughs. A climatology of 256 progressive derecho events is created for 1996--2013 and is categorized according to the developed classification scheme. Derecho initiation-relative composites are constructed for each of the seven groups using 0.5° Climate Forecast System Reanalysis data to document the environmental characteristics unique to each group as well as those shared among them. Finally, two in-depth case studies and five cursory case studies provide examples of the seven categories and reveal important nuances in mesoscale dynamic and thermodynamic structure inherent to all derecho cases. Results of the climatology show progressive derecho activity increases from 1 May through 1 July before decreasing again through the end of August and follows a northward trend in latitude from 1 May through 1 August before shifting slightly southward through the end of the warm season. Upslope flow in the vicinity of the Rocky Mountains initiates 28 percent of progressive derechos, upper-level troughs initiate 20 percent, 47 percent form in benign synoptic environments, and 5 percent are unclassifiable. Composite results show all progressive derecho initiation environments are marked by a long axis of instability caused by the overlap of high atmospheric moisture content and steep midlevel lapse rates, but the relative positions and strengths of upper-level troughs and ridges are crucial in determining how the instability axis develops and what its orientation in space will be. Case studies reveal instability axes forming in benign synoptic environments are generally zonally oriented and mainly the result of convergence of low-level moisture, whereas stronger synoptic-scale forcing forms meridionally oriented instability axes through the northward advection of Gulf moisture. The length and magnitude of these instability axes largely determines the duration and severity of a given progressive derecho.

High precision optical spectroscopy and quantum state selected photodissociation of ultracold 88Sr2 molecules in an optical lattice

NASA Astrophysics Data System (ADS)

McDonald, Mickey

2017-04-01

Over the past several decades, rapid progress has been made toward the accurate characterization and control of atoms, epitomized by the ever-increasing accuracy and precision of optical atomic lattice clocks. Extending this progress to molecules will have exciting implications for chemistry, condensed matter physics, and precision tests of physics beyond the Standard Model. My thesis describes work performed over the past six years to establish the state of the art in manipulation and quantum control of ultracold molecules. We describe a thorough set of measurements characterizing the rovibrational structure of weakly bound 88Sr2 molecules from several different perspectives, including determinations of binding energies; linear, quadratic, and higher order Zeeman shifts; transition strengths between bound states; and lifetimes of narrow subradiant states. Finally, we discuss measurements of photofragment angular distributions produced by photodissociation of molecules in single quantum states, leading to an exploration of quantum-state-resolved ultracold chemistry. The images of exploding photofragments produced in these studies exhibit dramatic interference effects and strongly violate semiclassical predictions, instead requiring a fully quantum mechanical description.

Experimental Investigation of the Acoustic Nonlinear Behavior in Granular Polymer Bonded Explosives with Progressive Fatigue Damage

PubMed Central

Yang, Zhanfeng; Tian, Yong; Li, Weibin; Zhou, Haiqiang; Zhang, Weibin; Li, Jingming

2017-01-01

The measurement of acoustic nonlinear response is known as a promising technique to characterize material micro-damages. In this paper, nonlinear ultrasonic approach is used to characterize the evolution of fatigue induced micro-cracks in polymer bonded explosives. The variations of acoustic nonlinearity with respect to fatigue cycles in the specimens are obtained in this investigation. The present results show a significant increase of acoustic nonlinearity with respect to fatigue cycles. The experimental observation of the correlation between the acoustic nonlinearity and fatigue cycles in carbon/epoxy laminates, verifies that an acoustic nonlinear response can be used to evaluate the progressive fatigue damage in the granular polymer bonded explosives. The sensitivity comparison of nonlinear and linear parameters of ultrasonic waves in the specimens shows that nonlinear acoustic parameters are more promising indicators to fatigue induced micro-damage than linear ones. The feasibility study of the micro-damage assessment of polymer bonded explosives by nonlinear ultrasonic technique in this work can be applied to damage identification, material degradation monitoring, and lifetime prediction of the explosive parts. PMID:28773017

Progress in digestive endoscopy: Flexible Spectral Imaging Colour Enhancement (FICE)-technical review.

PubMed

Negreanu, L; Preda, C M; Ionescu, D; Ferechide, D

2015-01-01

Background. A substantial advance in digestive endoscopy that has been made during the last decade is represented by digital chromoendoscopy, which was developed as a quicker and sometimes better alternative to the gold standard of dye spraying. Fujifilm developed a virtual coloration technique called Flexible spectral Imaging Color Enhancement (FICE). FICE provides a better detection of lesions of "minimal" esophagitis, of dysplasia in Barrett's esophagus and of squamous cell esophageal cancer. The use of FICE resulted in an improvement in the visualization of the early gastric cancer, being less invasive, and time consuming than the classic dye methods. Current evidence does not support FICE for screening purposes in colon cancer but it definitely improves characterization of colonic lesions. Its use in inflammatory bowel disease is still controversial and in video capsule endoscopy is considered a substantial progress. Conclusions. The use of FICE endoscopy in routine clinical practice can increase the diagnostic yield and can provide a better characterization of lesions. Future studies to validate its use, the good choice of channels, and the "perfect indications" and to provide common definitions and classifications are necessary.

Experimental Investigation of the Acoustic Nonlinear Behavior in Granular Polymer Bonded Explosives with Progressive Fatigue Damage.

PubMed

Yang, Zhanfeng; Tian, Yong; Li, Weibin; Zhou, Haiqiang; Zhang, Weibin; Li, Jingming

2017-06-16

The measurement of acoustic nonlinear response is known as a promising technique to characterize material micro-damages. In this paper, nonlinear ultrasonic approach is used to characterize the evolution of fatigue induced micro-cracks in polymer bonded explosives. The variations of acoustic nonlinearity with respect to fatigue cycles in the specimens are obtained in this investigation. The present results show a significant increase of acoustic nonlinearity with respect to fatigue cycles. The experimental observation of the correlation between the acoustic nonlinearity and fatigue cycles in carbon/epoxy laminates, verifies that an acoustic nonlinear response can be used to evaluate the progressive fatigue damage in the granular polymer bonded explosives. The sensitivity comparison of nonlinear and linear parameters of ultrasonic waves in the specimens shows that nonlinear acoustic parameters are more promising indicators to fatigue induced micro-damage than linear ones. The feasibility study of the micro-damage assessment of polymer bonded explosives by nonlinear ultrasonic technique in this work can be applied to damage identification, material degradation monitoring, and lifetime prediction of the explosive parts.

Quantitative Characterization of Cell Behaviors through Cell Cycle Progression via Automated Cell Tracking

PubMed Central

Wang, Yuliang; Jeong, Younkoo; Jhiang, Sissy M.; Yu, Lianbo; Menq, Chia-Hsiang

2014-01-01

Cell behaviors are reflections of intracellular tension dynamics and play important roles in many cellular processes. In this study, temporal variations in cell geometry and cell motion through cell cycle progression were quantitatively characterized via automated cell tracking for MCF-10A non-transformed breast cells, MCF-7 non-invasive breast cancer cells, and MDA-MB-231 highly metastatic breast cancer cells. A new cell segmentation method, which combines the threshold method and our modified edge based active contour method, was applied to optimize cell boundary detection for all cells in the field-of-view. An automated cell-tracking program was implemented to conduct live cell tracking over 40 hours for the three cell lines. The cell boundary and location information was measured and aligned with cell cycle progression with constructed cell lineage trees. Cell behaviors were studied in terms of cell geometry and cell motion. For cell geometry, cell area and cell axis ratio were investigated. For cell motion, instantaneous migration speed, cell motion type, as well as cell motion range were analyzed. We applied a cell-based approach that allows us to examine and compare temporal variations of cell behavior along with cell cycle progression at a single cell level. Cell body geometry along with distribution of peripheral protrusion structures appears to be associated with cell motion features. Migration speed together with motion type and motion ranges are required to distinguish the three cell-lines examined. We found that cells dividing or overlapping vertically are unique features of cell malignancy for both MCF-7 and MDA-MB-231 cells, whereas abrupt changes in cell body geometry and cell motion during mitosis are unique to highly metastatic MDA-MB-231 cells. Taken together, our live cell tracking system serves as an invaluable tool to identify cell behaviors that are unique to malignant and/or highly metastatic breast cancer cells. PMID:24911281

Localization to Xq22 and clinical update of a family with X-linked recessive mental retardation with progression sensorineural deafness, progressive tapeto-retinal degeneration and dystonia

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

Tranebjaerg, L.; Schwartz, C.; Huggins, K.

1994-07-15

In a reinvestigation of a six-generation Norwegian family, originally reported with non-syndromic X-linked recessive deafness by Mohr and Mageroy, we have demonstrated several syndromic manifestations. The 10 clinically characterized affected males range in age from 14-61 years, and show progressive mental deterioration and visual disability. Ophthalmological and electrophysiological studies showed myopia, decreased visual acuity, combined cone-rod dystrophy as well as central areolar dystrophy by means of ERG. Brain CT-scans showed cortical and central atrophy without predilection to specific areas. Linkage analysis, using X-chromosomal RFLPs and CA-repeats, yielded a maximum LOD score of 4.37 with linkage to DXS17. DXS17 is localizedmore » to Xq22. One recombinant with COL4A5 (deficient in Alport syndrome) was observed. Results from the studies of this family will be important in reclassification of non-syndromic X-linked deafness since the family now represents syndromic deafness and XLMR with a specific phenotype.« less

Vascular smooth muscle cells exhibit a progressive loss of rigidity with serial culture passaging.

PubMed

Dinardo, Carla Luana; Venturini, Gabriela; Omae, Samantha Vieira; Zhou, Enhua H; da Motta-Leal-Filho, Joaquim Maurício; Dariolli, Rafael; Krieger, José Eduardo; Alencar, Adriano Mesquita; Costa Pereira, Alexandre

2012-01-01

One drawback of in vitro cell culturing is the dedifferentiation process that cells experience. Smooth muscle cells (SMC) also change molecularly and morphologically with long term culture. The main objective of this study was to evaluate if culture passages interfere in vascular SMC mechanical behavior. SMC were obtained from five different porcine arterial beds. Optical magnetic twisting cytometry (OMTC) was used to characterize mechanically vascular SMC from different cultures in distinct passages and confocal microscopy/western blotting, to evaluate cytoskeleton and extracellular matrix proteins. We found that vascular SMC rigidity or viscoelastic complex modulus (G) decreases with progression of passages. A statistically significant negative correlation between G and passage was found in four of our five cultures studied. Phalloidin-stained SMC from higher passages exhibited lower mean signal intensity per cell (confocal microscopy) and quantitative western blotting analysis showed a decrease in collagen I content throughout passages. We concluded that vascular SMC progressively lose their stiffness with serial culture passaging. Thus, limiting the number of passages is essential for any experiment measuring viscoelastic properties of SMC in culture.

MRI Correlates of Disability in African-Americans with Multiple Sclerosis

PubMed Central

Howard, Jonathan; Battaglini, Marco; Babb, James Scott; Arienzo, Donatello; Holst, Brigitte; Omari, Mirza; De Stefano, Nicola; Herbert, Joseph; Inglese, Matilde

2012-01-01

Objectives Multiple sclerosis (MS) in African-Americans (AAs) is characterized by more rapid disease progression and poorer response to treatment than in Caucasian-Americans (CAs). MRI provides useful and non-invasive tools to investigate the pathological substrate of clinical progression. The aim of our study was to compare MRI measures of brain damage between AAs and CAs with MS. Methods Retrospective analysis of 97 AAs and 97 CAs with MS matched for age, gender, disease duration and age at MRI examination. Results AA patients had significantly greater T2- (p = 0.001) and T1-weighted (p = 0.0003) lesion volumes compared to CA patients. In contrast, measurements of global and regional brain volume did not significantly differ between the two ethnic groups (p>0.1). Conclusions By studying a quite large sample of well demographically and clinically matched CA and AA patients with a homogeneous MRI protocol we showed that higher lesion accumulation, rather than pronounced brain volume decrease might explain the early progress to ambulatory assistance of AAs with MS. PMID:22900088

Retinal Remodeling in the Tg P347L Rabbit, a Large-Eye Model of Retinal Degeneration

PubMed Central

Jones, Bryan William; Kondo, Mineo; Terasaki, Hiroko; Watt, Carl Brock; Rapp, Kevin; Anderson, James; Lin, Yanhua; Shaw, Marguerite Victoria; Yang, Jia-Hui; Marc, Robert Edward

2013-01-01

Retinitis pigmentosa (RP) is an inherited blinding disease characterized by progressive loss of retinal photo-receptors. There are numerous rodent models of retinal degeneration, but most are poor platforms for interventions that will translate into clinical practice. The rabbit possesses a number of desirable qualities for a model of retinal disease including a large eye and an existing and substantial knowledge base in retinal circuitry, anatomy, and ophthalmology. We have analyzed degeneration, remodeling, and reprogramming in a rabbit model of retinal degeneration, expressing a rhodopsin proline 347 to leucine transgene in a TgP347L rabbit as a powerful model to study the pathophysiology and treatment of retinal degeneration. We show that disease progression in the TgP347L rabbit closely tracks human cone-sparing RP, including the cone-associated preservation of bipolar cell signaling and triggering of reprogramming. The relatively fast disease progression makes the TgP347L rabbit an excellent model for gene therapy, cell biological intervention, progenitor cell transplantation, surgical interventions, and bionic prosthetic studies. PMID:21681749

Fibrosis progression in African Americans and Caucasian Americans with chronic hepatitis C.

PubMed

Terrault, Norah A; Im, Kelly; Boylan, Ross; Bacchetti, Peter; Kleiner, David E; Fontana, Robert J; Hoofnagle, Jay H; Belle, Steven H

2008-12-01

Prior studies suggest the rate of liver fibrosis progression is slower in African Americans (AAs) than Caucasian Americans (CAs) with chronic HCV infection. With a multi-state Markov model, fibrosis progression was evaluated in a well-characterized cohort of 143 AA and 157 CA adults with untreated chronic HCV genotype 1 infection. In subjects with a history of injection drug use, duration of infection was imputed from a fitted risk model rather than assumed to be the reported first year of use. The distribution of Ishak fibrosis stages was 0 (8.7%), 1/2 (55.7%), 3/4 (29.3%), and 5/6 (6.3%) and was similar in AAs and CAs (P = .22). After adjusting for biopsy adequacy, AAs had a 10% lower rate of fibrosis progression than did CAs, but the difference was not statistically significant (hazard ratio, 0.90; 95% confidence interval, 0.72-1.12). The overall 20-year estimates of probabilities of progression from stage 0 to stages 1/2, 3/4, and 5/6 were 59.3%, 28.8%, and 4.7%, respectively. The estimated median time from no fibrosis to cirrhosis was 79 years for the entire cohort and 74 and 83 years for CAs and AAs, respectively. In 3-variable models including race and biopsy adequacy, the factors significantly associated with fibrosis progression were age when infected, steatosis, ALT level, and necroinflammatory score. The rates of fibrosis progression were slow and did not appear to differ substantially between AAs and CAs.

Neutral atoms facility for space sensors characterization and BepiColombo/ELENA development instrument's progresses.

NASA Astrophysics Data System (ADS)

de Angelis, E.; di Lellis, A. M.; Orsini, S.; Zanza, V.; Maggi, M.; Vertolli, N.; D'Amicis, R.; Tilia, B.; Sibio, A.

2003-04-01

An Energetic Neutral Atoms facility to test and calibrate Neutral Atoms Analyzers has been developed in the Scientific Technical Unit of Fusion at the ENEA Research Center in Frascati (Rome-Italy). In the last years a collaboration with IFSI (Interplanetary Space and Physics Institute, CNR-Rome-Italy) has allowed to use this facility for space sensors and for characterization of crucial instruments elements. The ENA beam is realized with an ion source and a neutralization cell, and allows to test any instrument in the energy range 300eV-110keV with the available masses of Hydrogen, Deuterium or Helium. At the moment, the critical elements of ELENA (Emitted Low Energy Neutral Atoms) instrument proposed for BepiColombo ESA cornerstone mission to Mercury is under development testing. The facility, its potentiality and the instrument characterization progresses are presented.

Characterization of Degradation Progressive in Composite Laminates Subjected to Thermal Fatigue and Moisture Diffusion by Lamb Waves.

PubMed

Li, Weibin; Xu, Chunguang; Cho, Younho

2016-02-19

Laminate composites which are widely used in the aeronautical industry, are usually subjected to frequency variation of environmental temperature and excessive humidity in the in-service environment. The thermal fatigue and moisture absorption in composites may induce material degradation. There is a demand to investigate the coupling damages mechanism and characterize the degradation evolution of composite laminates for the particular application. In this paper, the degradation evolution in unidirectional carbon/epoxy composite laminates subjected to thermal fatigue and moisture absorption is characterized by Lamb waves. The decrease rate of Lamb wave velocity is used to track the degradation evolution in the specimens. The results show that there are two stages for the progressive degradation of composites under the coupling effect of thermal cyclic loading and moisture diffusion. The present work provides an alternative to monitoring the degradation evolution of in-service aircraft composite Laminates.

Histone 3.3 Participates in a Self-Sustaining Cascade of Apoptosis That Contributes to the Progression of Chronic Obstructive Pulmonary Disease

PubMed Central

Barrero, Carlos A.; Perez-Leal, Oscar; Aksoy, Mark; Moncada, Camilo; Ji, Rong; Lopez, Yolanda; Mallilankaraman, Karthik; Madesh, Muniswamy; Criner, Gerard J.; Kelsen, Steven G.

2013-01-01

Rationale: Shifts in the gene expression of nuclear protein in chronic obstructive pulmonary disease (COPD), a progressive disease that is characterized by extensive lung inflammation and apoptosis, are common; however, the extent of the elevation of the core histones, which are the major components of nuclear proteins and their consequences in COPD, has not been characterized, which is important because extracellular histones are cytotoxic to endothelial and airway epithelial cells. Objectives: To investigate the role of extracellular histones in COPD disease progression. Methods: We analyzed the nuclear lung proteomes of ex-smokers with and without the disease. Further studies on the consequences of H3.3 were also performed. Measurements and Main Results: A striking finding was a COPD-specific eightfold increase of hyperacetylated histone H3.3. The hyperacetylation renders H3.3 resistant to proteasomal degradation despite ubiquitination; when combined with the reduction in proteasome activity that is known for COPD, this resistance helps account for the increased levels of H3.3. Using anti-H3 antibodies, we found H3.3 in the airway lumen, alveolar fluid, and plasma of COPD samples. H3.3 was cytotoxic to lung structural cells via a mechanism that involves the perturbation of Ca2+ homeostasis and mitochondrial toxicity. We used the primary human airway epithelial cells and found that the antibodies to either the C or N terminus of H3 could partially reverse H3.3 toxicity. Conclusions: Our data indicate that there is an uncontrolled positive feedback loop in which the damaged cells release acetylated H3.3, which causes more damage, adds H3.3 release, and contributes toward the disease progression. PMID:23924319

A human prostatic bacterial isolate alters the prostatic microenvironment and accelerates prostate cancer progression.

PubMed

Simons, Brian W; Durham, Nicholas M; Bruno, Tullia C; Grosso, Joseph F; Schaeffer, Anthony J; Ross, Ashley E; Hurley, Paula J; Berman, David M; Drake, Charles G; Thumbikat, Praveen; Schaeffer, Edward M

2015-02-01

Inflammation is associated with several diseases of the prostate including benign enlargement and cancer, but a causal relationship has not been established. Our objective was to characterize the prostate inflammatory microenvironment after infection with a human prostate-derived bacterial strain and to determine the effect of inflammation on prostate cancer progression. To this end, we mimicked typical human prostate infection with retrograde urethral instillation of CP1, a human prostatic isolate of Escherichia coli. CP1 bacteria were tropic for the accessory sex glands and induced acute inflammation in the prostate and seminal vesicles, with chronic inflammation lasting at least 1 year. Compared to controls, infection induced both acute and chronic inflammation with epithelial hyperplasia, stromal hyperplasia, and inflammatory cell infiltrates. In areas of inflammation, epithelial proliferation and hyperplasia often persist, despite decreased expression of androgen receptor (AR). Inflammatory cells in the prostates of CP1-infected mice were characterized at 8 weeks post-infection by flow cytometry, which showed an increase in macrophages and lymphocytes, particularly Th17 cells. Inflammation was additionally assessed in the context of carcinogenesis. Multiplex cytokine profiles of inflamed prostates showed that distinct inflammatory cytokines were expressed during prostate inflammation and cancer, with a subset of cytokines synergistically increased during concurrent inflammation and cancer. Furthermore, CP1 infection in the Hi-Myc mouse model of prostate cancer accelerated the development of invasive prostate adenocarcinoma, with 70% more mice developing cancer by 4.5 months of age. This study provides direct evidence that prostate inflammation accelerates prostate cancer progression and gives insight into the microenvironment changes induced by inflammation that may accelerate tumour initiation or progression. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Characterization of caries progression on dentin after irradiation with Nd:YAG laser by FTIR spectroscopy and fluorescence imaging

NASA Astrophysics Data System (ADS)

Ana, P. A.; Brito, A. M. M.; Zezell, D. M.; Lins, E. C. C. C.

2015-06-01

Considering the use of high intensity lasers for preventing dental caries, this blind in vitro study evaluated the compositional and fluorescence effects promoted by Nd:YAG laser (λ=1064 nm) when applied for prevention of progression of dentin caries, in association or not with topical application of acidulated phosphate fluoride (APF). Sixty bovine root dentin slabs were prepared and demineralized by 32h in order to create early caries lesions. After, the slabs were distributed into six experimental groups: G1- untreated and not submitted to a pH-cycling model; G2- untreated and submitted to a pH-cycling model; G3- acidulated phosphate fluoride application (APF); G4- Nd:YAG irradiation (84.9 J/cm2, 60 mJ/pulse); G5- treated with Nd:YAG+APF; G6- treated with APF+Nd:YAG. After treatments, the samples of groups G2 to G6 were submitted to a 4-day pH-cycling model in order to simulate the progression of early caries lesions. All samples were characterized by the micro-attenuated total reflection technique of Fourier transformed infrared spectroscopy (μATR-FTIR), using a diamond crystal, and by a fluorescence imaging system (FIS), in which it was used an illuminating system at λ= 405±30 nm. Demineralization promoted reduction in carbonate and phosphate contents, exposing the organic matter; as well, it was observed a significant reduction of fluorescence intensity. Nd:YAG laser promoted additional chemical changes, and increased the fluorescence intensity even with the development of caries lesions. It was concluded that the compositional changes promoted by Nd:YAG, when associated to APF, are responsible for the reduction of demineralization progression observed on root dentin.

P2X7 receptor and klotho expressions in diabetic nephropathy progression.

PubMed

Rodrigues, A M; Serralha, R S; Farias, C; Punaro, G R; Fernandes, M J S; Higa, Elisa Mieko Suemitsu

2018-06-01

Diabetes mellitus is characterized by increased levels of reactive oxygen species (ROS), leading to high levels of adenosine triphosphate (ATP) and the activation of purinergic receptors (P2X 7 ), which results in cell death. Klotho was recently described as a modulator of oxidative stress and as having anti-apoptotic properties, among others. However, the roles of P2X 7 and klotho in the progression of diabetic nephropathy are still unclear. In this context, the aim of the present study was to characterize P2X 7 and klotho in several stages of diabetes in rats. Diabetes was induced in Wistar rats by streptozotocin, while the control group rats received the drug vehicle. From the 1st to 8th weeks after the diabetes induction, the animals were placed in metabolic cages on the 1st day of each week for 24 h to analyze metabolic parameters and for the urine collection. Then, blood samples and the kidneys were collected for biochemical analysis, including Western blotting and qPCR for P2X 7 and klotho. Diabetic rats presented a progressive loss of renal function, with reduced nitric oxide and increased lipid peroxidation. The P2X 7 and klotho expressions were similar up to the 4th week; then, P2X 7 expression increased in diabetes mellitus (DM), but klotho expression presented an opposite behavior, until the 8th week. Our data show an inverse correlation between P2X 7 and klotho expressions through the development of DM, which suggests that the management of these molecules could be useful for controlling the progression of this disease and diabetic nephropathy.

Characterization of a spontaneous disease of white leghorn chickens resembling progressive systemic sclerosis (scleroderma)

PubMed Central

1981-01-01

University of California, Davis (UCD) line 200 White Leghorn Chickens spontaneously develop a syndrome that has many analogous features to human progressive systemic sclerosis. This syndrome is characterized by progressive involution of comb, dermal fibrosis, and distal polyarthritis. These three features occur within 6 wk after hatching, and are accompanied by a 40% mortality as a result of vaso-occlusive disease, with development of secondary infection of peripheral gangrenous lesions. Birds that survive greater than 2 mo after hatching progressively develop fibrosis of the esophagous and mononuclear infiltration of heart and kidney, with prominent occlusion of small and medium sized blood vessels. In addition, line 200 chickens develop rheumatoid factors, antinuclear antibodies, and antibodies to collagen, but do not have antibodies to thymocytes, DNA, or extractable nuclear antigens. Moreover, antinuclear antibodies when studied using HEp-2 cells as substrate demonstrate predominantly a speckled pattern. This syndrome of line 200 chickens is not detectable in F1 crosses to several UCD inbred lines. F1 X parental line BC1 backcrosses have an approximately 50% incidence of disease, suggesting that this syndrome is inherited as autosomal recessive. However, only 4% of F2 generation birds show abnormal symptoms, suggesting the presence of modifying genes. There is no appearance of IgG deposition, as determined by immunofluorescence, in either skin, blood vessels, esophagus, or heart. However, approximately 20% of chickens have a glomerulonephritis; this feature appears to be a terminal event and does not appear clinically significant. Although this syndrome of line 200 chickens has several features that are in sharp distinction to human scleroderma, the presence of common immunologic and pathologic denominators suggest that this spontaneous disease may be an appropriate model to develop a better understanding of autoimmune connective tissue diseases. PMID:7252423

Ejaculate traits and sperm cryopreservation in the endangered Baird's tapir (Tapirus bairdii).

PubMed

Pukazhenthi, Budhan S; Togna, Gina Della; Padilla, Luis; Smith, Diorene; Sanchez, Carlos; Pelican, Katey; Sanjur, Oris I

2011-01-01

There is little information on the reproductive biology of the male Baird's tapir (Tapirus bairdii). In this study, we characterized the ejaculate traits and evaluated the efficacy of 2 cryodiluents on sperm cryosurvival. Ejaculates were assessed for volume, pH, sperm motility, forward progression, osmolality, sperm concentration, sperm morphology, and acrosomal integrity. For cryopreservation, ejaculates with >50% total sperm motility were washed, and sperm pellets were resuspended in either Botu-Crio (CryoVital, Grandau, Germany) or INRA 96 containing 2% egg yolk and 2.5% each of methyl- and dimethylformamide (INRA 96), and they were cryopreserved over liquid nitrogen vapor. Thawed samples were incubated in vitro (25 °C) and evaluated for percent total sperm motility, forward progression, and acrosomal integrity at hourly intervals for 4 hours. Spermic ejaculates were obtained from all males, and the mean seminal volume, sperm concentration per milliliter, percent sperm motility, progressive status, and percent morphologically normal cells were 20.4 ± 4.3 mL, 101.2 ± 24.0 × 10(6)/mL, 46.1% ± 5.0%, 2.9 ± 0.1, and 6.9% ± 1.4%, respectively. There was a positive significant correlation between percent normal sperm and animal age (r = 0.66; P < .004). Cryopreservation in either Botu-Crio or INRA 96 resulted in a decline (P < .05) in percent sperm motility and acrosomal integrity. Sperm forward progression remained unaffected immediately after thawing in INRA 96 but continued to decline over time. These results characterize, for the first time, the ejaculate traits of the tapir; demonstrate that tapir spermatozoa can be cryopreserved in diluents containing amides alone or in combination with glycerol; and provide fundamental information critical for development of assisted reproductive technologies for the Baird's tapir.

Pulmonary alveolar proteinosis in children on La Réunion Island: a new inherited disorder?

PubMed Central

2014-01-01

Background Pulmonary alveolar proteinosis (PAP) is very rare in children. Only a few small series have been published, with little information about long-term progression. The objective of our study was to describe the clinical, radiological and pathological features, and the long-term course of PAP in a cohort of 34 children from La Réunion Island. Methods Data were retrospectively collected from medical files. Radiological and pathological elements were reviewed by two pediatric radiologists and three pathologists, respectively. Results Thirteen cases were familial and 32/34 (94%) cases were family connected. Disease onset occurred in the first six months of life in 82% of the patients. Thoracic computed tomography scans showed the typical “crazy-paving” pattern in 94% of cases. Respiratory disease was associated with a liver disorder, with the detection of liver enlargement at diagnosis in 56% of cases. The course of the disease was characterized by frequent progression to chronic respiratory insufficiency, accompanied by the appearance of cholesterol granulomas and pulmonary fibrosis. Overall prognosis was poor, with a mortality of 59% and an overall five-year survival rate from birth of 64%. Whole-lung lavages were performed in 21 patients, with no significant effect on survival. Liver disease progressed to cirrhosis in 18% of children, with no severe complication. Conclusions PAP in children from la Réunion Island is characterized by an early onset, associated liver involvement, poor prognosis and frequent progression to lung fibrosis, despite whole-lung lavages treatment. The geographic clustering of patients and the detection of many familial links between most of the cases strongly suggest a genetic etiology, with an autosomal recessive mode of inheritance. PMID:24927752

Characterization of Visual Function, Interocular Variability and Progression Using Static Perimetry-Derived Metrics in RPGR-Associated Retinopathy.

PubMed

Tee, James J L; Yang, Yesa; Kalitzeos, Angelos; Webster, Andrew; Bainbridge, James; Weleber, Richard G; Michaelides, Michel

2018-05-01

To characterize bilateral visual function, interocular variability and progression by using static perimetry-derived volumetric and pointwise metrics in subjects with retinitis pigmentosa associated with mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene. This was a prospective longitudinal observational study of 47 genetically confirmed subjects. Visual function was assessed with ETDRS and Pelli-Robson charts; and Octopus 900 static perimetry using a customized, radially oriented 185-point grid. Three-dimensional hill-of-vision topographic models were produced and interrogated with the Visual Field Modeling and Analysis software to obtain three volumetric metrics: VTotal, V30, and V5. These were analyzed together with Octopus mean sensitivity values. Interocular differences were assessed with the Bland-Altman method. Metric-specific exponential decline rates were calculated. Baseline symmetry was demonstrated by relative interocular difference values of 1% for VTotal and 8% with V30. Degree of symmetry varied between subjects and was quantified with the subject percentage interocular difference (SPID). SPID was 16% for VTotal and 17% for V30. Interocular symmetry in progression was greatest when quantified by VTotal and V30, with 73% and 64% of subjects possessing interocular rate differences smaller in magnitude than respective annual progression rates. Functional decline was evident with increasing age. An overall annual exponential decline of 6% was evident with both VTotal and V30. In general, good interocular symmetry exists; however, there was both variation between subjects and with the use of various metrics. Our findings will guide patient selection and design of RPGR treatment trials, and provide clinicians with specific prognostic information to offer patients affected by this condition.

Filgotinib for the treatment of Crohn's disease.

PubMed

Labetoulle, Remi; Paul, Stephane; Roblin, Xavier

2018-03-01

Inflammatory bowel diseases, such as Crohn's disease (CD) and ulcerative colitis (UC), are widespread diseases (with an estimated 2.2 million Europeans affected), and even populations previously considered 'low risk' (such as Japan and India) are witnessing an increasing incidence. CD is a chronic, progressive immunologically driven disease, with an evolution characterized by succession of periods of progression and remission. New physiopathological pathways are continuously being discovered, the more we understand about how the disease appears and progresses, the more targets become available for the development of novel therapies. Areas covered: Filgotinib is one of these promising new therapies; this article discusses the currently available data. We used an exhaustive search of the PubMed database to corroborate information regarding its chemical characteristics, and the studies evaluating clinical efficacy and safety. Expert opinion: Up to now, the phase-II study evaluating Filgotinib yielded very promising results in moderate to severe CD patients, with good clinical response, mucosal healing, while having few and moderate adverse effects, both in anti-TNF naïve and resistant patients. Phase-III studies are still ongoing and will help decide whether Filgotinib will be a worthwhile drug in the treatment of CD and the best way to use it.

Investigating cellular network heterogeneity and modularity in cancer: a network entropy and unbalanced motif approach.

PubMed

Cheng, Feixiong; Liu, Chuang; Shen, Bairong; Zhao, Zhongming

2016-08-26

Cancer is increasingly recognized as a cellular system phenomenon that is attributed to the accumulation of genetic or epigenetic alterations leading to the perturbation of the molecular network architecture. Elucidation of network properties that can characterize tumor initiation and progression, or pinpoint the molecular targets related to the drug sensitivity or resistance, is therefore of critical importance for providing systems-level insights into tumorigenesis and clinical outcome in the molecularly targeted cancer therapy. In this study, we developed a network-based framework to quantitatively examine cellular network heterogeneity and modularity in cancer. Specifically, we constructed gene co-expressed protein interaction networks derived from large-scale RNA-Seq data across 8 cancer types generated in The Cancer Genome Atlas (TCGA) project. We performed gene network entropy and balanced versus unbalanced motif analysis to investigate cellular network heterogeneity and modularity in tumor versus normal tissues, different stages of progression, and drug resistant versus sensitive cancer cell lines. We found that tumorigenesis could be characterized by a significant increase of gene network entropy in all of the 8 cancer types. The ratio of the balanced motifs in normal tissues is higher than that of tumors, while the ratio of unbalanced motifs in tumors is higher than that of normal tissues in all of the 8 cancer types. Furthermore, we showed that network entropy could be used to characterize tumor progression and anticancer drug responses. For example, we found that kinase inhibitor resistant cancer cell lines had higher entropy compared to that of sensitive cell lines using the integrative analysis of microarray gene expression and drug pharmacological data collected from the Genomics of Drug Sensitivity in Cancer database. In addition, we provided potential network-level evidence that smoking might increase cancer cellular network heterogeneity and further contribute to tyrosine kinase inhibitor (e.g., gefitinib) resistance. In summary, we demonstrated that network properties such as network entropy and unbalanced motifs associated with tumor initiation, progression, and anticancer drug responses, suggesting new potential network-based prognostic and predictive measure in cancer.

Identification and characterization of kidney transplants with good glomerular filtration rate at 1 year but subsequent progressive loss of renal function.

PubMed

Park, Walter D; Larson, Timothy S; Griffin, Matthew D; Stegall, Mark D

2012-11-15

After the first year after kidney transplantation, 3% to 5% of grafts fail each year but detailed studies of how grafts progress to failure are lacking. This study aimed to analyze the functional stability of kidney transplants between 1 and 5 years after transplantation and to identify initially well-functioning grafts with progressive decline in allograft function. The study included 788 adult conventional kidney transplants performed at the Mayo Clinic Rochester between January 2000 and December 2005 with a minimum graft survival and follow-up of 2.6 years. The modification of diet in renal disease equation for estimating glomerular filtration rate (eGFR(MDRD)) was used to calculate the slope of renal function over time using all available serum creatinine values between 1 and 5 years after transplantation. Most transplants demonstrated good function (eGFR(MDRD) ≥40 mL/min) at 1 year with positive eGFR(MDRD) slope between 1 and 5 years after transplantation. However, a subset of grafts with 1-year eGFR(MDRD) ≥40 mL/min exhibited strongly negative eGFR(MDRD) slope between 1 and 5 years suggestive of progressive loss of graft function. Forty-one percent of this subset reached graft failure during follow-up, accounting for 69% of allograft failures occurring after 2.5 years after transplantation. This pattern of progressive decline in estimated glomerular filtration rate despite good early function was associated with but not fully attributable to factors suggestive of enhanced antidonor immunity. Longitudinal analysis of serial estimated glomerular filtration ratemeasurements identifies initially well-functioning kidney transplants at high risk for subsequent graft loss. For this subset, further studies are needed to identify modifiable causes of functional decline.

Characterization of an Early-Onset, Autosomal Recessive, Progressive Retinal Degeneration in Bengal Cats.

PubMed

Ofri, Ron; Reilly, Christopher M; Maggs, David J; Fitzgerald, Paul G; Shilo-Benjamini, Yael; Good, Kathryn L; Grahn, Robert A; Splawski, Danielle D; Lyons, Leslie A

2015-08-01

A form of retinal degeneration suspected to be hereditary was discovered in a family of Bengal cats. A breeding colony was established to characterize disease progression clinically, electrophysiologically, and morphologically, and to investigate the mode of inheritance. Affected and related cats were donated by owners for breeding trials and pedigree analysis. Kittens from test and complementation breedings underwent ophthalmic and neuro-ophthalmic examinations and ERG, and globes were evaluated using light microscopy. Pedigree analysis, along with test and complementation breedings, indicated autosomal recessive inheritance and suggested that this disease is nonallelic to a retinal degeneration found in Persian cats. Mutation analysis confirmed the disease is not caused by CEP290 or CRX variants found predominantly in Abyssinian and Siamese cats. Ophthalmoscopic signs of retinal degeneration were noted at 9 weeks of age and became more noticeable over the next 4 months. Visual deficits were behaviorally evident by 1 year of age. Electroretinogram demonstrated reduced rod and cone function at 7 and 9 weeks of age, respectively. Rod responses were mostly extinguished at 14 weeks of age; cone responses were minimal by 26 weeks. Histologic degeneration was first observed at 8 weeks, evidenced by reduced photoreceptor numbers, then rapid deterioration of the photoreceptor layer and, subsequently, severe outer retinal degeneration. A recessively inherited primary photoreceptor degeneration was characterized in the Bengal cat. The disease is characterized by early onset, with histologic, ophthalmoscopic, and electrophysiological signs evident by 2 months of age, and rapid progression to blindness.

Transmission Electron Microscopy for Nanomedicine: Novel Applications for Long-established Techniques

PubMed Central

2016-01-01

During the last twenty years, the research in nanoscience and nanotechnology has dramatically increased and, in the last decade, the interest has progressively been oriented towards biomedical applications, giving rise to a new field termed nanomedicine. Transmission electron microscopy is a valuable technique not only for the thorough physico-chemical characterization of newly synthesized nanoparticulates, but especially to explore the effects of nanocomposites on biological systems, providing essential information for the development of efficient therapeutic and diagnostic strategies. Thus, for the progress of nanotechnology in the biomedical field, experts in cell biology, histochemistry and ultramicroscopy should always support the chemists, physicists and pharmacologists engaged in the synthesis and characterization of innovative nanoconstructs. PMID:28076938

The Fourier Kelvin Stellar Interferometer (FKSI): A Progress Report and Update

NASA Technical Reports Server (NTRS)

Danchi, William C.; Barry, R. K.; Traub, W. A.; Unwin, S.

2008-01-01

The Fourier-Kelvin Stellar Interferometer (FKSI) mission is a two-telescope infrared space interferometer with a 12.5 meter baseline on a boom, operating from 3-8 (or 10) microns, and passively cooled to about 60 K. The main goals for the mission are the measurement an characterization of the exozodiacal light around nearby stars, debris disks, and characterization of the atmospheres of known exoplanets. We discuss progress on this mission in the context of the recent call from NASA for mission concepts for the upcoming National Academy of Sciences Decadal Survey, where it is considered a medium class mission ($600-800 million) in terms of the overall budget.

Progressive deterioration of beta-cell function in obese youth with type 2 diabetes

USDA-ARS?s Scientific Manuscript database

In adults, type 2 diabetes (T2DM) is characterized with progressive deterioration in insulin secretion. Data are scanty in youth. We investigated prospectively the change in ß-cell function and in insulin sensitivity in youth with T2DM. Six adolescents with T2DM [hemoglobin A1c (HbA1c) 6.6 +/- 1.0%]...

Macrodystrophia lipomatosa. A case report.

PubMed

Loro, A; Francechi, F; Dal Lago, A

1995-07-01

Macrodystrophia lipomatosa, a rare form of localized gigantism of unknown cause, is characterized by a dramatic overgrowth of all the mesenchymal elements, particularly the fibroadipose tissue, of one or more digits of the foot or hand. Of the known forms, static and progressive (1), we report the case of an African patient, of Bantu origin, who had a progressive deformity of his left hand.

Heavy-section steel technology program. Semiannual progress report for period ending February 28, 1973

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

None

1974-02-01

The materials investigations under the HSST program are divided into studies of unirradiated materials and studies of irradiation effects. The studies of unirradiated materials, which include inspection, characterization, metallurgy, variability determinations, transition temperature investigations, fracture mechanics studies, and fatigue-crack propagation tests, are discussed. The investigations of irradiated materials include studies of radiation effects on A-533-B steel. Results of studies on thick pressure vessels and pipes of ASTM A508 steel are also reported along with results of studies on Mode III crack extension in reactor piping. (JRD)

Influence of deflection on a fold-to-fault progression: field evidence from near Marietta, South Carolina

USGS Publications Warehouse

Clendenin, C.W.; Garihan, J.M.

2006-01-01

Four periods of deformation (D1-D4) are recognized in the Lion Park Road borrow pit near Marietta, South Carolina. Although each period is characterized by distinct structures, D3 produced two structural styles (D3a, D3b) resulting from layer-parallel shortening. D3a is characterized by detachment folding at the tip of an underlying thrust. D3b is a fold-to-fault progression that was localized by east-dipping, quartz-filled gash fractures. The fold-to-fault progression demonstrates the influence of a mechanical anisotropy on ramp development. The early stages of D3b were formed by deflection of northwest-directed, layer-parallel shortening and active, down-section propagation of folds and thrusts. Following connection with a splay of basal detachment, later D3b stages resulted from up-section movement that produced kink folding and a throughgoing thrust. This up-section movement deformed and modified the geometries of older, down-section structures. Detailed mesoscopic field observations, integrated with a combination of current thrust fault models, are used to interpret the D3b fold-to-fault progression. ?? 2006 Elsevier Ltd. All rights reserved.

Kinetics of Disease Progression and Host Response in a Rat Model of Bubonic Plague

PubMed Central

Sebbane, Florent; Gardner, Donald; Long, Daniel; Gowen, Brian B.; Hinnebusch, B. Joseph

2005-01-01

Plague, caused by the gram-negative bacterium Yersinia pestis, primarily affects rodents but is also an important zoonotic disease of humans. Bubonic plague in humans follows transmission by infected fleas and is characterized by an acute, necrotizing lymphadenitis in the regional lymph nodes that drain the intradermal flea bite site. Septicemia rapidly follows with spread to spleen, liver, and other organs. We developed a model of bubonic plague using the inbred Brown Norway strain of Rattus norvegicus to characterize the progression and kinetics of infection and the host immune response after intradermal inoculation of Y. pestis. The clinical signs and pathology in the rat closely resembled descriptions of human bubonic plague. The bacteriology; histopathology; host cellular response in infected lymph nodes, blood, and spleen; and serum cytokine levels were analyzed at various times after infection to determine the kinetics and route of disease progression and to evaluate hypothesized Y. pestis pathogenic mechanisms. Understanding disease progression in this rat infection model should facilitate further investigations into the molecular pathogenesis of bubonic plague and the immune response to Y. pestis at different stages of the disease. PMID:15855643

Technologies and methods used for the detection, enrichment and characterization of cancer stem cells.

PubMed

Williams, Anthony; Datar, Ram; Cote, Richard

2010-01-01

Cancer stem cells (CSCs) represent a subclass of tumour cells with the ability for self-renewal, production of differentiated progeny, prolonged survival, resistance to damaging therapeutic agents, and anchorage-independent survival, which together make this population effectively equipped to metastasize, invade and colonize secondary tissues in the face of therapeutic intervention. In recent years, investigators have increasingly focused on the characterization of CSCs to better understand the mechanisms that govern malignant disease progression in an effort to develop more effective, targeted therapeutic agents. The primary obstacle to the study of CSCs, however, is their rarity. Thus, the study of CSCs requires the use of sensitive and efficient technologies for their enrichment and detection. This review discusses technologies and methods that have been adapted and used to isolate and characterize CSCs to date, as well as new potential directions for the enhanced enrichment and detection of CSCs. While the technologies used for CSC enrichment and detection have been useful thus far for their characterization, each approach is not without limitations. Future studies of CSCs will depend on the enhanced sensitivity and specificity of currently available technologies, and the development of novel technologies for increased detection and enrichment of CSCs.

Declines in arrestin and rhodopsin in the macula with progression of age-related macular degeneration.

PubMed

Ethen, Cheryl M; Feng, Xiao; Olsen, Timothy W; Ferrington, Deborah A

2005-03-01

Biochemical analysis of age-related macular degeneration (AMD) at distinct stages of the disease will help further understanding of the molecular events associated with disease progression. This study was conducted to determine the ability of a new grading system for eye bank eyes, the Minnesota Grading System (MGS), to discern distinct stages of AMD so that retinal region-specific changes in rod photoreceptor protein expression from donors could be determined. Donor eyes were assigned to a specific level of AMD by using the MGS. Expression of the rod photoreceptor proteins rhodopsin and arrestin was evaluated by Western immunoblot analysis in the macular and peripheral regions of the neurosensory retina from donors at different stages of AMD. A significant linear decline in both arrestin and rhodopsin content correlated with progressive MGS levels in the macula. In contrast, the peripheral region showed no significant correlation between MGS level and the content of either protein. The statistically significant relationship between decreasing macular rod photoreceptor proteins and progressive MGS levels of AMD demonstrates the utility of the clinically based MGS to correspond with specific protein changes found at known, progressive stages of degeneration. Future biochemical analysis of clinically characterized donor eyes will further understanding of the pathobiochemistry of AMD.

