Vinblastine 20' Amides: Synthetic Analogues That Maintain or Improve Potency and Simultaneously Overcome Pgp-Derived Efflux and Resistance.

PubMed

Lukesh, John C; Carney, Daniel W; Dong, Huijun; Cross, R Matthew; Shukla, Vyom; Duncan, Katharine K; Yang, Shouliang; Brody, Daniel M; Brütsch, Manuela M; Radakovic, Aleksandar; Boger, Dale L

2017-09-14

A series of 180 vinblastine 20' amides were prepared in three steps from commercially available starting materials, systematically exploring a typically inaccessible site in the molecule enlisting a powerful functionalization strategy. Clear structure-activity relationships and a structural model were developed in the studies which provided many such 20' amides that exhibit substantial and some even remarkable enhancements in potency, many that exhibit further improvements in activity against a Pgp overexpressing resistant cancer cell line, and an important subset of the vinblastine analogues that display little or no differential in activity against a matched pair of vinblastine sensitive and resistant (Pgp overexpressing) cell lines. The improvements in potency directly correlated with target tubulin binding affinity, and the reduction in differential functional activity against the sensitive and Pgp overexpressing resistant cell lines was found to correlate directly with an impact on Pgp-derived efflux.

Adolescent behavioral and neural reward sensitivity: a test of the differential susceptibility theory

PubMed Central

Richards, J S; Arias Vásquez, A; von Rhein, D; van der Meer, D; Franke, B; Hoekstra, P J; Heslenfeld, D J; Oosterlaan, J; Faraone, S V; Buitelaar, J K; Hartman, C A

2016-01-01

Little is known about the causes of individual differences in reward sensitivity. We investigated gene–environment interactions (GxE) on behavioral and neural measures of reward sensitivity, in light of the differential susceptibility theory. This theory states that individuals carrying plasticity gene variants will be more disadvantaged in negative, but more advantaged in positive environments. Reward responses were assessed during a monetary incentive delay task in 178 participants with and 265 without attention-deficit/hyperactivity disorder (ADHD), from N=261 families. We examined interactions between variants in candidate plasticity genes (DAT1, 5-HTT and DRD4) and social environments (maternal expressed emotion and peer affiliation). HTTLPR short allele carriers showed the least reward speeding when exposed to high positive peer affiliation, but the most when faced with low positive peer affiliation or low maternal warmth. DAT1 10-repeat homozygotes displayed similar GxE patterns toward maternal warmth on general task performance. At the neural level, DRD4 7-repeat carriers showed the least striatal activation during reward anticipation when exposed to high maternal warmth, but the most when exposed to low warmth. Findings were independent of ADHD severity. Our results partially confirm the differential susceptibility theory and indicate the importance of positive social environments in reward sensitivity and general task performance for persons with specific genotypes. PMID:27045841

Dynamics of the association of heat shock protein HSPA6 (Hsp70B') and HSPA1A (Hsp70-1) with stress-sensitive cytoplasmic and nuclear structures in differentiated human neuronal cells.

PubMed

Shorbagi, Sadek; Brown, Ian R

2016-11-01

Heat shock proteins (Hsps) are cellular repair agents that counter the effects of protein misfolding that is a characteristic feature of neurodegenerative diseases. HSPA1A (Hsp70-1) is a widely studied member of the HSPA (Hsp70) family. The little-studied HSPA6 (Hsp70B') is present in the human genome and absent in mouse and rat; hence, it is missing in current animal models of neurodegenerative diseases. Differentiated human neuronal SH-SY5Y cells were employed to compare the dynamics of the association of YFP-tagged HSPA6 and HSPA1A with stress-sensitive cytoplasmic and nuclear structures. Following thermal stress, live-imaging confocal microscopy and Fluorescence Recovery After Photobleaching (FRAP) demonstrated that HSPA6 displayed a prolonged and more dynamic association, compared to HSPA1A, with centrioles that play critical roles in neuronal polarity and migration. HSPA6 and HSPA1A also targeted nuclear speckles, rich in RNA splicing factors, and the granular component of the nucleolus that is involved in rRNA processing and ribosomal subunit assembly. HSPA6 and HSPA1A displayed similar FRAP kinetics in their interaction with nuclear speckles and the nucleolus. Subsequently, during the recovery from neuronal stress, HSPA6, but not HSPA1A, localized with the periphery of nuclear speckles (perispeckles) that have been characterized as transcription sites. The stress-induced association of HSPA6 with perispeckles displayed the greatest dynamism compared to the interaction of HSPA6 or HSPA1A with other stress-sensitive cytoplasmic and nuclear structures. This suggests involvement of HSPA6 in transcriptional recovery of human neurons from cellular stress that is not apparent for HSPA1A.

Spectral domain optical coherence tomography of multi-MHz A-scan rates at 1310 nm range and real-time 4D-display up to 41 volumes/second

PubMed Central

Choi, Dong-hak; Hiro-Oka, Hideaki; Shimizu, Kimiya; Ohbayashi, Kohji

2012-01-01

An ultrafast frequency domain optical coherence tomography system was developed at A-scan rates between 2.5 and 10 MHz, a B-scan rate of 4 or 8 kHz, and volume-rates between 12 and 41 volumes/second. In the case of the worst duty ratio of 10%, the averaged A-scan rate was 1 MHz. Two optical demultiplexers at a center wavelength of 1310 nm were used for linear-k spectral dispersion and simultaneous differential signal detection at 320 wavelengths. The depth-range, sensitivity, sensitivity roll-off by 6 dB, and axial resolution were 4 mm, 97 dB, 6 mm, and 23 μm, respectively. Using FPGAs for FFT and a GPU for volume rendering, a real-time 4D display was demonstrated at a rate up to 41 volumes/second for an image size of 256 (axial) × 128 × 128 (lateral) voxels. PMID:23243560

Value of shear wave arrival time contour display in shear wave elastography for breast masses diagnosis.

PubMed

Zhou, Bang-Guo; Wang, Dan; Ren, Wei-Wei; Li, Xiao-Long; He, Ya-Ping; Liu, Bo-Ji; Wang, Qiao; Chen, Shi-Gao; Alizad, Azra; Xu, Hui-Xiong

2017-08-01

To evaluate the diagnostic performance of shear wave arrival time contour (SWATC) display for the diagnosis of breast lesions and to identify factors associated with the quality of shear wave propagation (QSWP) in breast lesions. This study included 277 pathologically confirmed breast lesions. Conventional B-mode ultrasound characteristics and shear wave elastography parameters were computed. Using the SWATC display, the QSWP of each lesion was assigned to a two-point scale: score 1 (low quality) and score 2 (high quality). Binary logistic regression analysis was performed to identify factors associated with QSWP. The area under the receiver operating characteristic curve (AUROC) for QSWP to differentiate benign from malignant lesions was 0.913, with a sensitivity of 91.9%, a specificity of 90.7%, a positive predictive value (PPV) of 74.0%, and a negative predictive value (NPV) of 97.5%. Compared with using the standard deviation of shear wave speed (SWS SD ) alone, SWS SD combined with QSWP increased the sensitivity from 75.8% to 93.5%, but decreased the specificity from 95.8% to 89.3% (P < 0.05). SWS SD was identified to be the strongest factor associated with the QSWP, followed by tumor malignancy and the depth of the lesion. In conclusion, SWATC display may be useful for characterization of breast lesions.

Cell adhesion and guidance by micropost-array chemical sensors

NASA Astrophysics Data System (ADS)

Pantano, Paul; Quah, Soo-Kim; Danowski, Kristine L.

2002-06-01

An array of ~50,000 individual polymeric micropost sensors was patterned across a glass coverslip by a photoimprint lithographic technique. Individual micropost sensors were ~3-micrometers tall and ~8-micrometers wide. The O2-sensitive micropost array sensors (MPASs) comprised a ruthenium complex encapsulated in a gas permeable photopolymerizable siloxane. The pH-sensitive MPASs comprised a fluorescein conjugate encapsulated in a photocrosslinkable poly(vinyl alcohol)-based polymer. PO2 and pH were quantitated by acquiring MPAS luminescence images with an epifluorescence microscope/charge coupled device imaging system. O2-sensitive MPASs displayed linear Stern-Volmer quenching behavior with a maximum Io/I of ~8.6. pH-sensitive MPASs displayed sigmoidal calibration curves with a pKa of ~5.8. The adhesion of undifferentiated rat pheochromocytoma (PC12) cells across these two polymeric surface types was investigated. The greatest PC12 cell proliferation and adhesion occurred across the poly(vinyl alcohol)-based micropost arrays relative to planar poly(vinyl alcohol)-based surfaces and both patterned and planar siloxane surfaces. An additional advantage of the patterned MPAS layers relative to planar sensing layers was the ability to direct the growth of biological cells. Preliminary data is presented whereby nerve growth factor-differentiated PC12 cells grew neurite-like processes that extended along paths defined by the micropost architecture.

Differential protein abundance in promastigotes of nitric oxide-sensitive and resistant Leishmania chagasi strains.

PubMed

Alcolea, Pedro J; Tuñón, Gabriel I L; Alonso, Ana; García-Tabares, Francisco; Ciordia, Sergio; Mena, María C; Campos, Roseane N S; Almeida, Roque P; Larraga, Vicente

2016-11-01

Leishmania chagasi is the causative agent of zoonotic visceral leishmaniasis in Brazil. Domestic and stray dogs are the main reservoirs. The life cycle of the parasite involves two stages. Promastigotes are extracellular and develop within the sand fly gut. Amastigotes survive inside the harsh environment of the phagolysosome of mammalian host phagocytes, which display the nitric oxide defense mechanism. Surprisingly, we were able to isolate promastigotes that are also resistant to NO. This finding may be explained by the preadaptative hypothesis. An insight into the proteome of NO-sensitive and resistant promastigotes is presented herein. Total protein extracts were prepared from promastigote cultures of an NO-sensitive and a resistant strain at early-logarithmic, mid-logarithmic and stationary phase. A population enriched in metacyclic promastigotes was also isolated by Percoll gradient centrifugation. In vitro infectivity of both strains was compared. Differential protein abundance was analyzed by 2DE-MALDI-TOF/TOF. The most striking results were tested at the mRNA level by qRT-PCR. Three biological replicates were performed in all cases. NO-resistant L. chagasi promastigotes are more infective than NO-sensitive ones. Among the differentially abundant spots, 40 proteins could be successfully identified in the sensitive strain and 38 in resistant promastigotes. The increase of G6PD and the decrease of ARG and GPX transcripts and proteins contribute to NO resistance in L. chagasi promastigotes. These proteins may be studied as potential drug targets and/or vaccine candidates in the future. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Identification of prostate cancer biomarkers in urinary exosomes