Loss of Intrinsic Organization of Cerebellar Networks in Spinocerebellar Ataxia Type 1: Correlates with Disease Severity and Duration

PubMed Central

Peri, Eitan; Chen, E. Elinor; Ben-Jacob, Eshel; Gomez, Christopher M.

2011-01-01

The spinocerebellar ataxias (SCAs) are a genetically heterogeneous group of cerebellar degenerative disorders, characterized by progressive gait unsteadiness, hand incoordination, and dysarthria. The mutational mechanism in SCA1, a dominantly inherited form of SCA, consists of an expanded trinucleotide CAG repeat. In SCA1, there is loss of Purkinje cells, neuronal loss in dentate nucleus, olives, and pontine nuclei. In the present study, we sought to apply intrinsic functional connectivity analysis combined with diffusion tensor imaging to define the state of cerebellar connectivity in SCA1. Our results on the intrinsic functional connectivity in lateral cerebellum and thalamus showed progressive organizational changes in SCA1 noted as a progressive increase in the absolute value of the correlation coefficients. In the lateral cerebellum, the anatomical organization of functional clusters seen as parasagittal bands in controls is lost, changing to a patchy appearance in SCA1. Lastly, only fractional anisotropy in the superior peduncle and changes in functional organization in thalamus showed a linear dependence to duration and severity of disease. The present pilot work represents an initial effort describing connectivity biomarkers of disease progression in SCA1. The functional changes detected with intrinsic functional analysis and diffusion tensor imaging suggest that disease progression can be analyzed as a disconnection syndrome. PMID:20886327

Recent advances in "bioartificial polymeric materials" based nanovectors

NASA Astrophysics Data System (ADS)

Conte, Raffaele; De Luca, Ilenia; Valentino, Anna; Di Salle, Anna; Calarco, Anna; Riccitiello, Francesco; Peluso, Gianfranco

2017-04-01

This chapter analyzes the advantages of the use of bioartificial polymers as carriers and the main strategies used for their design. Despite the enormous progresses in this field, more studies are required for the fully evaluation of these nanovectors in complex organisms and for the characterization of the pharmacodynamic and pharmacokinetic of the loaded drugs. Moreover, progresses in polymer chemistry are introducing a wide range of functionalities in the bioartificial polymeric material (BPM) nanostructures leading to a second generation of bioartificial polymer therapeutics based on novel and heterogeneous architectures with higher molecular weight and predictable structures, in order to achieve greater multivalency and increased loading capacity. Therefore, research on bioartificial polymeric nanovectors is an "on-going" field capable of attracting medical interest.

Genetic determinants of hepatic steatosis in man

PubMed Central

Hooper, Amanda J.; Adams, Leon A.; Burnett, John R.

2011-01-01

Hepatic steatosis is one of the most common liver disorders in the general population. The main cause of hepatic steatosis is nonalcoholic fatty liver disease (NAFLD), representing the hepatic component of the metabolic syndrome, which is characterized by type 2 diabetes, obesity, and dyslipidemia. Insulin resistance and excess adiposity are considered to play key roles in the pathogenesis of NAFLD. Although the risk factors for NAFLD are well established, the genetic basis of hepatic steatosis is largely unknown. Here we review recent progress on genomic variants and their association with hepatic steatosis and discuss the potential impact of these genetic studies on clinical practice. Identifying the genetic determinants of hepatic steatosis will lead to a better understanding of the pathogenesis and progression of NAFLD. PMID:21245030

A Ground-Based 2-Micron DIAL System to Profile Tropospheric CO2 and Aerosol Distributions for Atmospheric Studies

NASA Technical Reports Server (NTRS)

Ismail, Syed; Koch, Grady; Abedin, Nurul; Refaat, Tamer; Rubio, Manuel; Davis, Kenneth; Miller, Charles; Singh, Upendra

2006-01-01

System will operate at a temperature insensitive CO2 line (2050.967 nm) with side-line tuning and off-set locking. Demonstrated an order of magnitude improvement in laser line locking needed for high precision measurements, side-line operation, and simultaneously double pulsing and line locking. Detector testing of phototransistor has demonstrated sensitivity to aerosol features over long distances in the atmosphere and resolve features approx. 100m. Optical systems that collect light onto small area detectors work well. Receiver optical designs are being optimized and data acquisition systems developed. CO2 line parameter characterization in progress In situ sensor calibration in progress for validation of DIAL CO2 system.

Targeting BET bromodomain proteins in solid tumors

PubMed Central

Sahai, Vaibhav; Redig, Amanda J.; Collier, Katharine A.; Eckerdt, Frank D.; Munshi, Hidayatullah G.

2016-01-01

There is increasing interest in inhibitors targeting BET (bromodomain and extra-terminal) proteins because of the association between this family of proteins and cancer progression. BET inhibitors were initially shown to have efficacy in hematologic malignancies; however, a number of studies have now shown that BET inhibitors can also block progression of non-hematologic malignancies. In this Review, we summarize the efficacy of BET inhibitors in select solid tumors; evaluate the role of BET proteins in mediating resistance to current targeted therapies; and consider potential toxicities of BET inhibitors. We also evaluate recently characterized mechanisms of resistance to BET inhibitors; summarize ongoing clinical trials with these inhibitors; and discuss potential future roles of BET inhibitors in patients with solid tumors. PMID:27283767

Direct enzymatic extraction of starch from corn as an energy-saving alternative to production of high-fructose syrup

NASA Astrophysics Data System (ADS)

The liquefaction of pre-gelatinized starch was studied with various analytical techniques to determine the effects of starch molecular weight, granule structure, granule size, and mechanical depolymerization. Also, improvements were made in the chromatographic system used to characterize starch hydrolysates. Progress is reported on protein removal. The effects of pH, temperature, and ionic strength were examined for the removal of protein from a syrup stream by adsorption on a phenolic resin. Buffered systems, which maintain more stable pH values, were also examined. Mathematical modeling of the results is in progress. The pilot plant facility is complete and in operation. Starch streams containing 1% protein are being produced by the protein extraction process.

Taste Receptor Genes

PubMed Central

Bachmanov, Alexander A.; Beauchamp, Gary K.

2009-01-01

In the past several years, tremendous progress has been achieved with the discovery and characterization of vertebrate taste receptors from the T1R and T2R families, which are involved in recognition of bitter, sweet, and umami taste stimuli. Individual differences in taste, at least in some cases, can be attributed to allelic variants of the T1R and T2R genes. Progress with understanding how T1R and T2R receptors interact with taste stimuli and with identifying their patterns of expression in taste cells sheds light on coding of taste information by the nervous system. Candidate mechanisms for detection of salts, acids, fat, complex carbohydrates, and water have also been proposed, but further studies are needed to prove their identity. PMID:17444812

Electroencephalogram and Alzheimer's Disease: Clinical and Research Approaches

PubMed Central

Tsolaki, Anthoula; Kazis, Dimitrios; Kompatsiaris, Ioannis; Kosmidou, Vasiliki; Tsolaki, Magda

2014-01-01

Alzheimer's disease (AD) is a neurodegenerative disorder that is characterized by cognitive deficits, problems in activities of daily living, and behavioral disturbances. Electroencephalogram (EEG) has been demonstrated as a reliable tool in dementia research and diagnosis. The application of EEG in AD has a wide range of interest. EEG contributes to the differential diagnosis and the prognosis of the disease progression. Additionally such recordings can add important information related to the drug effectiveness. This review is prepared to form a knowledge platform for the project entitled “Cognitive Signal Processing Lab,” which is in progress in Information Technology Institute in Thessaloniki. The team tried to focus on the main research fields of AD via EEG and recent published studies. PMID:24868482

Solid-state optical refrigeration to sub-100 Kelvin regime

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

Melgaard, Seth D.; Albrecht, Alexander R.; Hehlen, Markus P.

We report that since the first demonstration of net cooling twenty years ago, optical refrigeration of solids has progressed to outperform all other solid-state cooling processes. It has become the first and only solid-state refrigerator capable of reaching cryogenic temperatures, and now the first solid-state cooling below 100 K. Such substantial progress required a multi-disciplinary approach of pump laser absorption enhancement, material characterization and purification, and thermal management. Here we present the culmination of two decades of progress, the record cooling to ≈91K from room temperature.

Solid-state optical refrigeration to sub-100 Kelvin regime

DOE PAGES

Melgaard, Seth D.; Albrecht, Alexander R.; Hehlen, Markus P.; ...

2016-02-05

We report that since the first demonstration of net cooling twenty years ago, optical refrigeration of solids has progressed to outperform all other solid-state cooling processes. It has become the first and only solid-state refrigerator capable of reaching cryogenic temperatures, and now the first solid-state cooling below 100 K. Such substantial progress required a multi-disciplinary approach of pump laser absorption enhancement, material characterization and purification, and thermal management. Here we present the culmination of two decades of progress, the record cooling to ≈91K from room temperature.

Solid-state optical refrigeration to sub-100 Kelvin regime

PubMed Central

Melgaard, Seth D.; Albrecht, Alexander R.; Hehlen, Markus P.; Sheik-Bahae, Mansoor

2016-01-01

Since the first demonstration of net cooling twenty years ago, optical refrigeration of solids has progressed to outperform all other solid-state cooling processes. It has become the first and only solid-state refrigerator capable of reaching cryogenic temperatures, and now the first solid-state cooling below 100 K. Such substantial progress required a multi-disciplinary approach of pump laser absorption enhancement, material characterization and purification, and thermal management. Here we present the culmination of two decades of progress, the record cooling to ≈ 91 K from room temperature. PMID:26847703

Resting State Brain Entropy Alterations in Relapsing Remitting Multiple Sclerosis.

PubMed

Zhou, Fuqing; Zhuang, Ying; Gong, Honghan; Zhan, Jie; Grossman, Murray; Wang, Ze

2016-01-01

Brain entropy (BEN) mapping provides a novel approach to characterize brain temporal dynamics, a key feature of human brain. Using resting state functional magnetic resonance imaging (rsfMRI), reliable and spatially distributed BEN patterns have been identified in normal brain, suggesting a potential use in clinical populations since temporal brain dynamics and entropy may be altered in disease conditions. The purpose of this study was to characterize BEN in multiple sclerosis (MS), a neurodegenerative disease that affects millions of people. Since currently there is no cure for MS, developing treatment or medication that can slow down its progression represents a high research priority, for which validating a brain marker sensitive to disease and the related functional impairments is essential. Because MS can start long time before any measurable symptoms and structural deficits, assessing the dynamic brain activity and correspondingly BEN may provide a critical way to study MS and its progression. Because BEN is new to MS, we aimed to assess BEN alterations in the relapsing-remitting MS (RRMS) patients using a patient versus control design, to examine the correlation of BEN to clinical measurements, and to check the correlation of BEN to structural brain measures which have been more often used in MS studies. As compared to controls, RRMS patients showed increased BEN in motor areas, executive control area, spatial coordinating area, and memory system. Increased BEN was related to greater disease severity as measured by the expanded disability status scale (EDSS) and greater tissue damage as indicated by the mean diffusivity. Patients also showed decreased BEN in other places, which was associated with less disability or fatigue, indicating a disease-related BEN re-distribution. Our results suggest BEN as a novel and useful tool for characterizing RRMS.

RESEARCH AND DEVELOPMENT ON ADVANCED GRAPHITE MATERIALS. Final Report

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

None

1962-04-01

A review is given of activities over the period October 15, 1960 to October 15, 1961 on a three year program for the research and development of materials, experimental techniques, and equipment for development of premium quality, reproducible graphite-base materials suitable for missile and astronautic applications. Progress is reported on research and development in the study areas of raw materials, fabrication, and material characterization and evaluation. (auth)

Dementia Research: Populations, Progress, Problems, and Predictions.

PubMed

Hunter, Sally; Smailagic, Nadja; Brayne, Carol

2018-05-16

Alzheimer's disease (AD) is a clinicopathologically defined syndrome leading to cognitive impairment. Following the recent failures of amyloid-based randomized controlled trials to change the course of AD, there are growing calls for a re-evaluation of basic AD research. Epidemiology offers one approach to integrating the available evidence. Here we examine relationships between evidence from population-based, clinicopathological studies of brain aging and a range of hypotheses from all areas of AD research. We identify various problems, including a lack of systematic approach to measurement of clinical and neuropathological factors associated with dementia in experimental and clinical settings, poor understanding of the strengths and weaknesses of different observational and experimental designs, a lack of clarity in relation to disease definitions from the clinical, neuropathological, and molecular perspectives, inadequate characterization of brain aging in the human population, difficulties in translation between laboratory-based and population-based evidence bases, and a lack of communication between different sections of the dementia research community. Population studies highlight complexity and predict that therapeutic approaches based on single disease features will not be successful. Better characterization of brain aging in the human population is urgently required to select biomarkers and therapeutic targets that are meaningful to human disease. The generation of detailed and reliable evidence must be addressed before progress toward therapeutic interventions can be made.

The meaning of PIWI proteins in cancer development.

PubMed

Litwin, Monika; Szczepańska-Buda, Anna; Piotrowska, Aleksandra; Dzięgiel, Piotr; Witkiewicz, Wojciech

2017-05-01

Cancer is a histologically and genetically heterogeneous population of tumor cells that exhibits distinct molecular profiles determined by epigenetic alterations. P-element-induced wimpy testis (PIWI) proteins in complex with PIWI-interacting RNA (piRNA) have been previously demonstrated to be involved in epigenetic regulation in germline cells. Recently, reactivation of PIWI expression, primarily PIWI-like protein 1 and 2, through aberrant DNA methylation resulting in genomic silencing has been identified in various types of tumors. It has been suggested that the PIWI-piRNA complex contributes to cancer development and progression by promoting a stem-like state of cancer cells, or cancer stem cells (CSCs). It has been identified that CSCs represent the cells that have undergone epithelial-mesenchymal transition (EMT) and acquired metastatic capacities. However, the molecular association between the EMT process and the stem-cell state remains unclear. Further extensive characterization of CSCs in individual types of tumors is required to identify specific markers for the heterogeneous population of CSCs and therefore selectively target CSCs. Previous studies indicate a reciprocal regulation between PIWI proteins and a complex signaling network linking markers characterized for CSCs and transcription factors involved in EMT. In the present review, studies of PIWI function are summarized, and the potential involvement of PIWI proteins in cancer development and progression is discussed.

The meaning of PIWI proteins in cancer development

PubMed Central

Litwin, Monika; Szczepańska-Buda, Anna; Piotrowska, Aleksandra; Dzięgiel, Piotr; Witkiewicz, Wojciech

2017-01-01

Cancer is a histologically and genetically heterogeneous population of tumor cells that exhibits distinct molecular profiles determined by epigenetic alterations. P-element-induced wimpy testis (PIWI) proteins in complex with PIWI-interacting RNA (piRNA) have been previously demonstrated to be involved in epigenetic regulation in germline cells. Recently, reactivation of PIWI expression, primarily PIWI-like protein 1 and 2, through aberrant DNA methylation resulting in genomic silencing has been identified in various types of tumors. It has been suggested that the PIWI-piRNA complex contributes to cancer development and progression by promoting a stem-like state of cancer cells, or cancer stem cells (CSCs). It has been identified that CSCs represent the cells that have undergone epithelial-mesenchymal transition (EMT) and acquired metastatic capacities. However, the molecular association between the EMT process and the stem-cell state remains unclear. Further extensive characterization of CSCs in individual types of tumors is required to identify specific markers for the heterogeneous population of CSCs and therefore selectively target CSCs. Previous studies indicate a reciprocal regulation between PIWI proteins and a complex signaling network linking markers characterized for CSCs and transcription factors involved in EMT. In the present review, studies of PIWI function are summarized, and the potential involvement of PIWI proteins in cancer development and progression is discussed. PMID:28529570

Arterial spin labelling reveals an abnormal cerebral perfusion pattern in Parkinson's disease.

PubMed

Melzer, Tracy R; Watts, Richard; MacAskill, Michael R; Pearson, John F; Rüeger, Sina; Pitcher, Toni L; Livingston, Leslie; Graham, Charlotte; Keenan, Ross; Shankaranarayanan, Ajit; Alsop, David C; Dalrymple-Alford, John C; Anderson, Tim J

2011-03-01

There is a need for objective imaging markers of Parkinson's disease status and progression. Positron emission tomography and single photon emission computed tomography studies have suggested patterns of abnormal cerebral perfusion in Parkinson's disease as potential functional biomarkers. This study aimed to identify an arterial spin labelling magnetic resonance-derived perfusion network as an accessible, non-invasive alternative. We used pseudo-continuous arterial spin labelling to measure cerebral grey matter perfusion in 61 subjects with Parkinson's disease with a range of motor and cognitive impairment, including patients with dementia and 29 age- and sex-matched controls. Principal component analysis was used to derive a Parkinson's disease-related perfusion network via logistic regression. Region of interest analysis of absolute perfusion values revealed that the Parkinson's disease pattern was characterized by decreased perfusion in posterior parieto-occipital cortex, precuneus and cuneus, and middle frontal gyri compared with healthy controls. Perfusion was preserved in globus pallidus, putamen, anterior cingulate and post- and pre-central gyri. Both motor and cognitive statuses were significant factors related to network score. A network approach, supported by arterial spin labelling-derived absolute perfusion values may provide a readily accessible neuroimaging method to characterize and track progression of both motor and cognitive status in Parkinson's disease.

Radiographic changes and factors associated with subsequent progression of damage in weight-bearing joints of patients with rheumatoid arthritis under TNF-blocking therapies-three-year observational study.

PubMed

Matsushita, Isao; Motomura, Hiraku; Seki, Eiko; Kimura, Tomoatsu

2017-07-01

The long-term effects of tumor necrosis factor (TNF)-blocking therapies on weight-bearing joints in patients with rheumatoid arthritis (RA) have not been fully characterized. The purpose of this study was to assess the radiographic changes of weight-bearing joints in patients with RA during 3-year of TNF-blocking therapies and to identify factors related to the progression of joint damage. Changes in clinical variables and radiological findings in 243 weight-bearing joints (63 hips, 54 knees, 71 ankles, and 55 subtalar joints) in 38 consecutive patients were investigated during three years of treatment with TNF-blocking agents. Multivariate logistic regression analysis was used to identify risk factors for the progression of weight-bearing joint damage. Seventeen (14.5%) of proximal weight-bearing joints (hips and knees) showed apparent radiographic progression during three years of treatment, whereas none of the proximal weight-bearing joints showed radiographic evidence of improvement or repair. In contrast, distal weight-bearing joints (ankle and subtalar joints) displayed radiographic progression and improvement in 20 (15.9%) and 8 (6.3%) joints, respectively. Multivariate logistic analysis for proximal weight-bearing joints identified the baseline Larsen grade (p < 0.001, OR:24.85, 95%CI: 5.07-121.79) and disease activity at one year after treatment (p = 0.003, OR:3.34, 95%CI:1.50-7.46) as independent factors associated with the progression of joint damage. On the other hand, multivariate analysis for distal weight-bearing joints identified disease activity at one year after treatment (p < 0.001, OR:2.13, 95%CI:1.43-3.18) as an independent factor related to the progression of damage. Baseline Larsen grade was strongly associated with the progression of damage in the proximal weight-bearing joints. Disease activity after treatment was an independent factor for progression of damage in proximal and distal weight-bearing joints. Early treatment with TNF-blocking agents and tight control of disease activity are necessary to prevent the progression of damage of the weight-bearing joints.

Novel AAV-based rat model of forebrain synucleinopathy shows extensive pathologies and progressive loss of cholinergic interneurons.

PubMed

Aldrin-Kirk, Patrick; Davidsson, Marcus; Holmqvist, Staffan; Li, Jia-Yi; Björklund, Tomas

2014-01-01

Synucleinopathies, characterized by intracellular aggregation of α-synuclein protein, share a number of features in pathology and disease progression. However, the vulnerable cell population differs significantly between the disorders, despite being caused by the same protein. While the vulnerability of dopamine cells in the substantia nigra to α-synuclein over-expression, and its link to Parkinson's disease, is well studied, animal models recapitulating the cortical degeneration in dementia with Lewy-bodies (DLB) are much less mature. The aim of this study was to develop a first rat model of widespread progressive synucleinopathy throughout the forebrain using adeno-associated viral (AAV) vector mediated gene delivery. Through bilateral injection of an AAV6 vector expressing human wild-type α-synuclein into the forebrain of neonatal rats, we were able to achieve widespread, robust α-synuclein expression with preferential expression in the frontal cortex. These animals displayed a progressive emergence of hyper-locomotion and dysregulated response to the dopaminergic agonist apomorphine. The animals receiving the α-synuclein vector displayed significant α-synuclein pathology including intra-cellular inclusion bodies, axonal pathology and elevated levels of phosphorylated α-synuclein, accompanied by significant loss of cortical neurons and a progressive reduction in both cortical and striatal ChAT positive interneurons. Furthermore, we found evidence of α-synuclein sequestered by IBA-1 positive microglia, which was coupled with a distinct change in morphology. In areas of most prominent pathology, the total α-synuclein levels were increased to, on average, two-fold, which is similar to the levels observed in patients with SNCA gene triplication, associated with cortical Lewy body pathology. This study provides a novel rat model of progressive cortical synucleinopathy, showing for the first time that cholinergic interneurons are vulnerable to α-synuclein over-expression. This animal model provides a powerful new tool for studies of neuronal degeneration in conditions of widespread cortical α-synuclein pathology, such as DLB, as well an attractive model for the exploration of novel biomarkers.

Longitudinal study of gastroesophageal reflux and erosive tooth wear.

PubMed

Wilder-Smith, Clive H; Materna, Andrea; Martig, Lukas; Lussi, Adrian

2017-10-25

Approximately 60% of patients presenting to dentists with erosive tooth wear have significant gastroesophageal reflux (GERD), despite minor reflux symptoms. No longitudinal studies of reflux-associated erosive tooth wear and of reflux characteristics have been reported to date. The aim of this study was to characterize the longitudinal course of GERD and of associated erosive tooth wear, as well as factors predictive of its progression, in a large group of patients. Seventy-two patients presenting to dentists with clinically significant erosive tooth wear and increased esophageal acid exposure by 24-h multichannel intraluminal pH-impedance measurement (MII-pH) were re-assessed clinically and by MII-pH after 1 year treatment with esomeprazole 20 mg twice-daily. Predictive factors for erosive tooth wear were assessed by logistic regression. At follow-up, no further progression in erosive tooth wear was observed in 53 (74%) of patients. The percentage of time with a pH < 4, the number of acid reflux episodes and the percentage of proximal esophageal reflux off-PPI did not change significantly after one year, but the number of weakly acidic reflux episodes decreased significantly in the large subgroup without progression. None of the baseline demographic, clinical, endoscopic or esophageal acid exposure characteristics were significantly associated with progression of erosive tooth wear at follow-up. In this longitudinal study in patients with erosive tooth wear and oligosymptomatic GERD receiving esomeprazole for one year, erosive tooth wear did not progress further in the majority of patients. Background acidic esophageal reflux exposure appeared stable over time, whereas weakly acidic exposure decreased significantly in patients without erosion progression. MII-pH measurements on-PPI and with healthy controls will be useful in the further elucidation of the causal role of reflux in erosive tooth wear. ClinicalTrials.gov , retrospectively registered: NCT02087345 .

White matter damage in primary progressive aphasias: a diffusion tensor tractography study.

PubMed

Galantucci, Sebastiano; Tartaglia, Maria Carmela; Wilson, Stephen M; Henry, Maya L; Filippi, Massimo; Agosta, Federica; Dronkers, Nina F; Henry, Roland G; Ogar, Jennifer M; Miller, Bruce L; Gorno-Tempini, Maria Luisa

2011-10-01

Primary progressive aphasia is a clinical syndrome that encompasses three major phenotypes: non-fluent/agrammatic, semantic and logopenic. These clinical entities have been associated with characteristic patterns of focal grey matter atrophy in left posterior frontoinsular, anterior temporal and left temporoparietal regions, respectively. Recently, network-level dysfunction has been hypothesized but research to date has focused largely on studying grey matter damage. The aim of this study was to assess the integrity of white matter tracts in the different primary progressive aphasia subtypes. We used diffusion tensor imaging in 48 individuals: nine non-fluent, nine semantic, nine logopenic and 21 age-matched controls. Probabilistic tractography was used to identify bilateral inferior longitudinal (anterior, middle, posterior) and uncinate fasciculi (referred to as the ventral pathway); and the superior longitudinal fasciculus segmented into its frontosupramarginal, frontoangular, frontotemporal and temporoparietal components, (referred to as the dorsal pathway). We compared the tracts' mean fractional anisotropy, axial, radial and mean diffusivities for each tract in the different diagnostic categories. The most prominent white matter changes were found in the dorsal pathways in non-fluent patients, in the two ventral pathways and the temporal components of the dorsal pathways in semantic variant, and in the temporoparietal component of the dorsal bundles in logopenic patients. Each of the primary progressive aphasia variants showed different patterns of diffusion tensor metrics alterations: non-fluent patients showed the greatest changes in fractional anisotropy and radial and mean diffusivities; semantic variant patients had severe changes in all metrics; and logopenic patients had the least white matter damage, mainly involving diffusivity, with fractional anisotropy altered only in the temporoparietal component of the dorsal pathway. This study demonstrates that both careful dissection of the main language tracts and consideration of all diffusion tensor metrics are necessary to characterize the white matter changes that occur in the variants of primary progressive aphasia. These results highlight the potential value of diffusion tensor imaging as a new tool in the multimodal diagnostic evaluation of primary progressive aphasia.

A Compositional Look at the Human Gastrointestinal Microbiome and Immune Activation Parameters in HIV Infected Subjects

PubMed Central

Mutlu, Ece A.; Keshavarzian, Ali; Losurdo, John; Swanson, Garth; Siewe, Basile; Forsyth, Christopher; French, Audrey; DeMarais, Patricia; Sun, Yan; Koenig, Lars; Cox, Stephen; Engen, Phillip; Chakradeo, Prachi; Abbasi, Rawan; Gorenz, Annika; Burns, Charles; Landay, Alan

2014-01-01

HIV progression is characterized by immune activation and microbial translocation. One factor that may be contributing to HIV progression could be a dysbiotic microbiome. We therefore hypothesized that the GI mucosal microbiome is altered in HIV patients and this alteration correlates with immune activation in HIV. 121 specimens were collected from 21 HIV positive and 22 control human subjects during colonoscopy. The composition of the lower gastrointestinal tract mucosal and luminal bacterial microbiome was characterized using 16S rDNA pyrosequencing and was correlated to clinical parameters as well as immune activation and circulating bacterial products in HIV patients on ART. The composition of the HIV microbiome was significantly different than that of controls; it was less diverse in the right colon and terminal ileum, and was characterized by loss of bacterial taxa that are typically considered commensals. In HIV samples, there was a gain of some pathogenic bacterial taxa. This is the first report characterizing the terminal ileal and colonic mucosal microbiome in HIV patients with next generation sequencing. Limitations include use of HIV-infected subjects on HAART therapy. PMID:24586144

Growth and characterization of binary and pseudo-binary 3-5 compounds exhibiting non-linear optical behavior. Undergraduate research opportunities in microgravity science and technology

NASA Technical Reports Server (NTRS)

Witt, August F.

1992-01-01

In line with the specified objectives, a Bridgman-type growth configuration in which unavoidable end effects - conventionally leading to growth interface relocation - are compensated by commensurate input-power changes is developed; the growth rate on a microscale is predictable and unaffected by changes in heat transfer conditions. To permit quantitative characterization of the growth furnace cavity (hot-zone), a 3-D thermal field mapping technique, based on the thermal image, is being tested for temperatures up to 1100 C. Computational NIR absorption analysis was modified to now permit characterization of semi-insulating single crystals. Work on growth and characterization of bismuth-silicate was initiated. Growth of BSO (B12SiO20) for seed material by the Czochralski technique is currently in progress. Undergraduate research currently in progress includes: ground based measurements of the wetting behavior (contact angles) of semiconductor melts on substrates consisting of potential confinement materials for solidification experiments in a reduced gravity environment. Hardware modifications required for execution of the wetting experiments in a KC-135 facility are developed.

Progressive disability and prefrontal shrinkage in schizophrenia patients with poor outcome: A 3-year longitudinal study.

PubMed

Dusi, N; Bellani, M; Perlini, C; Squarcina, L; Marinelli, V; Finos, L; Altamura, C A; Ruggeri, M; Brambilla, P

2017-01-01

Schizophrenia is a severe disabling disorder with heterogeneous illness courses. In this longitudinal study we characterized schizophrenia patients with poor and good outcome (POS, GOS), using functional and imaging metrics. Patients were defined in accordance to Keefe's criteria (i.e. Kraepelinian and non-Kraepelinian patients). 35 POS patients, 35 GOS patients and 76 healthy controls (H) underwent clinical, functioning and magnetic resonance imaging (MRI) assessments twice over three years of follow-up. Information on psychopathology, treatment, disability (using the World Health Organization Disability Assessment Scale II, WHO-DAS-2) and prefrontal morphology was collected. Dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex (OFC) were manually traced. At baseline, subjects with POS showed significantly decreased right dorsolateral prefrontal cortex (DLPFC) white matter volumes (WM) compared to healthy controls and GOS patients (POS VS HC, p<0.001; POS vs GOS, p=0.03), with shrinkage of left DLPFC WM volumes at follow up (t=2.66, p=0.01). Also, POS patients had higher disability in respect to GOS subjects both at baseline and after 3years at the WHO-DAS-2 (p<0.05). Our study supports the hypothesis that POS is characterized by progressive deficits in brain structure and in "real-life" functioning. These are particularly notable in the DLPFC. Copyright © 2016 Elsevier B.V. All rights reserved.

Rate and Pattern of Rim Area Loss in Healthy and Progressing Glaucoma Eyes

PubMed Central

Hammel, Na’ama; Belghith, Akram; Bowd, Christopher; Medeiros, Felipe A.; Sharpsten, Lucie; Mendoza, Nadia; Tatham, Andrew J.; Khachatryan, Naira; Liebmann, Jeffrey M.; Girkin, Christopher A.; Weinreb, Robert N.; Zangwill, Linda M.

2015-01-01

Objective To characterize the rate and pattern of age-related and glaucomatous neuroretinal rim area changes in subjects of African descent (AD) and European descent (ED). Design Prospective longitudinal study. Subjects 296 eyes of 157 healthy subjects (88 AD and 69 ED) and 73 progressing glaucoma eyes of 67 subjects (24 AD and 43 ED) from the Diagnostic Innovations in Glaucoma Study (DIGS) and the African Descent and Glaucoma Evaluation Study (ADAGES) were included. Methods Global and sectoral rim area was measured using confocal laser scanning ophthalmoscopy (CSLO). Progression of glaucomatous optic disc damage was determined by masked stereophoto review. The rates of absolute rim area loss and percent rim area loss in healthy and progressing glaucomatous eyes were compared using multivariable nested mixed-effects models. Main Outcome Measures Rate of rim area loss over time. Results The median (inter-quartile range) follow-up time was 5.0 years (2.0–7.4) for healthy eyes and 8.3 years (7.5–9.9) for progressing glaucoma eyes. The mean rate of global rim area loss was significantly faster in progressing glaucoma eyes compared with healthy eyes for both rim area loss (−10.2 ×10−3 mm2/year vs. −2.8 ×10−3 mm2/year, respectively, P<.001) and percent rim area loss (−1.1 %/year vs. −0.2 %/year, respectively, P<.001), but there was considerable overlap between the two groups. 63% of progressing glaucoma eyes had a rate of change faster than the 5th quantile of healthy eyes. For both healthy and progressing eyes, the pattern of rim area loss and percent rim area loss was similar; it tended to be fastest in the superior temporal and inferior temporal sectors. The rate of change was similar in AD and ED progressing eyes. Conclusions Compared with healthy eyes, the mean rate of global rim area loss was 3.7 times faster and the mean rate of global percent rim area loss was 5.4 times faster in progressing glaucoma eyes. A reference database of healthy eyes can be used to help clinicians distinguish age-related rim area loss from rim area loss due to glaucoma. PMID:26746597

The Challenge of Reproducibility and Accuracy in Nutrition Research: Resources and Pitfalls1234

PubMed Central

Kuszak, Adam J; Williamson, John S; Hopp, D Craig; Betz, Joseph M

2016-01-01

Inconsistent and contradictory results from nutrition studies conducted by different investigators continue to emerge, in part because of the inherent variability of natural products, as well as the unknown and therefore uncontrolled variables in study populations and experimental designs. Given these challenges inherent in nutrition research, it is critical for the progress of the field that researchers strive to minimize variability within studies and enhance comparability between studies by optimizing the characterization, control, and reporting of products, reagents, and model systems used, as well as the rigor and reporting of experimental designs, protocols, and data analysis. Here we describe some recent developments relevant to research on plant-derived products used in nutrition research, highlight some resources for optimizing the characterization and reporting of research using these products, and describe some of the pitfalls that may be avoided by adherence to these recommendations. PMID:26980822

Diabetes, cardiac disorders and asthma as risk factors for severe organ involvement among adult dengue patients: A matched case-control study.

PubMed

Pang, Junxiong; Hsu, Jung Pu; Yeo, Tsin Wen; Leo, Yee Sin; Lye, David C

2017-01-03

Progression to severe organ involvement due to dengue infection has been associated with severe dengue disease, intensive care treatment, and mortality. However, there is a lack of understanding of the impact of pre-existing comorbidities and other risk factors of severe organ involvement among dengue adults. The aim of this retrospective case-control study is to characterize and identify risk factors that predispose dengue adults at risk of progression with severe organ involvement. This study involved 174 dengue patients who had progressed with severe organ involvement and 865 dengue patients without severe organ involvement, matched by the year of presentation of the cases, who were admitted to Tan Tock Seng Hospital between year 2005 and 2008. Age group of 60 years or older, diabetes, cardiac disorders, asthma, and having two or more pre-existing comorbidities were independent risk factors of severe organ involvement. Abdominal pain, clinical fluid accumulation, and hematocrit rise and rapid platelet count drop at presentation were significantly associated with severe organ involvement. These risk factors, when validated in a larger study, will be useful for triage by clinicians for prompt monitoring and clinical management at first presentation, to minimize the risk of severe organ involvement and hence, disease severity.

RNA metabolism in the regulation of protein synthesis in plants. Progress report, 1975-1979

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

Key, J L

1979-01-01

The major objectives of the research for the contract period covered by this report were (1) to gain an insight into the sequence organization of the DNA of soybean, emphasizing the arrangement of single copy or unique sequences and repetitive sequences of DNA throughout the genome, (2) to characterize soybean RNAs relative to nucleotide sequence complexity and kinetics of synthesis and turnover of poly A/sup +/ mRNA, and (3) to study ribosomal proteins directed to an analysis of possible changes in proteins which relate to the activation of 80S ribosomes and thus mRNA utilization and protein synthesis in response tomore » environmental stimuli. Even with greatly reduced funding compared to that requested, objectives 1 and 2 were substantially accomplished. Because of reduced funding and the 20-month no cost extension, relatively little progress was made on objective 3. Accordingly objectives 1 and 2 will be summarized in some detail; a brief account of progress is presented on objective 3.« less

High resolution molecular and histological analysis of renal disease progression in ZSF1 fa/faCP rats, a model of type 2 diabetic nephropathy

PubMed Central

Zhao, Shanrong; Schlerman, Franklin J.; Savary, Leigh; Campanholle, Gabriela; Johnson, Bryce G.; Xi, Li; Nguyen, Vuong; Zhan, Yutian; Lech, Matthew P.; Wang, Ju; Nie, Qing; Karsdal, Morten A.; Genovese, Federica; Boucher, Germaine; Brown, Thomas P.; Zhang, Baohong; Homer, Bruce L.; Martinez, Robert V.

2017-01-01

ZSF1 rats exhibit spontaneous nephropathy secondary to obesity, hypertension, and diabetes, and have gained interest as a model system with potentially high translational value to progressive human disease. To thoroughly characterize this model, and to better understand how closely it recapitulates human disease, we performed a high resolution longitudinal analysis of renal disease progression in ZSF1 rats spanning from early disease to end stage renal disease. Analyses included metabolic endpoints, renal histology and ultrastructure, evaluation of a urinary biomarker of fibrosis, and transcriptome analysis of glomerular-enriched tissue over the course of disease. Our findings support the translational value of the ZSF1 rat model, and are provided here to assist researchers in the determination of the model’s suitability for testing a particular mechanism of interest, the design of therapeutic intervention studies, and the identification of new targets and biomarkers for type 2 diabetic nephropathy. PMID:28746409

A Systems Model of Parkinson's Disease Using Biochemical Systems Theory.

PubMed

Sasidharakurup, Hemalatha; Melethadathil, Nidheesh; Nair, Bipin; Diwakar, Shyam

2017-08-01

Parkinson's disease (PD), a neurodegenerative disorder, affects millions of people and has gained attention because of its clinical roles affecting behaviors related to motor and nonmotor symptoms. Although studies on PD from various aspects are becoming popular, few rely on predictive systems modeling approaches. Using Biochemical Systems Theory (BST), this article attempts to model and characterize dopaminergic cell death and understand pathophysiology of progression of PD. PD pathways were modeled using stochastic differential equations incorporating law of mass action, and initial concentrations for the modeled proteins were obtained from literature. Simulations suggest that dopamine levels were reduced significantly due to an increase in dopaminergic quinones and 3,4-dihydroxyphenylacetaldehyde (DOPAL) relating to imbalances compared to control during PD progression. Associating to clinically observed PD-related cell death, simulations show abnormal parkin and reactive oxygen species levels with an increase in neurofibrillary tangles. While relating molecular mechanistic roles, the BST modeling helps predicting dopaminergic cell death processes involved in the progression of PD and provides a predictive understanding of neuronal dysfunction for translational neuroscience.

High resolution molecular and histological analysis of renal disease progression in ZSF1 fa/faCP rats, a model of type 2 diabetic nephropathy.

PubMed

Dower, Ken; Zhao, Shanrong; Schlerman, Franklin J; Savary, Leigh; Campanholle, Gabriela; Johnson, Bryce G; Xi, Li; Nguyen, Vuong; Zhan, Yutian; Lech, Matthew P; Wang, Ju; Nie, Qing; Karsdal, Morten A; Genovese, Federica; Boucher, Germaine; Brown, Thomas P; Zhang, Baohong; Homer, Bruce L; Martinez, Robert V

2017-01-01

ZSF1 rats exhibit spontaneous nephropathy secondary to obesity, hypertension, and diabetes, and have gained interest as a model system with potentially high translational value to progressive human disease. To thoroughly characterize this model, and to better understand how closely it recapitulates human disease, we performed a high resolution longitudinal analysis of renal disease progression in ZSF1 rats spanning from early disease to end stage renal disease. Analyses included metabolic endpoints, renal histology and ultrastructure, evaluation of a urinary biomarker of fibrosis, and transcriptome analysis of glomerular-enriched tissue over the course of disease. Our findings support the translational value of the ZSF1 rat model, and are provided here to assist researchers in the determination of the model's suitability for testing a particular mechanism of interest, the design of therapeutic intervention studies, and the identification of new targets and biomarkers for type 2 diabetic nephropathy.

Evidence for ACTN3 as a genetic modifier of Duchenne muscular dystrophy

PubMed Central

Hogarth, Marshall W.; Houweling, Peter J.; Thomas, Kristen C.; Gordish-Dressman, Heather; Bello, Luca; Vishwanathan, V.; Chidambaranathan, S.; Douglas Biggar, W.; McAdam, Laura C.; Mah, Jean K.; Tulinius, Mar; Cnaan, Avital; Morgenroth, Lauren P.; Leshner, Robert; Tesi-Rocha, Carolina; Thangarajh, Mathula; Duong, Tina; Kornberg, Andrew; Ryan, Monique; Nevo, Yoram; Dubrovsky, Alberto; Clemens, Paula R.; Abdel-Hamid, Hoda; Connolly, Anne M.; Pestronk, Alan; Teasley, Jean; Bertorini, Tulio E.; Webster, Richard; Kolski, Hanna; Kuntz, Nancy; Driscoll, Sherilyn; Bodensteiner, John B.; Carlo, Jose; Gorni, Ksenija; Lotze, Timothy; Day, John W.; Karachunski, Peter; Henricson, Erik K.; Abresch, Richard T.; McDonald, Craig M.; Pegoraro, Elena; Hoffman, Eric P.; Head, Stewart I.; North, Kathryn N.

2017-01-01

Duchenne muscular dystrophy (DMD) is characterized by muscle degeneration and progressive weakness. There is considerable inter-patient variability in disease onset and progression, which can confound the results of clinical trials. Here we show that a common null polymorphism (R577X) in ACTN3 results in significantly reduced muscle strength and a longer 10 m walk test time in young, ambulant patients with DMD; both of which are primary outcome measures in clinical trials. We have developed a double knockout mouse model, which also shows reduced muscle strength, but is protected from stretch-induced eccentric damage with age. This suggests that α-actinin-3 deficiency reduces muscle performance at baseline, but ameliorates the progression of dystrophic pathology. Mechanistically, we show that α-actinin-3 deficiency triggers an increase in oxidative muscle metabolism through activation of calcineurin, which likely confers the protective effect. Our studies suggest that ACTN3 R577X genotype is a modifier of clinical phenotype in DMD patients. PMID:28139640

ROCK inhibition with Y27632 promotes the proliferation and cell cycle progression of cultured astrocyte from spinal cord.

PubMed

Yu, Zhiyuan; Liu, Miao; Fu, Peicai; Xie, Minjie; Wang, Wei; Luo, Xiang

2012-12-01

Rho-associated Kinase (ROCK) has been identified as an important regulator of proliferation and cell cycle progression in a number of cell types. Although its effects on astrocyte proliferation have not been well characterized, ROCK has been reported to play important roles in gap junction formation, morphology, and migration of astrocytes. In the present study, our aim was to investigate the effect of ROCK inhibition by [(+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl) cyclohexanecarboxamide dihydrochloride] (Y27632) on proliferation and DNA synthesis in cultured astrocytes from rat spinal cord and the possible mechanism involved. Western blots showed that treatment of astrocytes with Y27632 increased their expression of cyclin D1, CDK4, and cyclin E, thereby causing cell cycle progression. Furthermore, Y27632-induced astrocyte proliferation was mediated through the extracellular-signal-regulated kinase signaling cascade. These results indicate the importance of ROCK in astrocyte proliferation. Copyright © 2012 Elsevier Ltd. All rights reserved.

Further investigation of phenotypes and confounding factors of progressive ratio performance and feeding behavior in the BACHD rat model of Huntington disease.

PubMed

Clemensson, Erik Karl Håkan; Clemensson, Laura Emily; Fabry, Benedikt; Riess, Olaf; Nguyen, Huu Phuc

2017-01-01

Huntington disease is an inherited neurodegenerative disorder characterized by motor, cognitive, psychiatric and metabolic symptoms. We recently published a study describing that the BACHD rat model of HD shows an obesity phenotype, which might affect their motivation to perform food-based behavioral tests. Further, we argued that using a food restriction protocol based on matching BACHD and wild type rats' food consumption rates might resolve these motivational differences. In the current study, we followed up on these ideas in a longitudinal study of the rats' performance in a progressive ratio test. We also investigated the phenotype of reduced food consumption rate, which is typically seen in food-restricted BACHD rats, in greater detail. In line with our previous study, the BACHD rats were less motivated to perform the progressive ratio test compared to their wild type littermates, although the phenotype was no longer present when the rats' food consumption rates had been matched. However, video analysis of food consumption tests suggested that the reduced consumption rate found in the BACHD rats was not entirely based on differences in hunger, but likely involved motoric impairments. Thus, restriction protocols based on food consumption rates are not appropriate when working with BACHD rats. As an alternative, we suggest that studies where BACHD rats are used should investigate how the readouts of interest are affected by motivational differences, and use appropriate control tests to avoid misleading results. In addition, we show that BACHD rats display distinct behavioral changes in their progressive ratio performance, which might be indicative of striatal dysfunction.

Linear clinical progression, independent of age of onset, in Niemann-Pick disease, type C.

PubMed

Yanjanin, Nicole M; Vélez, Jorge I; Gropman, Andrea; King, Kelly; Bianconi, Simona E; Conley, Sandra K; Brewer, Carmen C; Solomon, Beth; Pavan, William J; Arcos-Burgos, Mauricio; Patterson, Marc C; Porter, Forbes D

2010-01-05

Niemann-Pick disease, type C is a neurodegenerative, lysosomal storage disorder with a broad clinical spectrum and a variable age of onset. The absence of a universally accepted clinical outcome measure is an impediment to the design of a therapeutic trial for NPC. Thus, we developed a clinical severity scale to characterize and quantify disease progression. Clinical signs and symptoms in nine major (ambulation, cognition, eye movement, fine motor, hearing, memory, seizures, speech, and swallowing) and eight minor (auditory brainstem response, behavior, gelastic cataplexy, hyperreflexia, incontinence, narcolepsy, psychiatric, and respiratory problems) domains were scored. Data were collected from 18 current NPC patients and were extracted from records of 19 patients. Both patient cohorts showed a linear increase in severity scores over time. Cross-sectional evaluation of current patients showed a linear increase in the severity score. Longitudinal chart review of historical data demonstrated that although age of onset varied significantly, the rate of progression appeared linear, independent of age of onset, and similar in all patients. Combining the data from both cohorts, disease progression could be modeled by the following equation: ŝ(t0+x) = ŝ(t0) + 1.87x; where ŝ(t0) is the initial score and ŝ(t0+x) is the predicted future score after x years. Our observation that disease progression is similar across patients and independent of age of onset is consistent with a biphasic pathological model for NPC. This scale may prove useful in the characterization of potential biomarkers, and as an outcome measure to monitor disease progression in NPC patients. (c) 2009 Wiley-Liss, Inc.