PubMed Central

Øverbye, Anders; Skotland, Tore; Koehler, Christian J.; Thiede, Bernd; Seierstad, Therese; Berge, Viktor; Sandvig, Kirsten; Llorente, Alicia

2015-01-01

Exosomes have recently appeared as a novel source of non-invasive cancer biomarkers since tumour-specific molecules can be found in exosomes isolated from biological fluids. We have here investigated the proteome of urinary exosomes by using mass spectrometry to identify proteins differentially expressed in prostate cancer patients compared to healthy male controls. In total, 15 control and 16 prostate cancer samples of urinary exosomes were analyzed. Importantly, 246 proteins were differentially expressed in the two groups. The majority of these proteins (221) were up-regulated in exosomes from prostate cancer patients. These proteins were analyzed according to specific criteria to create a focus list that contained 37 proteins. At 100% specificity, 17 of these proteins displayed individual sensitivities above 60%. Even though several of these proteins showed high sensitivity and specificity for prostate cancer as individual biomarkers, combining them in a multi-panel test has the potential for full differentiation of prostate cancer from non-disease controls. The highest sensitivity, 94%, was observed for transmembrane protein 256 (TM256; chromosome 17 open reading frame 61). LAMTOR proteins were also distinctly enriched with very high specificity for patient samples. TM256 and LAMTOR1 could be used to augment the sensitivity to 100%. Other prominent proteins were V-type proton ATPase 16 kDa proteolipid subunit (VATL), adipogenesis regulatory factor (ADIRF), and several Rab-class members and proteasomal proteins. In conclusion, this study clearly shows the potential of using urinary exosomes in the diagnosis and clinical management of prostate cancer. PMID:26196085

Identification of prostate cancer biomarkers in urinary exosomes.

PubMed

Øverbye, Anders; Skotland, Tore; Koehler, Christian J; Thiede, Bernd; Seierstad, Therese; Berge, Viktor; Sandvig, Kirsten; Llorente, Alicia

2015-10-06

Exosomes have recently appeared as a novel source of non-invasive cancer biomarkers since tumour-specific molecules can be found in exosomes isolated from biological fluids. We have here investigated the proteome of urinary exosomes by using mass spectrometry to identify proteins differentially expressed in prostate cancer patients compared to healthy male controls. In total, 15 control and 16 prostate cancer samples of urinary exosomes were analyzed. Importantly, 246 proteins were differentially expressed in the two groups. The majority of these proteins (221) were up-regulated in exosomes from prostate cancer patients. These proteins were analyzed according to specific criteria to create a focus list that contained 37 proteins. At 100% specificity, 17 of these proteins displayed individual sensitivities above 60%. Even though several of these proteins showed high sensitivity and specificity for prostate cancer as individual biomarkers, combining them in a multi-panel test has the potential for full differentiation of prostate cancer from non-disease controls. The highest sensitivity, 94%, was observed for transmembrane protein 256 (TM256; chromosome 17 open reading frame 61). LAMTOR proteins were also distinctly enriched with very high specificity for patient samples. TM256 and LAMTOR1 could be used to augment the sensitivity to 100%. Other prominent proteins were V-type proton ATPase 16 kDa proteolipid subunit (VATL), adipogenesis regulatory factor (ADIRF), and several Rab-class members and proteasomal proteins. In conclusion, this study clearly shows the potential of using urinary exosomes in the diagnosis and clinical management of prostate cancer.

Computational Analysis of Epidermal Growth Factor Receptor Mutations Predicts Differential Drug Sensitivity Profiles toward Kinase Inhibitors.

PubMed

Akula, Sravani; Kamasani, Swapna; Sivan, Sree Kanth; Manga, Vijjulatha; Vudem, Dashavantha Reddy; Kancha, Rama Krishna

2018-05-01

A significant proportion of patients with lung cancer carry mutations in the EGFR kinase domain. The presence of a deletion mutation in exon 19 or L858R point mutation in the EGFR kinase domain has been shown to cause enhanced efficacy of inhibitor treatment in patients with NSCLC. Several less frequent (uncommon) mutations in the EGFR kinase domain with potential implications in treatment response have also been reported. The role of a limited number of uncommon mutations in drug sensitivity was experimentally verified. However, a huge number of these mutations remain uncharacterized for inhibitor sensitivity or resistance. A large-scale computational analysis of clinically reported 298 point mutants of EGFR kinase domain has been performed, and drug sensitivity profiles for each mutant toward seven kinase inhibitors has been determined by molecular docking. In addition, the relative inhibitor binding affinity toward each drug as compared with that of adenosine triphosphate was calculated for each mutant. The inhibitor sensitivity profiles predicted in this study for a set of previously characterized mutants correlated well with the published clinical, experimental, and computational data. Both the single and compound mutations displayed differential inhibitor sensitivity toward first- and next-generation kinase inhibitors. The present study provides predicted drug sensitivity profiles for a large panel of uncommon EGFR mutations toward multiple inhibitors, which may help clinicians in deciding mutant-specific treatment strategies. Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Rotational and Translational Components of Motion Parallax: Observers' Sensitivity and Implications for Three-Dimensional Computer Graphics

NASA Technical Reports Server (NTRS)

Kaiser, Mary K.; Montegut, Michael J.; Proffitt, Dennis R.

1995-01-01

The motion of objects during motion parallax can be decomposed into 2 observer-relative components: translation and rotation. The depth ratio of objects in the visual field is specified by the inverse ratio of their angular displacement (from translation) or equivalently by the inverse ratio of their rotations. Despite the equal mathematical status of these 2 information sources, it was predicted that observers would be far more sensitive to the translational than rotational component. Such a differential sensitivity is implicitly assumed by the computer graphics technique billboarding, in which 3-dimensional (3-D) objects are drawn as planar forms (i.e., billboards) maintained normal to the line of sight. In 3 experiments, observers were found to be consistently less sensitive to rotational anomalies. The implications of these findings for kinetic depth effect displays and billboarding techniques are discussed.

A Quadruplex Real-Time PCR Assay for the Rapid Detection and Differentiation of the Most Relevant Members of the B. pseudomallei Complex: B. mallei, B. pseudomallei, and B. thailandensis

PubMed Central

Lowe, Chinn-Woan; Thiriot, Joseph D.; Heder, Michael J.; March, Jordon K.; Drake, David S.; Lew, Cynthia S.; Bunnell, Annette J.; Moore, Emily S.; O'Neill, Kim L.; Robison, Richard A.

2016-01-01

The Burkholderia pseudomallei complex classically consisted of B. mallei, B. pseudomallei, and B. thailandensis, but has now expanded to include B. oklahomensis, B. humptydooensis, and three unassigned Burkholderia clades. Methods for detecting and differentiating the B. pseudomallei complex has been the topic of recent research due to phenotypic and genotypic similarities of these species. B. mallei and B. pseudomallei are recognized as CDC Tier 1 select agents, and are the causative agents of glanders and melioidosis, respectively. Although B. thailandensis and B. oklahomensis are generally avirulent, both display similar phenotypic characteristics to that of B. pseudomallei. B. humptydooensis and the Burkholderia clades are genetically similar to the B. pseudomallei complex, and are not associated with disease. Optimal identification of these species remains problematic, and PCR-based methods can resolve issues with B. pseudomallei complex detection and differentiation. Currently, no PCR assay is available that detects the major species of the B. pseudomallei complex. A real-time PCR assay in a multiplex single-tube format was developed to simultaneously detect and differentiate B. mallei, B. pseudomallei, and B. thailandensis, and a common sequence found in B. pseudomallei, B. mallei, B. thailandensis, and B. oklahomensis. A total of 309 Burkholderia isolates and 5 other bacterial species were evaluated. The assay was 100% sensitive and specific, demonstrated sensitivity beyond culture and GC methods for the isolates tested, and is completed in about an hour with a detection limit between 2.6pg and 48.9pg of gDNA. Bioinformatic analyses also showed the assay is likely 100% specific and sensitive for all 84 fully sequenced B. pseudomallei, B. mallei, B. thailandensis, and B. oklahomensis strains currently available in GenBank. For these reasons, this assay could be a rapid and sensitive tool in the detection and differentiation for those species of the B. pseudomallei complex with recognized clinical and practical significance. PMID:27736903

A Quadruplex Real-Time PCR Assay for the Rapid Detection and Differentiation of the Most Relevant Members of the B. pseudomallei Complex: B. mallei, B. pseudomallei, and B. thailandensis.

PubMed

Lowe, Chinn-Woan; Satterfield, Benjamin A; Nelson, Daniel B; Thiriot, Joseph D; Heder, Michael J; March, Jordon K; Drake, David S; Lew, Cynthia S; Bunnell, Annette J; Moore, Emily S; O'Neill, Kim L; Robison, Richard A