Dissecting dysfunctional crosstalk pathways regulated by miRNAs during glioma progression

PubMed Central

Li, Feng; Li, Xiang; Feng, Li; Shi, Xinrui; Wang, Lihua; Li, Xia

2016-01-01

Glioma is a malignant nervous system tumor with a high fatality rate and poor prognosis. MicroRNAs (miRNAs) are important post-transcriptional modulators of glioma initiation and progression. Tumor progression often results from dysfunctional co-operation between pathways regulated by miRNAs. We therefore constructed a glioma progression-related miRNA-pathway crosstalk network that not only revealed some key miRNA-pathway patterns, but also helped characterize the functional roles of miRNAs during glioma progression. Our data indicate that crosstalk between cell cycle and p53 pathways is associated with grade II to grade III progression, while cell communications-related pathways involving regulation of actin cytoskeleton and adherens junctions are associated with grade IV glioblastoma progression. Furthermore, miRNAs and their crosstalk pathways may be useful for stratifying glioma and glioblastoma patients into groups with short or long survival times. Our data indicate that a combination of miRNA and pathway crosstalk information can be used for survival prediction. PMID:27013589

Anatomy of Language Impairments in Primary Progressive Aphasia

PubMed Central

Rogalski, Emily; Cobia, Derin; Harrison, Theresa M.; Wieneke, Christina; Thompson, Cynthia K; Weintraub, Sandra; Mesulam, M.-Marsel

2011-01-01

Primary progressive aphasia (PPA) is a clinical dementia syndrome characterized by progressive decline in language function but relative sparing of other cognitive domains. There are three recognized PPA variants: agrammatic, semantic, and logopenic. Although each PPA subtype is characterized by the nature of the principal deficit, individual patients frequently display subtle impairments in additional language domains. The present study investigated the distribution of atrophy related to performance in specific language domains (i.e., grammatical processing, semantic processing, fluency, and sentence repetition) across PPA variants to better understand the anatomical substrates of language. Results showed regionally specific relationships, primarily in the left hemisphere, between atrophy and impairments in language performance. Most notable was the neuroanatomical distinction between fluency and grammatical processing. Poor fluency was associated with regions dorsal to the traditional boundaries of Broca’s area in the inferior frontal sulcus and the posterior middle frontal gyrus, whereas grammatical processing was associated with more widespread atrophy, including the inferior frontal gyrus and supramarginal gyrus. Repetition performance was correlated with atrophy in the posterior superior temporal gyrus. The correlation of atrophy with semantic processing impairment was localized to the anterior temporal poles. Atrophy patterns were more closely correlated with domain-specific performance than with subtype. These results show that PPA reflects a selective disruption of the language network as a whole, with no rigid boundaries between subtypes. Further, these atrophy patterns reveal anatomical correlates of language that could not have been surmised in patients with aphasia resulting from cerebrovascular lesions. PMID:21368046

Anatomy of language impairments in primary progressive aphasia.

PubMed

Rogalski, Emily; Cobia, Derin; Harrison, Theresa M; Wieneke, Christina; Thompson, Cynthia K; Weintraub, Sandra; Mesulam, M-Marsel

2011-03-02

Primary progressive aphasia (PPA) is a clinical dementia syndrome characterized by progressive decline in language function but relative sparing of other cognitive domains. There are three recognized PPA variants: agrammatic, semantic, and logopenic. Although each PPA subtype is characterized by the nature of the principal deficit, individual patients frequently display subtle impairments in additional language domains. The present study investigated the distribution of atrophy related to performance in specific language domains (i.e., grammatical processing, semantic processing, fluency, and sentence repetition) across PPA variants to better understand the anatomical substrates of language. Results showed regionally specific relationships, primarily in the left hemisphere, between atrophy and impairments in language performance. Most notable was the neuroanatomical distinction between fluency and grammatical processing. Poor fluency was associated with regions dorsal to the traditional boundaries of Broca's area in the inferior frontal sulcus and the posterior middle frontal gyrus, whereas grammatical processing was associated with more widespread atrophy, including the inferior frontal gyrus and supramarginal gyrus. Repetition performance was correlated with atrophy in the posterior superior temporal gyrus. The correlation of atrophy with semantic processing impairment was localized to the anterior temporal poles. Atrophy patterns were more closely correlated with domain-specific performance than with subtype. These results show that PPA reflects a selective disruption of the language network as a whole, with no rigid boundaries between subtypes. Further, these atrophy patterns reveal anatomical correlates of language that could not have been surmised in patients with aphasia resulting from cerebrovascular lesions.

[Alport syndrome: Hereditary nephropathy associated with mutations in genes coding for type IV collagen chains].

PubMed

Heidet, Laurence; Gubler, Marie-Claire

2016-12-01

Alport syndrome is an inherited disorder characterized by the association of a progressive haematuric nephropathy with ultrastructural abnormalities of the glomerular basement membranes, a progressive sensorineural hearing loss and sometimes ocular involvement. Its incidence is less than 1 per 5000 individuals and the disease is the cause of about 2% of end stage renal disease in Europe and the United States. Alport syndrome is clinically and genetically heterogeneous. It is related to mutations in the genes encoding one of three chains, α3, α4 α5 of type IV collagen, the main component of basement membranes, expressed in the glomerular basement membrane. COL4A5 mutations are associated with X-linked Alport syndrome, which represents 80 to 85% of cases and is more severe in boys than in girls. Mutations in COL4A3 or COL4A4 are associated with autosomal Alport syndrome. The expression of collagen chains in skin and kidney basement membranes allows for the diagnosis and characterization of the mode of transmission in most patients. It is necessary to diagnose this syndrome because its family involvement, its severity, and the importance of genetic counseling. Angiotensin blockers are increasingly prescribed in proteinuric patients. Prospective studies are needed to assess the effectiveness of these treatments on proteinuria and progression of kidney failure, and to specify indications. Animal studies have shown the potential value of different molecules (protease inhibitors, chemokine receptor blockers, transforming growth factor-β1 inhibitors, hydroxy-methyl-coenzyme A reductase inhibitors, bone morphogenetic protein-7 inhibitors), hematopoietic stem cells, and of a anti-micro-RNA. Copyright © 2016. Published by Elsevier SAS.

Pneumonitis in Adult Onset Still's Disease: Uncommon or Under Diagnosed?

PubMed

Fernandes, Silvia; Almeida, Margarida; Pereira da Silva, José Alberto; Romeu, José Carlos

2017-08-31

The adult onset Still's Disease is an uncommon entity characterized by multiple clinical manifestations. Pneumonitis, less often considered, deserves particular emphasis given the need for differential diagnosis and because it can progress to severe respiratory failure. With the aim to highlight the pulmonary parenchyma involvement in patients with adult onset Still's Disease, we present a case report which progresses with pneumonitis.

Defining as a Mathematical Activity: A Framework for Characterizing Progress from Informal to More Formal Ways of Reasoning

ERIC Educational Resources Information Center

Zandieh, Michelle; Rasmussen, Chris

2010-01-01

The purpose of this paper is to further the notion of defining as a mathematical activity by elaborating a framework that structures the role of defining in student progress from informal to more formal ways of reasoning. The framework is the result of a retrospective account of a significant learning experience that occurred in an undergraduate…

Characterizing the Development of Students' Understandings regarding the Second Law of Thermodynamics: Using Learning Progressions to Illuminate Thinking in High School Chemistry

ERIC Educational Resources Information Center

Cunningham, Kevin D.

2011-01-01

As demonstrated by their emphasis in the new, national, science education standards, learning progressions (LPs) have become a valuable means of informing teaching and learning. LPs serve this role by isolating the key components of central skills and understandings, and by describing how those abilities and concepts tend to develop over time…

Characterization of Damage Accumulation in a C/SiC Composite at Elevated Temperatures

NASA Technical Reports Server (NTRS)

Telesman, Jack; Verrilli, Mike; Ghosn, Louis; Kantzos, Pete

1997-01-01

This research is part of a program aimed to evaluate and demonstrate the ability of candidate CMC materials for a variety of applications in reusable launch vehicles. The life and durability of these materials in rocket and engine applications are of major concern and there is a need to develop and validate life prediction methodology. In this study, material characterization and mechanical testing was performed in order to identify the failure modes, degradation mechanisms, and progression of damage in a C/SiC composite at elevated temperatures. The motivation for this work is to provide the relevant damage information that will form the basis for the development of a physically based life prediction methodology.

Explosively produced fracture of oil shale

NASA Astrophysics Data System (ADS)

Morris, W. A.

1982-05-01

Rock fragmentation research in oil shale to develop the blasting technologies and designs required to prepare a rubble bed for a modified in situ retort is reported. Experimental work is outlined, proposed studies in explosive characterization are detailed and progress in numerical calculation techniques to predict fracture of the shale is described. A detailed geologic characterization of two Anvil Points experiment sites is related to previous work at Colony Mine. The second section focuses on computer modeling and theory. The latest generation of the stress wave code SHALE, its three dimensional potential, and the slide line package for it are described. A general stress rate equation that takes energy dependence into account is discussed.

Simple and versatile heterodyne whole-field interferometer for phase optics characterization.

PubMed

Silva, D M; Barbosa, E A; Wetter, N U

2012-10-01

A wavefront sensor for thermally induced lens and passive lens characterization based on low-coherence digital speckle interferometry was developed and studied. By illuminating the optical setup with two slightly detuned red diode lasers, whole-field contour interference fringes were generated according to the resulting synthetic wavelength. For fringe pattern visualization the optical setup used the light transmitted through a ground glass plate as object beam. The performance of the sensor was investigated and its versatility was demonstrated by measuring the thermal lens induced in an Er-doped glass sample pumped by a 1.76-W diode laser emitting at 976 nm and by evaluating the wavefront distortion introduced by an ophthalmic progressive lens.

Plasma detachment in divertor tokamaks

DOE PAGES

Leonard, A. W.

2018-02-07

In this study, observations of divertor plasma detachment in tokamaks are reviewed. Plasma detachment is characterized in terms of transport and dissipation of power, momentum and particle flux along the open field lines from the midplane to the divertor. Asymmetries in detachment onset and other characteristics between the inboard and outboard divertor plasmas is found to be primarily driven by plasmamore » $$\\vec{E}$$ x $$\\vec{B}$$ drifts. The effect of divertor plate geometry and magnetic configuration on divertor detachment is summarized. Control of divertor detachment has progressed with a development of a number of diagnostics to characterize the detached state in real-time. Finally the compatibility of detached divertor operation with high performance core plasmas is examined.« less

Plasma detachment in divertor tokamaks

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

Leonard, A. W.

In this study, observations of divertor plasma detachment in tokamaks are reviewed. Plasma detachment is characterized in terms of transport and dissipation of power, momentum and particle flux along the open field lines from the midplane to the divertor. Asymmetries in detachment onset and other characteristics between the inboard and outboard divertor plasmas is found to be primarily driven by plasmamore » $$\\vec{E}$$ x $$\\vec{B}$$ drifts. The effect of divertor plate geometry and magnetic configuration on divertor detachment is summarized. Control of divertor detachment has progressed with a development of a number of diagnostics to characterize the detached state in real-time. Finally the compatibility of detached divertor operation with high performance core plasmas is examined.« less

Osteoporosis (image)

MedlinePlus

Osteoporosis is a condition characterized by progressive loss of bone density, thinning of bone tissue and increased vulnerability to fractures. Osteoporosis may result from disease, dietary or hormonal deficiency ...

Drosophila Models of Parkinson's Disease: Discovering Relevant Pathways and Novel Therapeutic Strategies

PubMed Central

Muñoz-Soriano, Verónica; Paricio, Nuria

2011-01-01

Parkinson's disease (PD) is the second most common neurodegenerative disorder and is mainly characterized by the selective and progressive loss of dopaminergic neurons, accompanied by locomotor defects. Although most PD cases are sporadic, several genes are associated with rare familial forms of the disease. Analyses of their function have provided important insights into the disease process, demonstrating that three types of cellular defects are mainly involved in the formation and/or progression of PD: abnormal protein aggregation, oxidative damage, and mitochondrial dysfunction. These studies have been mainly performed in PD models created in mice, fruit flies, and worms. Among them, Drosophila has emerged as a very valuable model organism in the study of either toxin-induced or genetically linked PD. Indeed, many of the existing fly PD models exhibit key features of the disease and have been instrumental to discover pathways relevant for PD pathogenesis, which could facilitate the development of therapeutic strategies. PMID:21512585

NALP3-mediated inflammation is a principal cause of progressive renal failure in oxalate nephropathy

PubMed Central

Knauf, Felix; Asplin, John R.; Granja, Ignacio; Schmidt, Insa M.; Moeckel, Gilbert; David, Rachel; Flavell, Richard A.; Aronson, Peter S.

2013-01-01

Oxalate nephropathy with renal failure is caused by multiple disorders causing hyperoxaluria due to either overproduction of oxalate (primary hyperoxaluria) or excessive absorption of dietary oxalate (enteric hyperoxaluria). To study the etiology of renal failure in crystal-induced kidney disease, we created a model of progressive oxalate nephropathy by feeding mice a diet high in soluble oxalate (high oxalate in the absence of dietary calcium). Renal histology was characterized by intratubular calcium-oxalate crystal deposition with an inflammatory response in the surrounding interstitium. Oxalate nephropathy was not found in mice fed a high oxalate diet that also contained calcium. NALP3, also known as cryopyrin, has been implicated in crystal-associated diseases such as gout and silicosis. Mice fed the diet high in soluble oxalate demonstrated increased NALP3 expression in the kidney. Nalp3-null mice were completely protected from the progressive renal failure and death that occurred in wild-type mice fed the diet high in soluble oxalate. NALP3-deficiency did not affect oxalate homeostasis, thereby excluding differences in intestinal oxalate handling to explain the observed phenotype. Thus, progressive renal failure in oxalate nephropathy results primarily from NALP3-mediated inflammation. PMID:23739234

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

Kienhuis, Anne S., E-mail: anne.kienhuis@rivm.nl; RIKILT, Institute of Food Safety, Wageningen UR, PO Box 230, 6700 AE, Wageningen; Netherlands Toxicogenomics Centre

Hepatic systems toxicology is the integrative analysis of toxicogenomic technologies, e.g., transcriptomics, proteomics, and metabolomics, in combination with traditional toxicology measures to improve the understanding of mechanisms of hepatotoxic action. Hepatic toxicology studies that have employed toxicogenomic technologies to date have already provided a proof of principle for the value of hepatic systems toxicology in hazard identification. In the present review, acetaminophen is used as a model compound to discuss the application of toxicogenomics in hepatic systems toxicology for its potential role in the risk assessment process, to progress from hazard identification towards hazard characterization. The toxicogenomics-based parallelogram is usedmore » to identify current achievements and limitations of acetaminophen toxicogenomic in vivo and in vitro studies for in vitro-to-in vivo and interspecies comparisons, with the ultimate aim to extrapolate animal studies to humans in vivo. This article provides a model for comparison of more species and more in vitro models enhancing the robustness of common toxicogenomic responses and their relevance to human risk assessment. To progress to quantitative dose-response analysis needed for hazard characterization, in hepatic systems toxicology studies, generation of toxicogenomic data of multiple doses/concentrations and time points is required. Newly developed bioinformatics tools for quantitative analysis of toxicogenomic data can aid in the elucidation of dose-responsive effects. The challenge herein is to assess which toxicogenomic responses are relevant for induction of the apical effect and whether perturbations are sufficient for the induction of downstream events, eventually causing toxicity.« less

Health information technology and implementation science: partners in progress in the VHA.

PubMed

Hynes, Denise M; Whittier, Erika R; Owens, Arika

2013-03-01

The Department of Veterans Affairs (VA) Quality Enhancement Research Initiative (QUERI) has demonstrated how implementation science can enhance the quality of health care. During this time an increasing number of implementation research projects have developed or utilized health information technology (HIT) innovations to leverage the VA's electronic health record and information systems. To describe the HIT approaches used and to characterize the facilitators and barriers to progress within implementation research projects in the VA QUERI program. Nine case studies were selected from among 88 projects and represented 8 of 14 HIT categories identified. Each case study included key informants whose roles on the project were principal investigator, implementation science and informatics development. We conducted documentation analysis and semistructured in-person interviews with key informants for each of the 9 case studies. We used qualitative analysis software to identify and thematically code information and interview responses. : Thematic analyses revealed 3 domains or pathways critical to progression through the QUERI steps. These pathways addressed: (1) compliance and collaboration with information technology policies and procedures; (2) operating within organizational policies and building collaborations with end users, clinicians, and administrators; and (3) obtaining and maintaining research resources and approvals. Sustained efforts in HIT innovation and in implementation science in the Veterans Health Administration demonstrates the interdependencies of these initiatives and the critical pathways that can contribute to progress. Other health care quality improvement efforts that rely on HIT can learn from the Veterans Health Administration experience.

Osteosarcoma

Cancer.gov

The TARGET Osteosarcoma (OS) project elucidates comprehensive molecular characterization to determine the genetic changes that drive the initiation and progression of high-risk or hard-to-treat childhood cancers.The OS project has produced comprehensive genomic profiles of nearly 100 clinically annotated patient cases within the discovery dataset. Each fully-characterized TARGET OS case includes data from nucleic acid samples extracted from tumor and normal tissue.

Optical Characterization of IV-VI Mid-Infrared VCSEL

DTIC Science & Technology

2002-01-01

vertical cavity surface emitting laser ( VCSEL ). A power...il quantum well (QW) devices [5], there has little progress until recently in developing mid-IR vertical cavity surface emitting laser ( VCSEL ). This...structures and PbSrSe thin films were grown on Bat; (111) substrates by molecular beam epitaxy ( MBE ) and characterized by Fourier transform infi-ared

Rating disease progression of Friedreich’s ataxia by the International Cooperative Ataxia Rating Scale: analysis of a 603-patient database

PubMed Central

Coppard, Nicholas; Cooper, Jonathon M.; Delatycki, Martin B.; Dürr, Alexandra; Di Prospero, Nicholas A.; Giunti, Paola; Lynch, David R.; Schulz, J. B.; Rummey, Christian; Meier, Thomas

2013-01-01

The aim of this cross-sectional study was to analyse disease progression in Friedreich’s ataxia as measured by the International Cooperative Ataxia Rating Scale. Single ratings from 603 patients with Friedreich’s ataxia were analysed as a function of disease duration, age of onset and GAA repeat lengths. The relative contribution of items and subscales to the total score was studied as a function of disease progression. In addition, the scaling properties were assessed using standard statistical measures. Average total scale progression per year depends on the age of disease onset, the time since diagnosis and the GAA repeat length. The age of onset inversely correlates with increased GAA repeat length. For patients with an age of onset ≤14 years associated with a longer repeat length, the average yearly rate of decline was 2.5 ± 0.18 points in the total International Cooperative Ataxia Rating Scale for the first 20 years of disease duration, whereas patients with a later onset progress more slowly (1.8 ± 0.27 points/year). Ceiling effects in posture, gait and lower limb scale items lead to a reduced sensitivity of the scale in the severely affected population with a total score of >60 points. Psychometric scaling analysis shows generally favourable properties for the total scale, but the subscale grouping could be improved. This cross-sectional study provides a detailed characterization of the International Cooperative Ataxia Rating Scale. The analysis further provides rates of change separated for patients with early and late disease onset, which is driven by the GAA repeat length. Differences in the subscale dynamics merit consideration in the design of future clinical trials applying this scale as a neurological assessment instrument in Friedreich’s ataxia. PMID:23365101

Draft report: Results of stainless steel canister corrosion studies and environmental sample investigations

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

Bryan, Charles R.; Enos, David

2014-09-01

This progress report describes work being done at Sandia National Laboratories (SNL) to assess the localized corrosion performance of container/cask materials used in the interim storage of used nuclear fuel. The work involves both characterization of the potential physical and chemical environment on the surface of the storage canisters and how it might evolve through time, and testing to evaluate performance of the canister materials under anticipated storage conditions.

Probing Cellular and Molecular Mechanisms of Cigarette Smoke-Induced Immune Response in the Progression of Chronic Obstructive Pulmonary Disease Using Multiscale Network Modeling

PubMed Central

Pan, Zhichao; Yu, Haishan; Liao, Jie-Lou

2016-01-01

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disorder characterized by progressive destruction of lung tissues and airway obstruction. COPD is currently the third leading cause of death worldwide and there is no curative treatment available so far. Cigarette smoke (CS) is the major risk factor for COPD. Yet, only a relatively small percentage of smokers develop the disease, showing that disease susceptibility varies significantly among smokers. As smoking cessation can prevent the disease in some smokers, quitting smoking cannot halt the progression of COPD in others. Despite extensive research efforts, cellular and molecular mechanisms of COPD remain elusive. In particular, the disease susceptibility and smoking cessation effects are poorly understood. To address these issues in this work, we develop a multiscale network model that consists of nodes, which represent molecular mediators, immune cells and lung tissues, and edges describing the interactions between the nodes. Our model study identifies several positive feedback loops and network elements playing a determinant role in the CS-induced immune response and COPD progression. The results are in agreement with clinic and laboratory measurements, offering novel insight into the cellular and molecular mechanisms of COPD. The study in this work also provides a rationale for targeted therapy and personalized medicine for the disease in future. PMID:27669518

Longitudinal magnetic resonance imaging study shows progressive pyramidal and callosal damage in Friedreich's ataxia.

PubMed

Rezende, Thiago J R; Silva, Cynthia B; Yassuda, Clarissa L; Campos, Brunno M; D'Abreu, Anelyssa; Cendes, Fernando; Lopes-Cendes, Iscia; França, Marcondes C

2016-01-01

Spinal cord and peripheral nerves are classically known to be damaged in Friedreich's ataxia, but the extent of cerebral involvement in the disease and its progression over time are not yet characterized. The aim of this study was to evaluate longitudinally cerebral damage in Friedreich's ataxia. We enrolled 31 patients and 40 controls, which were evaluated at baseline and after 1 and 2 years. To assess gray matter, we employed voxel-based morphometry and cortical thickness measurements. White matter was evaluated using diffusion tensor imaging. Statistical analyses were both cross-sectional and longitudinal (corrected for multiple comparisons). Group comparison between patients and controls revealed widespread macrostructural differences at baseline: gray matter atrophy in the dentate nuclei, brainstem, and precentral gyri; and white matter atrophy in the cerebellum and superior cerebellar peduncles, brainstem, and periventricular areas. We did not identify any longitudinal volumetric change over time. There were extensive microstructural alterations, including superior cerebellar peduncles, corpus callosum, and pyramidal tracts. Longitudinal analyses identified progressive microstructural abnormalities at the corpus callosum, pyramidal tracts, and superior cerebellar peduncles after 1 year of follow-up. Patients with Friedreich's ataxia present more widespread gray and white matter damage than previously reported, including not only infratentorial areas, but also supratentorial structures. Furthermore, patients with Friedreich's ataxia have progressive microstructural abnormalities amenable to detection in a short-term follow-up. © 2015 International Parkinson and Movement Disorder Society.

Rapid progression of familial amyloidotic polyneuropathy

PubMed Central

Coelho, Teresa; Obici, Laura; Merlini, Giampaolo; Mincheva, Zoia; Suanprasert, Narupat; Bettencourt, Brian R.; Gollob, Jared A.; Gandhi, Pritesh J.; Litchy, William J.; Dyck, Peter J.

2015-01-01

Objectives: To assess the association between severity of neuropathy and disease stage, and estimate the rate of neuropathy progression in a retrospective cross-sectional analysis of a multinational population of patients with familial amyloidotic polyneuropathy (FAP). Methods: We characterize neuropathy severity and rate of progression in available patients with FAP in France, the United States, Portugal, and Italy. Neuropathy Impairment Scores (NIS), time from symptom onset to NIS measurement, polyneuropathy disability (PND) scores, FAP disease stage, and manual grip strength data were collected. We estimated neuropathy progression using Loess Fit and Gompertz Fit models. Results: For the 283 patients studied (mean age, 56.4 years), intercountry genotypic variation in the transthyretin (TTR) mutation was observed, with the majority of patients in Portugal (92%) having early-onset Val30Met-FAP. There was also marked intercountry variation in PND score, FAP stage, and TTR stabilizer use. NIS was associated with PND score (NIS 10 and 99 for scores I and IV, respectively; p < 0.0001) and FAP stage (NIS 14 and 99 for stages 1 and 3, respectively; p < 0.0001). In addition, there was an association between NIS and TTR genotype. The estimated rate of NIS progression for a population with a median NIS of 32 was 14.3 points/year; the corresponding estimated rate for the modified NIS+7 is 17.8 points/year. Conclusions: In a multinational population of patients with FAP, rapid neuropathic progression is observed and the severity of neuropathy is associated with functional scales of locomotion. PMID:26208957

Characterization of an Early-Onset, Autosomal Recessive, Progressive Retinal Degeneration in Bengal Cats

PubMed Central

Ofri, Ron; Reilly, Christopher M.; Maggs, David J.; Fitzgerald, Paul G.; Shilo-Benjamini, Yael; Good, Kathryn L.; Grahn, Robert A.; Splawski, Danielle D.; Lyons, Leslie A.

2015-01-01

Purpose A form of retinal degeneration suspected to be hereditary was discovered in a family of Bengal cats. A breeding colony was established to characterize disease progression clinically, electrophysiologically, and morphologically, and to investigate the mode of inheritance. Methods Affected and related cats were donated by owners for breeding trials and pedigree analysis. Kittens from test and complementation breedings underwent ophthalmic and neuro-ophthalmic examinations and ERG, and globes were evaluated using light microscopy. Results Pedigree analysis, along with test and complementation breedings, indicated autosomal recessive inheritance and suggested that this disease is nonallelic to a retinal degeneration found in Persian cats. Mutation analysis confirmed the disease is not caused by CEP290 or CRX variants found predominantly in Abyssinian and Siamese cats. Ophthalmoscopic signs of retinal degeneration were noted at 9 weeks of age and became more noticeable over the next 4 months. Visual deficits were behaviorally evident by 1 year of age. Electroretinogram demonstrated reduced rod and cone function at 7 and 9 weeks of age, respectively. Rod responses were mostly extinguished at 14 weeks of age; cone responses were minimal by 26 weeks. Histologic degeneration was first observed at 8 weeks, evidenced by reduced photoreceptor numbers, then rapid deterioration of the photoreceptor layer and, subsequently, severe outer retinal degeneration. Conclusions A recessively inherited primary photoreceptor degeneration was characterized in the Bengal cat. The disease is characterized by early onset, with histologic, ophthalmoscopic, and electrophysiological signs evident by 2 months of age, and rapid progression to blindness. PMID:26258614

Using filtered forecasting techniques to determine personalized monitoring schedules for patients with open-angle glaucoma.

PubMed

Schell, Greggory J; Lavieri, Mariel S; Helm, Jonathan E; Liu, Xiang; Musch, David C; Van Oyen, Mark P; Stein, Joshua D

2014-08-01

To determine whether dynamic and personalized schedules of visual field (VF) testing and intraocular pressure (IOP) measurements result in an improvement in disease progression detection compared with fixed interval schedules for performing these tests when evaluating patients with open-angle glaucoma (OAG). Secondary analyses using longitudinal data from 2 randomized controlled trials. A total of 571 participants from the Advanced Glaucoma Intervention Study (AGIS) and the Collaborative Initial Glaucoma Treatment Study (CIGTS). Perimetric and tonometric data were obtained for AGIS and CIGTS trial participants and used to parameterize and validate a Kalman filter model. The Kalman filter updates knowledge about each participant's disease dynamics as additional VF tests and IOP measurements are obtained. After incorporating the most recent VF and IOP measurements, the model forecasts each participant's disease dynamics into the future and characterizes the forecasting error. To determine personalized schedules for future VF tests and IOP measurements, we developed an algorithm by combining the Kalman filter for state estimation with the predictive power of logistic regression to identify OAG progression. The algorithm was compared with 1-, 1.5-, and 2-year fixed interval schedules of obtaining VF and IOP measurements. Length of diagnostic delay in detecting OAG progression, efficiency of detecting progression, and number of VF and IOP measurements needed to assess for progression. Participants were followed in the AGIS and CIGTS trials for a mean (standard deviation) of 6.5 (2.8) years. Our forecasting model achieved a 29% increased efficiency in identifying OAG progression (P<0.0001) and detected OAG progression 57% sooner (reduced diagnostic delay) (P = 0.02) than following a fixed yearly monitoring schedule, without increasing the number of VF tests and IOP measurements required. The model performed well for patients with mild and advanced disease. The model performed significantly more testing of patients who exhibited OAG progression than nonprogressing patients (1.3 vs. 1.0 tests per year; P<0.0001). Use of dynamic and personalized testing schedules can enhance the efficiency of OAG progression detection and reduce diagnostic delay compared with yearly fixed monitoring intervals. If further validation studies confirm these findings, such algorithms may be able to greatly enhance OAG management. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Unusual early-onset Huntingtons disease.

PubMed

Vargas, Antonio P; Carod-Artal, Francisco J; Bomfim, Denise; Vázquez-Cabrera, Carolina; Dantas-Barbosa, Carmela

2003-06-01

Huntington's disease is an autosomal dominant progressive neurodegenerative disorder characterized by involuntary movements, cognitive decline, and behavioral disorders leading to functional disability. In contrast to patients with adult onset, in which chorea is the major motor abnormality, children often present with spasticity, rigidity, and significant intellectual decline associated with a more rapidly progressive course. An unusual early-onset Huntington's disease case of an 11-year-old boy with severe hypokinetic/rigid syndrome appearing at the age of 2.5 years is presented. Clinical diagnosis was confirmed by polymerase chain reaction study of the expanded IT-15 allele with a compatible size of 102 cytosine-adenosine-guanosine repeats L-Dopa mildly ameliorated rigidity, bradykinesia, and dystonia. We conclude that Huntington's disease should be included in the differential diagnoses of regressive syndromes of early childhood.

[Acquired amegacaryocytic thrombocytopenic purpura hiding acute myeloid leukemia].

PubMed

Eddou, Hicham; Zinebi, Ali; Khalloufi, Abdelaziz; Sina, Mohammed; Mahtat, Mehdi; Doghmi, Kamal; Mikdame, Mohammed; Moudden, Mohammed Karim; Baaj, Mohammed El

2017-01-01

Acquired amegakaryocytic thrombocytopenic purpura is a very rare condition characterized by severe thrombocytopenia linked to the reduction or disappearance of megakaryocytes in the bone marrow. It may be primary idiopathic or secondary to many pathological conditions including hematologic disorders. We report the case of a 24-year-old patient admitted for haemorrhagic syndrome caused by immunological thrombocytopenic purpura. The diagnosis was acquired amegakaryocytosis after the failure of corticotherapy and the performance of myelography. The patient was treated with ciclosporin with rapid progression to acute myeloblastic leukemia. The progression of acquired amegakaryocytosis to acute leukemia is reported but it is generally not so rapid and above all it is preceded by myelodysplastic syndrome or medullary aplasia. This study highlights the importance of a close follow-up of these pathologies with a benign-like appearance.

Metabolic Dysfunctions in Amyotrophic Lateral Sclerosis Pathogenesis and Potential Metabolic Treatments

PubMed Central

Tefera, Tesfaye W.; Borges, Karin

2017-01-01

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease primarily characterized by loss of motor neurons in brain and spinal cord. The death of motor neurons leads to denervation of muscle which in turn causes muscle weakness and paralysis, decreased respiratory function and eventually death. Growing evidence indicates disturbances in energy metabolism in patients with ALS and animal models of ALS, which are likely to contribute to disease progression. Particularly, defects in glucose metabolism and mitochondrial dysfunction limit the availability of ATP to CNS tissues and muscle. Several metabolic approaches improving mitochondrial function have been investigated in vitro and in vivo and showed varying effects in ALS. The effects of metabolic approaches in ALS models encompass delays in onset of motor symptoms, protection of motor neurons and extension of survival, which signifies an important role of metabolism in the pathogenesis of the disease. There is now an urgent need to test metabolic approaches in controlled clinical trials. In addition, more detailed studies to better characterize the abnormalities in energy metabolism in patients with ALS and ALS models are necessary to develop metabolically targeted effective therapies that can slow the progression of the disease and prolong life for patients with ALS. PMID:28119559

Old and new challenges in Parkinson's disease therapeutics.

PubMed

Pires, Ana O; Teixeira, F G; Mendes-Pinheiro, B; Serra, Sofia C; Sousa, Nuno; Salgado, António J

2017-09-01

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons and/or loss od neuronal projections, in several dopaminergic networks. Current treatments for idiopathic PD rely mainly on the use of pharmacologic agents to improve motor symptomatology of PD patients. Nevertheless, so far PD remains an incurable disease. Therefore, it is of utmost importance to establish new therapeutic strategies for PD treatment. Over the last 20 years, several molecular, gene and cell/stem-cell therapeutic approaches have been developed with the aim of counteracting or retarding PD progression. The scope of this review is to provide an overview of PD related therapies and major breakthroughs achieved within this field. In order to do so, this review will start by focusing on PD characterization and current treatment options covering thereafter molecular, gene and cell/stem cell-based therapies that are currently being studied in animal models of PD or have recently been tested in clinical trials. Among stem cell-based therapies, those using MSCs as possible disease modifying agents for PD therapy and, specifically, the MSCs secretome contribution to meet the clinical challenge of counteracting or retarding PD progression, will be more deeply explored. Copyright © 2017 Elsevier Ltd. All rights reserved.

An approach to achieve progress in spacecraft shielding

NASA Astrophysics Data System (ADS)

Thoma, K.; Schäfer, F.; Hiermaier, S.; Schneider, E.

2004-01-01

Progress in shield design against space debris can be achieved only when a combined approach based on several tools is used. This approach depends on the combined application of advanced numerical methods, specific material models and experimental determination of input parameters for these models. Examples of experimental methods for material characterization are given, covering the range from quasi static to very high strain rates for materials like Nextel and carbon fiber-reinforced materials. Mesh free numerical methods have extraordinary capabilities in the simulation of extreme material behaviour including complete failure with phase changes, combined with shock wave phenomena and the interaction with structural components. In this paper the benefits from combining numerical methods, material modelling and detailed experimental studies for shield design are demonstrated. The following examples are given: (1) Development of a material model for Nextel and Kevlar-Epoxy to enable numerical simulation of hypervelocity impacts on complex heavy protection shields for the International Space Station. (2) The influence of projectile shape on protection performance of Whipple Shields and how experimental problems in accelerating such shapes can be overcome by systematic numerical simulation. (3) The benefits of using metallic foams in "sandwich bumper shields" for spacecraft and how to approach systematic characterization of such materials.

Metabolism dysregulation induces a specific lipid signature of nonalcoholic steatohepatitis in patients

PubMed Central

Chiappini, Franck; Coilly, Audrey; Kadar, Hanane; Gual, Philippe; Tran, Albert; Desterke, Christophe; Samuel, Didier; Duclos-Vallée, Jean-Charles; Touboul, David; Bertrand-Michel, Justine; Brunelle, Alain; Guettier, Catherine; Le Naour, François

2017-01-01

Nonalcoholic steatohepatitis (NASH) is a condition which can progress to cirrhosis and hepatocellular carcinoma. Markers for NASH diagnosis are still lacking. We performed a comprehensive lipidomic analysis on human liver biopsies including normal liver, nonalcoholic fatty liver and NASH. Random forests-based machine learning approach allowed characterizing a signature of 32 lipids discriminating NASH with 100% sensitivity and specificity. Furthermore, we validated this signature in an independent group of NASH patients. Then, metabolism dysregulations were investigated in both patients and murine models. Alterations of elongase and desaturase activities were observed along the fatty acid synthesis pathway. The decreased activity of the desaturase FADS1 appeared as a bottleneck, leading upstream to an accumulation of fatty acids and downstream to a deficiency of long-chain fatty acids resulting to impaired phospholipid synthesis. In NASH, mass spectrometry imaging on tissue section revealed the spreading into the hepatic parenchyma of selectively accumulated fatty acids. Such lipids constituted a highly toxic mixture to human hepatocytes. In conclusion, this study characterized a specific and sensitive lipid signature of NASH and positioned FADS1 as a significant player in accumulating toxic lipids during NASH progression. PMID:28436449

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

Ernest A. Mancini

The University of Alabama in cooperation with Texas A&M University, McGill University, Longleaf Energy Group, Strago Petroleum Corporation, and Paramount Petroleum Company are undertaking an integrated, interdisciplinary geoscientific and engineering research project. The project is designed to characterize and model reservoir architecture, pore systems and rock-fluid interactions at the pore to field scale in Upper Jurassic Smackover reef and carbonate shoal reservoirs associated with varying degrees of relief on pre-Mesozoic basement paleohighs in the northeastern Gulf of Mexico. The project effort includes the prediction of fluid flow in carbonate reservoirs through reservoir simulation modeling that utilizes geologic reservoir characterization andmore » modeling and the prediction of carbonate reservoir architecture, heterogeneity and quality through seismic imaging. The primary objective of the project is to increase the profitability, producibility and efficiency of recovery of oil from existing and undiscovered Upper Jurassic fields characterized by reef and carbonate shoals associated with pre-Mesozoic basement paleohighs. The principal research effort for Year 3 of the project has been reservoir characterization, 3-D modeling, testing of the geologic-engineering model, and technology transfer. This effort has included six tasks: (1) the study of seismic attributes, (2) petrophysical characterization, (3) data integration, (4) the building of the geologic-engineering model, (5) the testing of the geologic-engineering model and (6) technology transfer. This work was scheduled for completion in Year 3. Progress on the project is as follows: geoscientific reservoir characterization is completed. The architecture, porosity types and heterogeneity of the reef and shoal reservoirs at Appleton and Vocation Fields have been characterized using geological and geophysical data. The study of rock-fluid interactions has been completed. Observations regarding the diagenetic processes influencing pore system development and heterogeneity in these reef and shoal reservoirs have been made. Petrophysical and engineering property characterization has been completed. Porosity and permeability data at Appleton and Vocation Fields have been analyzed, and well performance analysis has been conducted. Data integration is up to date, in that, the geological, geophysical, petrophysical and engineering data collected to date for Appleton and Vocation Fields have been compiled into a fieldwide digital database. 3-D geologic modeling of the structures and reservoirs at Appleton and Vocation Fields has been completed. The models represent an integration of geological, petrophysical and seismic data. 3-D reservoir simulation of the reservoirs at Appleton and Vocation Fields has been completed. The 3-D geologic models served as the framework for the simulations. The geologic-engineering models of the Appleton and Vocation Field reservoirs have been developed. These models are being tested. The geophysical interpretation for the paleotopographic feature being tested has been made, and the study of the data resulting from drilling of a well on this paleohigh is in progress. Numerous presentations on reservoir characterization and modeling at Appleton and Vocation Fields have been made at professional meetings and conferences and a short course on microbial reservoir characterization and modeling based on these fields has been prepared.« less

Melanoma: Genetic Abnormalities, Tumor Progression, Clonal Evolution and Tumor Initiating Cells.

PubMed

Testa, Ugo; Castelli, Germana; Pelosi, Elvira

2017-11-20

Melanoma is an aggressive neoplasia issued from the malignant transformation of melanocytes, the pigment-generating cells of the skin. It is responsible for about 75% of deaths due to skin cancers. Melanoma is a phenotypically and molecularly heterogeneous disease: cutaneous, uveal, acral, and mucosal melanomas have different clinical courses, are associated with different mutational profiles, and possess distinct risk factors. The discovery of the molecular abnormalities underlying melanomas has led to the promising improvement of therapy, and further progress is expected in the near future. The study of melanoma precursor lesions has led to the suggestion that the pathway of tumor evolution implies the progression from benign naevi, to dysplastic naevi, to melanoma in situ and then to invasive and metastatic melanoma. The gene alterations characterizing melanomas tend to accumulate in these precursor lesions in a sequential order. Studies carried out in recent years have, in part, elucidated the great tumorigenic potential of melanoma tumor cells. These findings have led to speculation that the cancer stem cell model cannot be applied to melanoma because, in this malignancy, tumor cells possess an intrinsic plasticity, conferring the capacity to initiate and maintain the neoplastic process to phenotypically different tumor cells.

Comprehensive Study on Small and Low Cost Satellite Technology for Earth Observation with Case Study for Indonesia: Projection for 2002-2022

NASA Astrophysics Data System (ADS)

Djojodihardjo, Harijono

and economic progress, while facing global competitiveness locally as opportunities and challenges. Of particular importance is the utilization and development of earth observation capabilities for environmental natural resources imperatives to this end is quite significant. On one hand there may appear challenges to achieve unique and high quality requirements on many of the elements of social and economic progress, i.e. natural resources, human resources, market opportunities and geographical advantage; on the other hand one may face constraints in the financial system, cultural inertia and paradigm, and the need to carry forward large momentum that may pull back technological and economic progress that may be characterized by a "roller coaster" dynamics. Satellite Technology for Earth Observation, its Utilization and Development is carried out with Indonesian Development Interest in mind. Space System Services and Players are identified. Mission objectives associated with Urban and Rural Areas as well as Satellite-Based Multimedia Technology Applications For Promoting Rural Development will be identified. System design analysis and synthesis will be elaborated and some alternatives will be presented following a unified system outlook. Ground Segment and Space Segment Architecture will be elaborated by carrying out Architecture Optimization.

Pathophysiology and Mechanisms of Nonalcoholic Fatty Liver Disease.

PubMed

Haas, Joel T; Francque, Sven; Staels, Bart

2016-01-01

Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver disorders characterized by abnormal hepatic fat accumulation, inflammation, and hepatocyte dysfunction. Importantly, it is also closely linked to obesity and the metabolic syndrome. NAFLD predisposes susceptible individuals to cirrhosis, hepatocellular carcinoma, and cardiovascular disease. Although the precise signals remain poorly understood, NAFLD pathogenesis likely involves actions of the different hepatic cell types and multiple extrahepatic signals. The complexity of this disease has been a major impediment to the development of appropriate metrics of its progression and effective therapies. Recent clinical data place increasing importance on identifying fibrosis, as it is a strong indicator of hepatic disease-related mortality. Preclinical modeling of the fibrotic process remains challenging, particularly in the contexts of obesity and the metabolic syndrome. Future studies are needed to define the molecular pathways determining the natural progression of NAFLD, including key determinants of fibrosis and disease-related outcomes. This review covers the evolving concepts of NAFLD from both human and animal studies. We discuss recent clinical and diagnostic methods assessing NAFLD diagnosis, progression, and outcomes; compare the features of genetic and dietary animal models of NAFLD; and highlight pharmacological approaches for disease treatment.