2016-01-01

The Burkholderia pseudomallei complex classically consisted of B. mallei, B. pseudomallei, and B. thailandensis, but has now expanded to include B. oklahomensis, B. humptydooensis, and three unassigned Burkholderia clades. Methods for detecting and differentiating the B. pseudomallei complex has been the topic of recent research due to phenotypic and genotypic similarities of these species. B. mallei and B. pseudomallei are recognized as CDC Tier 1 select agents, and are the causative agents of glanders and melioidosis, respectively. Although B. thailandensis and B. oklahomensis are generally avirulent, both display similar phenotypic characteristics to that of B. pseudomallei. B. humptydooensis and the Burkholderia clades are genetically similar to the B. pseudomallei complex, and are not associated with disease. Optimal identification of these species remains problematic, and PCR-based methods can resolve issues with B. pseudomallei complex detection and differentiation. Currently, no PCR assay is available that detects the major species of the B. pseudomallei complex. A real-time PCR assay in a multiplex single-tube format was developed to simultaneously detect and differentiate B. mallei, B. pseudomallei, and B. thailandensis, and a common sequence found in B. pseudomallei, B. mallei, B. thailandensis, and B. oklahomensis. A total of 309 Burkholderia isolates and 5 other bacterial species were evaluated. The assay was 100% sensitive and specific, demonstrated sensitivity beyond culture and GC methods for the isolates tested, and is completed in about an hour with a detection limit between 2.6pg and 48.9pg of gDNA. Bioinformatic analyses also showed the assay is likely 100% specific and sensitive for all 84 fully sequenced B. pseudomallei, B. mallei, B. thailandensis, and B. oklahomensis strains currently available in GenBank. For these reasons, this assay could be a rapid and sensitive tool in the detection and differentiation for those species of the B. pseudomallei complex with recognized clinical and practical significance.

PCR-based Methodologies Used to Detect and Differentiate the Burkholderia pseudomallei complex: B. pseudomallei, B. mallei, and B. thailandensis.

PubMed

Lowe, Woan; March, Jordon K; Bunnell, Annette J; O'Neill, Kim L; Robison, Richard A

2014-01-01

Methods for the rapid detection and differentiation of the Burkholderia pseudomallei complex comprising B. pseudomallei, B. mallei, and B. thailandensis, have been the topic of recent research due to the high degree of phenotypic and genotypic similarities of these species. B. pseudomallei and B. mallei are recognized by the CDC as tier 1 select agents. The high mortality rates of glanders and melioidosis, their potential use as bioweapons, and their low infectious dose, necessitate the need for rapid and accurate detection methods. Although B. thailandensis is generally avirulent in mammals, this species displays very similar phenotypic characteristics to that of B. pseudomallei. Optimal identification of these species remains problematic, due to the difficulty in developing a sensitive, selective, and accurate assay. The development of PCR technologies has revolutionized diagnostic testing and these detection methods have become popular due to their speed, sensitivity, and accuracy. The purpose of this review is to provide a comprehensive overview and evaluation of the advancements in PCR-based detection and differentiation methodologies for the B. pseudomallei complex, and examine their potential uses in diagnostic and environmental testing.

S36. DIFFERENTIAL ENCODING OF SENSITIZATION AND CROSS SENSITIZATION TO PSYCHOSTIMULANTS AND ANTIPSYCHOTICS IN NUCLEUS ACCUMBENS D1- AND D2- RECEPTOR EXPRESSING MEDIUM SPINY NEURONS

PubMed Central

Amato, Davide; Heinsbroek, Jasper; Kalivas, Peter W

2018-01-01

Abstract Background Nearly half of all individuals diagnosed with schizophrenia abuse addictive substances such as cocaine. Currently, the neurobiological mechanisms in patients with schizophrenia that lead to cocaine abuse are unknown. A possible explanation for the co-morbidity between schizophrenia and addiction is that the rewarding properties of cocaine reverse the diminished motivational drive caused by chronic antipsychotic regimen. Moreover, chronic antipsychotic treatment can sensitize and amplify cocaine rewarding effects and exacerbate psychoses. Methods The rewarding properties of cocaine are attributed to the differential effects of dopamine on D1 and D2 receptor-expressing medium spiny neurons (MSNs) in the nucleus accumbens (NAc). Using in vivo Ca2+ miniature microscopic imaging, we characterize the role of D1 and D2 MSN in mono- and a cross- sensitization paradigms. D1- and D2-Cre mice were injected with a Cre dependent calcium indicator (gCaMP6f) and implanted with a gradient index (GRIN) lens above the nucleus accumbens and calcium activity was recorded using a head mounted miniature microscope. Cocaine sensitization was measured after a classic repeated cocaine regiment and antipsychotic and psychostimulant cross-sensitization was measured by a single cocaine injection after chronic pre-treatment with haloperidol. Results We found that both D1-MSN and D2-MSN populations are modulated by initial cocaine experience and further modulated during the expression of cocaine sensitization. A subpopulation of D1-MSN displayed initial activation, but reduced activity during the expression of sensitization. By contrast, the majority of D2-MSNs were suppressed by initial cocaine experience, but became active during the expression of sensitization. Furthermore, activity of D1- and D2-MSNs bidirectionally related with the observed behavioral responses to cocaine. Cross-sensitization following haloperidol treatment led to increased behavioral responses to psychostimulants. Current experiments are set out to investigate the neuronal responses of D1 and D2-MSN during cross sensitization between haloperidol and cocaine. Discussion Cocaine sensitization leads to differential neuronal responses in D1- and D2-MSN and these responses are differentially correlated with the magnitude of the sensitized behavioral response. These results reveal important new insights in the neurobiological processes in the nucleus accumbens that underlie psychostimulant sensitization and provide an important new model for studying the pharmacology of antipsychotic effects on striatal function and its potential role in increasing the susceptibility of schizophrenic patients to developing drug addiction.

Highly repeatable room temperature negative differential resistance in AlN/GaN resonant tunneling diodes grown by molecular beam epitaxy

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

Growden, Tyler A.; Fakhimi, Parastou; Berger, Paul R., E-mail: pberger@ieee.org

AlN/GaN resonant tunneling diodes grown on low dislocation density semi-insulating bulk GaN substrates via plasma-assisted molecular-beam epitaxy are reported. The devices were fabricated using a six mask level, fully isolated process. Stable room temperature negative differential resistance (NDR) was observed across the entire sample. The NDR exhibited no hysteresis, background light sensitivity, or degradation of any kind after more than 1000 continuous up-and-down voltage sweeps. The sample exhibited a ∼90% yield of operational devices which routinely displayed an average peak current density of 2.7 kA/cm{sup 2} and a peak-to-valley current ratio of ≈1.15 across different sizes.

Time course of the response of carbohydrate metabolism to unloading of the soleus

NASA Technical Reports Server (NTRS)

Henriksen, Erik J.; Tischler, Marc E.

1988-01-01

The time course of the response of carbohydrate metabolism to unloading was studied in the soleus muscle of rats subjected to tail-cast suspension. In the fresh soleus, 12 hours of unloading led to higher concentrations of glycogen and lower activity ratios of both glycogen synthase and glycogen phosphorylase. These changes were still evident on day three. Thereafter, the increased glycogen concentration apparently diminished the activity ratio of glycogen synthase, leading to a subsequent fall in the total glycogen content after day one. After 24 hours of unloading, when no significant atrophy was detectable, there was no differential response to insulin for in vitro glucose metabolism. On day three, the soleus atrophied significantly and displayed a greater sensitivity to insulin for most of these parameters compared to the weight-bearing control muscle. However, insulin sensitivity for glycogen synthesis was unchanged. These results showed that the increased sensitivity to insulin of the unloaded soleus is associated with the degree of muscle atrophy, likely due to an increased insulin binding capacity relative to muscle mass. This study also showed that insulin regulation of glucose uptake and of glycogen synthesis is affected differentially in the unloaded soleus muscle.

Characterization of glioma stem cells through multiple stem cell markers and their specific sensitization to double-strand break-inducing agents by pharmacological inhibition of ataxia telangiectasia mutated protein.

PubMed

Raso, Alessandro; Vecchio, Donatella; Cappelli, Enrico; Ropolo, Monica; Poggi, Alessandro; Nozza, Paolo; Biassoni, Roberto; Mascelli, Samantha; Capra, Valeria; Kalfas, Fotios; Severi, Paolo; Frosina, Guido

2012-09-01

Previous studies have shown that tumor-driving glioma stem cells (GSC) may promote radio-resistance by constitutive activation of the DNA damage response started by the ataxia telangiectasia mutated (ATM) protein. We have investigated whether GSC may be specifically sensitized to ionizing radiation by inhibiting the DNA damage response. Two grade IV glioma cell lines (BORRU and DR177) were characterized for a number of immunocytochemical, karyotypic, proliferative and differentiative parameters. In particular, the expression of a panel of nine stem cell markers was quantified by reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometry. Overall, BORRU and DR177 displayed pronounced and poor stem phenotypes, respectively. In order to improve the therapeutic efficacy of radiation on GSC, the cells were preincubated with a nontoxic concentration of the ATM inhibitors KU-55933 and KU-60019 and then irradiated. BORRU cells were sensitized to radiation and radio-mimetic chemicals by ATM inhibitors whereas DR177 were protected under the same conditions. No sensitization was observed after cell differentiation or to drugs unable to induce double-strand breaks (DSB), indicating that ATM inhibitors specifically sensitize glioma cells possessing stem phenotype to DSB-inducing agents. In conclusion, pharmacological inhibition of ATM may specifically sensitize GSC to DSB-inducing agents while sparing nonstem cells. © 2012 The Authors; Brain Pathology © 2012 International Society of Neuropathology.

Detection of explosives by differential hyperspectral imaging

NASA Astrophysics Data System (ADS)

Dubroca, Thierry; Brown, Gregory; Hummel, Rolf E.

2014-02-01

Our team has pioneered an explosives detection technique based on hyperspectral imaging of surfaces. Briefly, differential reflectometry (DR) shines ultraviolet (UV) and blue light on two close-by areas on a surface (for example, a piece of luggage on a moving conveyer belt). Upon reflection, the light is collected with a spectrometer combined with a charge coupled device (CCD) camera. A computer processes the data and produces in turn differential reflection spectra taken from these two adjacent areas on the surface. This differential technique is highly sensitive and provides spectroscopic data of materials, particularly of explosives. As an example, 2,4,6-trinitrotoluene displays strong and distinct features in differential reflectograms near 420 and 250 nm, that is, in the near-UV region. Similar, but distinctly different features are observed for other explosives. Finally, a custom algorithm classifies the collected spectral data and outputs an acoustic signal if a threat is detected. This paper presents the complete DR hyperspectral imager which we have designed and built from the hardware to the software, complete with an analysis of the device specifications.