Melanoma: Genetic Abnormalities, Tumor Progression, Clonal Evolution and Tumor Initiating Cells

PubMed Central

Castelli, Germana; Pelosi, Elvira

2017-01-01

Melanoma is an aggressive neoplasia issued from the malignant transformation of melanocytes, the pigment-generating cells of the skin. It is responsible for about 75% of deaths due to skin cancers. Melanoma is a phenotypically and molecularly heterogeneous disease: cutaneous, uveal, acral, and mucosal melanomas have different clinical courses, are associated with different mutational profiles, and possess distinct risk factors. The discovery of the molecular abnormalities underlying melanomas has led to the promising improvement of therapy, and further progress is expected in the near future. The study of melanoma precursor lesions has led to the suggestion that the pathway of tumor evolution implies the progression from benign naevi, to dysplastic naevi, to melanoma in situ and then to invasive and metastatic melanoma. The gene alterations characterizing melanomas tend to accumulate in these precursor lesions in a sequential order. Studies carried out in recent years have, in part, elucidated the great tumorigenic potential of melanoma tumor cells. These findings have led to speculation that the cancer stem cell model cannot be applied to melanoma because, in this malignancy, tumor cells possess an intrinsic plasticity, conferring the capacity to initiate and maintain the neoplastic process to phenotypically different tumor cells. PMID:29156643

Decreased hepatotoxic bile acid composition and altered synthesis in progressive human nonalcoholic fatty liver disease

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

Lake, April D.; Novak, Petr; Shipkova, Petia

2013-04-15

Bile acids (BAs) have many physiological roles and exhibit both toxic and protective influences within the liver. Alterations in the BA profile may be the result of disease induced liver injury. Nonalcoholic fatty liver disease (NAFLD) is a prevalent form of chronic liver disease characterized by the pathophysiological progression from simple steatosis to nonalcoholic steatohepatitis (NASH). The hypothesis of this study is that the ‘classical’ (neutral) and ‘alternative’ (acidic) BA synthesis pathways are altered together with hepatic BA composition during progression of human NAFLD. This study employed the use of transcriptomic and metabolomic assays to study the hepatic toxicologic BAmore » profile in progressive human NAFLD. Individual human liver samples diagnosed as normal, steatosis, and NASH were utilized in the assays. The transcriptomic analysis of 70 BA genes revealed an enrichment of downregulated BA metabolism and transcription factor/receptor genes in livers diagnosed as NASH. Increased mRNA expression of BAAT and CYP7B1 was observed in contrast to decreased CYP8B1 expression in NASH samples. The BA metabolomic profile of NASH livers exhibited an increase in taurine together with elevated levels of conjugated BA species, taurocholic acid (TCA) and taurodeoxycholic acid (TDCA). Conversely, cholic acid (CA) and glycodeoxycholic acid (GDCA) were decreased in NASH liver. These findings reveal a potential shift toward the alternative pathway of BA synthesis during NASH, mediated by increased mRNA and protein expression of CYP7B1. Overall, the transcriptomic changes of BA synthesis pathway enzymes together with altered hepatic BA composition signify an attempt by the liver to reduce hepatotoxicity during disease progression to NASH. - Highlights: ► Altered hepatic bile acid composition is observed in progressive NAFLD. ► Bile acid synthesis enzymes are transcriptionally altered in NASH livers. ► Increased levels of taurine and conjugated bile acids are observed in NASH. ► Hepatic bile acid synthesis shifts toward the alternative pathway in NASH.« less

The Role of Heparanase and Sulfatases in the Modification of Heparan Sulfate Proteoglycans within the Tumor Microenvironment and Opportunities for Novel Cancer Therapeutics

PubMed Central

Hammond, Edward; Khurana, Ashwani; Shridhar, Viji; Dredge, Keith

2014-01-01

Heparan sulfate proteoglycans (HSPGs) are an integral and dynamic part of normal tissue architecture at the cell surface and within the extracellular matrix. The modification of HSPGs in the tumor microenvironment is known to result not just in structural but also functional consequences, which significantly impact cancer progression. As substrates for the key enzymes sulfatases and heparanase, the modification of HSPGs is typically characterized by the degradation of heparan sulfate (HS) chains/sulfation patterns via the endo-6-O-sulfatases (Sulf1 and Sulf2) or by heparanase, an endo-glycosidase that cleaves the HS polymers releasing smaller fragments from HSPG complexes. Numerous studies have demonstrated how these enzymes actively influence cancer cell proliferation, signaling, invasion, and metastasis. The activity or expression of these enzymes has been reported to be modified in a variety of cancers. Such observations are consistent with the degradation of normal architecture and basement membranes, which are typically compromised in metastatic disease. Moreover, recent studies elucidating the requirements for these proteins in tumor initiation and progression exemplify their importance in the development and progression of cancer. Thus, as the influence of the tumor microenvironment in cancer progression becomes more apparent, the focus on targeting enzymes that degrade HSPGs highlights one approach to maintain normal tissue architecture, inhibit tumor progression, and block metastasis. This review discusses the role of these enzymes in the context of the tumor microenvironment and their promise as therapeutic targets for the treatment of cancer. PMID:25105093

Radiation induced pulmonary fibrosis as a model of progressive fibrosis: Contributions of DNA damage, inflammatory response and cellular senescence genes.

PubMed

Beach, Tyler A; Johnston, Carl J; Groves, Angela M; Williams, Jacqueline P; Finkelstein, Jacob N

2017-04-01

Purpose/Aim of Study: Studies of pulmonary fibrosis (PF) have resulted in DNA damage, inflammatory response, and cellular senescence being widely hypothesized to play a role in the progression of the disease. Utilizing these aforementioned terms, genomics databases were interrogated along with the term, "pulmonary fibrosis," to identify genes common among all 4 search terms. Findings were compared to data derived from a model of radiation-induced progressive pulmonary fibrosis (RIPF) to verify that these genes are similarly expressed, supporting the use of radiation as a model for diseases involving PF, such as human idiopathic pulmonary fibrosis (IPF). In an established model of RIPF, C57BL/6J mice were exposed to 12.5 Gy thorax irradiation and sacrificed at 24 hours, 1, 4, 12, and 32 weeks following exposure, and lung tissue was compared to age-matched controls by RNA sequencing. Of 176 PF associated gene transcripts identified by database interrogation, 146 (>82%) were present in our experimental model, throughout the progression of RIPF. Analysis revealed that nearly 85% of PF gene transcripts were associated with at least 1 other search term. Furthermore, of 22 genes common to all four terms, 16 were present experimentally in RIPF. This illustrates the validity of RIPF as a model of progressive PF/IPF based on the numbers of transcripts reported in both literature and observed experimentally. Well characterized genes and proteins are implicated in this model, supporting the hypotheses that DNA damage, inflammatory response and cellular senescence are associated with the pathogenesis of PF.

Adaptive characterization of recrystallization kinetics in IF steel by electron backscatter diffraction.

PubMed

Kim, Dong-Kyu; Park, Won-Woong; Lee, Ho Won; Kang, Seong-Hoon; Im, Yong-Taek

2013-12-01

In this study, a rigorous methodology for quantifying recrystallization kinetics by electron backscatter diffraction is proposed in order to reduce errors associated with the operator's skill. An adaptive criterion to determine adjustable grain orientation spread depending on the recrystallization stage is proposed to better identify the recrystallized grains in the partially recrystallized microstructure. The proposed method was applied in characterizing the microstructure evolution during annealing of interstitial-free steel cold rolled to low and high true strain levels of 0.7 and 1.6, respectively. The recrystallization kinetics determined by the proposed method was found to be consistent with the standard method of Vickers microhardness. The application of the proposed method to the overall recrystallization stages showed that it can be used for the rigorous characterization of progressive microstructure evolution, especially for the severely deformed material. © 2013 The Authors Journal of Microscopy © 2013 Royal Microscopical Society.

Rectal Microbicide Development

PubMed Central

Dezzutti, Charlene

2014-01-01

The last few years have seen important progress in demonstrating the efficacy of oral pre-exposure prophylaxis, vaginal microbicides, and treatment as prevention as effective strategies for reducing the risk of acquiring or transmitting HIV infection. There has also been significant progress in the development of rectal microbicides. Preclinical non-human primate studies have demonstrated that antiretroviral microbicides can provide significant protection from rectal challenge with SIV or SHIV. Recent Phase 1 rectal microbicide studies have characterized the safety, acceptability, compartmental pharmacokinetics (PK), and pharmaco-dynamics (PD) of both UC781 and tenofovir gels. The tenofovir gel formulation used in vaginal studies was not well tolerated in the rectum and newer rectal-specific formulations have been developed and evaluated in Phase 1 studies. The PK/PD data generated in these Phase 1 studies may reduce the risk of advancing ineffective candidate rectal microbicides into late stage development. Tenofovir gel is currently poised to move into Phase 2 evaluation and it is possible that a Phase 2B/3 effectiveness study with this product could be initiated in the next 2–3 years. PMID:23612991

Synthesis and characterization of binary titania-silica mixed oxides

NASA Astrophysics Data System (ADS)

Budhi, Sridhar

A series of binary titania-silica mixed oxides were synthesized by the sol-gel method at room temperature. The mixed oxides were prepared that involved the hydrolysis of titanium isopropoxide and tetraethylorthosilicate (TEOS) by co-solvent induced gelation usually in acidic media. The resulting gels were dried, calcined and then characterized by powder X-ray diffractometric studies, nitrogen sorption studies (at 77K), diffuse reflectance spectroscopy, Raman microscopy and transmission electron microscopic studies. The nitrogen sorption studies indicate that the specific surface areas, pore volume, pore diameter and pore size distribution of the mixed oxides were substantially enhanced when non-polar solvents such as toluene, p-xylene or mesitylene were added as co-solvents to the synthesis gel. Transmission electron microscopic (TEM) studies confirm the results obtained from the nitrogen sorption studies. Our results indicate that we can obtain binary metal oxides possessing high surface area and large pore volumes with tunable pore size distribution at room temperature. Photocatalytic evaluation of the mixed oxides is currently in progress.

Emotions evoked by the sound of music: characterization, classification, and measurement.

PubMed

Zentner, Marcel; Grandjean, Didier; Scherer, Klaus R

2008-08-01

One reason for the universal appeal of music lies in the emotional rewards that music offers to its listeners. But what makes these rewards so special? The authors addressed this question by progressively characterizing music-induced emotions in 4 interrelated studies. Studies 1 and 2 (n=354) were conducted to compile a list of music-relevant emotion terms and to study the frequency of both felt and perceived emotions across 5 groups of listeners with distinct music preferences. Emotional responses varied greatly according to musical genre and type of response (felt vs. perceived). Study 3 (n=801)--a field study carried out during a music festival--examined the structure of music-induced emotions via confirmatory factor analysis of emotion ratings, resulting in a 9-factorial model of music-induced emotions. Study 4 (n=238) replicated this model and found that it accounted for music-elicited emotions better than the basic emotion and dimensional emotion models. A domain-specific device to measure musically induced emotions is introduced--the Geneva Emotional Music Scale.

Frontotemporal Lobar Degeneration

PubMed Central

Rabinovici, Gil D.; Miller, Bruce L.

2010-01-01

Frontotemporal lobar degeneration (FTLD) is a clinically and pathologically heterogeneous syndrome, characterized by progressive decline in behaviour or language associated with degeneration of the frontal and anterior temporal lobes. While the seminal cases were described at the turn of the 20th century, FTLD has only recently been appreciated as a leading cause of dementia, particularly in patients presenting before the age of 65 years. Three distinct clinical variants of FTLD have been described: (i) behavioural-variant frontotemporal dementia, characterized by changes in behaviour and personality in association with frontal-predominant cortical degeneration; (ii) semantic dementia, a syndrome of progressive loss of knowledge about words and objects associated with anterior temporal neuronal loss; and (iii) progressive nonfluent aphasia, characterized by effortful language output, loss of grammar and motor speech deficits in the setting of left perisylvian cortical atrophy. The majority of pathologies associated with FTLD clinical syndromes include either tau-positive (FTLD-TAU) or TAR DNA-binding protein 43 (TDP-43)-positive (FTLD-TDP) inclusion bodies. FTLD overlaps clinically and pathologically with the atypical parkinsonian disorders corticobasal degeneration and progressive supranuclear palsy, and with amyotrophic lateral sclerosis. The majority of familial FTLD cases are caused by mutations in the genes encoding microtubule-associated protein tau (leading to FTLD-TAU) or progranulin (leading to FTLD-TDP). The clinical and pathologic heterogeneity of FTLD poses a significant diagnostic challenge, and in vivo prediction of underlying histopathology can be significantly improved by supplementing the clinical evaluation with genetic tests and emerging biological markers. Current pharmacotherapy for FTLD focuses on manipulating serotonergic or dopaminergic neurotransmitter systems to ameliorate behavioural or motor symptoms. However, recent advances in FTLD genetics and molecular pathology make the prospect of biologically driven, disease-specific therapies for FTLD seem closer than ever. PMID:20369906

Applications of synchrotron-based spectroscopic techniques in studying nucleic acids and nucleic acid-functionalized nanomaterials

PubMed Central

Wu, Peiwen; Yu, Yang; McGhee, Claire E.; Tan, Li Huey

2014-01-01

In this review, we summarize recent progresses in the application of synchrotron-based spectroscopic techniques for nucleic acid research that takes advantage of high-flux and high-brilliance electromagnetic radiation from synchrotron sources. The first section of the review focuses on the characterization of the structure and folding processes of nucleic acids using different types of synchrotron-based spectroscopies, such as X-ray absorption spectroscopy, X-ray emission spectroscopy, X-ray photoelectron spectroscopy, synchrotron radiation circular dichroism, X-ray footprinting and small-angle X-ray scattering. In the second section, the characterization of nucleic acid-based nanostructures, nucleic acid-functionalized nanomaterials and nucleic acid-lipid interactions using these spectroscopic techniques is summarized. Insights gained from these studies are described and future directions of this field are also discussed. PMID:25205057

Applications of synchrotron-based spectroscopic techniques in studying nucleic acids and nucleic acid-functionalized nanomaterials

DOE PAGES

Wu, Peiwen; Yu, Yang; McGhee, Claire E.; ...

2014-09-10

In this paper, we summarize recent progress in the application of synchrotron-based spectroscopic techniques for nucleic acid research that takes advantage of high-flux and high-brilliance electromagnetic radiation from synchrotron sources. The first section of the review focuses on the characterization of the structure and folding processes of nucleic acids using different types of synchrotron-based spectroscopies, such as X-ray absorption spectroscopy, X-ray emission spectroscopy, X-ray photoelectron spectroscopy, synchrotron radiation circular dichroism, X-ray footprinting and small-angle X-ray scattering. In the second section, the characterization of nucleic acid-based nanostructures, nucleic acid-functionalized nanomaterials and nucleic acid-lipid interactions using these spectroscopic techniques is summarized. Insightsmore » gained from these studies are described and future directions of this field are also discussed.« less

Review on physical and chemical characterizations of contaminated sediments from urban stormwater infiltration basins within the framework of the French observatory for urban hydrology (SOERE URBIS).

PubMed

El-Mufleh, Amelène; Béchet, Béatrice; Ruban, Véronique; Legret, Michel; Clozel, Blandine; Barraud, Sylvie; Gonzalez-Merchan, Carolina; Bedell, Jean-Philippe; Delolme, Cécile

2014-04-01

Urban stormwater infiltration basins are designed to hold runoff from impervious surfaces and allow the settling of sediments and associated pollutants. However concerns have been expressed about the environmental impacts that may be exerted by the trapped pollutants on groundwater, soils and ecosystems. In this context, sediment characterization represents a key issue for local authorities in terms of management strategies. During the last two decades, several studies were launched including either physical or chemical characterization of stormwater sediments but without real synthesis of data and methods used. Consequently, there is an important need for reviewing the current experimental techniques devoted to the physico-chemical characterization of sediment. The review is based on the outcomes of two experimental sites for which long term monitoring and data collection have been done: the Cheviré basin (near Nantes) and the Django Reinhardt basin (near Lyon). The authors summarize the studies dealing with bulk properties, pollutant contents, their potential mobility and speciation. This paper aims at promoting the significant progresses that were made through a multidisciplinary approach involving multi-scaled and combined experimental techniques.

Applications of UV/Vis Spectroscopy in Characterization and Catalytic Activity of Noble Metal Nanoparticles Fabricated in Responsive Polymer Microgels: A Review.

PubMed

Begum, Robina; Farooqi, Zahoor H; Naseem, Khalida; Ali, Faisal; Batool, Madeeha; Xiao, Jianliang; Irfan, Ahmad

2018-11-02

Noble metal nanoparticles loaded smart polymer microgels have gained much attention due to fascinating combination of their properties in a single system. These hybrid systems have been extensively used in biomedicines, photonics, and catalysis. Hybrid microgels are characterized by using various techniques but UV/Vis spectroscopy is an easily available technique for characterization of noble metal nanoparticles loaded microgels. This technique is widely used for determination of size and shape of metal nanoparticles. The tuning of optical properties of noble metal nanoparticles under various stimuli can be studied using UV/Vis spectroscopic method. Time course UV/Vis spectroscopy can also be used to monitor the kinetics of swelling and deswelling of microgels and hybrid microgels. Growth of metal nanoparticles in polymeric network or growth of polymeric network around metal nanoparticle core can be studied by using UV/Vis spectroscopy. This technique can also be used for investigation of various applications of hybrid materials in catalysis, photonics, and sensing. This tutorial review describes the uses of UV/Vis spectroscopy in characterization and catalytic applications of responsive hybrid microgels with respect to recent research progress in this area.

Scaffolding Students' Skill Development by First Introducing Advanced Techniques through the Synthesis and [superscript 15]N NMR Analysis of Cinnamamides

ERIC Educational Resources Information Center

Shuldburg, Sara; Carroll, Jennifer

2017-01-01

An advanced undergraduate experiment involving the synthesis and characterization of a series of six unique cinnamamides is described. This experiment allows for a progressive mastery of skills students need to tackle more complex NMR structure elucidation problems. Characterization of the products involves IR spectroscopy, GCMS, and proton,…

Voice characteristics in the progression of Parkinson's disease.

PubMed

Holmes, R J; Oates, J M; Phyland, D J; Hughes, A J

2000-01-01

This study examined the acoustic and perceptual voice characteristics of patients with Parkinson's disease according to disease severity. The perceptual and acoustic voice characteristics of 30 patients with early stage PD and 30 patients with later stage PD were compared with data from 30 normal control subjects. Voice recordings consisted of prolongation of the vowel /a/, scale singing, and a 1-min monologue. In comparison with controls and previously published normative data, both early and later stage PD patients' voices were characterized perceptually by limited pitch and loudness variability, breathiness, harshness and reduced loudness. High modal pitch levels also characterized the voices of males in both early and later stages of PD. Acoustically, the voices of both groups of PD patients demonstrated lower mean intensity levels and reduced maximum phonational frequency ranges in comparison with normative data. Although less clear, the present data also suggested that the PD patients' voices were characterized by excess jitter, a high-speaking fundamental frequency for males and a reduced fundamental frequency variability for females. While several of these voice features did not appear to deteriorate with disease progression (i.e. harshness, high modal pitch and speaking fundamental frequency in males, fundamental frequency variability in females, low intensity and jitter), breathiness, monopitch and monoloudness, low loudness and reduced maximum phonational frequency range were all worse in the later stages of PD. Tremor was the sole voice feature which was associated only with later stage PD.

Ion beams provided by small accelerators for material synthesis and characterization

NASA Astrophysics Data System (ADS)

Mackova, Anna; Havranek, Vladimir

2017-06-01

The compact, multipurpose electrostatic tandem accelerators are extensively used for production of ion beams with energies in the range from 400 keV to 24 MeV of almost all elements of the periodic system for the trace element analysis by means of nuclear analytical methods. The ion beams produced by small accelerators have a broad application, mainly for material characterization (Rutherford Back-Scattering spectrometry, Particle Induced X ray Emission analysis, Nuclear Reaction Analysis and Ion-Microprobe with 1 μm lateral resolution among others) and for high-energy implantation. Material research belongs to traditionally progressive fields of technology. Due to the continuous miniaturization, the underlying structures are far beyond the analytical limits of the most conventional methods. Ion Beam Analysis (IBA) techniques provide this possibility as they use probes of similar or much smaller dimensions (particles, radiation). Ion beams can be used for the synthesis of new progressive functional nanomaterials for optics, electronics and other applications. Ion beams are extensively used in studies of the fundamental energetic ion interaction with matter as well as in the novel nanostructure synthesis using ion beam irradiation in various amorphous and crystalline materials in order to get structures with extraordinary functional properties. IBA methods serve for investigation of materials coming from material research, industry, micro- and nano-technology, electronics, optics and laser technology, chemical, biological and environmental investigation in general. Main research directions in laboratories employing small accelerators are also the preparation and characterization of micro- and nano-structured materials which are of interest for basic and oriented research in material science, and various studies of biological, geological, environmental and cultural heritage artefacts are provided too.

Short-term Automated Quantification of Radiologic Changes in the Characterization of Idiopathic Pulmonary Fibrosis Versus Nonspecific Interstitial Pneumonia and Prediction of Long-term Survival.

PubMed

De Giacomi, Federica; Raghunath, Sushravya; Karwoski, Ronald; Bartholmai, Brian J; Moua, Teng

2018-03-01

Fibrotic interstitial lung diseases presenting with nonspecific and overlapping radiologic findings may be difficult to diagnose without surgical biopsy. We hypothesized that baseline quantifiable radiologic features and their short-term interval change may be predictive of underlying histologic diagnosis as well as long-term survival in idiopathic pulmonary fibrosis (IPF) presenting without honeycombing versus nonspecific interstitial pneumonia (NSIP). Forty biopsy-confirmed IPF and 20 biopsy-confirmed NSIP patients with available high-resolution chest computed tomography 4 to 24 months apart were studied. CALIPER software was used for the automated characterization and quantification of radiologic findings. IPF subjects were older (66 vs. 48; P<0.0001) with lower diffusion capacity for carbon monoxide and higher volumes of baseline reticulation (193 vs. 83 mL; P<0.0001). Over the interval period, compared with NSIP, IPF patients experienced greater functional decline (forced vital capacity, -6.3% vs. -1.7%; P=0.02) and radiologic progression, as noted by greater increase in reticulation volume (24 vs. 1.74 mL; P=0.048), and decrease in normal (-220 vs. -37.7 mL; P=0.045) and total lung volumes (-198 vs. 58.1 mL; P=0.03). Older age, male gender, higher reticulation volumes at baseline, and greater interval decrease in normal lung volumes were predictive of IPF. Both baseline and short-term changes in quantitative radiologic findings were predictive of mortality. Baseline quantitative radiologic findings and assessment of short-term disease progression may help characterize underlying IPF versus NSIP in those with difficult to differentiate clinicoradiologic presentations. Our study supports the possible utility of assessing serial quantifiable high-resolution chest computed tomographic findings for disease differentiation in these 2 entities.

Subclones dominate at MDS progression following allogeneic hematopoietic cell transplant

PubMed Central

Jacoby, Meagan A.; Duncavage, Eric J.; Chang, Gue Su; Miller, Christopher A.; Shao, Jin; Elliott, Kevin; Robinson, Joshua; Fulton, Robert S.; Fronick, Catrina C.; O’Laughlin, Michelle; Heath, Sharon E.; Welch, John S.; Link, Daniel C.; DiPersio, John F.; Westervelt, Peter; Ley, Timothy J.; Graubert, Timothy A.; Walter, Matthew J.

2018-01-01

Allogeneic hematopoietic cell transplantation (alloHCT) is a potentially curative treatment for myelodysplastic syndromes (MDS), but patients who relapse after transplant have poor outcomes. In order to understand the contribution of tumor clonal evolution to disease progression,we applied exome and error-corrected targeted sequencing coupled with copy number analysis to comprehensively define changes in the clonal architecture of MDS in response to therapy using 51 serially acquired tumor samples from 9 patients who progressed after an alloHCT. We show that small subclones before alloHCT can drive progression after alloHCT. Notably, at least one subclone expanded or emerged at progression in all patients. Newly acquired structural variants (SVs) were present in an emergent/expanding subclone in 8 of 9 patients at progression, implicating the acquisition of SVs as important late subclonal progression events. In addition, pretransplant therapy with azacitidine likely influenced the mutation spectrum and evolution of emergent subclones after alloHCT. Although subclone evolution is common, founding clone mutations are always present at progression and could be detected in the bone marrow as early as 30 and/or 100 days after alloHCT in 6 of 8 (75%) patients, often prior to clinical progression. In conclusion, MDS progression after alloHCT is characterized by subclonal expansion and evolution, which can be influenced by pretransplant therapy. PMID:29515031

Gene Expression Differences in Peripheral Blood of Parkinson’s Disease Patients with Distinct Progression Profiles

PubMed Central

Soreq, Lilach; Lobo, Patrícia P.; Mestre, Tiago; Coelho, Miguel; Rosa, Mário M.; Gonçalves, Nilza; Wales, Pauline; Mendes, Tiago; Gerhardt, Ellen; Fahlbusch, Christiane; Bonifati, Vincenzo; Bonin, Michael; Miltenberger-Miltényi, Gabriel; Borovecki, Fran; Soreq, Hermona; Ferreira, Joaquim J.; F. Outeiro, Tiago

2016-01-01

The prognosis of neurodegenerative disorders is clinically challenging due to the inexistence of established biomarkers for predicting disease progression. Here, we performed an exploratory cross-sectional, case-control study aimed at determining whether gene expression differences in peripheral blood may be used as a signature of Parkinson’s disease (PD) progression, thereby shedding light into potential molecular mechanisms underlying disease development. We compared transcriptional profiles in the blood from 34 PD patients who developed postural instability within ten years with those of 33 patients who did not develop postural instability within this time frame. Our study identified >200 differentially expressed genes between the two groups. The expression of several of the genes identified was previously found deregulated in animal models of PD and in PD patients. Relevant genes were selected for validation by real-time PCR in a subset of patients. The genes validated were linked to nucleic acid metabolism, mitochondria, immune response and intracellular-transport. Interestingly, we also found deregulation of these genes in a dopaminergic cell model of PD, a simple paradigm that can now be used to further dissect the role of these molecular players on dopaminergic cell loss. Altogether, our study provides preliminary evidence that expression changes in specific groups of genes and pathways, detected in peripheral blood samples, may be correlated with differential PD progression. Our exploratory study suggests that peripheral gene expression profiling may prove valuable for assisting in prediction of PD prognosis, and identifies novel culprits possibly involved in dopaminergic cell death. Given the exploratory nature of our study, further investigations using independent, well-characterized cohorts will be essential in order to validate our candidates as predictors of PD prognosis and to definitively confirm the value of gene expression analysis in aiding patient stratification and therapeutic intervention. PMID:27322389

Further investigation of phenotypes and confounding factors of progressive ratio performance and feeding behavior in the BACHD rat model of Huntington disease

PubMed Central

Clemensson, Laura Emily; Fabry, Benedikt; Riess, Olaf; Nguyen, Huu Phuc

2017-01-01

Huntington disease is an inherited neurodegenerative disorder characterized by motor, cognitive, psychiatric and metabolic symptoms. We recently published a study describing that the BACHD rat model of HD shows an obesity phenotype, which might affect their motivation to perform food-based behavioral tests. Further, we argued that using a food restriction protocol based on matching BACHD and wild type rats’ food consumption rates might resolve these motivational differences. In the current study, we followed up on these ideas in a longitudinal study of the rats’ performance in a progressive ratio test. We also investigated the phenotype of reduced food consumption rate, which is typically seen in food-restricted BACHD rats, in greater detail. In line with our previous study, the BACHD rats were less motivated to perform the progressive ratio test compared to their wild type littermates, although the phenotype was no longer present when the rats’ food consumption rates had been matched. However, video analysis of food consumption tests suggested that the reduced consumption rate found in the BACHD rats was not entirely based on differences in hunger, but likely involved motoric impairments. Thus, restriction protocols based on food consumption rates are not appropriate when working with BACHD rats. As an alternative, we suggest that studies where BACHD rats are used should investigate how the readouts of interest are affected by motivational differences, and use appropriate control tests to avoid misleading results. In addition, we show that BACHD rats display distinct behavioral changes in their progressive ratio performance, which might be indicative of striatal dysfunction. PMID:28273120

Application of biocompatible magnetite nanoparticles for the removal of arsenic and copper from water

NASA Astrophysics Data System (ADS)

Iconaru, S. L.; Beuran, M.; Turculet, C. S.; Negoi, I.; Teleanu, G.; Prodan, A. M.; Motelica-Heino, M.; Guégan, R.; Ciobanu, C. S.; Jiga, G.; Predoi, Daniela

2018-02-01

The progress of nanotechnology made possible the use of nanomaterials as adsorbents and magnetic iron oxides represents one of the first generations of nanoscale materials used in environment technologies [1]. A systematic characterization of commercial magnetite (Fe3O4) is presented in this research. The commercial (Fe3O4) magnetic adsorbents were characterized by various characterizations methods such as X-ray diffraction (XRD), Scanning Electron Microscopy (SEM) and Energy Dispersive X-ray analysis (EDX). This study was also focused on the study of adsorption isotherms and the kinetics evaluation. X-ray studies indicated that As3+ and Cu2+ removed by Fe3O4 did not seem to alter the structure of Fe3O4 but they were highlighted in the EDX analysis. In addition, the SEM studies were consistent with the XRD results. The rate of adsorption of contaminants, in contaminated solutions decreases when the amount of contaminant increases in all experiments performed. The results revealed that Fe3O4 nanoparticles are promising candidates which could be used as sorbents for the removal of arsenic from the marine environment, for site remediation and groundwater treatment.

Translational progress on tumor biomarkers

PubMed Central

Guo, Hongwei; Zhou, Xiaolin; Lu, Yi; Xie, Liye; Chen, Qian; Keller, Evan T; Liu, Qian; Zhou, Qinghua; Zhang, Jian

2015-01-01

There is an urgent need to apply basic research achievements to the clinic. In particular, mechanistic studies should be developed by bench researchers, depending upon clinical demands, in order to improve the survival and quality of life of cancer patients. To date, translational medicine has been addressed in cancer biology, particularly in the identification and characterization of novel tumor biomarkers. This review focuses on the recent achievements and clinical application prospects in tumor biomarkers based on translational medicine. PMID:26557902

Characterizing and Targeting Bone Marrow-Derived Inflammatory Cells in Driving the Malignancy and Progression of Childhood Astrocytic Brain Tumors

DTIC Science & Technology

2016-11-01

importance of myeloid derived ID2/VEGFR2 signaling in low-grade to high-grade glioma transformation . 15. SUBJECT TERMS Glioma, Pediatric, bone-marrow...derived-cells, endothelial, mesenchymal, myeloid, hematopoietic, differentiation, malignant, transformation , VEGFR2, ID2. 16. SECURITY CLASSIFICATION OF...subsequent recruitment, in order to suppress the malignant transformation of gliomas. In this project, we have initiated the study of BMDCs with RCAS and

Synthetic Progress toward Azadirachtins. 1. Enantio- and Diastereoselective Synthesis of the Left-Wing Fragment of 11-epi-Azadirachtin I.

PubMed

Shi, Hang; Tan, Ceheng; Zhang, Weibin; Zhang, Zichun; Long, Rong; Luo, Tuoping; Yang, Zhen

2015-05-15

A highly enantio- and diastereoselective synthesis of the left-wing fragment of 11-epi-azadirachtin I characterized with the pairwise use of palladium- and gold-catalyzed cascade reactions is presented. By enlisting a sequence of stereocontrolled transformations, our 21-step route established the stereocenters of the left-wing fragment from one chiral starting material, (-)-carvone, which would significantly facilitate the synthetic studies of the azadirachtin-type limonoids.

Circulating Tumor Cells: A Review of Non-EpCAM-Based Approaches for Cell Enrichment and Isolation.

PubMed

Gabriel, Marta Tellez; Calleja, Lidia Rodriguez; Chalopin, Antoine; Ory, Benjamin; Heymann, Dominique

2016-04-01

Circulating tumor cells (CTCs) are biomarkers for noninvasively measuring the evolution of tumor genotypes during treatment and disease progression. Recent technical progress has made it possible to detect and characterize CTCs at the single-cell level in blood. Most current methods are based on epithelial cell adhesion molecule (EpCAM) detection, but numerous studies have demonstrated that EpCAM is not a universal marker for CTC detection because it fails to detect both carcinoma cells that undergo epithelial-mesenchymal transition (EMT) and CTCs of mesenchymal origin. Moreover, EpCAM expression has been found in patients with benign diseases. A large proportion of the current studies and reviews about CTCs describe EpCAM-based methods, but there is evidence that not all tumor cells can be detected using this marker. Here we describe the most recent EpCAM-independent methods for enriching, isolating, and characterizing CTCs on the basis of physical and biological characteristics and point out the main advantages and disadvantages of these methods. CTCs offer an opportunity to obtain key biological information required for the development of personalized medicine. However, there is no universal marker of these cells. To strengthen the clinical utility of CTCs, it is important to improve existing technologies and develop new, non-EpCAM-based systems to enrich and isolate CTCs. © 2016 American Association for Clinical Chemistry.

Parkinson disease and progressive supranuclear palsy: protein expression in skin.

PubMed

Rodríguez-Leyva, Ildefonso; Chi-Ahumada, Erika G; Carrizales, Juan; Rodríguez-Violante, Mayela; Velázquez-Osuna, Salvador; Medina-Mier, Verónica; Martel-Gallegos, María G; Zarazúa, Sergio; Enríquez-Macías, Lourdes; Castro, Adriana; Calderón-Garcidueñas, Ana Laura; Jiménez-Capdeville, María E

2016-03-01

This study characterizes the expression of tau (p-tau) and α-synuclein (α-syn) by immunohistochemistry in the skin of three different populations: healthy control (HC), Parkinson disease (PD), and progressive supranuclear paralysis (PSP) subjects, with the purpose of finding a biomarker that could differentiate between subjects with PD and PSP. We evaluated the presence of p-tau and α-syn in a pilot study in the skin of three distinct groups of patients: 17 healthy subjects, 17 patients with PD, and 10 patients with PSP. Four millimeters punch biopsies were obtained from the occipital area and analyzed by immunohistochemistry using antibodies against α-syn and phosphorylated species of tau. PHF (paired helical filaments) antibody identifies p-tau in both normal and pathological conditions and AT8 recognizes p-tau characteristic of pathological conditions. Differences between the three groups were assessed by quantification of immunopositive areas in the epidermis. The immunopositivity pattern of p-tau and α-syn was significantly different among the three groups. Healthy subjects showed minimal staining using AT8 and α-syn. The PD group showed significantly higher α-syn and AT8 immunopositivity, while the PSP group only expressed higher AT8 immunopositivity than HCs. These data suggest that the skin reflects brain pathology. Therefore, immunohistochemical analysis of p-tau and α-syn in the skin can be useful for further characterization of PD and PSP.

Baseline Performance Predicts tDCS-Mediated Improvements in Language Symptoms in Primary Progressive Aphasia

PubMed Central

McConathey, Eric M.; White, Nicole C.; Gervits, Felix; Ash, Sherry; Coslett, H. Branch; Grossman, Murray; Hamilton, Roy H.

2017-01-01

Primary Progressive Aphasia (PPA) is a neurodegenerative condition characterized by insidious irreversible loss of language abilities. Prior studies suggest that transcranial direct current stimulation (tDCS) directed toward language areas of the brain may help to ameliorate symptoms of PPA. In the present sham-controlled study, we examined whether tDCS could be used to enhance language abilities (e.g., picture naming) in individuals with PPA variants primarily characterized by difficulties with speech production (non-fluent and logopenic). Participants were recruited from the Penn Frontotemporal Dementia Center to receive 10 days of both real and sham tDCS (counter-balanced, full-crossover design; participants were naïve to stimulation condition). A battery of language tests was administered at baseline, immediately post-tDCS (real and sham), and 6 weeks and 12 weeks following stimulation. When we accounted for individuals’ baseline performance, our analyses demonstrated a stratification of tDCS effects. Individuals who performed worse at baseline showed tDCS-related improvements in global language performance, grammatical comprehension and semantic processing. Individuals who performed better at baseline showed a slight tDCS-related benefit on our speech repetition metric. Real tDCS may improve language performance in some individuals with PPA. Severity of deficits at baseline may be an important factor in predicting which patients will respond positively to language-targeted tDCS therapies. Clinicaltrials.gov ID: NCT02928848 PMID:28713256

Variable patterns of ectopic mineralization in Enpp1asj-2J mice, a model for generalized arterial calcification of infancy

PubMed Central

Siu, Sarah Y.; Dyment, Nathaniel A.; Rowe, David W.; Sundberg, John P.; Uitto, Jouni; Li, Qiaoli

2016-01-01

Generalized arterial calcification of infancy (GACI) is an autosomal recessive disorder characterized by early onset of extensive mineralization of the cardiovascular system. The classical forms of GACI are caused by mutations in the ENPP1 gene, encoding a membrane-bound pyrophosphatase/phosphodiesterase that hydrolyzes ATP to AMP and inorganic pyrophosphate. The asj-2J mouse harboring a spontaneous mutation in the Enpp1 gene has been characterized as a model for GACI. These mutant mice develop ectopic mineralization in skin and vascular connective tissues as well as in cartilage and collagen-rich tendons and ligaments. This study examined in detail the temporal ectopic mineralization phenotype of connective tissues in this mouse model, utilizing a novel cryo-histological method that does not require decalcification of bones. The wild type, heterozygous, and homozygous mice were administered fluorescent mineralization labels at 4 weeks (calcein), 10 weeks (alizarin complexone), and 11 weeks of age (demeclocycline). Twenty-four hours later, outer ears, muzzle skin, trachea, aorta, shoulders, and vertebrae were collected from these mice and examined for progression of mineralization. The results revealed differential timeline for disease initiation and progression in various tissues of this mouse model. It also highlights the advantages of cryo-histological fluorescent imaging technique to study mineral deposition in mouse models of ectopic mineralization disorders. PMID:27863377

Pathophysiology of obesity on knee joint homeostasis: contributions of the infrapatellar fat pad.

PubMed

Santangelo, Kelly S; Radakovich, Lauren B; Fouts, Josie; Foster, Michelle T

2016-05-01

Osteoarthritis (OA) is a debilitating condition characterized by inflammation, breakdown, and consequent loss of cartilage of the joints. Epidemiological studies indicate obesity is an important risk factor involved in OA initiation and progression. Traditional views propose OA to be a biomechanical consequence of excess weight on weight-bearing joints; however, emerging data demonstrates that systemic and local factors released from white adipose depots play a role. Hence, current views characterize OA as a condition exacerbated by a metabolic link related to adipose tissue, and not solely related to redistributed/altered weight load. Factors demonstrated to influence cartilage and bone homeostasis include adipocyte-derived hormones ("adipokines") and adipose depot released cytokines. Epidemiological studies demonstrate a positive relation between systemic circulating cytokines, leptin, and resistin with OA types, while the association with adiponectin is controversial. Local factors in joints have also been shown to play a role in OA. In particular, this includes the knee, a weight-bearing joint that encloses a relatively large adipose depot, the infrapatellar fat pad (IFP), which serves as a source of local inflammatory factors. This review summarizes the relation of obesity and OA as it specifically relates to the IFP and other integral supporting structures. Overall, studies support the concept that metabolic effects associated with systemic obesity also extend to the IFP, which promotes inflammation, pain, and cartilage destruction within the local knee joint environment, thus contributing to development and progression of OA.

Ultrasonic Nondestructive Evaluation Techniques Applied to the Quantitative Characterization of Textile Composite Materials

NASA Technical Reports Server (NTRS)

Miller, James G.

1997-01-01

In this Progress Report, we describe our recent developments of advanced ultrasonic nondestructive evaluation methods applied to the characterization of anisotropic materials. We present images obtained from experimental measurements of ultrasonic diffraction patterns for a thin woven composite in an immersion setup. In addition, we compare apparent signal loss measurements of the thin woven composite for phase-sensitive and phase-insensitive detection methods. All images of diffraction patterns have been included on the accompanying CD-ROM in the Adobe(Trademark) Portable Document Format (PDF). Due to the extensive amount of data, however, hardcopies of only a small representative selection of the images are included within the printed report. This Progress Report presents experimental results that support successful implementation of single element as well as one and two-dimensional ultrasonic array technologies for the inspection of textile composite structures. In our previous reports, we have addressed issues regarding beam profiles of ultrasonic pressure fields transmitted through a water reference path and transmitted through a thin woven composite sample path. Furthermore, we presented experimental results of the effect of a thin woven composite on the magnitude of an insonifying ultrasonic pressure field. In addition to the study of ultrasonic beam profiles, we consider issues relevant to the application of single-element, one-dimensional, and two-dimensional array technologies towards probing the mechanical properties of advanced engineering composites and structures. We provide comparisons between phase-sensitive and phase-insensitive detection methods for determination of textile composite structure parameters. We also compare phase-sensitive and phase-insensitive - - ---- ----- apparent signal loss measurements in an effort to study the phenomenon of phase cancellation at the face of a finite-aperture single-element receiver. Furthermore, in this Progress Report we extend our work on ultrasonic beam profile issues through investigation of the phase fronts of the pressure field. In Section H of this Progress Report we briefly describe the experimental arrangement and methods for data acquisition of the ultrasonic diffraction patterns upon transmission through a thin woven composite. Section III details the analysis of the experimental data followed by the experimental results in Section IV. Finally, a discussion of the observations and conclusions is found in Section V.

Critical pathogenic steps to high risk Helicobacter pylori gastritis and gastric carcinogenesis

PubMed Central

Lee, Inchul

2014-01-01

Helicobacter pylori (H. pylori) gastritis may progress to high risk gastropathy and cancer. However, the pathological progression has not been characterized in detail. H. pylori induce persistent inflammatory infiltration. Neutrophils are unique in that they directly infiltrate into foveolar epithelium aiming the proliferative zone specifically. Neutrophilic proliferative zone foveolitis is a critical pathogenic step in H. pylori gastritis inducing intensive epithelial damage. Epithelial cells carrying accumulated genomic damage and mutations show the Malgun (clear) cell change, characterized by large clear nucleus and prominent nucleolus. Malgun cells further undergo atypical changes, showing nuclear folding, coarse chromatin, and multiple nucleoli. The atypical Malgun cell (AMC) change is a novel premalignant condition in high risk gastropathy, which may progress and undergo malignant transformation directly. The pathobiological significance of AMC in gastric carcinogenesis is reviewed. A new diagnosis system of gastritis is proposed based on the critical pathologic steps classifying low and high risk gastritis for separate treatment modality. It is suggested that the regulation of H. pylori-induced neutrophilic foveolitis might be a future therapeutic goal replacing bactericidal antibiotics approach. PMID:24914362

Critical pathogenic steps to high risk Helicobacter pylori gastritis and gastric carcinogenesis.

PubMed

Lee, Inchul

2014-06-07

Helicobacter pylori (H. pylori) gastritis may progress to high risk gastropathy and cancer. However, the pathological progression has not been characterized in detail. H. pylori induce persistent inflammatory infiltration. Neutrophils are unique in that they directly infiltrate into foveolar epithelium aiming the proliferative zone specifically. Neutrophilic proliferative zone foveolitis is a critical pathogenic step in H. pylori gastritis inducing intensive epithelial damage. Epithelial cells carrying accumulated genomic damage and mutations show the Malgun (clear) cell change, characterized by large clear nucleus and prominent nucleolus. Malgun cells further undergo atypical changes, showing nuclear folding, coarse chromatin, and multiple nucleoli. The atypical Malgun cell (AMC) change is a novel premalignant condition in high risk gastropathy, which may progress and undergo malignant transformation directly. The pathobiological significance of AMC in gastric carcinogenesis is reviewed. A new diagnosis system of gastritis is proposed based on the critical pathologic steps classifying low and high risk gastritis for separate treatment modality. It is suggested that the regulation of H. pylori-induced neutrophilic foveolitis might be a future therapeutic goal replacing bactericidal antibiotics approach.

MDM2 copy numbers in well-differentiated and dedifferentiated liposarcoma: characterizing progression to high-grade tumors.

PubMed

Ware, Patrick L; Snow, Anthony N; Gvalani, Maya; Pettenati, Mark J; Qasem, Shadi A

2014-03-01

MDM2 gene amplification is associated with well-differentiated (WDL) and dedifferentiated liposarcomas (DDL). Using fluorescent in situ hybridization (FISH), we sought to characterize various patterns of MDM2 amplification among the morphologic spectrum of liposarcoma. Forty-six cases of liposarcoma in various sites were examined and included 22 WDLs, 14 DLLs, and 10 negative control subjects. The MDM2 amplification ratio (MDM2/CEP12) was lower in WDL (10.2) compared with DDL (18.3) cases (P = .0000002). An amplification ratio of 16 showed optimal sensitivity (0.86) and specificity (0.96) as a cutoff point for progression to DDL. Borderline areas, defined as tumors with increased cellularity and atypia but with preserved lipomatous differentiation, showed a significantly higher MDM2 ratio (17.5; P = .0007) compared with WDL. Central (retroperitoneal and intra-abdominal) tumors also showed a significantly higher MDM2 ratio than peripheral ones (P = .02). Differences in MDM2 amplification profiles among liposarcomas could help further define and predict progression to high-grade neoplasia.

Vibrating-Wire, Supercooled Liquid Water Content Sensor Calibration and Characterization Progress

NASA Technical Reports Server (NTRS)

King, Michael C.; Bognar, John A.; Guest, Daniel; Bunt, Fred

2016-01-01

NASA conducted a winter 2015 field campaign using weather balloons at the NASA Glenn Research Center to generate a validation database for the NASA Icing Remote Sensing System. The weather balloons carried a specialized, disposable, vibrating-wire sensor to determine supercooled liquid water content aloft. Significant progress has been made to calibrate and characterize these sensors. Calibration testing of the vibrating-wire sensors was carried out in a specially developed, low-speed, icing wind tunnel, and the results were analyzed. The sensor ice accretion behavior was also documented and analyzed. Finally, post-campaign evaluation of the balloon soundings revealed a gradual drift in the sensor data with increasing altitude. This behavior was analyzed and a method to correct for the drift in the data was developed.

Universal measurement-based quantum computation in two-dimensional symmetry-protected topological phases

NASA Astrophysics Data System (ADS)

Wei, Tzu-Chieh; Huang, Ching-Yu

2017-09-01

Recent progress in the characterization of gapped quantum phases has also triggered the search for a universal resource for quantum computation in symmetric gapped phases. Prior works in one dimension suggest that it is a feature more common than previously thought, in that nontrivial one-dimensional symmetry-protected topological (SPT) phases provide quantum computational power characterized by the algebraic structure defining these phases. Progress in two and higher dimensions so far has been limited to special fixed points. Here we provide two families of two-dimensional Z2 symmetric wave functions such that there exists a finite region of the parameter in the SPT phases that supports universal quantum computation. The quantum computational power appears to lose its universality at the boundary between the SPT and the symmetry-breaking phases.