Cellular Levels of Oxidative Stress Affect the Response of Cervical Cancer Cells to Chemotherapeutic Agents

PubMed Central

Williams, Vonetta M.; Kokoza, Anatolii; Bashkirova, Svetlana; Duerksen-Hughes, Penelope

2014-01-01

Treatment of advanced and relapsed cervical cancer is frequently ineffective, due in large part to chemoresistance. To examine the pathways responsible, we employed the cervical carcinoma-derived SiHa and CaSki cells as cellular models of resistance and sensitivity, respectively, to treatment with chemotherapeutic agents, doxorubicin, and cisplatin. We compared the proteomic profiles of SiHa and CaSki cells and identified pathways with the potential to contribute to the differential response. We then extended these findings by comparing the expression level of genes involved in reactive oxygen species (ROS) metabolism through the use of a RT-PCR array. The analyses demonstrated that the resistant SiHa cells expressed higher levels of antioxidant enzymes. Decreasing or increasing oxidative stress led to protection or sensitization, respectively, in both cell lines, supporting the idea that cellular levels of oxidative stress affect responsiveness to treatment. Interestingly, doxorubicin and cisplatin induced different profiles of ROS, and these differences appear to contribute to the sensitivity to treatment displayed by cervical cancer cells. Overall, our findings demonstrate that cervical cancer cells display variable profiles with respect to their redox-generating and -adaptive systems, and that these different profiles have the potential to contribute to their responses to treatments with chemotherapy. PMID:25478571

Isolation of an essential Schizosaccharomyces pombe gene, prp31+, that links splicing and meiosis

PubMed Central

Bishop, Danielle T.; McDonald, W. Hayes; Gould, Kathleen L.; Forsburg, Susan L.

2000-01-01

We carried out a screen for mutants that arrest prior to premeiotic S phase. One of the strains we isolated contains a temperature-sensitive allele mutation in the fission yeast prp31+ gene. The prp31-E1 mutant is defective in vegetative cell growth and in meiotic progression. It is synthetically lethal with prp6 and displays a pre-mRNA splicing defect at the restrictive temperature. We cloned the wild-type gene by complementation of the temperature-sensitive mutant phenotype. Prp31p is closely related to human and budding yeast PRP31 homologs and is likely to function as a general splicing factor in both vegetative growth and sexual differentiation. PMID:10871341

Departure from the onset-onset rule.

PubMed

Chow, S L

1994-09-01

Using a signal-detection task, the generality of Turvey's (1973) onset-onset rule was tested in our experiments. After seeing, in succession, (1) one or two letters (target display), (2) a multiletter detection display, and (3) a mask display, subjects decided whether or not the letter or letters in the target display reappeared in the succeeding detection display at different levels of detection-display duration in various situations. The subjects' sensitivity was inconsistent with the onset-onset rule. More specifically, sensitivity increased with increases in display duration within a fixed stimulus onset asynchrony of 150 msec. Display duration, however, had no effect on response bias. Nor was there any interaction between display duration and display size in terms of either sensitivity or response bias. The more complicated relationship between display duration and display size does not invalidate the departure from the onset-onset rule.

RuO2 pH Sensor with Super-Glue-Inspired Reference Electrode

PubMed Central

Wajrak, Magdalena; Alameh, Kamal

2017-01-01

A pH-sensitive RuO2 electrode coated in a commercial cyanoacrylate adhesive typically exhibits very low pH sensitivity, and could be paired with a RuO2 working electrode as a differential type pH sensor. However, such sensors display poor performance in real sample matrices. A pH sensor employing a RuO2 pH-sensitive working electrode and a SiO2-PVB junction-modified RuO2 reference electrode is developed as an alternative high-performance solution. This sensor exhibits a performance similar to that of a commercial glass pH sensor in some common sample matrices, particularly, an excellent pH sensitivity of 55.7 mV/pH, a hysteresis as low as 2.7 mV, and a drift below 2.2 mV/h. The developed sensor structure opens the way towards the development of a simple, cost effective, and robust pH sensor for pH analysis in various sample matrices. PMID:28878182

RuO₂ pH Sensor with Super-Glue-Inspired Reference Electrode.

PubMed

Lonsdale, Wade; Wajrak, Magdalena; Alameh, Kamal

2017-09-06

A pH-sensitive RuO₂ electrode coated in a commercial cyanoacrylate adhesive typically exhibits very low pH sensitivity, and could be paired with a RuO₂ working electrode as a differential type pH sensor. However, such sensors display poor performance in real sample matrices. A pH sensor employing a RuO₂ pH-sensitive working electrode and a SiO₂-PVB junction-modified RuO₂ reference electrode is developed as an alternative high-performance solution. This sensor exhibits a performance similar to that of a commercial glass pH sensor in some common sample matrices, particularly, an excellent pH sensitivity of 55.7 mV/pH, a hysteresis as low as 2.7 mV, and a drift below 2.2 mV/h. The developed sensor structure opens the way towards the development of a simple, cost effective, and robust pH sensor for pH analysis in various sample matrices.