Adhesive Characterization and Progressive Damage Analysis of Bonded Composite Joints

NASA Technical Reports Server (NTRS)

Girolamo, Donato; Davila, Carlos G.; Leone, Frank A.; Lin, Shih-Yung

2014-01-01

The results of an experimental/numerical campaign aimed to develop progressive damage analysis (PDA) tools for predicting the strength of a composite bonded joint under tensile loads are presented. The PDA is based on continuum damage mechanics (CDM) to account for intralaminar damage, and cohesive laws to account for interlaminar and adhesive damage. The adhesive response is characterized using standard fracture specimens and digital image correlation (DIC). The displacement fields measured by DIC are used to calculate the J-integrals, from which the associated cohesive laws of the structural adhesive can be derived. A finite element model of a sandwich conventional splice joint (CSJ) under tensile loads was developed. The simulations indicate that the model is capable of predicting the interactions of damage modes that lead to the failure of the joint.

Dark Signal Characterization of 1.7 micron cutoff devices for SNAP

NASA Astrophysics Data System (ADS)

Smith, R. M.; SNAP Collaboration

2004-12-01

We report initial progress characterizing non-photometric sources of error -- dark current, noise, and zero point drift -- for 1.7 micron cutoff HgCdTe and InGaAs detectors under development by Raytheon, Rockwell, and Sensors Unlimited for SNAP. Dark current specifications can already be met with several detector types. Changes to the manufacturing process are being explored to improve the noise reduction available through multiple sampling. In some cases, a significant number of pixels suffer from popcorn noise, with a few percent of all pixels exhibiting a ten fold noise increase. A careful study of zero point drifts is also under way, since these errors can dominate dark current, and may contribute to the noise degradation seen in long exposures.

Advanced mass spectrometry-based methods for the analysis of conformational integrity of biopharmaceutical products

PubMed Central

Bobst, Cedric E.; Kaltashov, Igor A.

2012-01-01

Mass spectrometry has already become an indispensable tool in the analytical armamentarium of the biopharmaceutical industry, although its current uses are limited to characterization of covalent structure of recombinant protein drugs. However, the scope of applications of mass spectrometry-based methods is beginning to expand to include characterization of the higher order structure and dynamics of biopharmaceutical products, a development which is catalyzed by the recent progress in mass spectrometry-based methods to study higher order protein structure. The two particularly promising methods that are likely to have the most significant and lasting impact in many areas of biopharmaceutical analysis, direct ESI MS and hydrogen/deuterium exchange, are focus of this article. PMID:21542797

Electrical storm and calcium signaling: a review.

PubMed

Tsuji, Yukiomi

2011-01-01

Electrical storm (ES), characterized by recurrent ventricular tachycardia/fibrillation, is a serious condition, adversely affecting prognosis in patients with implantable cardioverter/defibrillators. Electrical storm patients often die of progressive heart failure, but the underlying molecular basis is poorly understood. We have recently created an animal model of ES that features repetitive implantable cardioverter/defibrillator firing for recurrent ventricular fibrillation and found that ES events cause striking activation of Ca(2+)/calmodulin-dependent protein kinase II and prominent alteration of Ca(2+)-handling protein phosphorylation, possibly explaining mechanical dysfunction and arrhythmia promotion that characterize ES. Here, the pathophysiology and potential therapeutic strategies for ES, based on experimental and clinical studies by us and others, are described. Copyright © 2011 Elsevier Inc. All rights reserved.

Histological characterization of regression in acquired immunodeficiency syndrome-related Kaposi's sarcoma.

PubMed

Pantanowitz, Liron; Dezube, Bruce J; Pinkus, Geraldine S; Tahan, Steven R

2004-01-01

Kaposi's sarcoma (KS) is an angioproliferative lesion that may regress or progress. Progression is related to spindle cell proliferation and the expression of human herpes virus-8 latency genes, including latent nuclear antigen-1 (LNA-1), cyclin-D1, and bcl-2. KS regression has not been well characterized histologically. Therefore, this study was undertaken to characterize the histopathology of pharmacologically induced regressed cutaneous KS. Skin punch biopsies from eight patients with acquired immunodeficiency syndrome (AIDS)-related KS, that regressed following chemotherapy with paclitaxel or the angiogenesis inhibitor Col-3, were investigated by light microscopy. Comparative immunophenotyping on pre- and post-treatment specimens for CD31, LNA-1, cyclin-D1, bcl-2, and CD117 (c-kit) was performed. Clinical and histologic features of regression were similar for paclitaxel and Col-3 treatment. On clinical examination, lesions flattened, became smaller, and lost their purple-red appearance, resulting in an orange-brown macule. Histological regression was divided into partial (n = 3) and complete (n = 5) regression. Partially regressed lesions had a significant reduction of spindle cells in the dermal interstitium, with residual spindle cells arranged around superficial and mid-dermal capillaries. Complete regression was characterized by an absence of detectable spindle cells, with a slight increase in capillaries of the superficial plexus. All regressed samples exhibited a prominent, superficial, perivascular, lymphocytic infiltrate and abundant dermal hemosiderin-laden macrophages. This clinicopathologic picture resembled the findings of pigmented purpura. CD31 staining correlated with the reduction of spindle cells. Regression was accompanied by a quantitative and qualitative decrease in LNA-1 and cyclin-D1 immunoreactivity, but no change in bcl-2 or c-kit expression. Pharmacologically induced regression of AIDS-related cutaneous KS is characterized by a complete loss or decrease of spindle cells, increased lymphocytes, and prominent dermal siderophage deposition. Without any prior knowledge of the history of KS regression following therapy, regressed KS lesions may be misdiagnosed clinically and histologically as pigmented purpuric dermatitis.

Prevention and Treatment of ER-Negative Breast Cancer

DTIC Science & Technology

2005-10-01

human breast epithelial cell lines that express several levels of P13 kinase and AKT activity. These lines will be characterized with respect to...cancer. (4)Defined a putative role for psoriasin in breast tumor progression. (5) Progress in the analysis of the role of NFkappaB signaling in ER...press.. 9 PREVENTION AND TREATMENT OF ER-NEGATIVE BREAST CANCERPrincipal Investigator: Brown, Mvles A. 4) IGF-1 Receptor and the Akt protein kinase Akt

Characterizing a neurodegenerative syndrome: primary progressive apraxia of speech

PubMed Central

Duffy, Joseph R.; Strand, Edythe A.; Machulda, Mary M.; Senjem, Matthew L.; Master, Ankit V.; Lowe, Val J.; Jack, Clifford R.; Whitwell, Jennifer L.

2012-01-01

Apraxia of speech is a disorder of speech motor planning and/or programming that is distinguishable from aphasia and dysarthria. It most commonly results from vascular insults but can occur in degenerative diseases where it has typically been subsumed under aphasia, or it occurs in the context of more widespread neurodegeneration. The aim of this study was to determine whether apraxia of speech can present as an isolated sign of neurodegenerative disease. Between July 2010 and July 2011, 37 subjects with a neurodegenerative speech and language disorder were prospectively recruited and underwent detailed speech and language, neurological, neuropsychological and neuroimaging testing. The neuroimaging battery included 3.0 tesla volumetric head magnetic resonance imaging, [18F]-fluorodeoxyglucose and [11C] Pittsburg compound B positron emission tomography scanning. Twelve subjects were identified as having apraxia of speech without any signs of aphasia based on a comprehensive battery of language tests; hence, none met criteria for primary progressive aphasia. These subjects with primary progressive apraxia of speech included eight females and four males, with a mean age of onset of 73 years (range: 49–82). There were no specific additional shared patterns of neurological or neuropsychological impairment in the subjects with primary progressive apraxia of speech, but there was individual variability. Some subjects, for example, had mild features of behavioural change, executive dysfunction, limb apraxia or Parkinsonism. Voxel-based morphometry of grey matter revealed focal atrophy of superior lateral premotor cortex and supplementary motor area. Voxel-based morphometry of white matter showed volume loss in these same regions but with extension of loss involving the inferior premotor cortex and body of the corpus callosum. These same areas of white matter loss were observed with diffusion tensor imaging analysis, which also demonstrated reduced fractional anisotropy and increased mean diffusivity of the superior longitudinal fasciculus, particularly the premotor components. Statistical parametric mapping of the [18F]-fluorodeoxyglucose positron emission tomography scans revealed focal hypometabolism of superior lateral premotor cortex and supplementary motor area, although there was some variability across subjects noted with CortexID analysis. [11C]-Pittsburg compound B positron emission tomography binding was increased in only one of the 12 subjects, although it was unclear whether the increase was actually related to the primary progressive apraxia of speech. A syndrome characterized by progressive pure apraxia of speech clearly exists, with a neuroanatomic correlate of superior lateral premotor and supplementary motor atrophy, making this syndrome distinct from primary progressive aphasia. PMID:22382356

Ablation of CD11c(hi) dendritic cells exacerbates Japanese encephalitis by regulating blood-brain barrier permeability and altering tight junction/adhesion molecules.

PubMed

Kim, Jin Hyoung; Hossain, Ferdaus Mohd Altaf; Patil, Ajit Mahadev; Choi, Jin Young; Kim, Seong Bum; Uyangaa, Erdenebelig; Park, Sang-Youel; Lee, John-Hwa; Kim, Bumseok; Kim, Koanhoi; Eo, Seong Kug

2016-10-01

Japanese encephalitis (JE), characterized by extensive neuroinflammation following infection with neurotropic JE virus (JEV), is becoming a leading cause of viral encephalitis due to rapid changes in climate and demography. The blood-brain barrier (BBB) plays an important role in restricting neuroinvasion of peripheral leukocytes and virus, thereby regulating the progression of viral encephalitis. In this study, we explored the role of CD11c(hi) dendritic cells (DCs) in regulating BBB integrity and JE progression using a conditional depletion model of CD11c(hi) DCs. Transient ablation of CD11c(hi) DCs resulted in markedly increased susceptibility to JE progression along with highly increased neuro-invasion of JEV. In addition, exacerbated JE progression in CD11c(hi) DC-ablated hosts was closely associated with increased expression of proinflammatory cytokines (IFN-β, IL-6, and TNF-α) and CC chemokines (CCL2, CCL3, CXCL2) in the brain. Moreover, our results revealed that the exacerbation of JE progression in CD11c(hi) DC-ablated hosts was correlated with enhanced BBB permeability and reduced expression of tight junction and adhesion molecules (claudin-5, ZO-1, occluding, JAMs). Ultimately, our data conclude that the ablation of CD11c(hi) DCs provided a subsidiary impact on BBB integrity and the expression of tight junction/adhesion molecules, thereby leading to exacerbated JE progression. These findings provide insight into the secondary role of CD11c(hi) DCs in JE progression through regulation of BBB integrity and the expression of tight junction/adhesion molecules. Copyright © 2016 Elsevier Ltd. All rights reserved.

Intermediate Volume on Computed Tomography Imaging Defines a Fibrotic Compartment that Predicts Glomerular Filtration Rate Decline in Autosomal Dominant Polycystic Kidney Disease Patients

PubMed Central

Caroli, Anna; Antiga, Luca; Conti, Sara; Sonzogni, Aurelio; Fasolini, Giorgio; Ondei, Patrizia; Perico, Norberto; Remuzzi, Giuseppe; Remuzzi, Andrea

2011-01-01

Total kidney and cyst volumes have been used to quantify disease progression in autosomal dominant polycystic kidney disease (ADPKD), but a causal relationship with progression to renal failure has not been demonstrated. Advanced image processing recently allowed to quantify extracystic tissue, and to identify an additional tissue component named “intermediate,” appearing hypoenhanced on contrast-enhanced computed tomography (CT). The aim of this study is to provide a histological characterization of intermediate volume, investigate its relation with renal function, and provide preliminary evidence of its role in long-term prediction of functional loss. Three ADPKD patients underwent contrast-enhanced CT scans before nephrectomy. Histological samples of intermediate volume were drawn from the excised kidneys, and stained with hematoxylin and eosin and with saturated picrosirius solution for histological analysis. Intermediate volume showed major structural changes, characterized by tubular dilation and atrophy, microcysts, inflammatory cell infiltrate, vascular sclerosis, and extended peritubular interstitial fibrosis. A significant correlation (r = −0.69, P < 0.001) between relative intermediate volume and baseline renal function was found in 21 ADPKD patients. Long-term prediction of renal functional loss was investigated in an independent cohort of 13 ADPKD patients, followed for 3 to 8 years. Intermediate volume, but not total kidney or cyst volume, significantly correlated with glomerular filtration rate decline (r = −0.79, P < 0.005). These findings suggest that intermediate volume may represent a suitable surrogate marker of ADPKD progression and a novel therapeutic target. PMID:21683674

Meniscal Extrusion or Subchondral Damage Characterize Incident Accelerated Osteoarthritis: Data from the Osteoarthritis Initiative

PubMed Central

Driban, Jeffrey B.; Ward, Robert J.; Eaton, Charles B.; Lo, Grace H.; Price, Lori Lyn; Lu, Bing; McAlindon, Timothy E.

2015-01-01

Introduction Knee osteoarthritis (KOA) is typically a slowly progressive disorder; however, a subset of knees progress with dramatic rapidity. We aimed to describe magnetic resonance imaging (MRI) findings that are associated with accelerated KOA. Materials and Methods We conducted a longitudinal descriptive study in the Osteoarthritis Initiative (OAI) cohort. We selected participants who had no radiographic KOA at baseline with one of the following in the most severe knee: 1) accelerated KOA (progressed to end-stage KOA within 48 months), 2) common KOA, and 3) no KOA at all visits. We enriched the sample by selecting knees with a self-reported or suspected knee injury. A musculoskeletal radiologist blinded to group assignments but not to time sequence performed MRI readings for the visit before and after an injury. Results We assessed 38 participants (knees), 66% were female, mean age 61 (9) years, and mean body mass index 28.5 (4.9) kg/m2. Fifteen of 20 knees with no or common KOA, had no incident findings consistent with acute damage. Among the 18 knees with accelerated KOA most had incident findings: 13 (72%) had incident medial meniscal pathology with extrusion and 5 (28%) knees had subchondral damage. Conclusions Incident MRI findings that are associated with incident accelerated KOA are characterized by structural damage that compromises subchondral bone or the function of the meniscus. Recognizing meniscal extrusion and/or change in shape, lateral meniscal tear, or acute subchondral damage may be vital for identifying individuals at risk for accelerated KOA. PMID:26149125

Clinical and genetic characterization of an autosomal dominant nephropathy.

PubMed

Parvari, R; Shnaider, A; Basok, A; Katchko, L; Borochovich, Z; Kanis, A; Landau, D

2001-03-15

Autosomal dominant familial nephropathies with adult onset, no macroscopic cysts, and progressive deterioration include medullary cystic disease (ADMCKD) as well as other less specific entities. We studied a kindred of Jewish ancestry in which 15 members (both male and female) have suffered from chronic renal failure. The first evidence of renal involvement was observed between 18 and 38 years. It included hypertension followed by progressive renal insufficiency. No polyuria, anemia, gout, hematuria, nor proteinuria were seen. An average of 4.5 years elapsed from diagnosis to end-stage renal disease. Renal pathology at early stages of the disease showed extensive tubulointerstitial fibrosis and global glomerulosclerosis. Linkage analysis was performed at the two known loci of ADMCKD, on Chromosomes 1 and 16. Linkage to the chromosome 16 locus was excluded. However, linkage to the chromosome 1q21 locus of ADMCKD was established with a maximum two-point LOD score of 3.82 to D1S394. The disease interval could be narrowed to about 9 cM/7.4 Mb between D1S1156 and D1S2635. Multiple-point linkage analysis revealed a maximum LOD of 4.21, with a broad peak from markers D1S2858 and D1S2624. This report establishes linkage between a familial nephropathy characterized by hypertension and progressive renal failure to the locus described for ADMCKD, a disease classically associated with macroscopic corticomedullary cysts, salt-losing tubulointerstitial nephropathy, and anemia. This finding broadens the clinical spectrum of ADMCKD positioned on chromosome 1q21 locus. Copyright 2001 Wiley-Liss. Inc.

Oxidative stress in dry age-related macular degeneration and exfoliation syndrome.

PubMed

Chiras, Dimitrios; Kitsos, George; Petersen, Michael B; Skalidakis, Iosif; Kroupis, Christos

2015-02-01

Oxidative stress refers to cellular or molecular damage caused by reactive oxygen species, which especially occurs in age-related conditions as a result of an imbalance between the production of reactive oxygen species and the antioxidant defense response. Dry age-related macular degeneration (AMD) and exfoliation syndrome (XFS) are two common and complex age-related conditions that can cause irreversible vision loss. Two subtypes of AMD, which is the leading cause of blindness in the Western world, exist: the most prevalent dry type and the most severe wet type. Early dry AMD is characterized by formation of drusen, which are sub-retinal deposits, in the macular area and may progress to geographic atrophy with more dramatic manifestation. XFS is a systemic disorder of the extracellular matrix characterized by the accumulation of elastic fibrils that leads, in most cases, to glaucoma development with progressive and irreversible vision loss. Due to the aging population, the prevalence of these already-widespread conditions is increasing and is resulting in significant economic and psychological costs for individuals and for society. The exact composition of the abnormal drusen and XFS material as well as the mechanisms responsible for their production and accumulation still remain elusive, and consequently treatment for both diseases is lacking. However, recent epidemiologic, genetic and molecular studies support a major role for oxidative stress in both dry AMD and XFS development. Understanding the early molecular events in their pathogenesis and the exact role of oxidative stress may provide novel opportunities for therapeutic intervention for the prevention of progression to advanced disease.

Polyethylene damage and deformation on fixed-bearing, non-conforming unicondylar knee replacements corresponding to progressive changes in alignment and fixation.

PubMed

Harman, Melinda K; Schmitt, Sabine; Rössing, Sven; Banks, Scott A; Sharf, Hans-Peter; Viceconti, Marco; Hodge, W Andrew

2010-07-01

Deviations from nominal alignment of unicondylar knee replacements impact knee biomechanics, including the load and stress distribution at the articular contact surfaces. This study characterizes relationships between the biomechanical environment, distinguished by progressive changes in alignment and fixation, and articular damage and deformation in a consecutive series of retrieved unicondylar knee replacements. Twenty seven fixed-bearing, non-conforming unicondylar knee replacements of one design were retrieved after 2 to 13 years of in vivo function. The in vivo biomechanical environment was characterized by grading component migration measured from full-length radiographs and grading component fixation based on intraoperative manual palpation. Articular damage patterns and linear deformation on the polyethylene inserts were measured using optical photogrammetry and contact point digitization. Articular damage patterns and surface deformation on the explanted polyethylene inserts corresponded to progressive changes in component alignment and fixation. Component migration produced higher deformation rates, whereas loosening contributed to larger damage areas but lower deformation rates. Migration and loosening of the femoral component, but not the tibial component, were factors contributing to large regions of abrasion concentrated on the articular periphery. Classifying component migration and fixation at revision proved useful for distinguishing common biomechanical conditions associated with the varied polyethylene damage patterns and linear deformation for this fixed-bearing, non-conforming design. Pre-clinical evaluations of unicondylar knee replacements that are capable of reproducing variations in clinical alignment and predicting the observed wear mechanisms are necessary to better understand the impact of knee biomechanics and design on unicondylar knee replacement longevity. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Sequential Progressions in a Theory of Mind Scale: Longitudinal Perspectives

PubMed Central

Wellman, Henry M.; Fuxi, Fang; Peterson, Candida C.

2011-01-01

Consecutive re-testings of 92 U.S. preschoolers (n = 30), Chinese preschoolers (n = 31), and deaf children (n = 31) examined whether the sequences of development apparent in cross-sectional results with a theory-of-mind scale also appeared in longitudinal assessment. Longitudinal data confirmed that theory-of-mind progressions apparent in cross-sectional scaling data also characterized longitudinal sequences of understanding for individual children. The match between cross-sectional and longitudinal sequences appeared for children who exhibit different progressions across cultures (U.S. vs. China) and for children with substantial delays (deaf children of hearing parents). Moreover, greater scale distances reflected larger longitudinal age differences. PMID:21428982

A retrospective study of correlation of morphologic patterns, MIB1 proliferation index, and survival analysis in 134 cases of plasmacytoma.

PubMed

Ghodke, Kiran; Shet, Tanuja; Epari, Sridhar; Sengar, Manju; Menon, Hari; Gujral, Sumeet

2015-06-01

Plasmacytoma classified into solitary plasmacytoma of bone (SPB) and extramedullary plasmacytoma (EMP) is characterized by infiltrate of plasma cells of diverse maturity and by their monoclonal immunoglobulin products. Both SPB and EMP represent different groups of neoplasm in terms of location, tumor progression, and overall survival rate. There is a need for features that indicate likelihood of myeloma in patients with plasmacytoma without other manifestations. This study was an attempt to study the morphologic patterns of plasmacytoma (SPB and EMP), MIB1 proliferation index, and correlation of these with clinicopathologic features and survival of the patients. The study group comprised of 134 cases of plasmacytoma (88 SPB and 46 EMP) over duration of 8 years and were graded as per Bartl's histologic grading system. Commonest site was vertebral body in SPB (36%) and upper aerodigestive tract in EMP (48%). On serum electrophoresis, overall M band was detected in 41% cases. Both SPB and EMP on histology revealed similar morphologic features. MIB1 proliferation index ranged from less than 1% to 80%. It was slightly higher in EMP in comparison with SPB (P value = .002). Seventy percent of cases, which progressed to multiple myeloma (MM) showed MIB1 labeling index more than 10%; however, it was not statistically significant in predicting the disease progression. With the median follow-up of 19 months (range, 1-99 months), 10 SPB had disease progression of which 7 converted to MM, and 3 developed EMP, with a median interval of 21 months (range, 8-75 months) for the development of MM and 3 months (range, 3-9 months) for the progression to EMP. Five-year survival for EMP varied by site, with poorest survival in brain/central nervous system EMP as compared with EMP at other sites. To conclude, grade and MIB1 proliferation index help in predicting aggressive course in plasmacytoma. Copyright © 2015 Elsevier Inc. All rights reserved.

Arrested Hydrocephalus in Childhood: Case Series and Review of the Literature.

PubMed

Hurni, Yannick; Poretti, Andrea; Schneider, Jacques; Guzman, Raphael; Ramelli, Gian Paolo

2018-06-22

 Hydrocephalus can be progressive or spontaneously arrested. In arrested hydrocephalus, the balance between production and absorption of the cerebrospinal fluid is restored. Patients are mostly asymptomatic, and no surgical treatment is necessary for them.  We performed a two-center consecutive case series study, aimed at investigating the safety of nonsurgical management of hydrocephalus in selected pediatric patients. We retrospectively selected all consecutive patients, suspected to suffer from arrested hydrocephalus and referred to our two institutions between January 2011 and December 2013. Data on clinical and radiological follow-up were collected until June 2017.  Five children diagnosed with arrested hydrocephalus were included in the study. All patients presented macrocephaly as the main presenting sign. Associated mild-to-moderate stable motor disorders were assessed in four out of five cases. Typical symptoms and signs associated with acute raised intracranial pressure were absent in all patients. Magnetic resonance imaging studies showed ventriculomegaly in all patients. A diagnosis of arrested hydrocephalus was made in all five cases based on stable clinical and radiological findings during the initial observation. Conservative management based on active surveillance was, therefore, proposed. During the follow-up period, we observed stable or improved conditions in four out of five patients, while the remaining patient presented progressive hydrocephalus.  Making a distinction between arrested and progressive hydrocephalus is fundamental, because of the opposed appropriate management. Any newly discovered case of hydrocephalus, not characterized by clear signs of progressive hydrocephalus, should benefit from active surveillance before any definitive decision is taken. Georg Thieme Verlag KG Stuttgart · New York.

Randomized controlled trials in mild cognitive impairment

PubMed Central

Thomas, Ronald G.; Aisen, Paul S.; Mohs, Richard C.; Carrillo, Maria C.; Albert, Marilyn S.

2017-01-01

Objective: To examine the variability in performance among placebo groups in randomized controlled trials for mild cognitive impairment (MCI). Methods: Placebo group data were obtained from 2 National Institute on Aging (NIA) MCI randomized controlled trials, the Alzheimer's Disease Cooperative Study (ADCS) MCI trial and the Alzheimer's Disease Neuroimaging Initiative (ADNI), which is a simulated clinical trial, in addition to industry-sponsored clinical trials involving rivastigmine, galantamine, rofecoxib, and donepezil. The data were collated for common measurement instruments. The performance of the placebo participants from these studies was tracked on the Alzheimer's Disease Assessment Scale–cognitive subscale, Mini-Mental State Examination, and Clinical Dementia Rating–sum of boxes, and for progression on these measures to prespecified clinical study endpoints. APOE status, where available, was also analyzed for its effects. Results: The progression to clinical endpoints varied a great deal among the trials. The expected performances were seen for the participants in the 2 NIA trials, ADCS and ADNI, with generally worsening of performance over time; however, the industry-sponsored trials largely showed stable or improved performance in their placebo participants. APOE4 carrier status influenced results in an expected fashion on the study outcomes, including rates of progression and cognitive subscales. Conclusions: In spite of apparently similar criteria for MCI being adopted by the 7 studies, the implementation of the criteria varied a great deal. Several explanations including instruments used to characterize participants and variability among study populations contributed to the findings. PMID:28381516

[Tuberculosis: steady dynamics between past and present to imagine the future].

PubMed

Cabello C, Felipe

2011-07-01

Progress in understanding the biological processes that allow Mycobacterium tuberculosis to be a successful parasite have accelerated in the last twenty years. This progress has been stimulated by the return of tuberculosis (TB) as an important disease in industrialized countries, by its increase in emergent nations in the tail of population increases and poverty and by the spread of multiple drug resistant (MDR) and extensively drug resistant (XDR) M. tuberculosis as a result of treatment failures. Progress on M. tuberculosis biology has also been fueled by advances in microbiology and molecular biology, including molecular genetics, genomics, proteomics and in vitro and in vivo models of infection. The study of latency or dormancy, a phenomenon central to understanding the persistence of M. tuberculosis and the development of TB in individuals, its spread in human populations and the emergence of antibiotic-resistant/tolerant organisms, has been preferred targets for investigators in this area. In this manner, factors that trigger M. tuberculosis latency (e. g, hypoxia, nutrient starvation, NO exposure) have been characterized and the metabolic shifts to host lipid utilization, tolerance to antimicrobials and resistance to host immune mechanisms involved in latency have been determined. Similarly, genetic changes and the resulting antimicrobial mechanisms mediating the MDR and XDR states have been characterized and potential new vaccines that avoid reactivation from latency and infection are being developed. Despite this progress, and given the fact that effective anti tuberculosis therapy was developed and first introduced clinically at the end of the 1940s, there are now more cases of latent and active TB worldwide than ever before. This reinforces the concept of TB as a bacterial disease with strong social and economical! determinants which are presently stimulating increased transmission in many human groups, undermining diagnostics, treatment and prevention. It suggests that in a scenario of global economical crisis the struggle against TB will be weakened, unless efforts are included to alleviate poverty, decrease economic inequality, improve public health and allow democracy and political organization.

First Year of WFIRST/AFTA Coronagraph Technology Development: Testbed Progress Update

NASA Astrophysics Data System (ADS)

Poberezhskiy, Ilya; Poberezhskiy, Ilya; Zhao, Feng; An, Xin; Balasubramanian, Kunjithapatham; Belikov, Rus; Cady, Eric; Diaz, Rosemary; Gordon, Brian; Guyon, Olivier; Kasdin, N. Jeremy; Kern, Brian; Kuhnert, Andreas; Moody, Dwight; Muller, Richard; Nemati, Bijan; Patterson, Keith; Riggs, A. J.; Ryan, Daniel; Seo, Byoung-Joon; Sidick, Erkin; Shi, Fang; Tang, Hong; Trauger, John; Wallace, Kent; Wang, Xu; Wilson, Daniel; White, Victor; Yee, Karl; Zhou, Hanying; Zimmerman, Neil

2015-01-01

NASA's WFIRST/AFTA mission study includes the first high-contrast stellar coronagraph in space. This coronagraph will be capable of imaging and spectrally characterizing giant exoplanets similar to Neptune and Jupiter and possibly super-Earths, as well as circumstellar disks. After a transparent and rigorous downselect process, NASA chose in December of 2013 a primary design called an Occulting Mask Coronagraph (OMC) that combines two technical approaches, Shaped Pupil and Hybrid Lyot, in one instrument. The Phase-Induced Amplitude Apodization Complex Mask Coronagraph was selected as the backup design.The OMC coronagraph technologies were assessed to have the highest likelihood of passing the WFIRST/AFTA flight readiness gates and the ability to produce compelling science by working with the existing 2.4-meter telescope 'as is,' including its central obscuration, expected thermal drift, and the observatory pointing jitter. NASA set us the objective of maturing the WFIRST/AFTA coronagraph to Technology Readiness Level (TRL) 5 by October 1, 2016. A set of technical milestones was agreed upon to track the progress toward achieving TRL 5.Substantial advances in WFIRST/AFTA coronagraph technology have been made during 2014, and the OMC progress is currently running ahead of the schedule laid out by the milestones. Our poster will present some of these key recent results to the community, including:(1) Fabrication and characterization of WFIRST/AFTA coronagraph pupil plane and focal plane masks designed to work with the existing 2.4 telescope.(2) Experimental results demonstrating high contrast achieved on a coronagraph testbed in narrowband and broadband light - first such results obtained with an obscured pupil.(3) Progress in the development of the low-order wavefront sensing and control subsystem that will use rejected starlight to sense and correct both high frequency pointing jitter and slow varying low order aberrations. This subsystem will be integrated with the OMC coronagraph in mid-2015 for the next phase of starlight suppression experiments with dynamic input wavefront.

White matter damage in primary progressive aphasias: a diffusion tensor tractography study

PubMed Central

Galantucci, Sebastiano; Tartaglia, Maria Carmela; Wilson, Stephen M.; Henry, Maya L.; Filippi, Massimo; Agosta, Federica; Dronkers, Nina F.; Henry, Roland G.; Ogar, Jennifer M.; Miller, Bruce L.

2011-01-01

Primary progressive aphasia is a clinical syndrome that encompasses three major phenotypes: non-fluent/agrammatic, semantic and logopenic. These clinical entities have been associated with characteristic patterns of focal grey matter atrophy in left posterior frontoinsular, anterior temporal and left temporoparietal regions, respectively. Recently, network-level dysfunction has been hypothesized but research to date has focused largely on studying grey matter damage. The aim of this study was to assess the integrity of white matter tracts in the different primary progressive aphasia subtypes. We used diffusion tensor imaging in 48 individuals: nine non-fluent, nine semantic, nine logopenic and 21 age-matched controls. Probabilistic tractography was used to identify bilateral inferior longitudinal (anterior, middle, posterior) and uncinate fasciculi (referred to as the ventral pathway); and the superior longitudinal fasciculus segmented into its frontosupramarginal, frontoangular, frontotemporal and temporoparietal components, (referred to as the dorsal pathway). We compared the tracts’ mean fractional anisotropy, axial, radial and mean diffusivities for each tract in the different diagnostic categories. The most prominent white matter changes were found in the dorsal pathways in non-fluent patients, in the two ventral pathways and the temporal components of the dorsal pathways in semantic variant, and in the temporoparietal component of the dorsal bundles in logopenic patients. Each of the primary progressive aphasia variants showed different patterns of diffusion tensor metrics alterations: non-fluent patients showed the greatest changes in fractional anisotropy and radial and mean diffusivities; semantic variant patients had severe changes in all metrics; and logopenic patients had the least white matter damage, mainly involving diffusivity, with fractional anisotropy altered only in the temporoparietal component of the dorsal pathway. This study demonstrates that both careful dissection of the main language tracts and consideration of all diffusion tensor metrics are necessary to characterize the white matter changes that occur in the variants of primary progressive aphasia. These results highlight the potential value of diffusion tensor imaging as a new tool in the multimodal diagnostic evaluation of primary progressive aphasia. PMID:21666264

Characterizing and Targeting Replication Stress Response Defects in Breast Cancer

DTIC Science & Technology

2013-08-01

This project is to use cutting-edge technologies to characterize novel RSR genes and their functions in tumor suppression; identify gene signature...and membrane proteins associated with defective RSR; identify drugs that target these defects; and develop RSR-defect-targeting nanoparticles for...screening and validation of drugs that target RSR-defect cells. The progress of our third year research is described below. BODY The tasks

High-risk carotid plaque: lessons learned from histopathology.

PubMed

Kolodgie, Frank D; Yahagi, Kazuyuki; Mori, Hiroyoshi; Romero, Maria E; Trout, Hugh H; Finn, Aloke V; Virmani, Renu

2017-03-01

The pathophysiology and natural history of atherosclerotic carotid disease is predicated on a more extensive knowledge of lesion progression gained in the studies conducted in the coronary arteries, and these will be reviewed. While the precise sequence of lesion progression leading to carotid plaque vulnerability and cerebrovascular events remain less well understood, specific early and more advanced progressive lesion morphologies associated with stroke risk have been characterized. Of late, there has been a conscious effort for stroke prevention in symptomatic and asymptomatic patients to move beyond luminal stenosis as the only guidance to predict future cerebrovascular events. Driving this strategy are recent advances in medical imaging modalities to assess carotid atherosclerosis vulnerability particularly involving molecular imaging, which is now positioned at the forefront to provide a more detailed and mechanistic assessment of stroke risk. As such, we will spotlight the pathology of high-risk carotid plaques in patients with symptomatic and asymptomatic carotid disease with further reference into more recent mechanistic insights involving a recognized macrophage-mediated inflammatory change, intraplaque neoangiogenesis/hemorrhage, hypoxia, and microcalcification, as potential morphologic indicators of stroke risk. Copyright © 2017 Elsevier Inc. All rights reserved.

Mechanisms and cell signaling in alcoholic liver disease

PubMed Central

Beier, Juliane I.; McClain, Craig J.

2013-01-01

Alcoholic liver disease (ALD) remains a major cause of morbidity and mortality worldwide. For example, the Veterans Administration Cooperative Studies reported that patients with cirrhosis and superimposed alcoholic hepatitis had a 4-year mortality of >60%. The poor prognosis of ALD implies that preventing disease progression would be more effective than treating end-stage liver disease. An obvious avenue of prevention would be to remove the damaging agent; however, the infamously high rate of recidivism in alcoholics makes maintaining abstinence a difficult treatment goal to prevent ALD. Indeed, although the progression of ALD is well-characterized, there is no universally accepted therapy available to halt or reverse this process in humans. With better understanding of the mechanism(s) and risk factors that mediate the initiation and progression of ALD, rational targeted therapy can be developed to treat or prevent ALD. The purpose of this review is to summarize the established and proposed mechanisms by which chronic alcohol abuse damages the liver and to highlight key signaling events known or hypothesized to mediate these effects. PMID:20868231

Progressive but Previously Untreated CLL Patients with Greater Array CGH Complexity Exhibit a Less Durable Response to Chemoimmunotherapy

PubMed Central

Kay, Neil E.; Eckel-Passow, Jeanette E.; Braggio, Esteban; VanWier, Scott; Shanafelt, Tait D.; Van Dyke, Daniel L.; Jelinek, Diane F.; Tschumper, Renee C.; Kipps, Thomas; Byrd, John C.; Fonseca, Rafael

2010-01-01

To better understand the implications of genomic instability and outcome in B-cell CLL, we sought to address genomic complexity as a predictor of chemosensitivity and ultimately clinical outcome in this disease. We employed array-based comparative genomic hybridization (aCGH), using a one-million probe array and identified gains and losses of genetic material in 48 patients treated on a chemoimmunotherapy (CIT) clinical trial. We identified chromosomal gain or loss in ≥6% of the patients on chromosomes 3, 8, 9, 10, 11, 12, 13, 14 and 17. Higher genomic complexity, as a mechanism favoring clonal selection, was associated with shorter progression-free survival and predicted a poor response to treatment. Of interest, CLL cases with loss of p53 surveillance showed more complex genomic features and were found both in patients with a 17p13.1 deletion and in the more favorable genetic subtype characterized by the presence of 13q14.1 deletion. This aCGH study adds information on the association between inferior trial response and increasing genetic complexity as CLL progresses. PMID:21156228

Integrating Transcriptomics with Metabolic Modeling Predicts Biomarkers and Drug Targets for Alzheimer's Disease

PubMed Central

Stempler, Shiri; Yizhak, Keren; Ruppin, Eytan

2014-01-01

Accumulating evidence links numerous abnormalities in cerebral metabolism with the progression of Alzheimer's disease (AD), beginning in its early stages. Here, we integrate transcriptomic data from AD patients with a genome-scale computational human metabolic model to characterize the altered metabolism in AD, and employ state-of-the-art metabolic modelling methods to predict metabolic biomarkers and drug targets in AD. The metabolic descriptions derived are first tested and validated on a large scale versus existing AD proteomics and metabolomics data. Our analysis shows a significant decrease in the activity of several key metabolic pathways, including the carnitine shuttle, folate metabolism and mitochondrial transport. We predict several metabolic biomarkers of AD progression in the blood and the CSF, including succinate and prostaglandin D2. Vitamin D and steroid metabolism pathways are enriched with predicted drug targets that could mitigate the metabolic alterations observed. Taken together, this study provides the first network wide view of the metabolic alterations associated with AD progression. Most importantly, it offers a cohort of new metabolic leads for the diagnosis of AD and its treatment. PMID:25127241

Multi-optical-axis measurement of freeform progressive addition lenses using a Hartmann-Shack wavefront sensor

NASA Astrophysics Data System (ADS)

Xiang, Huazhong; Guo, Hang; Fu, Dongxiang; Zheng, Gang; Zhuang, Songlin; Chen, JiaBi; Wang, Cheng; Wu, Jie

2018-05-01

To precisely measure the whole-surface characterization of freeform progressive addition lenses (PALs), considering the multi-optical-axis conditions is becoming particularly important. Spherical power and astigmatism (cylinder) measurements for freeform PALs, using a Hartmann-Shack wavefront sensor (HSWFS) are proposed herein. Conversion formulas for the optical performance results were provided as HSWFS Zernike polynomial expansions. For each selected zone, the studied PALs were placed and tilted to simulate the multi-optical-axis conditions. The results of two tested PALs were analyzed using MATLAB programs and represented as contour plots of the spherical equivalent and cylinder of the whole-surface. The proposed experimental setup can provide a high accuracy as well as a possibility of choosing 12 lines and positions of 193 measurement zones on the entire surface. This approach to PAL analysis is potentially an efficient and useful method to objectively evaluate the optical performances, in which the full lens surface is defined and expressed as the contour plots of power in different regions (i.e., the distance region, progressive region, and near region) of the lens for regions of interest.

Quantitative imaging with Fucci and mathematics to uncover temporal dynamics of cell cycle progression.

PubMed

Saitou, Takashi; Imamura, Takeshi

2016-01-01

Cell cycle progression is strictly coordinated to ensure proper tissue growth, development, and regeneration of multicellular organisms. Spatiotemporal visualization of cell cycle phases directly helps us to obtain a deeper understanding of controlled, multicellular, cell cycle progression. The fluorescent ubiquitination-based cell cycle indicator (Fucci) system allows us to monitor, in living cells, the G1 and the S/G2/M phases of the cell cycle in red and green fluorescent colors, respectively. Since the discovery of Fucci technology, it has found numerous applications in the characterization of the timing of cell cycle phase transitions under diverse conditions and various biological processes. However, due to the complexity of cell cycle dynamics, understanding of specific patterns of cell cycle progression is still far from complete. In order to tackle this issue, quantitative approaches combined with mathematical modeling seem to be essential. Here, we review several studies that attempted to integrate Fucci technology and mathematical models to obtain quantitative information regarding cell cycle regulatory patterns. Focusing on the technological development of utilizing mathematics to retrieve meaningful information from the Fucci producing data, we discuss how the combined methods advance a quantitative understanding of cell cycle regulation. © 2015 Japanese Society of Developmental Biologists.

Correlation between Gene Expression and Osteoarthritis Progression in Human.

PubMed

Zhong, Leilei; Huang, Xiaobin; Karperien, Marcel; Post, Janine N

2016-07-14

Osteoarthritis (OA) is a multifactorial disease characterized by gradual degradation of joint cartilage. This study aimed to quantify major pathogenetic factors during OA progression in human cartilage. Cartilage specimens were isolated from OA patients and scored 0-5 according to the Osteoarthritis Research Society International (OARSI) guidelines. Protein and gene expressions were measured by immunohistochemistry and qPCR, respectively. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays were used to detect apoptotic cells. Cartilage degeneration in OA is a gradual progress accompanied with gradual loss of collagen type II and a gradual decrease in mRNA expression of SOX9, ACAN and COL2A1. Expression of WNT antagonists DKK1 and FRZB was lost, while hypertrophic markers (RUNX2, COL10A1 and IHH) increased during OA progression. Moreover, DKK1 and FRZB negatively correlated with OA grading, while RUNX2 and IHH showed a significantly positive correlation with OA grading. The number of apoptotic cells was increased with the severity of OA. Taken together, our results suggested that genetic profiling of the gene expression could be used as markers for staging OA at the molecular level. This helps to understand the molecular pathology of OA and may lead to the development of therapies based on OA stage.

Aberrant DNA Methylation in Chronic Myeloid Leukemia: Cell Fate Control, Prognosis, and Therapeutic Response.

PubMed

Behzad, Masumeh Maleki; Shahrabi, Saeid; Jaseb, Kaveh; Bertacchini, Jessika; Ketabchi, Neda; Saki, Najmaldin

2018-01-31

Chronic myeloid leukemia (CML) is a hematopoietic stem cell malignancy characterized by the expression of the BCR-ABL1 fusion gene with different chimeric transcripts. Despite the crucial impact of constitutively active tyrosine kinase in CML pathogenesis, aberrant DNA methylation of certain genes plays an important role in disease progression and the development of drug resistance. This article reviews recent findings relevant to the effect of DNA methylation pattern of regulatory genes on various cellular activities such as cell proliferation and survival, as well as cell-signaling molecules in CML. These data might contribute to defining the role of aberrant DNA methylation in disease initiation and progression. However, further studies are needed on the validation of specific aberrant methylation markers regarding the prognosis and prediction of response among the CML patients.

Apatinib in the treatment of advanced lung adenocarcinoma with KRAS mutation.

PubMed

Zeng, Da-Xiong; Wang, Chang-Guo; Huang, Jian-An; Jiang, Jun-Hong

2017-01-01

Activating KRAS mutations in lung adenocarcinoma are characterized with treatment resistance and poor prognosis. As a small molecule inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase, apatinib has been proven successful in advanced gastric cancer and breast cancer. In this study, we show the result of apatinib as salvage treatment in lung adenocarcinoma patients with KRAS mutation. Four advanced lung adenocarcinoma patients with KRAS mutation were orally administered apatinib (250 mg/d) after second-line treatment. One patient showed progressive disease, while 3 patients showed stable disease response to apatinib, with a median progression-free survival (PFS) of 3.8 months (1.5-5.5 months). The main toxicities were hoarseness and hemoptysis, which were manageable. Therefore, apatinib might be an optional choice for advanced lung adenocarcinoma patients with KRAS mutation in post second-line treatment.

A novel image-based quantitative method for the characterization of NETosis

PubMed Central

Zhao, Wenpu; Fogg, Darin K.; Kaplan, Mariana J.

2015-01-01

NETosis is a newly recognized mechanism of programmed neutrophil death. It is characterized by a stepwise progression of chromatin decondensation, membrane rupture, and release of bactericidal DNA-based structures called neutrophil extracellular traps (NETs). Conventional ‘suicidal’ NETosis has been described in pathogenic models of systemic autoimmune disorders. Recent in vivo studies suggest that a process of ‘vital’ NETosis also exists, in which chromatin is condensed and membrane integrity is preserved. Techniques to assess ‘suicidal’ or ‘vital’ NET formation in a specific, quantitative, rapid and semiautomated way have been lacking, hindering the characterization of this process. Here we have developed a new method to simultaneously assess both ‘suicidal’ and ‘vital’ NETosis, using high-speed multi-spectral imaging coupled to morphometric image analysis, to quantify spontaneous NET formation observed ex-vivo or stimulus-induced NET formation triggered in vitro. Use of imaging flow cytometry allows automated, quantitative and rapid analysis of subcellular morphology and texture, and introduces the potential for further investigation using NETosis as a biomarker in pre-clinical and clinical studies. PMID:26003624

Dynamic Tumor Growth Patterns in a Novel Murine Model of Colorectal Cancer

PubMed Central

Olson, Terrah J. Paul; Hadac, Jamie N.; Sievers, Chelsie K.; Leystra, Alyssa A.; Deming, Dustin A.; Zahm, Christopher D.; Albrecht, Dawn M.; Nomura, Alice; Nettekoven, Laura A.; Plesh, Lauren K.; Clipson, Linda; Sullivan, Ruth; Newton, Michael A.; Schelman, William R.; Halberg, Richard B.

2014-01-01

Colorectal cancer (CRC) often arises from adenomatous colonic polyps. Polyps can grow and progress to cancer, but may also remain static in size, regress, or resolve. Predicting which progress and which remain benign is difficult. We developed a novel long-lived murine model of CRC with tumors that can be followed by colonoscopy. Our aim was to assess whether these tumors have similar growth patterns and histologic fates to human colorectal polyps to identify features to aid in risk-stratification of colonic tumors. Long-lived ApcMin/+ mice were treated with dextran sodium sulfate to promote colonic tumorigenesis. Tumor growth patterns were characterized by serial colonoscopy with biopsies obtained for immunohistochemistry and gene expression profiling. Tumors grew, remained static, regressed, or resolved over time with different relative frequencies. Newly developed tumors demonstrated higher rates of growth and resolution than more established tumors that tended to remain static in size. Colonic tumors were hyperplastic lesions (3%), adenomas (73%), intramucosal carcinomas (20%), or adenocarcinomas (3%). Interestingly, the level of β-catenin was higher in adenomas that became intratumoral carcinomas as compared to those that failed to progress. In addition, differentially expressed genes between adenomas and intramucosal carcinomas were identified. This novel murine model of intestinal tumorigenesis develops colonic tumors that can be monitored by serial colonoscopy, mirror growth patterns seen in human colorectal polyps, and progress to CRC. Further characterization of cellular and molecular features are needed to determine which features can be used to risk-stratify polyps for progression to CRC and potentially guide prevention strategies. PMID:24196829

Deep remission: a new concept?

PubMed

Colombel, Jean-Frédéric; Louis, Edouard; Peyrin-Biroulet, Laurent; Sandborn, William J; Panaccione, Remo

2012-01-01

Crohn's disease (CD) is a chronic inflammatory disorder characterized by periods of clinical remission alternating with periods of relapse defined by recurrent clinical symptoms. Persistent inflammation is believed to lead to progressive bowel damage over time, which manifests with the development of strictures, fistulae and abscesses. These disease complications frequently lead to a need for surgical resection, which in turn leads to disability. So CD can be characterized as a chronic, progressive, destructive and disabling disease. In rheumatoid arthritis, treatment paradigms have evolved beyond partial symptom control alone toward the induction and maintenance of sustained biological remission, also known as a 'treat to target' strategy, with the goal of improving long-term disease outcomes. In CD, there is currently no accepted, well-defined, comprehensive treatment goal that entails the treatment of both clinical symptoms and biologic inflammation. It is important that such a treatment concept begins to evolve for CD. A treatment strategy that delays or halts the progression of CD to increasing damage and disability is a priority. As a starting point, a working definition of sustained deep remission (that includes long-term biological remission and symptom control) with defined patient outcomes (including no disease progression) has been proposed. The concept of sustained deep remission represents a goal for CD management that may still evolve. It is not clear if the concept also applies to ulcerative colitis. Clinical trials are needed to evaluate whether treatment algorithms that tailor therapy to achieve deep remission in patients with CD can prevent disease progression and disability. Copyright © 2012 S. Karger AG, Basel.

Motor onset and diagnosis in Huntington disease using the diagnostic confidence level.

PubMed

Liu, Dawei; Long, Jeffrey D; Zhang, Ying; Raymond, Lynn A; Marder, Karen; Rosser, Anne; McCusker, Elizabeth A; Mills, James A; Paulsen, Jane S

2015-12-01

Huntington disease (HD) is a neurodegenerative disorder characterized by motor dysfunction, cognitive deterioration, and psychiatric symptoms, with progressive motor impairments being a prominent feature. The primary objectives of this study are to delineate the disease course of motor function in HD, to provide estimates of the onset of motor impairments and motor diagnosis, and to examine the effects of genetic and demographic variables on the progression of motor impairments. Data from an international multisite, longitudinal observational study of 905 prodromal HD participants with cytosine-adenine-guanine (CAG) repeats of at least 36 and with at least two visits during the followup period from 2001 to 2012 was examined for changes in the diagnostic confidence level from the Unified Huntington's Disease Rating Scale. HD progression from unimpaired to impaired motor function, as well as the progression from motor impairment to diagnosis, was associated with the linear effect of age and CAG repeat length. Specifically, for every 1-year increase in age, the risk of transition in diagnostic confidence level increased by 11% (95% CI 7-15%) and for one repeat length increase in CAG, the risk of transition in diagnostic confidence level increased by 47% (95% CI 27-69%). Findings show that CAG repeat length and age increased the likelihood of the first onset of motor impairment as well as the age at diagnosis. Results suggest that more accurate estimates of HD onset age can be obtained by incorporating the current status of diagnostic confidence level into predictive models.

Mito-Apocynin Prevents Mitochondrial Dysfunction, Microglial Activation, Oxidative Damage, and Progressive Neurodegeneration in MitoPark Transgenic Mice.

PubMed

Langley, Monica; Ghosh, Anamitra; Charli, Adhithiya; Sarkar, Souvarish; Ay, Muhammet; Luo, Jie; Zielonka, Jacek; Brenza, Timothy; Bennett, Brian; Jin, Huajun; Ghaisas, Shivani; Schlichtmann, Benjamin; Kim, Dongsuk; Anantharam, Vellareddy; Kanthasamy, Arthi; Narasimhan, Balaji; Kalyanaraman, Balaraman; Kanthasamy, Anumantha G

2017-11-10

Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive motor deficits and degeneration of dopaminergic neurons. Caused by a number of genetic and environmental factors, mitochondrial dysfunction and oxidative stress play a role in neurodegeneration in PD. By selectively knocking out mitochondrial transcription factor A (TFAM) in dopaminergic neurons, the transgenic MitoPark mice recapitulate many signature features of the disease, including progressive motor deficits, neuronal loss, and protein inclusions. In the present study, we evaluated the neuroprotective efficacy of a novel mitochondrially targeted antioxidant, Mito-apocynin, in MitoPark mice and cell culture models of neuroinflammation and mitochondrial dysfunction. Oral administration of Mito-apocynin (10 mg/kg, thrice a week) showed excellent central nervous system bioavailability and significantly improved locomotor activity and coordination in MitoPark mice. Importantly, Mito-apocynin also partially attenuated severe nigrostriatal degeneration in MitoPark mice. Mechanistic studies revealed that Mito-apo improves mitochondrial function and inhibits NOX2 activation, oxidative damage, and neuroinflammation. The properties of Mito-apocynin identified in the MitoPark transgenic mouse model strongly support potential clinical applications for Mito-apocynin as a viable neuroprotective and anti-neuroinflammatory drug for treating PD when compared to conventional therapeutic approaches. Collectively, our data demonstrate, for the first time, that a novel orally active apocynin derivative improves behavioral, inflammatory, and neurodegenerative processes in a severe progressive dopaminergic neurodegenerative model of PD. Antioxid. Redox Signal. 27, 1048-1066.

HIV-1 Genetic Variability in Cuba and Implications for Transmission and Clinical Progression.

PubMed

Blanco, Madeline; Machado, Liuber Y; Díaz, Héctor; Ruiz, Nancy; Romay, Dania; Silva, Eladio

2015-10-01

INTRODUCTION Serological and molecular HIV-1 studies in Cuba have shown very low prevalence of seropositivity, but an increasing genetic diversity attributable to introduction of many HIV-1 variants from different areas, exchange of such variants among HIV-positive people with several coinciding routes of infection and other epidemiologic risk factors in the seropositive population. The high HIV-1 genetic variability observed in Cuba has possible implications for transmission and clinical progression. OBJECTIVE Study genetic variability for the HIV-1 env, gag and pol structural genes in Cuba; determine the prevalence of B and non-B subtypes according to epidemiologic and behavioral variables and determine whether a relationship exists between genetic variability and transmissibility, and between genetic variability and clinical disease progression in people living with HIV/AIDS. METHODS Using two molecular assays (heteroduplex mobility assay and nucleic acid sequencing), structural genes were characterized in 590 people with HIV-1 (480 men and 110 women), accounting for 3.4% of seropositive individuals in Cuba as of December 31, 2013. Nonrandom sampling, proportional to HIV prevalence by province, was conducted. Relationships between molecular results and viral factors, host characteristics, and patients' clinical, epidemiologic and behavioral variables were studied for molecular epidemiology, transmission, and progression analyses. RESULTS Molecular analysis of the three HIV-1 structural genes classified 297 samples as subtype B (50.3%), 269 as non-B subtypes (45.6%) and 24 were not typeable. Subtype B prevailed overall and in men, mainly in those who have sex with men. Non-B subtypes were prevalent in women and heterosexual men, showing multiple circulating variants and recombinant forms. Sexual transmission was the predominant form of infection for all. B and non-B subtypes were encountered throughout Cuba. No association was found between subtypes and transmission or clinical progression, although the proportion of deaths was higher for subtype B. Among those who died during the study period, there were no differences between subtypes in the mean time from HIV or AIDS diagnosis to death. CONCLUSIONS Our results suggest that B and non-B HIV-1 subtypes found in Cuba do not differ in transmissibility and in clinical disease progression. KEYWORDS HIV-1, AIDS, molecular epidemiology, transmissibility, clinical progression, subtypes, circulating recombinant forms, pathogenesis, Cuba.

Separation techniques. [in space experiments

NASA Technical Reports Server (NTRS)

Snyder, R. S.

1986-01-01

Progress in developing three technologies for separating proteins in a microgravity environment is reviewed. NASA research on electrophoresis, electroosmosis, and phase partitioning is summarized. Future STS missions will characterize these processes in more detail.

Statistical Modeling of Disease Progression for Chronic Obstructive Pulmonary Disease Using Data from the ECLIPSE Study.

PubMed

Exuzides, Alex; Colby, Chris; Briggs, Andrew H; Lomas, David A; Rutten-van Mölken, Maureen P M H; Tabberer, Maggie; Chambers, Mike; Muellerova, Hana; Locantore, Nicholas; Risebrough, Nancy A; Ismaila, Afisi S; Gonzalez-McQuire, Sebastian

2017-05-01

To develop statistical models predicting disease progression and outcomes in chronic obstructive pulmonary disease (COPD), using data from ECLIPSE, a large, observational study of current and former smokers with COPD. Based on a conceptual model of COPD disease progression and data from 2164 patients, associations were made between baseline characteristics, COPD disease progression attributes (exacerbations, lung function, exercise capacity, and symptoms), health-related quality of life (HRQoL), and survival. Linear and nonlinear functional forms of random intercept models were used to characterize these relationships. Endogeneity was addressed by time-lagging variables in the regression models. At the 5% significance level, an exacerbation history in the year before baseline was associated with increased risk of future exacerbations (moderate: +125.8%; severe: +89.2%) and decline in lung function (forced expiratory volume in 1 second [FEV 1 ]) (-94.20 mL per year). Each 1% increase in FEV 1 % predicted was associated with decreased risk of exacerbations (moderate: -1.1%; severe: -3.0%) and increased 6-minute walk test distance (6MWD) (+1.5 m). Increases in baseline exercise capacity (6MWD, per meter) were associated with slightly increased risk of moderate exacerbations (+0.04%) and increased FEV 1 (+0.62 mL). Symptoms (dyspnea, cough, and/or sputum) were associated with an increased risk of moderate exacerbations (+13.4% to +31.1%), and baseline dyspnea (modified Medical Research Council score ≥2 v. <2) was associated with lower FEV 1 (-112.3 mL). A series of linked statistical regression equations have been developed to express associations between indicators of COPD disease severity and HRQoL and survival. These can be used to represent disease progression, for example, in new economic models of COPD.

Trait Mindfulness and Progression to Injection Use in Youth With Opioid Addiction.

PubMed

Wilson, J Deanna; Vo, Hoa; Matson, Pamela; Adger, Hoover; Barnett, Gabriela; Fishman, Marc

2017-09-19

Many youth initiate opioid misuse with prescription opioids and transition over time to more severe substance-using behaviors, including injection. Trait mindfulness is a potentially protective factor. This is a cross-sectional study characterizing a sample of opioid-using youth by level of mindfulness and examines the potential effect modification of emotion regulation on the relationship between mindfulness and progression to injection opioid use. A convenience sample of 112 youth (ages 14-24) was recruited during an episode of inpatient detoxification and residential treatment for opioid use disorders. We examined emotion regulation (Difficulties in Emotion Regulation Scale), mindfulness (Child Acceptance and Mindfulness Measure), and opioid use. We completed multivariable regressions stratified by degree of emotion regulation looking at relationship of mindfulness on time to injection use from age of first prescription opioid. Youth had difficulties in emotion regulation (m = 104.2; SD = 2.41) and low mindfulness (m = 19.1;SD = 0.59). While we found overall that mindfulness was associated with time to progression to injection opioid use, there was significant effect modification. Among youth with high levels of difficulty in emotion regulation, those with high mindfulness trait had quicker progressions to injection (-1.31 years; p =.003). In contrast, youth with normal emotion regulation and high mindfulness trait had a slower progression to injection (1.67 years; p =.041). Conclusion/Importance: Our study showed a majority of youth presenting with opioid use disorders have impairments in emotion regulation and deficits in trait mindfulness. The relationship between mindfulness and opioid use is impacted by emotion regulation capacity. More research is needed to understand the various facets of mindfulness and how they interact with emotion regulation in youth.

Mineralogical characterization of selected shales in support of nuclear waste repository studies: Progress report, October 1987--September 1988

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

Lee, S. Y.; Hyder, L. K.; Baxter, P. M.

1989-07-01

One objective of the Sedimentary Rock Program at the Oak Ridge National Laboratory has been to examine end-member shales to develop a data base that will aid in evaluations if shales are ever considered as a repository host rock. Five end-member shales were selected for comprehensive characterization: the Chattanooga Shale from Fentress County, Tennessee; the Pierre Shale from Gregory County, South Dakota; the Green River Formation from Garfield County, Colorado; and the Nolichucky Shale and Pumpkin Valley Shale from Roane County, Tennessee. Detailed micromorphological and mineralogical characterizations of the shales were completed by Lee et al. (1987) in ORNL/TM-10567. Thismore » report is a supplemental characterization study that was necessary because second batches of the shale samples were needed for additional studies. Selected physical, chemical, and mineralogical properties were determined for the second batches; and their properties were compared with the results from the first batches. Physical characterization indicated that the second-batch and first-batch samples had a noticeable difference in apparent-size distributions but had similar primary-particle-size distributions. There were some differences in chemical composition between the batches, but these differences were not considered important in comparison with the differences among the end-member shales. The results of x-ray diffraction analyses showed that the second batches had mineralogical compositions very similar to the first batches. 9 refs., 9 figs., 4 tabs.« less

Toward high-resolution computational design of helical membrane protein structure and function

PubMed Central

Barth, Patrick; Senes, Alessandro

2016-01-01

The computational design of α-helical membrane proteins is still in its infancy but has made important progress. De novo design has produced stable, specific and active minimalistic oligomeric systems. Computational re-engineering can improve stability and modulate the function of natural membrane proteins. Currently, the major hurdle for the field is not computational, but the experimental characterization of the designs. The emergence of new structural methods for membrane proteins will accelerate progress PMID:27273630

Toward high-resolution computational design of the structure and function of helical membrane proteins.

PubMed

Barth, Patrick; Senes, Alessandro

2016-06-07

The computational design of α-helical membrane proteins is still in its infancy but has already made great progress. De novo design allows stable, specific and active minimal oligomeric systems to be obtained. Computational reengineering can improve the stability and function of naturally occurring membrane proteins. Currently, the major hurdle for the field is the experimental characterization of the designs. The emergence of new structural methods for membrane proteins will accelerate progress.

Fungal-bacterial interactions and their relevance to oral health: linking the clinic and the bench

PubMed Central

Diaz, Patricia I.; Strausbaugh, Linda D.; Dongari-Bagtzoglou, Anna

2014-01-01

High throughput sequencing has accelerated knowledge on the oral microbiome. While the bacterial component of oral communities has been extensively characterized, the role of the fungal microbiota in the oral cavity is largely unknown. Interactions among fungi and bacteria are likely to influence oral health as exemplified by the synergistic relationship between Candida albicans and oral streptococci. In this perspective, we discuss the current state of the field of fungal-bacterial interactions in the context of the oral cavity. We highlight the need to conduct longitudinal clinical studies to simultaneously characterize the bacterial and fungal components of the human oral microbiome in health and during disease progression. Such studies need to be coupled with investigations using disease-relevant models to mechanistically test the associations observed in humans and eventually identify fungal-bacterial interactions that could serve as preventive or therapeutic targets for oral diseases. PMID:25120959

Fungal-bacterial interactions and their relevance to oral health: linking the clinic and the bench.

PubMed

Diaz, Patricia I; Strausbaugh, Linda D; Dongari-Bagtzoglou, Anna

2014-01-01

High throughput sequencing has accelerated knowledge on the oral microbiome. While the bacterial component of oral communities has been extensively characterized, the role of the fungal microbiota in the oral cavity is largely unknown. Interactions among fungi and bacteria are likely to influence oral health as exemplified by the synergistic relationship between Candida albicans and oral streptococci. In this perspective, we discuss the current state of the field of fungal-bacterial interactions in the context of the oral cavity. We highlight the need to conduct longitudinal clinical studies to simultaneously characterize the bacterial and fungal components of the human oral microbiome in health and during disease progression. Such studies need to be coupled with investigations using disease-relevant models to mechanistically test the associations observed in humans and eventually identify fungal-bacterial interactions that could serve as preventive or therapeutic targets for oral diseases.

ECX and PEX rheology. Progress report, October--December 1975

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

West, G.T.

1975-01-01

The objectives of this project are: (1) to evaluate the capillary rheometer as a device to qualitatively measure the extrusion properties of extrusion cast and paste explosives; (2) to study and determine means to distinguish and characterize the rheological properties of different lots of ECX and PEX; and (3) to apply results from (1) and (2) to production loading operations involving ECX and PEX. The second objective (to study and determine means to distinguish and characterize rheological properties) of this project has been accomplished. Testing procedures were finalized, and general knowledge of the rheometer itself was gained. Three batches ofmore » 85/15 (wt. percent) RDX/Sylgard were tested in the Instron Capillary Rheometer. Each lot was statistically distinguishable from the other two lots. One lot exhibited a significantly lower apparent viscosity than the other two lots, which were statistically different from each other, but which were in fairly close agreement.« less

Seminar: Developmental Dyslexia

PubMed Central

Peterson, Robin L.; Pennington, Bruce F.

2012-01-01

Summary Dyslexia is a neurodevelopmental disorder that is characterized by slow and inaccurate word recognition. Dyslexia has been found in every culture studied, and mounting evidence underscores cross-linguistic similarity in its neurobiological and neurocognitive bases. There has been considerable progress across levels of analysis in the last five years. At a neuropsychological level, the phonological theory remains the most compelling, though it is increasingly clear that phonological problems interact with other cognitive risk factors. At a neurobiological level, recent research confirms that dyslexia is characterized by dysfunction of the normal left hemisphere language network and also implicates abnormal white matter development. Studies accounting for reading experience demonstrate that many observed neural differences reflect causes rather than effects of dyslexia. At an etiologic risk level, six candidate genes have been identified, and there is evidence for gene by environment interaction. This review includes a focus on these and other recent developments. PMID:22513218

Characterization of Atmospheric Waves at the upper clouds in the Polar Region of Venus

NASA Astrophysics Data System (ADS)

Peralta, J.; Luz, D.; Berry, D. L.; Tsang, C. C. C.; Migliorini, A.; Piccioni, G.; Drossart, P.

2012-09-01

Non solar-fixed waves at the cloud tops of the southern polar region of Venus are studied in the winds measured with 3.9 and 5.0 μm images taken by the instrument VIRTIS-M onboard Venus Express. Wavenumbers 1, 2 and 3 are detected, with wave amplitudes ranging from 3.6 to 8.0 m/s. The evolution of the phase has been studied in 16 orbits, finding in a subset of orbits wavenumbers 1 and 2 propagating in different directions (zonal wind), and a westward progression with a phase velocity of approximately 5.7 m/s for the wavenumber 1 in the meridional wind. Finally, a new set of analytical solutions to the atmospheric waves is obtained for the planet Venus, and these are used to characterize the found waves in terms of the horizontal wavelength and phase velocity.

Thinking about Bacillus subtilis as a multicellular organism.

PubMed

Aguilar, Claudio; Vlamakis, Hera; Losick, Richard; Kolter, Roberto

2007-12-01

Initial attempts to use colony morphogenesis as a tool to investigate bacterial multicellularity were limited by the fact that laboratory strains often have lost many of their developmental properties. Recent advances in elucidating the molecular mechanisms underlying colony morphogenesis have been made possible through the use of undomesticated strains. In particular, Bacillus subtilis has proven to be a remarkable model system to study colony morphogenesis because of its well-characterized developmental features. Genetic screens that analyze mutants defective in colony morphology have led to the discovery of an intricate regulatory network that controls the production of an extracellular matrix. This matrix is essential for the development of complex colony architecture characterized by aerial projections that serve as preferential sites for sporulation. While much progress has been made, the challenge for future studies will be to determine the underlying mechanisms that regulate development such that differentiation occurs in a spatially and temporally organized manner.

Mitochondrial and ER Calcium Uptake and Release Fluxes and their Interplay in Intact Nerve Cells

NASA Astrophysics Data System (ADS)

Friel, David D.

Ionized free Ca ( Ca 2+) is a ubiquitous signaling ion that serves as the critical link between a variety of physiological stimuli and their intracellular effectors. Previous studies of reduced in vitro preparations have provided functional characterizations of various Ca 2+ channels, pumps and exchangers that regulate cellular Ca 2+ movements. However, little is known about the functional interplay between transporters that are expressed together in intact cells and orchestrate stimulus-evoked changes in [ Ca 2+]. This review summarizes recent progress in characterizing Ca 2+ transporters in sympathetic neurons, which provide an ideal model for studying Ca 2+ dynamics in neurons. Our results show how the functional interplay between Ca 2+ transport systems that are regulated by Ca 2+ in quantitatively differ-ent ways leads to emergent properties of Ca 2+ signaling that are expected to play a critical role in defining how Ca 2+ serves its role as a signaling ion.

Neutrophils, platelets, and inflammatory pathways at the nexus of sickle cell disease pathophysiology

PubMed Central

Zhang, Dachuan; Xu, Chunliang; Manwani, Deepa

2016-01-01

Sickle cell disease (SCD) is a severe genetic blood disorder characterized by hemolytic anemia, episodic vaso-occlusion, and progressive organ damage. Current management of the disease remains symptomatic or preventative. Specific treatment targeting major complications such as vaso-occlusion is still lacking. Recent studies have identified various cellular and molecular factors that contribute to the pathophysiology of SCD. Here, we review the role of these elements and discuss the opportunities for therapeutic intervention. PMID:26758915

Quarterly Technical Progress Report

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

Mary K. Banken

This project has identified all FDD oil reservoirs in Oklahoma; grouped those reservoirs into plays that have similar depositional origins; collected, organized, and analyzed all available data; conducted characterization and simulation studies on selected reservoirs in each plays; and implemented a technology transfer program targeted to the operators of FDD reservoirs. By fulfilling these objectives, the FDD project has had the goal of helping to sustain the life expectancy of existing wells and provide incentive for development and exploratory wells with the ultimate objective of increasing oil recovery.

Comparative aspects of the purification and properties of cholinesterases

PubMed Central

Augustinsson, Klas-Bertil

1971-01-01

Recent years have seen great progress in the purification and characterization of cholinesterases. Investigation has indicated the existence of two principal groups: a fairly homogeneous group of acetylcholinesterases and a group of enzymes that utilize butyrylcholine, propionycholine, or benzoylcholine as substrates and that differ widely in their properties. This paper reviews the different types of cholinesterase and their sources, the importance of a proper choice of substrate in cholinesterase studies, methods for the purification of cholinesterases, and some of the properties of these enzymes. PMID:4938026

Fatigue behavior of a cross-ply ceramic matrix composite at elevated temperature under tension-tension loading. Master`s thesis

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

Steiner, C.D.

This study investigated the fatigue behavior and damage mechanisms of a (0/90)4s SiC/MAS ceramic matrix composite under tension-tension loading at two elevated temperatures and two frequencies. Stress and strain hystereses, maximum and minimum strain, and modulus of elasticity were evaluated to characterize the material behavior. Microscopy and fractography were used to evaluate damage progression and mechanisms. Fatigue life was independent of frequency at both temperatures.

Transmembrane proteins of tight junctions.

PubMed

Chiba, Hideki; Osanai, Makoto; Murata, Masaki; Kojima, Takashi; Sawada, Norimasa

2008-03-01

Tight junctions contribute to the paracellular barrier, the fence dividing plasma membranes, and signal transduction, acting as a multifunctional complex in vertebrate epithelial and endothelial cells. The identification and characterization of the transmembrane proteins of tight junctions, claudins, junctional adhesion molecules (JAMs), occludin and tricellulin, have led to insights into the molecular nature of tight junctions. We provide an overview of recent progress in studies on these proteins and highlight their roles and regulation, as well as their functional significance in human diseases.

Characteristics of American coals in relation to their conversion into clean energy fuels. Quarterly technical progress report, July-September 1978

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

Spackman, W.; Davis, A.; Walker, P. L.

1979-05-01

Certain important aspects of the chemical and physical composition of American lignite coals are being characterized. Differential scanning calorimetry and thermogravimetric analysis were used to study the interaction between oxygen and seventeen coal chars (40 x 100 mesh) at 100/sup 0/C. The same techniques were used to investigate briefly the interaction between air and a highly caking coal at selected isothermal temperatures in the range 100 to 275/sup 0/C.

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

Balkwill, D.L.; Reeves, R.H.

The present document is an interim technical report in which we describe the research which has been completed during the seven-month period since the start of the grant. Progress is summarized in two main areas. The first is microbiological characterization of subsurface materials from the Hanford reservation and the Idaho National Engineering Laboratory, and the second is phylogenetic characterization of these microorganisms. The major tools used for phylogenetic characterization are RFLP analysis of PCR derived material and 16S rRNA sequencing. A description of manuscripts ready for publication is also provided. 4 refs. (MHB)

Progression of the epidemiological transition in a rural South African setting: findings from population surveillance in Agincourt, 1993-2013.

PubMed

Kabudula, Chodziwadziwa W; Houle, Brian; Collinson, Mark A; Kahn, Kathleen; Gómez-Olivé, Francesc Xavier; Clark, Samuel J; Tollman, Stephen

2017-05-10

Virtually all low- and middle-income countries are undergoing an epidemiological transition whose progression is more varied than experienced in high-income countries. Observed changes in mortality and disease patterns reveal that the transition in most low- and middle-income countries is characterized by reversals, partial changes and the simultaneous occurrence of different types of diseases of varying magnitude. Localized characterization of this shifting burden, frequently lacking, is essential to guide decentralised health and social systems on the effective targeting of limited resources. Based on a rigorous compilation of mortality data over two decades, this paper provides a comprehensive assessment of the epidemiological transition in a rural South African population. We estimate overall and cause-specific hazards of death as functions of sex, age and time period from mortality data from the Agincourt Health and socio-Demographic Surveillance System and conduct statistical tests of changes and differentials to assess the progression of the epidemiological transition over the period 1993-2013. From the early 1990s until 2007 the population experienced a reversal in its epidemiological transition, driven mostly by increased HIV/AIDS and TB related mortality. In recent years, the transition is following a positive trajectory as a result of declining HIV/AIDS and TB related mortality. However, in most age groups the cause of death distribution is yet to reach the levels it occupied in the early 1990s. The transition is also characterized by persistent gender differences with more rapid positive progression in females than males. This typical rural South African population is experiencing a protracted epidemiological transition. The intersection and interaction of HIV/AIDS and antiretroviral treatment, non-communicable disease risk factors and complex social and behavioral changes will impact on continued progress in reducing preventable mortality and improving health across the life course. Integrated healthcare planning and program delivery is required to improve access and adherence for HIV and non-communicable disease treatment. These findings from a local, rural setting over an extended period contribute to the evidence needed to inform further refinement and advancement of epidemiological transition theory.

Genetics Home Reference: pulmonary arterial hypertension

MedlinePlus

... Home Health Conditions Pulmonary arterial hypertension Pulmonary arterial hypertension Printable PDF Open All Close All Enable Javascript ... view the expand/collapse boxes. Description Pulmonary arterial hypertension is a progressive disorder characterized by abnormally high ...

Low-level laser therapy promotes dendrite growth via upregulating brain-derived neurotrophic factor expression

NASA Astrophysics Data System (ADS)

Meng, Chengbo; He, Zhiyong; Xing, Da

2014-09-01

Downregulation of brain-derived neurotrophic factor (BDNF) in the hippocampus occurs early in the progression of Alzheimer's disease (AD). Since BDNF plays a critical role in neuronal survival and dendrite growth, BDNF upregulation may contribute to rescue dendrite atrophy and cell loss in AD. Low-level laser therapy (LLLT) has been demonstrated to regulate neuronal function both in vitro and in vivo. In the present study, we found that LLLT rescued neurons loss and dendritic atrophy via the increase of both BDNF mRNA and protein expression. In addition, dendrite growth was improved after LLLT, characterized by upregulation of PSD95 expression, and the increase in length, branching, and spine density of dendrites in hippocampal neurons. Together, these studies suggest that upregulation of BDNF with LLLT can ameliorate Aβ-induced neurons loss and dendritic atrophy, thus identifying a novel pathway by which LLLT protects against Aβ-induced neurotoxicity. Our research may provide a feasible therapeutic approach to control the progression of Alzheimer's disease.

Making sense of OMICS data in population-based environmental health studies.

PubMed

Kyrtopoulos, Soterios A

2013-08-01

Although experience from the application of OMICS technologies in population-based environmental health studies is still relatively limited, the accumulated evidence shows that it can allow the identification of features (genes, proteins, and metabolites), or sets of such features, which are targeted by particular exposures or correlate with disease risk. Such features or profiles can therefore serve as biomarkers of exposure or disease risk. Blood-based OMIC profiles appear to reflect to some extent events occurring in target tissues and are associated with toxicity or disease and therefore have the potential to facilitate the elucidation of exposure-disease relationships. Further progress in this direction requires better understanding of the significance of exposure-induced network perturbations for disease initiation and progression and the development of a framework that combines agnostic searches with the utilization of prior knowledge, taking account of particular elements which characterize the structure and evolution of complex systems and brings in principles of systems biology. Copyright © 2013 Wiley Periodicals, Inc.

Prospective Characterization of Cognitive Function in Typical and 'Brainstem Predominant'Progressive Supranuclear Palsy Phenotypes.

PubMed

Lee, Young-Eun C; Williams, David R; Anderson, Jacqueline F I

2018-05-01

Clinicopathological studies over the last decade have broadened the clinical spectrum of progressive supranuclear palsy (PSP) to include several distinct clinical syndromes. We examined the cognitive profiles of patients with PSP-Richardson's syndrome (PSP-RS) and two atypical 'brainstem predominant' PSP phenotypes (PSP-parkinsonism, PSP-P; and PSP-pure akinesia with gait freezing, PSP-PAGF) using a comprehensive neuropsychological battery. Fourteen patients diagnosed as PSP-RS, three patients with PSP-P and four patients with PSP-PAGF were assessed using a comprehensive battery of neuropsychological tests. The typical PSP-RS subgroup demonstrated greater impairments in processing speed [t(19) = -4.10, p = 0.001 (d =1.66)] and executive function [t(19) = -2.63, p = 0.02 (d = 1.20)] compared to the 'brainstem predominant' PSP phenotype. This is the first prospective study to demonstrate that PSP-RS and 'brainstem predominant' PSP phenotypes can be differentiated on cognitive grounds. These differences correspond with variations in pathological profiles reported in the literature.

Transcranial direct current stimulation for the treatment of primary progressive aphasia: An open-label pilot study.

PubMed

Gervits, Felix; Ash, Sharon; Coslett, H Branch; Rascovsky, Katya; Grossman, Murray; Hamilton, Roy

2016-11-01

Primary progressive aphasia (PPA) is a neurodegenerative condition characterized by gradual deterioration of language function. We investigated whether two weeks of daily transcranial direct current stimulation (tDCS) treatment would improve language abilities in six people with a non-fluent form of PPA. tDCS was applied in an unblinded trial at an intensity of 1.5mA for 20min/day over 10days. At the time of stimulation, patients were engaged in narrating one of several children's wordless picture stories. A battery of neuropsychological assessments was administered four times: at baseline, immediately following the 2-week stimulation period, and then 6-weeks and 12-weeks following the end of stimulation. We observed improvement in linguistic performance in the domains of speech production and grammatical comprehension. Our encouraging results indicate that larger, sham-controlled studies of tDCS as a potential intervention for PPA are warranted. Copyright © 2016 Elsevier Inc. All rights reserved.

Subclinical hypothyroidism in children.

PubMed

Shriraam, M; Sridhar, M

2014-11-01

Subclinical hypothyroidism is a biochemical diagnosis characterized by raised thyroid stimulating hormone and normal free T4, without clinical features of hypothyroidism. This review analyzes the current evidence to arrive at a consensus and algorithm to manage this condition. We searched Pubmed, Cochrane and Embase for articles published between 1990 to 2014, and identified 13 relevant articles dealing with pediatric subclinical hypothyroidism which were suitable to include in our review. Subclinical hypothyroidism is often a benign problem which requires expectant management with periodic monitoring of thyroid function tests and natural progression to overt hypothyroidism occur lot less frequently than expected. There is a paucity of robust randomized intervention studies, especially studies focusing on clinical outcomes. Thyroid replacement therapy is not justified in children with subclinical hypothyroidism when Thyroid stimulating hormone is <10 mIU/L. The main risk factors for progression to overt hypothyroidism are female sex, goiter, family history of thyroid disorder, strongly positive thyroid peroxidase antibodies and symptoms suggesting hypothyroidism. An algorithm for managing this condition is suggested.

Brief intervention for agrammatism in Primary Progressive Nonfluent Aphasia: A case report

PubMed Central

Machado, Thais Helena; Campanha, Aline Carvalho; Caramelli, Paulo; Carthery-Goulart, Maria Teresa

2014-01-01

The non-fluent and agrammatic variant of Primary Progressive Aphasia (NFPPA) is characterized by reduced verbal production with deficits in building grammatically correct sentences, involving dysfunctions in syntactic and morphological levels of language. There are a growing number of studies about non-pharmacological alternatives focusing on the rehabilitation of functional aspects or specific cognitive impairments of each variant of PPA. This study reports a short-term treatment administered to a patient with NFPPA focusing on the production of sentences. The patient had significant reduction in verbal fluency, use of keywords, phrasal and grammatical simplifying as well as anomia. Using the method of errorless learning, six sessions were structured to stimulate the formation of sentences in the present and past with the cloze technique. The patient had improvement restricted to the strategy, with 100% accuracy on the trained phrases and generalization to untrained similar syntactic structure after training. These results persisted one month after the treatment. PMID:29213916

Identification of a Novel Mutation in the ABCA4 Gene in a Chinese Family with Retinitis Pigmentosa Using Exome Sequencing.

PubMed

Huang, Xiangjun; Yuan, Lamei; Xu, Hongbo; Zheng, Wen; Cao, Yanna; Yi, Junhui; Guo, Yi; Yang, Zhijian; Li, Yu; Deng, Hao

2018-02-05

Retinitis pigmentosa (RP) is a group of hereditary, degenerative retinal disorders characterized by progressive retinal dysfunction, outer retina cell loss, and retinal tissue atrophy. It eventually leads to tunnel vision and legal, or total blindness. Here we aimed to reveal the causal gene and mutation contributing to the development of autosomal recessive RP (arRP) in a consanguineous family. A novel homozygous mutation, c.4845delT (p.K1616Rfs*46), in the ATP-binding cassette subfamily A member 4gene ( ABCA4 ) was identified. It may reduce ABCA4 protein activity, leading to progressive degeneration of both rod and cone photoreceptors. The study extends the arRP genotypic spectrum and confirms a genotype-phenotype relationship. This study may also disclose some new clues for RP genetic causes and pathogenesis, as well as clinical and genetic diagnosis. The research findings may contribute to improvement in clinical care, therapy, genetic screening, and counseling. ©2018 The Author(s).

Defining the Role of Solid Stress and Matrix Stiffness in Cancer Cell Proliferation and Metastasis

PubMed Central

Kalli, Maria; Stylianopoulos, Triantafyllos

2018-01-01

Solid tumors are characterized by an abnormal stroma that contributes to the development of biomechanical abnormalities in the tumor microenvironment. In particular, these abnormalities include an increase in matrix stiffness and an accumulation of solid stress in the tumor interior. So far, it is not clearly defined whether matrix stiffness and solid stress are strongly related to each other or they have distinct roles in tumor progression. Moreover, while the effects of stiffness on tumor progression are extensively studied compared to the contribution of solid stress, it is important to ascertain the biological outcomes of both abnormalities in tumorigenesis and metastasis. In this review, we discuss how each of these parameters is evolved during tumor growth and how these parameters are influenced by each other. We further review the effects of matrix stiffness and solid stress on the proliferative and metastatic potential of cancer and stromal cells and summarize the in vitro experimental setups that have been designed to study the individual contribution of these parameters. PMID:29594037

Primary cultures of human colon cancer as a model to study cancer stem cells.

PubMed

Koshkin, Sergey; Danilova, Anna; Raskin, Grigory; Petrov, Nikolai; Bajenova, Olga; O'Brien, Stephen J; Tomilin, Alexey; Tolkunova, Elena

2016-09-01

The principal cause of death in cancer involves tumor progression and metastasis. Since only a small proportion of the primary tumor cells, cancer stem cells (CSCs), which are the most aggressive, have the capacity to metastasize and display properties of stem cells, it is imperative to characterize the gene expression of diagnostic markers and to evaluate the drug sensitivity in the CSCs themselves. Here, we have examined the key genes that are involved in the progression of colorectal cancer and are expressed in cancer stem cells. Primary cultures of colorectal cancer cells from a patient's tumors were studied using the flow cytometry and cytological methods. We have evaluated the clinical and stem cell marker expression in these cells, their resistance to 5-fluorouracil and irinotecan, and the ability of cells to form tumors in mice. The data shows the role of stem cell marker Oct4 in the resistance of primary colorectal cancer tumor cells to 5-fluorouracil.

Copper/MYC/CTR1 interplay: a dangerous relationship in hepatocellular carcinoma.

PubMed

Porcu, Cristiana; Antonucci, Laura; Barbaro, Barbara; Illi, Barbara; Nasi, Sergio; Martini, Maurizio; Licata, Anna; Miele, Luca; Grieco, Antonio; Balsano, Clara

2018-02-06

Free serum copper correlates with tumor incidence and progression of human cancers, including hepatocellular carcinoma (HCC). Copper extracellular uptake is provided by the transporter CTR1, whose expression is regulated to avoid excessive intracellular copper entry. Inadequate copper serum concentration is involved in the pathogenesis of Non Alcoholic Fatty Liver Disease (NAFLD), which is becoming a major cause of liver damage progression and HCC incidence. Finally, MYC is over-expressed in most of HCCs and is a critical regulator of cellular growth, tumor invasion and metastasis. The purpose of our study was to understand if higher serum copper concentrations might be involved in the progression of NAFLD-cirrhosis toward-HCC. We investigated whether high exogenous copper levels sensitize liver cells to transformation and if it exists an interplay between copper-related proteins and MYC oncogene. NAFLD-cirrhotic patients were characterized by a statistical significant enhancement of serum copper levels, even more evident in HCC patients. We demonstrated that high extracellular copper concentrations increase cell growth, migration, and invasion of liver cancer cells by modulating MYC/CTR1 axis. We highlighted that MYC binds a specific region of the CTR1 promoter, regulating its transcription. Accordingly, CTR1 and MYC proteins expression were progressively up-regulated in liver tissues from NAFLD-cirrhotic to HCC patients. This work provides novel insights on the molecular mechanisms by which copper may favor the progression from cirrhosis to cancer. The Cu/MYC/CTR1 interplay opens a window to refine HCC diagnosis and design new combined therapies.

[The phonological variant of primary progressive aphasia, a single case study].

PubMed

Diesfeldt, H F A

2011-04-01

Primary progressive aphasia (PPA) is a neurodegenerative syndrome characterized by an insidious onset and gradual progression of deficits that can involve any aspect of language, including word finding, object naming, fluency, syntax, phonology and word comprehension. The initial symptoms occur in the absence of major deficits in other cognitive domains, including episodic memory, visuospatial abilities and visuoconstruction. According to recent diagnostic guidelines, PPA is typically divided into three variants: nonfluent variant PPA (also termed progressive nonfluent aphasia), semantic variant PPA (also termed semantic dementia) and logopenic/phonological variant PPA (also termed logopenic progressive aphasia). The paper describes a 79-yr old man, who presented with normal motor speech and production rate, impaired single word retrieval and phonemic errors in spontaneous speech and confrontational naming. Confrontation naming was strongly affected by lexical frequency. He was impaired on repetition of sentences and phrases. Reading was intact for regularly spelled words but not for irregular words (surface dyslexia). Comprehension was spared at the single word level, but impaired for complex sentences. He performed within the normal range on the Dutch equivalent of the Pyramids and Palm Trees (PPT) Pictures Test, indicating that semantic processing was preserved. There was, however, a slight deficiency on the PPT Words Test, which appeals to semantic knowledge of verbal associations. His core deficit was interpreted as an inability to retrieve stored lexical-phonological information for spoken word production in spontaneous speech, confrontation naming, repetition and reading aloud.

Scoliosis-Specific exercises can reduce the progression of severe curves in adult idiopathic scoliosis: a long-term cohort study.

PubMed

Negrini, Alessandra; Negrini, Maria Gabriella; Donzelli, Sabrina; Romano, Michele; Zaina, Fabio; Negrini, Stefano

2015-01-01

Scoliosis fusion surgery is generally considered the only means to stop the progression of adult idiopathic scoliosis (ADIS), but for patients refusing surgery there is lack of evidence in favour of conservative treatment. The aim of the present study was to verify the possible effectiveness of scoliosis-specific exercises when facing ADIS progression. We designed a retrospective cohort study. We included 34 ADIS patients in treatment at our Institute (5 males and 29 females, mean age was 38.0 ± 11.0), exclusively treated with specific Scoliosis Specific SEAS exercises. SEAS exercises are scoliosis-specific exercises. In adult patients they are aimed to recover postural collapse, postural control and vertebral stability through an active self-correction. Postural integration is a key element, including the neuromotor integration of correct postures and an ergonomic education program. Therapy includes at least two weekly exercise sessions each lasting 45 min. Radiographic progression was the main outcome and it was analysed as a continuous variable. One way ANOVA and paired t-test were applied for continuous data, while chi-square test was applied for categorical data. Alpha was set at 0.05. The mean Cobb angle of the patients included into the present study, was 55.8 ± 13.2 °. Fifteen patients had previous x-rays testifying scoliosis progression: the average curve progression (worsening) was 9.8 ± 6.6 ° at a median of 25 (range 17-48) years. The remaining were characterized by more severe curves, exceeding 40 ° Cobb (mean curvature 50.9 ± 13.6) but it was not possible to prove that the curves had progressed in these cases. After an average period of 2 years of treatment (range 1-18y), 68 % of the patients experienced an improvement in their scoliosis. However in one patient (3 %) the scoliosis worsened by 5 ° in 18 years (progression rate reduced from 0.5 ° to 0.27 ° per year). Patients improved 4.6 ± 5.0 ° Cobb (P < 0.05), with no differences based on the localization of the curve, gender, age, length of treatment, Cobb degrees at the start of observation or treatment. Scoliosis Specific SEAS Exercises proved to be superior to natural history in ADIS, at least in individual cases and should be considered as a first line treatment especially in patients refusing scoliosis surgery.

BPH progression: concept and key learning from MTOPS, ALTESS, COMBAT, and ALF-ONE.

PubMed

Roehrborn, Claus G

2008-03-01

Benign prostatic hyperplasia (BPH) represents a significant burden in ageing men due to frequently associated lower urinary tract symptoms (LUTS), which may impair quality of life. BPH is also a progressive disease, mainly characterized by a deterioration of LUTS over time, and in some patients by the occurrence of serious outcomes such as acute urinary retention (AUR) and need for BPH-related surgery. The goals of therapy for BPH are not only to improve bothersome LUTS but also to identify those patients at risk of unfavourable outcomes, to optimize their management. In selected patients, combination of an alpha(1)-blocker and a 5alpha-reductase inhibitor is the most effective form of BPH medical therapy to reduce the risk of clinical progression and relieve LUTS. Monotherapy also significantly reduces the risk of BPH clinical progression, mainly through a reduction of LUTS deterioration for alpha(1)-blockers while 5alpha-reductase inhibitors also reduce the risk of AUR and need for BPH-related surgery. Enlarged prostate and high serum prostate-specific antigen levels have been consistently found to be good clinical predictors of AUR and BPH-related surgery in longitudinal population-based studies and placebo arms of controlled studies. High post-void residual urine (PVR) is also associated with an increased risk of LUTS deterioration and should thus be reconsidered in practice as a predictor of BPH progression. Conversely, baseline LUTS severity and low peak flow rate, initially identified as predictors of unfavourable outcomes in community setting, behave paradoxically in controlled trials, probably as a consequence of strict inclusion criteria and subsequent regression to the mean and glass ceiling effects. Lastly, there is increasing evidence that dynamic variables, such as LUTS and PVR worsening, and lack of symptomatic improvement with alpha(1)-blockers are important predictors of future LUTS/BPH-related events, allowing better identification and management of patients at risk of BPH progression.

Similarities and differences between pediatric and adult nonalcoholic fatty liver disease.

PubMed

Crespo, Maricruz; Lappe, Sara; Feldstein, Ariel E; Alkhouri, Naim

2016-08-01

Nonalcoholic fatty liver disease (NAFLD) is highly common and potentially serious in children and adolescents. The term NAFLD refers to a spectrum of diseases ranging from accumulation of fat in the liver (simple steatosis or nonalcoholic fatty liver "NAFL") to the potentially progressive form of nonalcoholic steatohepatitis (NASH) characterized by hepatocyte ballooning, inflammation, and often associated with fibrosis. While large prospective longitudinal studies in pediatric NAFLD are still lacking, growing evidence suggests that children with NAFL are at increased risk for cardiometabolic complications, while those with NASH and advance fibrosis are also at risk for significant liver-related morbidity including cirrhosis and its complications. Pediatric NAFLD shares features of adult NAFLD but also shows many different characteristics in terms of prevalence, histology, diagnosis and management. Translational studies suggest that NAFLD is a highly heritable disease in which genetic variations and environment closely interact to determine the disease phenotype and the progression to the more advanced forms of the disease. Changes in lifestyle, targeting gradual weight reduction, and physical exercise continue to be the mainstay of treatment for NAFLD in children. Recent advances in development of noninvasive diagnostic modalities and the potential for identifying effective pharmacological interventions may result in significant progress in the management of NAFLD in the pediatric population. Copyright © 2016 Elsevier Inc. All rights reserved.

Review of nonalcoholic fatty liver disease in women with polycystic ovary syndrome

PubMed Central

Kelley, Carly E; Brown, Ann J; Diehl, Anna Mae; Setji, Tracy L

2014-01-01

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-aged women. Women with PCOS frequently have metabolic complications including insulin resistance (IR), early diabetes, hypertension and dyslipidemia. Recent studies have demonstrated an association between PCOS and another metabolic complication: nonalcoholic fatty liver disease (NAFLD). NAFLD occurs as a result of abnormal lipid handling by the liver, which sensitizes the liver to injury and inflammation. It can progress to nonalcoholic steatohepatitis (NASH), which is characterized by hepatocyte injury and apoptosis. With time and further inflammation, NASH can progress to cirrhosis. Thus, given the young age at which NAFLD may occur in PCOS, these women may be at significant risk for progressive hepatic injury over the course of their lives. Many potential links between PCOS and NAFLD have been proposed, most notably IR and hyperandrogenemia. Further studies are needed to clarify the association between PCOS and NAFLD. In the interim, clinicians should be aware of this connection and consider screening for NAFLD in PCOS patients who have other metabolic risk factors. The optimal method of screening is unknown. However, measuring alanine aminotransferase and/or obtaining ultrasound on high-risk patients can be considered. First line treatment consists of lifestyle interventions and weight loss, with possible pharmacologic interventions in some cases. PMID:25339805

Inflammation occurs early during the Abeta deposition process in TgCRND8 mice.

PubMed

Dudal, Sherri; Krzywkowski, Pascale; Paquette, Julie; Morissette, Céline; Lacombe, Diane; Tremblay, Patrick; Gervais, Francine

2004-08-01

Alzheimer's disease (AD) is characterized by a progressive cognitive decline leading to dementia and involves the deposition of amyloid-beta (Abeta) peptides into senile plaques. Other neuropathological features that accompany progression of the disease include a decrease in synaptic density, neurofibrillary tangles, dystrophic neurites, inflammation, and neuronal cell loss. In this study, we report the early kinetics of brain amyloid deposition and its associated inflammation in an early onset transgenic mouse model of AD (TgCRND8) harboring the human amyloid precursor protein gene with the Indiana and Swedish mutations. Both diffuse and compact plaques were detected as early as 9-10 weeks of age. Abeta-immunoreactive (Abeta-IR) plaques (4G8-positive) appeared first in the neocortex and amygdala, then in the hippocampal formation, and lastly in the thalamus. Compact plaques (ThioS-positive) with an amyloid core were observed as early as diffuse plaques were detected, but in lower numbers. Amyloid deposition increased progressively with age. The formation of plaques was concurrent with the appearance of activated microglial cells and shortly followed by the clustering of activated astrocytes around plaques at 13-14 weeks of age. This TgCRND8 mouse model allows for a rapid, time-dependent study of the relationship between the fibrillogenic process and the inflammatory response during the brain amyloidogenic process.

Role of renal urothelium in the development and progression of kidney disease.

PubMed

Carpenter, Ashley R; McHugh, Kirk M

2017-04-01

The clinical and financial impact of chronic kidney disease (CKD) is significant, while its progression and prognosis is variable and often poor. Studies using the megabladder (mgb -/- ) model of CKD show that renal urothelium plays a key role in modulating early injury responses following the development of congenital obstruction. The aim of this review is to examine the role that urothelium has in normal urinary tract development and pathogenesis. We discuss normal morphology of renal urothelium and then examine the role that uroplakins (Upks) play in its development. Histologic, biochemical, and molecular characterization of Upk1b RFP/RFP mice indicated Upk1b expression is essential for normal urinary tract development, apical plaque/asymmetric membrane unit (AUM) formation, and differentiation and functional integrity of the renal urothelium. Our studies provide the first evidence that Upk1b is directly associated with the development of congenital anomalies of the urinary tract (CAKUT), spontaneous age-dependent hydronephrosis, and dysplastic urothelia. These observations demonstrate the importance of proper urothelial differentiation in normal development and pathogenesis of the urinary tract and provide a unique working model to test the hypothesis that the complex etiology associated with CKD is dependent upon predetermined genetic susceptibilities that establish pathogenic thresholds for disease initiation and progression.

Role of Renal Urothelium in the Development and Progression of Kidney Disease

PubMed Central

Carpenter, Ashley R.; McHugh, Kirk M.

2016-01-01

The clinical and financial impact of chronic kidney disease (CKD) is significant, while the progression and prognosis of CKD is variable and often poor. Studies using the megabladder (mgb−/−) model of CKD have shown that renal urothelium plays a key role in modulating the early injury responses following the development of congenital obstruction. The aim of this review is to examine the role that urothelium has in normal urinary tract development and pathogenesis. We discuss normal morphology of renal urothelium and then examine the role that uroplakins (Upks) play in its development. Histologic, biochemical and molecular characterization of Upk1bRFP/RFP mice indicated Upk1b expression is essential for normal urinary tract development, apical plaque/AUM formation and differentiation and functional integrity of the renal urothelium. Our studies provide the first evidence Upk1b is directly associated with the development of congenital anomalies of the urinary tract (CAKUT), spontaneous age-dependent hydronephrosis and dysplastic urothelia. These observations demonstrate the importance of proper urothelial differentiation in the normal development and pathogenesis of the urinary tract, and provide a unique working model to test the hypothesis that the complex etiology associated with CKD is dependent upon predetermined genetic susceptibilities that establish pathogenic thresholds for disease initiation and progression. PMID:27115886

Validation of a preclinical model of diethylnitrosamine-induced hepatic neoplasia in Yucatan miniature pigs

PubMed Central

Mitchell, Jennifer; Tinkey, Peggy T.; Avritscher, Rony; Van Pelt, Carolyn; Eskandari, Ghazaleh; George, Suraj Konnath; Xiao, Lianchun; Cressman, Erik; Morris, Jeffrey S.; Rashid, Asif; Kaseb, Ahmed O.; Amin, Hesham M.; Uthamanthil, Rajesh

2016-01-01

Objective The purpose of this study was to reduce time to tumor onset in a diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) swine model via partial liver embolization (PLE) and to characterize the model for use in translational research. Methods Eight Yucatan miniature pigs were injected intraperitoneally with either saline (n=2) or DEN (n=6) solution weekly for 12 weeks. Three of the DEN-treated pigs underwent PLE. Animals underwent periodic radiological evaluation, liver biopsy, and blood sampling, and full necropsy was performed at study termination (~29 months). Results All DEN-treated pigs developed hepatic adenoma and HCC. PLE accelerated the time to adenoma development but not to HCC development. Biomarker analysis results showed that IGF1 levels decreased in all DEN-treated pigs, as functional liver capacity decreased with progression of HCC. VEGF and IL-6 levels were positively correlated with disease progression. Immunohistochemical probing of HCC tissues demonstrated the expression of several important survival-promoting proteins. Conclusion To our knowledge, we are the first to demonstrate accelerated development of hepatic neoplasia in Yucatan miniature pigs. Our HCC swine model closely mimics the human condition (i.e., progressive disease stages and expression of relevant molecular markers) and is a viable translational model. PMID:27305144

Physiological Aβ Concentrations Produce a More Biomimetic Representation of the Alzheimer's Disease Phenotype in iPSC Derived Human Neurons.

PubMed

Berry, Bonnie J; Smith, Alec S T; Long, Christopher J; Martin, Candace C; Hickman, James J

2018-05-22

Alzheimer's disease (AD) is characterized by slow, progressive neurodegeneration leading to severe neurological impairment, but current drug development efforts are limited by the lack of robust, human-based disease models. Amyloid-β (Aβ) is known to play an integral role in AD progression as it has been shown to interfere with neurological function. However, studies into AD pathology commonly apply Aβ to neurons for short durations at nonphysiological concentrations to induce an exaggerated dysfunctional phenotype. Such methods are unlikely to elucidate early stage disease dysfunction, when treatment is still possible, since damage to neurons by these high concentrations is extensive. In this study, we investigated chronic, pathologically relevant Aβ oligomer concentrations to induce an electrophysiological phenotype that is more representative of early AD progression compared to an acute high-dose application in human cortical neurons. The high, acute oligomer dose resulted in severe neuronal toxicity as well as upregulation of tau and phosphorylated tau. Chronic, low-dose treatment produced significant functional impairment without increased cell death or accumulation of tau protein. This in vitro phenotype more closely mirrors the status of early stage neural decline in AD pathology and could provide a valuable tool to further understanding of early stage AD pathophysiology and for screening potential therapeutic compounds.

Spatial Distribution of Coffee Wilt Disease Under Roguing and Replanting Conditions: A Case Study from Kaweri Estate in Uganda.

PubMed

Pinard, F; Makune, S E; Campagne, P; Mwangi, J

2016-11-01

Based on time and spatial dynamic considerations, this study evaluates the potential role of short- and long-distance dispersal in the spread of coffee wilt disease (CWD) in a large commercial Robusta coffee estate in Uganda (Kaweri, 1,755 ha) over a 4-year period (2008 to 2012). In monthly surveys, total disease incidence, expansion of infection foci, and the occurrence of isolated infected trees were recorded and submitted to spatial analysis. Incidence was higher and disease progression faster in old coffee plantings compared with young plantings, indicating a lack of efficiency of roguing for reducing disease development in old plantings. At large spatial scale (approximately 1 km), Moran indices (both global and local) revealed the existence of clusters characterized by contrasting disease incidences. This suggested that local environmental conditions were heterogeneous or there were spatial interactions among blocks. At finer spatial scale (approximately 200 m), O-ring statistics revealed positive correlation between distant infection sites across distances as great as 60 m. Although these observations indicate the role of short-distance dispersal in foci expansion, dispersal at greater distances (>20 m) appeared to also contribute to both initiation of new foci and disease progression at coarser spatial scales. Therefore, our results suggested the role of aerial dispersal in CWD progression.

Synergistic Effects of GDNF and VEGF on Lifespan and Disease Progression in a Familial ALS Rat Model

PubMed Central

Krakora, Dan; Mulcrone, Patrick; Meyer, Michael; Lewis, Christina; Bernau, Ksenija; Gowing, Genevieve; Zimprich, Chad; Aebischer, Patrick; Svendsen, Clive N; Suzuki, Masatoshi

2013-01-01

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons in the brain and spinal cord. We have recently shown that human mesenchymal stem cells (hMSCs) modified to release glial cell line-derived neurotrophic factor (GDNF) decrease disease progression in a rat model of ALS when delivered to skeletal muscle. In the current study, we determined whether or not this effect could be enhanced by delivering GDNF in concert with other trophic factors. hMSC engineered to secrete GDNF (hMSC-GDNF), vascular endothelial growth factor (hMSC-VEGF), insulin-like growth factor-I (hMSC-IGF-I), or brain-derived neurotrophic factor (hMSC-BDNF), were prepared and transplanted bilaterally into three muscle groups. hMSC-GDNF and hMSC-VEGF prolonged survival and slowed the loss of motor function, but hMSC-IGF-I and hMSC-BDNF did not have any effect. We then tested the efficacy of a combined ex vivo delivery of GDNF and VEGF in extending survival and protecting neuromuscular junctions (NMJs) and motor neurons. Interestingly, the combined delivery of these neurotrophic factors showed a strong synergistic effect. These studies further support ex vivo gene therapy approaches for ALS that target skeletal muscle. PMID:23712039

Impact of social relationships on Alzheimer's memory impairment: mechanistic studies.

PubMed

Hsiao, Ya-Hsin; Chang, Chih-Hua; Gean, Po-Wu

2018-01-11

Alzheimer's disease (AD) is characterized by progressive memory and neuronal loss culminating in cognitive impairment that not only affects a person's living ability but also becomes a society's as well as a family's economic burden. AD is the most common form of dementia in older persons. It is expected that the number of people with AD dementia will increase dramatically in the next 30 years, projecting to 75 million in 2030 and 131.5 million in 2050 worldwide. So far, no sufficient evidence is available to support that any medicine is able to prevent or reverse the progression of the disease. Early studies have shown that social environment, particularly social relationships, can affect one's behavior and mental health. A study analyzing the correlation between loneliness and risk of developing AD revealed that lonely persons had higher risk of AD compared with persons who were not lonely. On the other hand, it has been reported that we can prevent cognitive decline and delay the onset of AD if we keep mentally active and frequently participate in social activities. In this review, we focus on the impact of social behaviors on the progression of cognitive deficit in animal models of AD with a particular emphasis on a mechanistic scheme that explains how social isolation exacerbates cognitive impairment and how social interaction with conspecifics rescues AD patients' memory deficit.

[Topical haemotherapy as treatment for necrotic angiodermatitis: a pilot study].

PubMed

Courivaud, D; Ségard, M; Darras, S; Carpentier, O; Thomas, P

2005-03-01

Necrotic angiodermatitis is a variety of leg ulcer, characterized by very painful and rapidly spreading lesions. Healing takes time, a mean of 4 to 11 months. Current treatment is difficult and rarely satisfactory. Only early skin grafts lead to rapid sedation of pain and stop the lesion from extending. However, this technique, performed during a progressive phase, enhances the risk of losing a certain number of grafts. We wanted to confirm the efficacy of local auto-haemo-therapy proposed in 2 non-controlled studies. Eleven patients with necrotic angiodermatitis were included in our non-controlled prospective study. The topical hemotherapy was applied three times a week for one month, with initial hospitalization for 15 days. The criteria of assessment were: evolution of pain, surface of the ulcer, colorimetric scale and the date of disappearance of the purple halo. Ten patients were relieved by the treatment, with progressive withdrawal of the analgesics. The progression of the lesion had stopped and the purple halo had disappeared in general by D6 (range: 2 to 21 days). The percentage of granulation tissue with regard to the surface of the ulcer was of 45.4 p. 100 on D0, 80 p. 100 on D14 and 85 p. 100 on D28. Topical hemotherapy applied during the initial phase of treatment would reduce the pain and prepare the lesion for a secondary skin graft.

RECENT PROGRESS IN THE FABRICATION AND CHARACTERIZATION OF DUCTILE-PHASE-TOUGHENED TUNGSTEN LAMINATES FOR PLASMA-FACING MATERIALS

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

Cunningham, Kevin; Odette, G Robert; Fields, Kirk A.

2015-09-23

A promising approach to increasing the fracture toughness of W-alloys is ductile-phase toughening (DPT). A ductile phase reinforcement in a brittle matrix increases toughness primarily by crack bridging. A W-Cu laminate was fabricated and the properties of the constituent metals were characterized along with those for the composite. Development of a design model for large-scale crack bridging continued.

Trends in access to water supply and sanitation in 31 major sub-Saharan African cities: an analysis of DHS data from 2000 to 2012.

PubMed

Hopewell, Mike R; Graham, Jay P

2014-02-28

By 2050, sub-Saharan Africa's (SSA) urban population is expected to grow from 414 million to over 1.2 billion. This growth will likely increase challenges to municipalities attempting to provide access to water supply and sanitation (WS&S). This study aims to characterize trends in access to WS&S in SSA cities and identify factors affecting those trends. DHS data collected between 2000 and 2012 were used for this analysis of thirty-one cities in SSA. Four categories of household access to WS&S were studied using data from demographic and health surveys--these included: 1) household access to an improved water supply, 2) household's time spent collecting water, 3) household access to improved sanitation, and 4) households reporting to engage in open defecation. An exploratory analysis of these measures was then conducted to assess the relationship of access to several independent variables. Among the 31 cities, there was wide variability in coverage levels and trends in coverage with respect to the four categories of access. The majority of cities were found to be increasing access in the categories of improved water supply and improved sanitation (65% and 83% of cities, respectively), while fewer were making progress in reducing the amount of time spent collecting water and reducing open defecation (50% and 38% of cities, respectively). Additionally, the prevalence of open defecation in study cities was found to be, on average, increasing. Based on DHS data, cities appeared to be making the most progress in gaining access to WS&S along metrics which reflect specified targets of the Millennium Development Goals. Nearly half of the cities, however, did not make progress in reducing open defecation or the time spent collecting water. This may reflect that the MDGs have led to a focus on "improved" services while other measures, potentially more relevant to the extreme poor, are being neglected. This study highlights the need to better characterize access, beyond definitions of improved and unimproved, as well as the need to target resources to cities where changes in WS&S access have stalled, or in some cases regressed.

Cancer stem cell as therapeutic target for melanoma treatment.

PubMed

Alamodi, Abdulhadi A; Eshaq, Abdulaziz M; Hassan, Sofie-Yasmin; Al Hmada, Youssef; El Jamal, Siraj M; Fothan, Ahmed M; Arain, Omair M; Hassan, Sarah-Lilly; Haikel, Youssef; Megahed, Mosaad; Hassan, Mohamed

2016-12-01

Human malignant melanoma is a highly aggressive skin tumor that is characterized by its extraordinary heterogeneity, propensity for dissemination to distant organs and resistance to cytotoxic agents. Although chemo- and immune-based therapies have been evaluated in clinical trials, most of these therapeutics do not show significant benefit for patients with advanced disease. Treatment failure in melanoma patients is attributed mainly to the development of tumor heterogeneity resulting from the formation of genetically divergent subpopulations. These subpopulations are composed of cancer stem-like cells (CSCs) as a small fraction and non-cancer stem cells that form the majority of the tumor mass. In recent years, CSCs gained more attention and suggested as valuable experimental model system for tumor study. In melanoma, intratumoral heterogeneity, progression and drug resistance result from the unique characteristics of melanoma stem cells (MSCs). These MSCs are characterized by their distinct protein signature and tumor growth-driving pathways, whose activation is mediated by driver mutation-dependent signal. The molecular features of MSCs are either in a causal or consequential relationship to melanoma progression, drug resistance and relapse. Here, we review the current scientific evidence that supports CSC hypothesis and the validity of MSCs-dependent pathways and their key molecules as potential therapeutic target for melanoma treatment.

[The role of the human microbiom in the pathogenesis of rheumatoid arthritis - a literature review].

PubMed

Krajewska-Włodarczyk, Magdalena

Rheumatoid arthritis is a chronic, progressive, autoimmune disease with numerous articular, extra-articular and systemic manifestations. The cause of rheumatoid arthritis is multifactorial including genetic and environmental factors. Recent advantages in sequencing techniques have allowed the deep characterization of the human microbiota. Available evidence confirms the existence of an association between dysbiosis and rheumatoid arthritis but it still remains unclear whether alterations in the microbiome are a pathogenic cause or an effect of autoimmune disease. In patients with rheumatoid arthritis the most supported association between disease and microbiota is with the oral dysbiosis usually observed in patients with periodontitis. Given the strong variability and abundance of microbes living in close relation with human host, it becomes a difficult task to define what should be considered the favorable microbiome. There is need for broader studies to establish how the human microbiome contributes to disease susceptibility, and to characterize the role of microbial diversity in the pathogenesis of rheumatoid arthritis, disease manifestation, and progression. The identification of dysbiosis specific for rheumatoid arthritis and the understanding of the dynamic interaction between microbiota and their host may help in establishing an individualized management for each patient with rheumatoid arthritis, and achieve a better efficacy of the therapy.

Fundus autofluorescence and optical coherence tomography in the management of progressive outer retinal necrosis

PubMed Central

Yeh, Steven; Wong, Wai T.; Weichel, Eric D.; Lew, Julie C.; Chew, Emily Y.; Nussenblatt, Robert B.

2011-01-01

A 41 year-old female patient with acquired immune deficiency syndrome (AIDS) presented with progressive nasal visual field loss in her right eye. Ophthalmic exam revealed widespread areas of retinal opacification with hemorrhage consistent with progressive outer retinal necrosis (PORN), which was confirmed by polymerase chain reaction (PCR) for varicella zoster virus (VZV) DNA. The patient was treated with intravenous and intravitreal foscarnet and ganciclovir with a resultant improvement clinically. Optical coherence tomography (OCT) and fundus autofluorescence (FAF) imaging revealed progressive changes indicative of widespread retinal pigment epithelial (RPE) and outer retinal dysfunction. OCT was useful in documenting progressive changes in macular architecture during therapy including neurosensory elevation, cystoid macular edema, and severe outer retinal necrosis, at initial exam, 1 week, and 1 month follow-up. Fundus autofluorescence revealed areas of stippled, hyperfluorescence within extensive zones of hypofluorescence, which progressed during the follow-up period. These areas appeared to represent lipofuscin or its photoreactive components within larger regions of RPE loss. The combination of OCT and FAF was useful in the characterization of the RPE and retinal anatomy in this patient with PORN. PMID:20337261

Cell Size Clues for the Allee Effect in Vegetative Amoeba Suspension Culture

NASA Astrophysics Data System (ADS)

Franck, Carl; Rappazzo, Brendan; Wang, Xiaoning; Segota, Igor

That cells proliferate at higher rates with increasing density helps us appreciate and understand the development of multicellular behavior through the study of dilute cell systems. However, arduous cell counting with a microscope reveals that in the model eukaryote, Dictyostelium discoideum this transition is difficult to ascertain and thereby further explore despite our earlier progress (Phys. Rev. E 77, 041905, (2008)). Here we report preliminary evidence that the slow proliferation phase is well characterized by reduced cell size compared to the wide distribution of cell sizes in the familiar exponential proliferation phase of moderate densities. This observation is enabled by a new system for characterizing cells in stirred suspension cultures. Our technique relies on quickly acquiring magnitude distributions of detected flashes of laser light scattered in situ by cell targets.

A Framework for the Evaluation of Biosecurity, Commercial, Regulatory, and Scientific Impacts of Plant Viruses and Viroids Identified by NGS Technologies

PubMed Central

Massart, Sebastien; Candresse, Thierry; Gil, José; Lacomme, Christophe; Predajna, Lukas; Ravnikar, Maja; Reynard, Jean-Sébastien; Rumbou, Artemis; Saldarelli, Pasquale; Škorić, Dijana; Vainio, Eeva J.; Valkonen, Jari P. T.; Vanderschuren, Hervé; Varveri, Christina; Wetzel, Thierry

2017-01-01

Recent advances in high-throughput sequencing technologies and bioinformatics have generated huge new opportunities for discovering and diagnosing plant viruses and viroids. Plant virology has undoubtedly benefited from these new methodologies, but at the same time, faces now substantial bottlenecks, namely the biological characterization of the newly discovered viruses and the analysis of their impact at the biosecurity, commercial, regulatory, and scientific levels. This paper proposes a scaled and progressive scientific framework for efficient biological characterization and risk assessment when a previously known or a new plant virus is detected by next generation sequencing (NGS) technologies. Four case studies are also presented to illustrate the need for such a framework, and to discuss the scenarios. PMID:28174561

Recent Progress in Nanoelectrical Characterizations of CdTe and Cu(In,Ga)Se2

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

Jiang, Chun-Sheng; To, Bobby; Glynn, Stephen

2016-11-21

We report two recent nanoelectrical characterizations of CdTe and Cu(In, Ga)Se2 (CIGS) thin-film solar cells by developing atomic force microscopy-based nanoelectrical probes. Charges trapped at defects at the CdS/CdTe interface were probed by Kelvin probe force microscopy (KPFM) potential mapping and by ion-milling the CdTe superstrate device in a bevel glancing angle of ~0.5 degrees. The results show randomly distributed donor-like defects at the interface. The effect of K post-deposition treatment on the near-surface region of the CIGS film was studied by KPFM potential and scanning spreading resistance microscopy (SSRM) resistivity mapping, which shows passivation of grain-boundary potential and improvementmore » of resistivity uniformity by the K treatment.« less

[Rapidly progressive glomerulonephritis: a diagnostic and therapeutic emergency].

PubMed

Halfon, Matthieu; Teta, Daniel; Rotman, Samuel; Pruijm, Menno; Humbert, Antoine

2014-02-26

Rapidly progressive glomerulonephritis (RPG) is a rare clinical syndrome characterized by kidney damage that can lead to irreversible kidney failure. RPG can be caused by primary glomerular disease or can be part of a systemic autoimmune disorder. All RPG have a similar pathophysiology (proliferation of cells in Bowman's capsule and formation of crescents) and clinical evolution (rapidly progressive kidney failure with proteinuria and an active urine sediment). Immunosuppressive therapy and sometimes plasma exchanges are required. Overall- and kidney survival are closely linked to the blood creatinine level at presentation, the percentage of damaged glomeruli, and to the underlying cause. RPG is therefore a diagnostic and therapeutic emergency that needs quick referral to a nephrologist.

The Female Pattern Hair Loss: Review of Etiopathogenesis and Diagnosis

PubMed Central

Vujovic, Anja; Del Marmol, Véronique

2014-01-01

Female pattern hair loss (FPHL) is the most common hair loss disorder in women. Initial signs may develop during teenage years leading to a progressive hair loss with a characteristic pattern distribution. The condition is characterized by progressive replacement of terminal hair follicles over the frontal and vertex regions by miniaturized follicles, that leads progressively to a visible reduction in hair density. Women diagnosed with FPHL may undergo significant impairment of quality of life. FPHL diagnosis is mostly clinical. Depending on patient history and clinical evaluation, further diagnostic testing may be useful. The purpose of the paper is to review the current knowledge about epidemiology, pathogenesis, clinical manifestations, and diagnosis of FPHL. PMID:24812631

Childhood-onset HAM/TSP with progressive cognitive impairment.

PubMed

Zorzi, Giovanna; Mancuso, Roberta; Nardocci, Nardo; Farina, Laura; Guerini, Franca Rosa; Ferrante, Pasquale

2010-04-01

HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic myelopathy, usually with adult-onset. Very few cases of childhood-onset have been described, most presenting with progressive paraparesis and sphincteric disturbances as in the adult form. Here we report a young male with childhood-onset of HAM/TSP and progressive cognitive and behavioral disturbances. A serological screening revealed HTLV-I infection, confirmed by Western Immunoblotting analysis. Molecular characterization of amplified HTLV-I proviral DNA has been performed both in the patient and his mother by LTR sequence analysis, and HLA genotype inheritance was evaluated. Our case indicates the possibility that cognitive dysfunctions may be one manifestation of HTLV-I infection in childhood.

Decontamination of combustion gases in fluidized bed incinerators

DOEpatents

Leon, Albert M.

1982-01-01

Sulfur-containing atmospheric pollutants are effectively removed from exit gas streams produced in a fluidized bed combustion system by providing a fluidized bed of particulate material, i.e. limestone and/or dolomite wherein a concentration gradient is maintained in the vertical direction. Countercurrent contacting between upwardly directed sulfur containing combustion gases and descending sorbent particulate material creates a concentration gradient across the vertical extent of the bed characterized in progressively decreasing concentration of sulfur, sulfur dioxide and like contaminants upwardly and decreasing concentration of e.g. calcium oxide, downwardly. In this manner, gases having progressively decreasing sulfur contents contact correspondingly atmospheres having progressively increasing concentrations of calcium oxide thus assuring optimum sulfur removal.

Fishing for causes and cures of motor neuron disorders

PubMed Central

Patten, Shunmoogum A.; Armstrong, Gary A. B.; Lissouba, Alexandra; Kabashi, Edor; Parker, J. Alex; Drapeau, Pierre

2014-01-01

Motor neuron disorders (MNDs) are a clinically heterogeneous group of neurological diseases characterized by progressive degeneration of motor neurons, and share some common pathological pathways. Despite remarkable advances in our understanding of these diseases, no curative treatment for MNDs exists. To better understand the pathogenesis of MNDs and to help develop new treatments, the establishment of animal models that can be studied efficiently and thoroughly is paramount. The zebrafish (Danio rerio) is increasingly becoming a valuable model for studying human diseases and in screening for potential therapeutics. In this Review, we highlight recent progress in using zebrafish to study the pathology of the most common MNDs: spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS) and hereditary spastic paraplegia (HSP). These studies indicate the power of zebrafish as a model to study the consequences of disease-related genes, because zebrafish homologues of human genes have conserved functions with respect to the aetiology of MNDs. Zebrafish also complement other animal models for the study of pathological mechanisms of MNDs and are particularly advantageous for the screening of compounds with therapeutic potential. We present an overview of their potential usefulness in MND drug discovery, which is just beginning and holds much promise for future therapeutic development. PMID:24973750

Nurse-physician leadership: insights into interprofessional collaboration.

PubMed

Clark, Rebecca Culver; Greenawald, Mark

2013-12-01

The objective of this qualitative research study was to identify themes characterizing collaboration from the perspectives of nurses and physicians serving in complementary leadership roles in intensive and progressive care hospital units. Failures of communication are reported as a major cause of sentinel events. Most frequently, communication breakdown occurs between physicians and nurses. In this qualitative research study, taped interviews with nursing and medical unit directors (physicians) were analyzed for themes regarding factors influencing collaboration. Themes identified included the impact of organizational support, shared expectations, relationships, and communication. Findings of this study support the need for organizations and professionals to facilitate deliberate, structured interprofessional communication to advance collaboration between nurses and physicians.

Latent Cognitive Phenotypes in De Novo Parkinson's Disease: A Person-Centered Approach.

PubMed

LaBelle, Denise R; Walsh, Ryan R; Banks, Sarah J

2017-08-01

Cognitive impairment is an important aspect of Parkinson's disease (PD), but there is considerable heterogeneity in its presentation. This investigation aims to identify and characterize latent cognitive phenotypes in early PD. Latent class analysis, a data-driven, person-centered, cluster analysis was performed on cognitive data from the Parkinson's Progressive Markers Initiative baseline visit. This analytic method facilitates identification of naturally occurring endophenotypes. Resulting classes were compared across biomarker, symptom, and demographic data. Six cognitive phenotypes were identified. Three demonstrated consistent performance across indicators, representing poor ("Weak-Overall"), average ("Typical-Overall"), and strong ("Strong-Overall") cognition. The remaining classes demonstrated unique patterns of cognition, characterized by "Strong-Memory," "Weak-Visuospatial," and "Amnestic" profiles. The Amnestic class evidenced greater tremor severity and anosmia, but was unassociated with biomarkers linked with Alzheimer's disease. The Weak-Overall class was older and reported more non-motor features associated with cognitive decline, including anxiety, depression, autonomic dysfunction, anosmia, and REM sleep behaviors. The Strong-Overall class was younger, more female, and reported less dysautonomia and anosmia. Classes were unrelated to disease duration, functional independence, or available biomarkers. Latent cognitive phenotypes with focal patterns of impairment were observed in recently diagnosed individuals with PD. Cognitive profiles were found to be independent of traditional biomarkers and motoric indices of disease progression. Only globally impaired class was associated with previously reported indicators of cognitive decline, suggesting this group may drive the effects reported in studies using variable-based analysis. Longitudinal and neuroanatomical characterization of classes will yield further insight into the evolution of cognitive change in the disease. (JINS, 2017, 23, 551-563).

Solid State Division progress report for period ending March 31, 1997

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

Green, P.H.; Hinton, L.W.

1997-12-01

This report covers research progress in the Solid State Division from April 1, 1995, through March 31, 1997. During this period, the division conducted a broad, interdisciplinary materials research program in support of Department of Energy science and technology missions. The report includes brief summaries of research activities in condensed matter theory, neutron scattering, synthesis and characterization of materials, ion beam and laser processing, and the structure of solids and surfaces. An addendum includes listings of division publications and professional activities.

Genetic disorders with heterotopic ossificans

PubMed Central

Sankar, Ruthiramurthy; Gowrishankar, Kalpana; Viswanathan, Saraswati

2015-01-01

Fibrodysplasia ossificans progressiva (FOP) and progressive ossific heteroplasia (POH) are rare genetic disorders characterized by heterotopic bone formation leading to progressive loss of mobility and function. We report three cases of these rare disorders (two cases of FOP and one case of POH), which were clinically diagnosed and underwent genetic analysis. The aim of this report is to highlight the clinical features and the differences between these two conditions. We would also like to emphasize on the morbidity that can arise from unnecessary invasive investigations for diagnostic purposes. PMID:26015640

Chronic lymphadenopathic toxoplasmosis. A case with marked hyperglobulinemia and impaired delayed hypersensitivity responses during active infection.

PubMed

Sheagren, J N; Lunde, M N; Simon, H B

1976-02-01

A patient with lymphadenopathic toxoplasmosis characterized by prolonged symptoms and repeated relapses with isolation of toxoplasma from lymph nodes is described. As the disease persisted and progressed, striking immunologic changes occurred that ultimately resulted in a state of extreme hyperglobulinemia associated with impaired delayed hypersensitivity responses. The case in question illustrates that progressive infection may occur in the face of high antibody levels of all immunoglobulin types whereas the only demonstrable immunologic impairment was of delayed hypersensitivity.

Quarterly technical progress report, April-June 1982

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

None

1984-04-01

Progress reports are presented for the following tasks: (1) preparation of low-rank coals; application of liquefaction processes to low-rank coals; (2) slagging fixed-bed gasification; (3) atmospheric fluidized-bed combustion of low-rank coal; (4) ash fouling and combustion modification for low-rank coal; (5) combined flue gas cleanup/simultaneous SO/sub x/-NO/sub x/ control; (6) particulate control and hydrocarbons and trace element emissions from low-rank coals; (7) waste characterization and disposal; and (9) exploratory research.

Failure to thrive, interstitial lung disease, and progressive digital necrosis with onset in infancy.

PubMed

Chia, Justin; Eroglu, Fehime Kara; Özen, Seza; Orhan, Dicle; Montealegre-Sanchez, Gina; de Jesus, Adriana A; Goldbach-Mansky, Raphaela; Cowen, Edward W

2016-01-01

Key teaching points • SAVI is a recently described interferonopathy resulting from constitutive action of STING and up-regulation of IFN-β signaling. • SAVI is characterized by facial erythema with telangiectasia, acral/cold-sensitive tissue ulceration and amputations, and interstitial lung disease. It has overlapping features with Aicardi-Goutières syndrome and familial chilblain lupus. • Traditional immunosuppressive medications and biologic therapies appear to be of limited benefit, but JAK inhibitors may impact disease progression. Published by Elsevier Inc.

Genetics Home Reference: spinocerebellar ataxia type 6

MedlinePlus

... Twitter Home Health Conditions SCA6 Spinocerebellar ataxia type 6 Printable PDF Open All Close All Enable Javascript ... the expand/collapse boxes. Description Spinocerebellar ataxia type 6 ( SCA6 ) is a condition characterized by progressive problems ...

Hearing Loss Associated with Retinitis Pigmentosa. Short Reports.

ERIC Educational Resources Information Center

Karp, Adrienne

1985-01-01

The article describes a variation of Usher's Syndrome, a genetic condition characterized by visual and auditory impairments, in which moderate, postlingual, and sometimes progressive hearing impairments may go undetected. Identification guidelines are offered. (Author/CL)

Solid state division progress report, period ending February 29, 1980

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

Not Available

1980-09-01

Research is reported concerning theoretical solid state physics; surface and near-surface properties of solids; defects in solids; transport properties of solids; neutron scattering; crystal growth and characterization; and isotope research materials.

Endothelial necrosis at 1h post-burn predicts progression of tissue injury

PubMed Central

Hirth, Douglas; McClain, Steve A.; Singer, Adam J.; Clark, Richard A.F.

2013-01-01

Burn injury progression has not been well characterized at the cellular level. To define burn injury progression in terms of cell death, histopathologic spatiotemporal relationships of cellular necrosis and apoptosis were investigated in a validated porcine model of vertical burn injury progression. Cell necrosis was identified by High Mobility Group Box 1 protein and apoptosis by Caspase 3a staining of tissue samples taken 1h, 24h and 7 days post-burn. Level of endothelial cell necrosis at 1h was predictive of level of apoptosis at 24h (Pearson's r=0.87) and of level of tissue necrosis at 7 days (Pearson's r=0.87). Furthermore, endothelial cell necrosis was deeper than interstitial cell necrosis at 1h (p<0.001). Endothelial cell necrosis at 1h divided the zone of injury progression (Jackson's zone of stasis) into an upper subzone with necrotic endothelial cells and initially viable adnexal and interstitial cells at 1h that progressed to necrosis by 24h, and a lower zone with initially viable endothelial cells at 1h, but necrosis and apoptosis of all cell types by 24h. Importantly, this spatiotemporal series of events and rapid progression resembles myocardial infarction and stroke, and implicates mechanisms of these injuries, ischemia, ischemia reperfusion, and programmed cell death, in burn progression. PMID:23627744

Understanding aneuploidy in cancer through the lens of system inheritance, fuzzy inheritance and emergence of new genome systems.

PubMed

Ye, Christine J; Regan, Sarah; Liu, Guo; Alemara, Sarah; Heng, Henry H

2018-01-01

In the past 15 years, impressive progress has been made to understand the molecular mechanism behind aneuploidy, largely due to the effort of using various -omics approaches to study model systems (e.g. yeast and mouse models) and patient samples, as well as the new realization that chromosome alteration-mediated genome instability plays the key role in cancer. As the molecular characterization of the causes and effects of aneuploidy progresses, the search for the general mechanism of how aneuploidy contributes to cancer becomes increasingly challenging: since aneuploidy can be linked to diverse molecular pathways (in regards to both cause and effect), the chances of it being cancerous is highly context-dependent, making it more difficult to study than individual molecular mechanisms. When so many genomic and environmental factors can be linked to aneuploidy, and most of them not commonly shared among patients, the practical value of characterizing additional genetic/epigenetic factors contributing to aneuploidy decreases. Based on the fact that cancer typically represents a complex adaptive system, where there is no linear relationship between lower-level agents (such as each individual gene mutation) and emergent properties (such as cancer phenotypes), we call for a new strategy based on the evolutionary mechanism of aneuploidy in cancer, rather than continuous analysis of various individual molecular mechanisms. To illustrate our viewpoint, we have briefly reviewed both the progress and challenges in this field, suggesting the incorporation of an evolutionary-based mechanism to unify diverse molecular mechanisms. To further clarify this rationale, we will discuss some key concepts of the genome theory of cancer evolution, including system inheritance, fuzzy inheritance, and cancer as a newly emergent cellular system. Illustrating how aneuploidy impacts system inheritance, fuzzy inheritance and the emergence of new systems is of great importance. Such synthesis encourages efforts to apply the principles/approaches of complex adaptive systems to ultimately understand aneuploidy in cancer.

Improving the stability of coal slurries. Quarterly progress report, March 15-June 15, 1986. [Sedimentation tests in the presence and absence of gum tragacanth

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

Fogler, H.S.

1986-01-01

In this report, we will describe the progress of our research in two key areas. The twin objectives of this research are: (a) to examine the effectiveness of hydrocolloids as stabilizers of coal-water slurries and (b) to gain an understanding of the mechanism of stabilization through the use of monodisperse polystyrene lattices as model systems. Sedimentation tests with ultrafine ground coal in presence and absence of gum tragacanth have been carried out. An isotherm of gum tragacanth binding to coal surface has been generated. We have also conducted rheological studies to characterize the stabilized coal-water slurries. Similar experiments with -200more » mesh coal are currently under way. In the case of model system studies, the effect of article size on the gum tragacanth induced stability has been studied. Initial experiments on the effects of increased electrolyte concentration and the addition of nonsolvents like ethanol to the continuous phase have been undertaken. 9 refs., 16 figs., 1 tab.« less

Transcriptome profiles in sarcoidosis and their potential role in disease prediction.

PubMed

Schupp, Jonas C; Vukmirovic, Milica; Kaminski, Naftali; Prasse, Antje

2017-09-01

Sarcoidosis is a systemic disease defined by the presence of nonnecrotizing granuloma in the absence of any known cause. Although the heterogeneity of sarcoidosis is well characterized clinically, the transcriptome of sarcoidosis and underlying molecular mechanisms are not. The signal of all transcripts, small and long noncoding RNAs, can be detected using microarrays or RNA-Sequencing. Analyzing the transcriptome of tissues that are directly affected by granulomas is of great importance to understand biology of the disease and may be predictive of disease and treatment outcome. Multiple genome wide expression studies performed on sarcoidosis affected tissues were published in the last 11 years. Published studies focused on differences in gene expression between sarcoidosis vs. control tissues, stable vs. progressive sarcoidosis, as well as sarcoidosis vs. other diseases. Strikingly, all these transcriptomics data confirm the key role of TH1 immune response in sarcoidosis and particularly of interferon-γ (IFN-γ) and type I IFN-driven signaling pathways. The steps toward transcriptomics of sarcoidosis in precision medicine highlight the potentials of this approach. Large prospective follow-up studies are required to identify signatures predictive of disease progression and outcome.

Label-free SERS in biological and biomedical applications: Recent progress, current challenges and opportunities

NASA Astrophysics Data System (ADS)

Zheng, Xiao-Shan; Jahn, Izabella Jolan; Weber, Karina; Cialla-May, Dana; Popp, Jürgen

2018-05-01

To achieve an insightful look within biomolecular processes on the cellular level, the development of diseases as well as the reliable detection of metabolites and pathogens, a modern analytical tool is needed that is highly sensitive, molecular-specific and exhibits fast detection. Surface-enhanced Raman spectroscopy (SERS) is known to meet these requirements and, within this review article, the recent progress of label-free SERS in biological and biomedical applications is summarized and discussed. This includes the detection of biomolecules such as metabolites, nucleic acids and proteins. Further, the characterization and identification of microorganisms has been achieved by label-free SERS-based approaches. Eukaryotic cells can be characterized by SERS in order to gain information about the outer cell wall or to detect intracellular molecules and metabolites. The potential of SERS for medically relevant detection schemes is emphasized by the label-free detection of tissue, the investigation of body fluids as well as applications for therapeutic and illicit drug monitoring. The review article is concluded with an evaluation of the recent progress and current challenges in order to highlight the direction of label-free SERS in the future.

Alcoholic Liver Disease: Pathogenesis and Current Management

PubMed Central

Osna, Natalia A.; Donohue, Terrence M.; Kharbanda, Kusum K.

2017-01-01

Excessive alcohol consumption is a global healthcare problem. The liver sustains the greatest degree of tissue injury by heavy drinking because it is the primary site of ethanol metabolism. Chronic and excessive alcohol consumption produces a wide spectrum of hepatic lesions, the most characteristic of which are steatosis, hepatitis, and fibrosis/cirrhosis. Steatosis is the earliest response to heavy drinking and is characterized by the deposition of fat in hepatocytes. Steatosis can progress to steatohepatitis, which is a more severe, inflammatory type of liver injury. This stage of liver disease can lead to the development of fibrosis, during which there is excessive deposition of extracellular matrix proteins. The fibrotic response begins with active pericellular fibrosis, which may progress to cirrhosis, characterized by excessive liver scarring, vascular alterations, and eventual liver failure. Among problem drinkers, about 35 percent develop advanced liver disease because a number of disease modifiers exacerbate, slow, or prevent alcoholic liver disease progression. There are still no FDA-approved pharmacological or nutritional therapies for treating patients with alcoholic liver disease. Cessation of drinking (i.e., abstinence) is an integral part of therapy. Liver transplantation remains the life-saving strategy for patients with end-stage alcoholic liver disease. PMID:28988570

Temporal Characterization of Marburg Virus Angola Infection following Aerosol Challenge in Rhesus Macaques.

PubMed

Lin, Kenny L; Twenhafel, Nancy A; Connor, John H; Cashman, Kathleen A; Shamblin, Joshua D; Donnelly, Ginger C; Esham, Heather L; Wlazlowski, Carly B; Johnson, Joshua C; Honko, Anna N; Botto, Miriam A; Yen, Judy; Hensley, Lisa E; Goff, Arthur J

2015-10-01

Marburg virus (MARV) infection is a lethal hemorrhagic fever for which no licensed vaccines or therapeutics are available. Development of appropriate medical countermeasures requires a thorough understanding of the interaction between the host and the pathogen and the resulting disease course. In this study, 15 rhesus macaques were sequentially sacrificed following aerosol exposure to the MARV variant Angola, with longitudinal changes in physiology, immunology, and histopathology used to assess disease progression. Immunohistochemical evidence of infection and resulting histopathological changes were identified as early as day 3 postexposure (p.e.). The appearance of fever in infected animals coincided with the detection of serum viremia and plasma viral genomes on day 4 p.e. High (>10(7) PFU/ml) viral loads were detected in all major organs (lung, liver, spleen, kidney, brain, etc.) beginning day 6 p.e. Clinical pathology findings included coagulopathy, leukocytosis, and profound liver destruction as indicated by elevated liver transaminases, azotemia, and hypoalbuminemia. Altered cytokine expression in response to infection included early increases in Th2 cytokines such as interleukin 10 (IL-10) and IL-5 and late-stage increases in Th1 cytokines such as IL-2, IL-15, and granulocyte-macrophage colony-stimulating factor (GM-CSF). This study provides a longitudinal examination of clinical disease of aerosol MARV Angola infection in the rhesus macaque model. In this study, we carefully analyzed the timeline of Marburg virus infection in nonhuman primates in order to provide a well-characterized model of disease progression following aerosol exposure. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Longitudinal analysis of Prototheca zopfii-specific immune responses: correlation with disease progression and carriage in dairy cows.

PubMed

Roesler, Uwe; Hensel, Andreas

2003-03-01

In order to characterize the humoral and cellular immune responses to bovine mammary protothecosis, serum and whey samples obtained from 72 dairy cows assigned to four different clinical stages of infection were examined for specific antibodies by indirect enzyme-linked immunosorbent assay techniques. Milk samples were analyzed for the total numbers of excreted algal cells and somatic cells. After characterization of the course of immune induction in bovine protothecal mastitis, a long-term sentinel study was performed in an affected herd in order to investigate disease progression. A total of 61 dairy cows with protothecal mastitis were examined for shedding of algae cells and for local immune responses three times in 6-month intervals. During acute and chronic stages of protothecosis, significantly elevated specific antibody activities in sera were detected. A strong correlation of whey immunoglobulin A (IgA) and whey IgG1 antibody activity with the total counts of somatic cells in milk was observed, whereas only a weak correlation of whey IgA and whey IgG1 concentrations to the number of algal cells excreted with the milk was seen. Our results from the sentinel long-term study of infected cows revealed that 70.5% of the persistently infected animals were continuously shedding the pathogen. About 4.9% of the animals showed an intermittent shedding, whereas 18% of the cows were tested culturally negative throughout the study. It can be assumed that Prototheca zopfii mastitis in dairy cows is maintained on the herd level by subclinically infected alga-shedding cows.

Longitudinal Analysis of Prototheca zopfii-Specific Immune Responses: Correlation with Disease Progression and Carriage in Dairy Cows

PubMed Central

Roesler, Uwe; Hensel, Andreas

2003-01-01

In order to characterize the humoral and cellular immune responses to bovine mammary protothecosis, serum and whey samples obtained from 72 dairy cows assigned to four different clinical stages of infection were examined for specific antibodies by indirect enzyme-linked immunosorbent assay techniques. Milk samples were analyzed for the total numbers of excreted algal cells and somatic cells. After characterization of the course of immune induction in bovine protothecal mastitis, a long-term sentinel study was performed in an affected herd in order to investigate disease progression. A total of 61 dairy cows with protothecal mastitis were examined for shedding of algae cells and for local immune responses three times in 6-month intervals. During acute and chronic stages of protothecosis, significantly elevated specific antibody activities in sera were detected. A strong correlation of whey immunoglobulin A (IgA) and whey IgG1 antibody activity with the total counts of somatic cells in milk was observed, whereas only a weak correlation of whey IgA and whey IgG1 concentrations to the number of algal cells excreted with the milk was seen. Our results from the sentinel long-term study of infected cows revealed that 70.5% of the persistently infected animals were continuously shedding the pathogen. About 4.9% of the animals showed an intermittent shedding, whereas 18% of the cows were tested culturally negative throughout the study. It can be assumed that Prototheca zopfii mastitis in dairy cows is maintained on the herd level by subclinically infected alga-shedding cows. PMID:12624049

Gait and Functional Mobility Deficits in Fragile X-Associated Tremor/Ataxia Syndrome.

PubMed

O'Keefe, Joan A; Robertson-Dick, Erin E; Hall, Deborah A; Berry-Kravis, Elizabeth

2016-08-01

Fragile X-associated tremor/ataxia syndrome (FXTAS) results from a "premutation" (PM) size CGG repeat expansion in the fragile X mental retardation 1 (FMR1) gene. Cerebellar gait ataxia is the primary feature in some FXTAS patients causing progressive disability. However, no studies have quantitatively characterized gait and mobility deficits in FXTAS. We performed quantitative gait and mobility analysis in seven FMR1 PM carriers with FXTAS and ataxia, six PM carriers without FXTAS, and 18 age-matched controls. We studied four independent gait domains, trunk range of motion (ROM), and movement transitions using an instrumented Timed Up and Go (i-TUG). We correlated these outcome measures with FMR1 molecular variables and clinical severity scales. PM carriers with FXTAS were globally impaired in every gait performance domain except trunk ROM compared to controls. These included total i-TUG duration, stride velocity, gait cycle time, cadence, double-limb support and swing phase times, turn duration, step time before turn, and turn-to-sit duration, and increased gait variability on several measures. Carriers without FXTAS did not differ from controls on any parameters, but double-limb support time was close to significance. Balance and disability scales correlated with multiple gait and movement transition parameters, while the FXTAS Rating Scale did not. This is the first study to quantitatively examine gait and movement transitions in FXTAS patients. Gait characteristics were consistent with those from previous cohorts with cerebellar ataxia. Sensitive measures like the i-TUG may help determine efficacy of interventions, characterize disease progression, and provide early markers of disease in FXTAS.

3D Texture Analysis Reveals Imperceptible MRI Textural Alterations in the Thalamus and Putamen in Progressive Myoclonic Epilepsy Type 1, EPM1

PubMed Central

Suoranta, Sanna; Holli-Helenius, Kirsi; Koskenkorva, Päivi; Niskanen, Eini; Könönen, Mervi; Äikiä, Marja; Eskola, Hannu; Kälviäinen, Reetta; Vanninen, Ritva

2013-01-01

Progressive myoclonic epilepsy type 1 (EPM1) is an autosomal recessively inherited neurodegenerative disorder characterized by young onset age, myoclonus and tonic-clonic epileptic seizures. At the time of diagnosis, the visual assessment of the brain MRI is usually normal, with no major changes found later. Therefore, we utilized texture analysis (TA) to characterize and classify the underlying properties of the affected brain tissue by means of 3D texture features. Sixteen genetically verified patients with EPM1 and 16 healthy controls were included in the study. TA was performed upon 3D volumes of interest that were placed bilaterally in the thalamus, amygdala, hippocampus, caudate nucleus and putamen. Compared to the healthy controls, EPM1 patients had significant textural differences especially in the thalamus and right putamen. The most significantly differing texture features included parameters that measure the complexity and heterogeneity of the tissue, such as the co-occurrence matrix-based entropy and angular second moment, and also the run-length matrix-based parameters of gray-level non-uniformity, short run emphasis and long run emphasis. This study demonstrates the usability of 3D TA for extracting additional information from MR images. Textural alterations which suggest complex, coarse and heterogeneous appearance were found bilaterally in the thalamus, supporting the previous literature on thalamic pathology in EPM1. The observed putamenal involvement is a novel finding. Our results encourage further studies on the clinical applications, feasibility, reproducibility and reliability of 3D TA. PMID:23922849

Status of characterization techniques for carbon nanotubes and suggestions towards standards suitable for toxicological assessment

NASA Astrophysics Data System (ADS)

Schweinberger, Florian F.; Meyer-Plath, Asmus

2011-07-01

Nanotechnologies promise to contribute significantly to major technological challenges of the upcoming century. Despite profound scientific progress in the last decades, only minor advances have been made in the field of nanomaterial toxicology. The International Team in Nanosafety (TITNT) is an international and multidisciplinary group of scientists, which aims at better understanding the risks of nanomaterials. Carbon nanotubes (CNT) account for one of the most promising nanomaterials and have therefore been chosen as representative material for nanoscaled particles. They are currently investigated by the different platforms of TITNT. As a starting point, the present report summarizes a literature-based study on the physico-chemical properties of CNT, as they are closely linked with toxicological properties. A brief introduction to synthesis, purification and material properties is given. Characterization methods for CNT are discussed with respect to their reliability and the information content on chemical properties. Recommendations for a set of standard characterizations mandatory for toxicological assessment are derived.

Pharmaceutical aspects of salt and cocrystal forms of APIs and characterization challenges.

PubMed

Cerreia Vioglio, Paolo; Chierotti, Michele R; Gobetto, Roberto

2017-08-01

In recent years many efforts have been devoted to the screening and the study of new solid-state forms of old active pharmaceutical ingredients (APIs) with salification or co-crystallization processes, thus modulating final properties without changing the pharmacological nature. Salts, hydrates/solvates, and cocrystals are the common solid-state forms employed. They offer the intriguing possibility of exploring different pharmaceutical properties for a single API in the quest of enhancing the final drug product. New synthetic strategies and advanced characterization techniques have been recently proposed in this hot topic for pharmaceutical companies. This paper reviews the recent progresses in the field particularly focusing on the characterization challenges encountered when the nature of the solid-state form must be determined. The aim of this article is to offer the state-of-the-art on this subject in order to develop new insights and to promote cooperative efforts in the fascinating field of API salt and cocrystal forms. Copyright © 2017 Elsevier B.V. All rights reserved.

Characterization of bone microstructure using photoacoustic spectrum analysis

NASA Astrophysics Data System (ADS)

Feng, Ting; Kozloff, Kenneth M.; Xu, Guan; Du, Sidan; Yuan, Jie; Deng, Cheri X.; Wang, Xueding

2015-03-01

Osteoporosis is a progressive bone disease that is characterized by a decrease in bone mass and deterioration in microarchitecture. This study investigates the feasibility of characterizing bone microstructure by analyzing the frequency spectrum of the photoacoustic signals from the bone. Modeling and numerical simulation of photoacoustic signals and their frequency-domain analysis were performed on trabecular bones with different mineral densities. The resulting quasilinear photoacoustic spectra were fit by linear regression, from which spectral parameter slope can be quantified. The modeling demonstrates that, at an optical wavelength of 685 nm, bone specimens with lower mineral densities have higher slope. Preliminary experiment on osteoporosis rat tibia bones with different mineral contents has also been conducted. The finding from the experiment has a good agreement with the modeling, both demonstrating that the frequency-domain analysis of photoacoustic signals can provide objective assessment of bone microstructure and deterioration. Considering that photoacoustic measurement is non-ionizing, non-invasive, and has sufficient penetration in both calcified and noncalcified tissues, this new technology holds unique potential for clinical translation.

Characterization and treatment of chronic active Epstein-Barr virus disease: a 28-year experience in the United States.

PubMed

Cohen, Jeffrey I; Jaffe, Elaine S; Dale, Janet K; Pittaluga, Stefania; Heslop, Helen E; Rooney, Cliona M; Gottschalk, Stephen; Bollard, Catherine M; Rao, V Koneti; Marques, Adriana; Burbelo, Peter D; Turk, Siu-Ping; Fulton, Rachael; Wayne, Alan S; Little, Richard F; Cairo, Mitchell S; El-Mallawany, Nader K; Fowler, Daniel; Sportes, Claude; Bishop, Michael R; Wilson, Wyndham; Straus, Stephen E

2011-06-02

Chronic active EBV disease (CAEBV) is a lymphoproliferative disorder characterized by markedly elevated levels of antibody to EBV or EBV DNA in the blood and EBV RNA or protein in lymphocytes in tissues. We present our experience with CAEBV during the last 28 years, including the first 8 cases treated with hematopoietic stem cell transplantation in the United States. Most cases of CAEBV have been reported from Japan. Unlike CAEBV in Japan, where EBV is nearly always found in T or natural killer (NK) cells in tissues, EBV was usually detected in B cells in tissues from our patients. Most patients presented with lymphadenopathy and splenomegaly; fever, hepatitis, and pancytopenia were common. Most patients died of infection or progressive lymphoproliferation. Unlike cases reported from Japan, our patients often showed a progressive loss of B cells and hypogammaglobulinemia. Although patients with CAEBV from Japan have normal or increased numbers of NK cells, many of our patients had reduced NK-cell numbers. Although immunosuppressive agents, rituximab, autologous cytotoxic T cells, or cytotoxic chemotherapy often resulted in short-term remissions, they were not curative. Hematopoietic stem cell transplantation was often curative for CAEBV, even in patients with active lymphoproliferative disease that was unresponsive to chemotherapy. These studies are registered at http://www.clinicaltrials.gov as NCT00032513 for CAEBV, NCT00062868 and NCT00058812 for EBV-specific T-cell studies, and NCT00578539 for the hematopoietic stem cell transplantation protocol.

Characterization and treatment of chronic active Epstein-Barr virus disease: a 28-year experience in the United States

PubMed Central

Jaffe, Elaine S.; Dale, Janet K.; Pittaluga, Stefania; Heslop, Helen E.; Rooney, Cliona M.; Gottschalk, Stephen; Bollard, Catherine M.; Rao, V. Koneti; Marques, Adriana; Burbelo, Peter D.; Turk, Siu-Ping; Fulton, Rachael; Wayne, Alan S.; Little, Richard F.; Cairo, Mitchell S.; El-Mallawany, Nader K.; Fowler, Daniel; Sportes, Claude; Bishop, Michael R.; Wilson, Wyndham; Straus, Stephen E.

2011-01-01

Chronic active EBV disease (CAEBV) is a lymphoproliferative disorder characterized by markedly elevated levels of antibody to EBV or EBV DNA in the blood and EBV RNA or protein in lymphocytes in tissues. We present our experience with CAEBV during the last 28 years, including the first 8 cases treated with hematopoietic stem cell transplantation in the United States. Most cases of CAEBV have been reported from Japan. Unlike CAEBV in Japan, where EBV is nearly always found in T or natural killer (NK) cells in tissues, EBV was usually detected in B cells in tissues from our patients. Most patients presented with lymphadenopathy and splenomegaly; fever, hepatitis, and pancytopenia were common. Most patients died of infection or progressive lymphoproliferation. Unlike cases reported from Japan, our patients often showed a progressive loss of B cells and hypogammaglobulinemia. Although patients with CAEBV from Japan have normal or increased numbers of NK cells, many of our patients had reduced NK-cell numbers. Although immunosuppressive agents, rituximab, autologous cytotoxic T cells, or cytotoxic chemotherapy often resulted in short-term remissions, they were not curative. Hematopoietic stem cell transplantation was often curative for CAEBV, even in patients with active lymphoproliferative disease that was unresponsive to chemotherapy. These studies are registered at http://www.clinicaltrials.gov as NCT00032513 for CAEBV, NCT00062868 and NCT00058812 for EBV-specific T-cell studies, and NCT00578539 for the hematopoietic stem cell transplantation protocol. PMID:21454450

Complement anaphylatoxins as immune regulators in cancer.

PubMed

Sayegh, Eli T; Bloch, Orin; Parsa, Andrew T

2014-08-01

The role of the complement system in innate immunity is well characterized. However, a recent body of research implicates the complement anaphylatoxins C3a and C5a as insidious propagators of tumor growth and progression. It is now recognized that certain tumors elaborate C3a and C5a and that complement, as a mediator of chronic inflammation and regulator of immune function, may in fact foster rather than defend against tumor growth. A putative mechanism for this function is complement-mediated suppression of immune effector cells responsible for immunosurveillance within the tumor microenvironment. This paradigm accords with models of immune dysregulation, such as autoimmunity and infectious disease, which have defined a pathophysiological role for abnormal complement signaling. Several types of immune cells express the cognate receptors for the complement anaphylatoxins, C3aR and C5aR, and demonstrate functional modulation in response to complement stimulation. In turn, impairment of antitumor immunity has been intimately tied to tumor progression in animal models of cancer. In this article, the literature was systematically reviewed to identify studies that have characterized the effects of the complement anaphylatoxins on the composition and function of immune cells within the tumor microenvironment. The search identified six studies based upon models of lymphoma and ovarian, cervical, lung, breast, and mammary cancer, which collectively support the paradigm of complement as an immune regulator in the tumor microenvironment. © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

The Potential Utility of Eye Movements in the Detection and Characterization of Everyday Functional Difficulties in Mild Cognitive Impairment.

PubMed

Seligman, Sarah C; Giovannetti, Tania

2015-06-01

Mild cognitive impairment (MCI) refers to the intermediate period between the typical cognitive decline of normal aging and more severe decline associated with dementia, and it is associated with greater risk for progression to dementia. Research has suggested that functional abilities are compromised in MCI, but the degree of impairment and underlying mechanisms remain poorly understood. The development of sensitive measures to assess subtle functional decline poses a major challenge for characterizing functional limitations in MCI. Eye-tracking methodology has been used to describe visual processes in everyday, naturalistic action among healthy older adults as well as several case studies of severely impaired individuals, and it has successfully differentiated healthy older adults from those with MCI on specific visual tasks. These studies highlight the promise of eye-tracking technology as a method to characterize subtle functional decline in MCI. However, to date no studies have examined visual behaviors during completion of naturalistic tasks in MCI. This review describes the current understanding of functional ability in MCI, summarizes findings of eye-tracking studies in healthy individuals, severe impairment, and MCI, and presents future research directions to aid with early identification and prevention of functional decline in disorders of aging.

Coexistence of Eph receptor B1 and ephrin B2 in port-wine stain endothelial progenitor cells contributes to clinicopathological vasculature dilatation.

PubMed

Tan, W; Wang, J; Zhou, F; Gao, L; Yin, R; Liu, H; Sukanthanag, A; Wang, G; Mihm, M C; Chen, D-B; Nelson, J S

2017-12-01

Port-wine stain (PWS) is a vascular malformation characterized by progressive dilatation of postcapillary venules, but the molecular pathogenesis remains obscure. To illustrate that PWS endothelial cells (ECs) present a unique molecular phenotype that leads to pathoanatomical PWS vasculatures. Immunohistochemistry and transmission electron microscopy were used to characterize the ultrastructure and molecular phenotypes of PWS blood vessels. Primary culture of human dermal microvascular endothelial cells and in vitro tube formation assay were used for confirmative functional studies. Multiple clinicopathological features of PWS blood vessels during the development and progression of the disease were shown. There were no normal arterioles and venules observed phenotypically and morphologically in PWS skin; arterioles and venules both showed differentiation impairments, resulting in a reduction of arteriole-like vasculatures and defects in capillary loop formation in PWS lesions. PWS ECs showed stemness properties with expression of endothelial progenitor cell markers CD133 and CD166 in non-nodular lesions. They also expressed dual venous/arterial identities, Eph receptor B1 (EphB1) and ephrin B2 (EfnB2). Co-expression of EphB1 and EfnB2 in normal human dermal microvascular ECs led to the formation of PWS-like vasculatures in vitro, for example larger-diameter and thick-walled capillaries. PWS ECs are differentiation-impaired, late-stage endothelial progenitor cells with a specific phenotype of CD133 + /CD166 + /EphB1 + /EfnB2 + , which form immature venule-like pathoanatomical vasculatures. The disruption of normal EC-EC interactions by coexistence of EphB1 and EfnB2 contributes to progressive dilatation of PWS vasculatures. © 2017 British Association of Dermatologists.

Disease Progression Modeling to Evaluate the Effects of Enzyme Replacement Therapy on Kidney Function in Adult Patients with the Classic Phenotype of Fabry Disease.

PubMed

Nowak, Albina; Koch, Gilbert; Huynh-Do, Uyen; Siegenthaler, Martin; Marti, Hans-Peter; Pfister, Marc

2017-01-01

Fabry disease (FD) is a rare inherited lysosomal storage disease with common and serious kidney complications. Enzyme replacement therapies (ERT) with agalsidase-α and -β were investigated to characterize their therapeutic effect on kidney function in FD patients with Classic phenotype. The prospective FD cohort consisted of 98 genetically confirmed patients (females, n = 61, males, n = 37). The median [interquartile range] follow-up time (time difference from first to last visit) was 9 [6, 12] years. The median age of ERT start was 36 [21 - 54] years for females and 39 [28 - 49] years for males. A disease progression model was developed to (i) characterize the time course of estimated glomerular filtration rate (eGFR) and (ii) evaluate therapeutic effects of ERT on kidney function. Change in eGFR over time was best described by the linear model. Females had stable kidney function with and without ERT (eGFR slopes of -0.07 ml/min/1.73m^2 per year and 0.52 ml/min/1.73m^2 per year, respectively). Males with ERT showed an eGFR decrease of -3.07 ml/min/1.73m^2 per year. Mathematical disease progression modeling indicates that there is no clear therapeutic effect of ERT on kidney function in adult patients with Classic Phenotype of FD. Interpretation of these findings should take into account that the study is not randomized and lacks a placebo controlled group. Further investigations are warranted to clarify whether earlier ERT initiation before 18 years of age, higher ERT dose or more intensive therapies can preserve kidney function. © 2017 The Author(s)Published by S. Karger AG, Basel.

Presentation and progression of childhood-onset inflammatory bowel disease in Northern Stockholm County.

PubMed

Malmborg, Petter; Grahnquist, Lena; Ideström, Maja; Lindholm, Johan; Befrits, Ragnar; Björk, Jan; Montgomery, Scott; Hildebrand, Hans

2015-05-01

Some studies have suggested that childhood-onset inflammatory bowel disease (IBD) is characterized by extensive intestinal involvement and rapid progression to complications. Here, we report the presentation and progression of patients diagnosed with IBD during childhood in a population-based cohort from northern Stockholm County. Medical records for all 280 patients diagnosed in the period 1990-2007 with childhood-onset IBD in northern Stockholm County were followed until 2011 (median follow-up time, 8.8 yr). Disease phenotypes were classified according to the Paris pediatric IBD classification. Among the 74 patients with ulcerative colitis, 72% presented with pancolitis. Among the 200 patients with Crohn's disease (CD), 75% presented with colitis. Complicated disease behavior was observed in 18% of patients with CD by end of follow-up. Extension of the disease territory was observed in 22% of patients with ulcerative colitis and 15% of patients with CD. The cumulative risk of intra-abdominal surgery after 10 years was 8% (95% confidence interval, 4%-20%) for ulcerative colitis and 22% (95% confidence interval, 15%-28%) for patients with CD. Nonmucosal healing at 1 year was associated with a complicated disease course in patients with CD (hazard ratio = 14.56; 95% confidence interval, 1.79-118.68; P = 0.01). Patients with childhood-onset IBD were characterized by extensive colitis that was relatively stable over time and associated with a relatively low risk of complications and abdominal surgery. Our findings confirm the more extensive disease location in pediatric IBD but did not identify the proposed dynamic and aggressive nature of the childhood-onset phenotype. The association of nonmucosal healing with a complicated disease course suggests that endoscopy should guide treatment intensity in childhood-onset CD.

Color Doppler imaging of the retrobulbar vessels in diabetic retinopathy.

PubMed

Pauk-Domańska, Magdalena; Walasik-Szemplińska, Dorota

2014-03-01

Diabetes is a metabolic disease characterized by elevated blood glucose level due to impaired insulin secretion and activity. Chronic hyperglycemia leads to functional disorders of numerous organs and to their damage. Vascular lesions belong to the most common late complications of diabetes. Microangiopathic lesions can be found in the eyeball, kidneys and nervous system. Macroangiopathy is associated with coronary and peripheral vessels. Diabetic retinopathy is the most common microangiopathic complication characterized by closure of slight retinal blood vessels and their permeability. Despite intensive research, the pathomechanism that leads to the development and progression of diabetic retinopathy is not fully understood. The examinations used in assessing diabetic retinopathy usually involve imaging of the vessels in the eyeball and the retina. Therefore, the examinations include: fluorescein angiography, optical coherence tomography of the retina, B-mode ultrasound imaging, perimetry and digital retinal photography. There are many papers that discuss the correlations between retrobulbar circulation alterations and progression of diabetic retinopathy based on Doppler sonography. Color Doppler imaging is a non-invasive method enabling measurements of blood flow velocities in small vessels of the eyeball. The most frequently assessed vessels include: the ophthalmic artery, which is the first branch of the internal carotid artery, as well as the central retinal vein and artery, and the posterior ciliary arteries. The analysis of hemodynamic alterations in the retrobulbar vessels may deliver important information concerning circulation in diabetes and help to answer the question whether there is a relation between the progression of diabetic retinopathy and the changes observed in blood flow in the vessels of the eyeball. This paper presents the overview of literature regarding studies on blood flow in the vessels of the eyeball in patients with diabetic retinopathy.

Can cannabinoids be a potential therapeutic tool in amyotrophic lateral sclerosis?

PubMed

Giacoppo, Sabrina; Mazzon, Emanuela

2016-12-01

Amyotrophic lateral sclerosis (ALS) is the most common degenerative disease of the motor neuron system. Over the last years, a growing interest was aimed to discovery new innovative and safer therapeutic approaches in the ALS treatment. In this context, the bioactive compounds of Cannabis sativa have shown antioxidant, anti-inflammatory and neuroprotective effects in preclinical models of central nervous system disease. However, most of the studies proving the ability of cannabinoids in delay disease progression and prolong survival in ALS were performed in animal model, whereas the few clinical trials that investigated cannabinoids-based medicines were focused only on the alleviation of ALS-related symptoms, not on the control of disease progression. The aim of this report was to provide a short but important overview of evidences that are useful to better characterize the efficacy as well as the molecular pathways modulated by cannabinoids.

The James Webb Space Telescope and its Potential for Exoplanet Science

NASA Technical Reports Server (NTRS)

Clampin, Mark

2008-01-01

The James Webb Space Telescope (JWST) is a large aperture (6.5 meter), cryogenic space telescope with a suite of near and mid-infrared instruments covering the wavelength range of 0.6 microns to 28 microns. JWST s primary science goal is to detect and characterize the first galaxies. It will also study the assembly of galaxies, star formation, and the formation of evolution of planetary systems. Recent progress in hardware development for the observatory will be presented, including a discussion of the status of JWST s optical system and Beryllium mirror fabrication, progress with sunshield prototypes, and recent changes in the integration and test configuration. We also review the expected scientific performance of the observatory for observations of exosolar planets by means of transit imaging and spectroscopy and direct imaging. We also review the recent discovery of Fomalhaut B and implications for debris disk imaging nd exoplanet detection with JWST.

Postmenopausal frontal fibrosing alopecia.

PubMed

Naz, E; Vidaurrázaga, C; Hernández-Cano, N; Herranz, P; Mayor, M; Hervella, M; Casado, M

2003-01-01

Recently a new entity, postmenopausal frontal fibrosing alopecia, was added to the established subtypes of scarring alopecias affecting postmenopausal women. This condition is characterized by a progressive frontal hairline recession associated with scarring. We studied the clinical and histopathologic features in four women with this disorder. Of note, a history of bilateral oophorectomy in two of them appears to be a new association. All four cases had frontoparietal recession of the hairline and two of them also had loss of their eyebrows. None of our four patients had any mucous membrane or other skin lesions. Histological examination showed perifollicular fibrosis and lymphocytic inflammation around the isthmus and infundibular areas of the follicles. No effective treatments have emerged for this type of postmenopausal alopecia, but progression of the hair loss and scarring appears to be self-limiting. We believe that this condition is a distinct clinicopathological variant of lichen planopilaris.

No exonic mutations at GJB2, GJB3, GJB4, GJB6, ARS (Component B), and LOR genes responsible for a Chinese patient affected by progressive symmetric erythrokeratodermia with pseudoainhum.

PubMed

Zhou, Fusheng; Fu, Hongyang; Liu, Linghua; Cui, Yong; Zhang, Zhengzhong; Chang, Ruixue; Yue, Zhen; Yang, Sen; Zhang, Xuejun

2014-09-01

Progressive symmetric erythrokeratodermia (PSEK) is characterized by symmetric and growing erythematous hyperkeratotic patches over the body shortly after birth, particularly trunk and limbs, the buttocks, and the face, sometimes together with palmoplantar keratoderma (PPK). The GJB2, GJB3, GJB4, GJB6, ARS (Component B), and LOR gene mutation might contribute to PSEK manifestation. This study aimed to identify sequence alteration of these genes in a Chinese PSEK patient with pseudoainhum. Genomic DNA was purified from the patient's peripheral blood. Mutation analysis of target genes was performed by direct sequencing using ABI 3730 sequencer No exonic mutations was identified in the aforementioned genes. The result underlines the genetic heterogeneity of PSEK and other related erythrokeratodermas. © 2014 The International Society of Dermatology.

Recent advances in the neurobiology and neuropharmacology of Alzheimer's disease.

PubMed

Kumar, Kushal; Kumar, Ashwani; Keegan, Richard M; Deshmukh, Rahul

2018-02-01

Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by progressive deterioration of cognitive functions. The pathological hallmarks are extracellular deposits of amyloid plaques and intracellular neurofibrillary tangles of tau protein. The cognitive deficits seen are thought to be due to synaptic dysfunction and neurochemical deficiencies. Various neurochemical abnormalities have been observed during progressive ageing, and are linked to cognitive abnormalities as seen with the sporadic form of AD. Acetylcholinesterase inhibitors are one of the major therapeutic strategies used for the treatment of AD. During the last decade, various new therapeutic strategies have shown beneficial effects in preclinical studies and under clinical development for the treatment of AD. The present review is aimed at discussing the neurobiology of AD and association of neurochemical abnormalities associated with cognitive deterioration and new therapeutic strategies for the treatment of AD. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

The evolutionary diversity of insect retinal mosaics: Common design principles and emerging molecular logic

PubMed Central

Wernet, Mathias F.; Perry, Michael W.; Desplan, Claude

2015-01-01

Independent evolution has resulted in a vast diversity of eyes. Despite the lack of a common Bauplan or ancestral structure, similar developmental strategies are used. For instance, different classes of photoreceptor cells (PRs) are distributed stochastically and/or localized in different regions of the retina. Here we focus on recent progress made towards understanding the molecular principles behind patterning retinal mosaics of insects, one of the most diverse groups of animals adapted to life on land, in the air, under water, or on the water surface. Morphological, physiological, and behavioral studies from many species provide detailed descriptions of the vast variation in retinal design and function. By integrating this knowledge with recent progress in the characterization of insect Rhodopsins as well as insight from the model organism Drosophila melanogaster, we seek to identify the molecular logic behind the adaptation of retinal mosaics to an animal’s habitat and way of life. PMID:26025917

Common Drugs for Stabilization of Renal Function in the Progression of Diabetic Nephropathy and Their Relations with Hypertension Therapy.

PubMed

Wang, Yuxuan; Wang, Chengcheng; Zhang, Xiuli; Gu, Harvest F; Wu, Liang

2018-01-01

Diabetic nephropathy is characterized by hypertension, progressive albuminuria, glomerulosclerosis and declines in glomerular filtration rate leading to end stage renal disease. Although the pathogenesis of diabetic nephropathy is not fully understood, current treatment of the patients with diabetic nephropathy is mainly based upon the control of hyperglycaemia and management of blood pressures. Several drugs, which are originally developed for hypertension therapy, have been adopted for stabilization of renal function in diabetic nephropathy. In this review, we first discussed the relationships between diabetic nephropathy and hypertension particularly in the renin-angiotensinaldosterone system. We then summarized chemical structures, pharmacological characteristics and clinical studies of the common drugs used for treatment of diabetic nephropathy, while these drugs have effects against hypertension. This review may provide the constructive information for further drug development in diabetic nephropathy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Segmentation and classification of cell cycle phases in fluorescence imaging.

PubMed

Ersoy, Ilker; Bunyak, Filiz; Chagin, Vadim; Cardoso, M Christina; Palaniappan, Kannappan

2009-01-01

Current chemical biology methods for studying spatiotemporal correlation between biochemical networks and cell cycle phase progression in live-cells typically use fluorescence-based imaging of fusion proteins. Stable cell lines expressing fluorescently tagged protein GFP-PCNA produce rich, dynamically varying sub-cellular foci patterns characterizing the cell cycle phases, including the progress during the S-phase. Variable fluorescence patterns, drastic changes in SNR, shape and position changes and abundance of touching cells require sophisticated algorithms for reliable automatic segmentation and cell cycle classification. We extend the recently proposed graph partitioning active contours (GPAC) for fluorescence-based nucleus segmentation using regional density functions and dramatically improve its efficiency, making it scalable for high content microscopy imaging. We utilize surface shape properties of GFP-PCNA intensity field to obtain descriptors of foci patterns and perform automated cell cycle phase classification, and give quantitative performance by comparing our results to manually labeled data.

Potential Modes of Intercellular α-Synuclein Transmission

PubMed Central

Valdinocci, Dario; Radford, Rowan A. W.; Siow, Sue Maye; Chung, Roger S.; Pountney, Dean L.

2017-01-01

Intracellular aggregates of the α-synuclein protein result in cell loss and dysfunction in Parkinson’s disease and atypical Parkinsonism, such as multiple system atrophy and dementia with Lewy bodies. Each of these neurodegenerative conditions, known collectively as α-synucleinopathies, may be characterized by a different suite of molecular triggers that initiate pathogenesis. The mechanisms whereby α-synuclein aggregates mediate cytotoxicity also remain to be fully elucidated. However, recent studies have implicated the cell-to-cell spread of α-synuclein as the major mode of disease propagation between brain regions during disease progression. Here, we review the current evidence for different modes of α-synuclein cellular release, movement and uptake, including exocytosis, exosomes, tunneling nanotubes, glymphatic flow and endocytosis. A more detailed understanding of the major modes by which α-synuclein pathology spreads throughout the brain may provide new targets for therapies that halt the progression of disease. PMID:28241427

Potential Modes of Intercellular α-Synuclein Transmission.

PubMed

Valdinocci, Dario; Radford, Rowan A W; Siow, Sue Maye; Chung, Roger S; Pountney, Dean L

2017-02-22

Intracellular aggregates of the α-synuclein protein result in cell loss and dysfunction in Parkinson's disease and atypical Parkinsonism, such as multiple system atrophy and dementia with Lewy bodies. Each of these neurodegenerative conditions, known collectively as α-synucleinopathies, may be characterized by a different suite of molecular triggers that initiate pathogenesis. The mechanisms whereby α-synuclein aggregates mediate cytotoxicity also remain to be fully elucidated. However, recent studies have implicated the cell-to-cell spread of α-synuclein as the major mode of disease propagation between brain regions during disease progression. Here, we review the current evidence for different modes of α-synuclein cellular release, movement and uptake, including exocytosis, exosomes, tunneling nanotubes, glymphatic flow and endocytosis. A more detailed understanding of the major modes by which α-synuclein pathology spreads throughout the brain may provide new targets for therapies that halt the progression of disease.

ATMOSPHERIC AEROSOL SOURCE-RECEPTOR RELATIONSHIPS: THE ROLE OF COAL-FIRED POWER PLANTS

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

Allen L. Robinson; Spyros N. Pandis; Cliff I. Davidson

2004-12-01

This report describes the technical progress made on the Pittsburgh Air Quality Study (PAQS) during the period of March 2004 through August 2004. Significant progress was made this project period on the analysis of ambient data, source apportionment, and deterministic modeling activities. Results highlighted in this report include evaluation of the performance of PMCAMx+ for an air pollution episode in the Eastern US, an emission profile for a coke production facility, ultrafine particle composition during a nucleation event, and a new hybrid approach for source apportionment. An agreement was reached with a utility to characterize fine particle and mercury emissionsmore » from a commercial coal fired power. Research in the next project period will include source testing of a coal fired power plant, source apportionment analysis, emission scenario modeling with PMCAMx+, and writing up results for submission as journal articles.« less

Dark Agouti rat model of chemotherapy-induced mucositis: establishment and current state of the art.

PubMed

Vanhoecke, Barbara; Bateman, Emma; Mayo, Bronwen; Vanlancker, Eline; Stringer, Andrea; Thorpe, Daniel; Keefe, Dorothy

2015-06-01

Mucositis is a major oncological problem. The entire gastrointestinal and genitourinary tract and also other mucosal surfaces can be affected in recipients of radiotherapy, and/or chemotherapy. Major progress has been made in recent years in understanding the mechanisms of oral and small intestinal mucositis, which appears to be more prominent than colonic damage. This progress is largely due to the development of representative laboratory animal models of mucositis. This review focuses on the development and establishment of the Dark Agouti rat mammary adenocarcinoma model by the Mucositis Research Group of the University of Adelaide over the past 20 years to characterize the mechanisms underlying methotrexate-, 5-fluorouracil-, and irinotecan-induced mucositis. It also aims to summarize the results from studies using different animal model systems to identify new molecular and cellular markers of mucositis. © 2015 by the Society for Experimental Biology and Medicine.

Decoy receptor 3 inhibits renal mononuclear leukocyte infiltration and apoptosis and prevents progression of IgA nephropathy in mice.

PubMed

Ka, Shuk-Man; Hsieh, Tai-Tzu; Lin, Shih-Hua; Yang, Sung-Sen; Wu, Chin-Chen; Sytwu, Huey-Kang; Chen, Ann

2011-12-01

The progression of IgA nephropathy (IgAN), the most frequent type of primary glomerulonephritis, is associated with high levels of mononuclear leukocyte infiltration into the kidney. These cells consist mainly of T cells and macrophages. Our previous study showed that a decoy receptor 3 (DCR3) gene therapy can prevent the development of a mouse autoimmune glomerulonephritis model by its potent immune modulating effects (Ka SM, Sytwu HK, Chang DM, Hsieh SL, Tsai PY, Chen A. J Am Soc Nephrol 18: 2473-2485, 2007). Here, we tested the hypothesis that DCR3 might prevent the progression of IgAN, an immune complex-mediated primary glomerulonephritis, by inhibiting T cell activation, renal T cell/macrophage infiltration, and protecting the kidney from apoptosis. We used a progressive IgAN (Prg-IgAN) model in B cell-deficient mice, because the mice are characterized by a dramatic proliferation of activated T cells systemically and progressive NF-κB activation in the kidney. We treated the animals with short-term gene therapy with DCR3 plasmids by hydrodynamics-based gene delivery. When the mice were euthanized on day 21, we found that, compared with empty vector-treated (disease control) Prg-IgAN mice, DCR3 gene therapy resulted in 1) systemic inhibition of T cell activation and proliferation; 2) lower serum levels of proinflammatory cytokines; 3) improved proteinuria, renal function, and renal pathology (inhibiting the development of marked glomerular proliferation, crescent formation, glomerulosclerosis, and interstitial inflammation); 5) suppression of T cell and macrophage infiltration into the periglomerular interstitium of the kidney; and 5) a reduction in apoptotic figures in the kidney. On the basis of these findings, DCR3 might be useful therapeutically in preventing the progression of IgAN.

Monitoring progression of clinical reasoning skills during health sciences education using the case method - a qualitative observational study.

PubMed

Orban, Kristina; Ekelin, Maria; Edgren, Gudrun; Sandgren, Olof; Hovbrandt, Pia; Persson, Eva K

2017-09-11

Outcome- or competency-based education is well established in medical and health sciences education. Curricula are based on courses where students develop their competences and assessment is also usually course-based. Clinical reasoning is an important competence, and the aim of this study was to monitor and describe students' progression in professional clinical reasoning skills during health sciences education using observations of group discussions following the case method. In this qualitative study students from three different health education programmes were observed while discussing clinical cases in a modified Harvard case method session. A rubric with four dimensions - problem-solving process, disciplinary knowledge, character of discussion and communication - was used as an observational tool to identify clinical reasoning. A deductive content analysis was performed. The results revealed the students' transition over time from reasoning based strictly on theoretical knowledge to reasoning ability characterized by clinical considerations and experiences. Students who were approaching the end of their education immediately identified the most important problem and then focused on this in their discussion. Practice knowledge increased over time, which was seen as progression in the use of professional language, concepts, terms and the use of prior clinical experience. The character of the discussion evolved from theoretical considerations early in the education to clinical reasoning in later years. Communication within the groups was supportive and conducted with a professional tone. Our observations revealed progression in several aspects of students' clinical reasoning skills on a group level in their discussions of clinical cases. We suggest that the case method can be a useful tool in assessing quality in health sciences education.

Developmental Trajectories of Body Mass Index Among Japanese Children and Impact of Maternal Factors during Pregnancy

PubMed Central

Haga, Chiyori; Kondo, Naoki; Suzuki, Kohta; Sato, Miri; Ando, Daisuke; Yokomichi, Hiroshi; Tanaka, Taichiro; Yamagata, Zentaro

2012-01-01

Background The aims of this study were to 1) determine the distinct patterns of body mass index (BMI) trajectories in Japanese children, and 2) elucidate the maternal factors during pregnancy, which contribute to the determination of those patterns. Methodology/Principal Findings All of the children (1,644 individuals) born in Koshu City, Japan, between 1991 and 1998 were followed in a longitudinal study exploring the subjects’ BMI. The BMI was calculated 11 times for each child between birth and 12 years of age. Exploratory latent class growth analyses were conducted to identify trajectory patterns of the BMI z-scores. The distribution of BMI trajectories were best characterized by a five-group model for boys and a six-group model for girls. The groups were named “stable thin,” “stable average,” “stable high average,” “progressive overweight,” and “progressive obesity” in both sexes; girls were allocated to an additional group called “progressive average.” Multinomial logistic regression found that maternal weight, smoking, and skipping breakfast during pregnancy were associated with children included in the progressive obesity pattern rather than the stable average pattern. These associations were stronger for boys than for girls. Conclusions/Significance Multiple developmental patterns in Japanese boys and girls were identified, some of which have not been identified in Western countries. Maternal BMI and some unfavorable behaviors during early pregnancy may impact a child’s pattern of body mass development. Further studies to explain the gender and regional differences that were identified are warranted, as these may be important for early life prevention of weight-associated health problems. PMID:23272187

Fibromyalgia with severe forms of progression in a multidisciplinary therapy setting with emphasis on hyperthermia therapy--a prospective controlled study.

PubMed

Romeyke, Tobias; Scheuer, Hans Christoph; Stummer, Harald

2015-01-01

Fibromyalgia syndrome (FMS) is a multi-factorial disease involving physiological as well as psychological factors. The aim of the study was to investigate a multidisciplinary inpatient treatment with emphasis on hyperthermia therapy by patients with widespread pain. The study involved 104 patients suffering from severely progressive FMS. A convenience sample and a prospective cohort design were used. The patients were treated in an acute hospital focusing on rheumatologic pain therapy and multidisciplinary complementary medicine. One patient group was treated with inclusion of hyperthermia therapy and the other group without. The therapy density (number of performed therapies per patient) was determined for every patient. Functional capacity measured by the Hannover functional status questionnaire (Funktionsfragebogen Hannover) and symptoms (von Zerssen complaint list) were analyzed for both groups on admission and on discharge. On admission, no significant difference could be established between control group (CG; multimodal without hyperthermia) and hyperthermia group (HG; multimodal with hyperthermia) (functional capacity, P=0.936). Functional capacity improved for the CG and the HG. On discharge, there was a significant difference between the two groups (functional capacity, P=0.039). There were no significant differences in fibromyalgia symptoms between CG (mean 41.8) and HG (mean 41.8) on their admission to hospital (P=0.988). On discharge, there was a significant difference (P=0.024) between the two groups (HG, mean 30.6; CG, mean 36.6). The inpatient therapy of patients with severely progressive fibromyalgia is characterized by a high frequency of therapy input. FMS, especially with severe progression and a high degree of chronification, demands a multidisciplinary approach. In addition to the use of complementary medical procedures, integration of hyperthermia in the treatment process is a useful option.

Aldehydic load and aldehyde dehydrogenase 2 profile during the progression of post-myocardial infarction cardiomyopathy: benefits of Alda-1

PubMed Central

Gomes, Katia M.S.; Bechara, Luiz R.G.; Lima, Vanessa M.; Ribeiro, Márcio A.C.; Campos, Juliane C.; Dourado, Paulo M.; Kowaltowski, Alicia J.; Mochly-Rosen, Daria; Ferreira, Julio C.B.

2015-01-01

Background/Objectives We previously demonstrated that reducing cardiac aldehydic load by aldehyde dehydrogenase 2 (ALDH2), a mitochondrial enzyme responsible for metabolizing the major lipid peroxidation product, protects against acute ischemia/reperfusion injury and chronic heart failure. However, time-dependent changes in ALDH2 profile, aldehydic load and mitochondrial bioenergetics during progression of post-myocardial infarction (post-MI) cardiomyopathy is unknown and should be established to determine the optimal time window for drug treatment. Methods Here we characterized cardiac ALDH2 activity and expression, lipid peroxidation, 4-hydroxy-2-nonenal (4-HNE) adduct formation, glutathione pool and mitochondrial energy metabolism and H2O2 release during the 4 weeks after permanent left anterior descending (LAD) coronary artery occlusion in rats. Results We observed a sustained disruption of cardiac mitochondrial function during the progression of post-MI cardiomyopathy, characterized by >50% reduced mitochondrial respiratory control ratios and up to 2 fold increase in H2O2 release. Mitochondrial dysfunction was accompanied by accumulation of cardiac and circulating lipid peroxides and 4-HNE protein adducts and down-regulation of electron transport chain complexes I and V. Moreover, increased aldehydic load was associated with a 90% reduction in cardiac ALDH2 activity and increased glutathione pool. Further supporting an ALDH2 mechanism, sustained Alda-1 treatment (starting 24hrs after permanent LAD occlusion surgery) prevented aldehydic overload, mitochondrial dysfunction and improved ventricular function in post-MI cardiomyopathy rats. Conclusion Taken together, our findings demonstrate a disrupted mitochondrial metabolism along with an insufficient cardiac ALDH2-mediated aldehyde clearance during the progression of ventricular dysfunction, suggesting a potential therapeutic value of ALDH2 activators during the progression of post-myocardial infarction cardiomyopathy. PMID:25464432