Multiple Genetic Mechanisms Contribute to Visual Sensitivity Variation in the Labridae

PubMed Central

Phillips, Genevieve A.C.; Carleton, Karen L.; Marshall, N. Justin

2016-01-01

Coral reefs are one of the most spectrally diverse environments, both in terms of habitat and animal color. Species identity, sex, and camouflage are drivers of the phenotypic diversity seen in coral reef fishes, but how the phenotypic diversity is reflected in the genotype remains to be answered. The labrids are a large, polyphyletic family of coral reef fishes that display a diverse range of colors, including developmental color morphs and extensive behavioral ecologies. Here, we assess the opsin sequence and expression diversity among labrids from the Great Barrier Reef, Australia. We found that labrids express a diverse palette of visual opsins, with gene duplications in both RH2 and LWS genes. The majority of opsins expressed were within the mid-to-long wavelength sensitive classes (RH2 and LWS). Three of the labrid species expressed SWS1 (ultra-violet sensitive) opsins with the majority expressing the violet-sensitive SWS2B gene and none expressing SWS2A. We used knowledge about spectral tuning sites to calculate approximate spectral sensitivities (λmax) for individual species’ visual pigments, which corresponded well with previously published λmax values for closely related species (SWS1: 356–370 nm; SWS2B: 421–451 nm; RH2B: 452–492 nm; RH2A: 516–528 nm; LWS1: 554–555 nm; LWS2: 561–562 nm). In contrast to the phenotypic diversity displayed via color patterns and feeding ecology, there was little amino acid diversity within the known opsin sequence tuning sites. However, gene duplications and differential expression provide alternative mechanisms for tuning visual pigments, resulting in variable visual sensitivities among labrid species. PMID:26464127

The bromodomain inhibitor JQ1 triggers growth arrest and apoptosis in testicular germ cell tumours in vitro and in vivo.

PubMed

Jostes, Sina; Nettersheim, Daniel; Fellermeyer, Martin; Schneider, Simon; Hafezi, François; Honecker, Friedemann; Schumacher, Valerie; Geyer, Matthias; Kristiansen, Glen; Schorle, Hubert

2017-07-01

Type II testicular germ cell cancers (TGCT) are the most frequently diagnosed tumours in young men (20-40 years) and are classified as seminoma or non-seminoma. TGCTs are commonly treated by orchiectomy and chemo- or radiotherapy. However, a subset of metastatic non-seminomas (embryonal carcinomas) displays only incomplete remission or relapse and requires novel treatment options. Recent studies have shown effective application of the small-molecule inhibitor JQ1 in tumour therapy, which interferes with the function of 'bromodomain and extraterminal (BET)' proteins. JQ1-treated TGCT cell lines display up-regulation of genes indicative for DNA damage and cellular stress response and induce cell cycle arrest. Embryonal carcinoma (EC) cell lines, which presented as JQ1 sensitive, display down-regulation of pluripotency factors and induction of mesodermal differentiation. In contrast, seminoma-like TCam-2 cells tolerated higher JQ1 concentrations and were resistant to differentiation. ECs xenografted in vivo showed a reduction in tumour size, proliferation rate and angiogenesis in response to JQ1. Finally, the combination of JQ1 and the histone deacetylase inhibitor romidepsin allowed for lower doses and less frequent application, compared with monotherapy. Thus, we propose that JQ1 in combination with romidepsin may serve as a novel therapeutic option for (mixed) TGCTs. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

FOXP2 drives neuronal differentiation by interacting with retinoic acid signaling pathways.

PubMed

Devanna, Paolo; Middelbeek, Jeroen; Vernes, Sonja C

2014-01-01

FOXP2 was the first gene shown to cause a Mendelian form of speech and language disorder. Although developmentally expressed in many organs, loss of a single copy of FOXP2 leads to a phenotype that is largely restricted to orofacial impairment during articulation and linguistic processing deficits. Why perturbed FOXP2 function affects specific aspects of the developing brain remains elusive. We investigated the role of FOXP2 in neuronal differentiation and found that FOXP2 drives molecular changes consistent with neuronal differentiation in a human model system. We identified a network of FOXP2 regulated genes related to retinoic acid signaling and neuronal differentiation. FOXP2 also produced phenotypic changes associated with neuronal differentiation including increased neurite outgrowth and reduced migration. Crucially, cells expressing FOXP2 displayed increased sensitivity to retinoic acid exposure. This suggests a mechanism by which FOXP2 may be able to increase the cellular differentiation response to environmental retinoic acid cues for specific subsets of neurons in the brain. These data demonstrate that FOXP2 promotes neuronal differentiation by interacting with the retinoic acid signaling pathway and regulates key processes required for normal circuit formation such as neuronal migration and neurite outgrowth. In this way, FOXP2, which is found only in specific subpopulations of neurons in the brain, may drive precise neuronal differentiation patterns and/or control localization and connectivity of these FOXP2 positive cells.

FOXP2 drives neuronal differentiation by interacting with retinoic acid signaling pathways

PubMed Central

Devanna, Paolo; Middelbeek, Jeroen; Vernes, Sonja C.

2014-01-01

FOXP2 was the first gene shown to cause a Mendelian form of speech and language disorder. Although developmentally expressed in many organs, loss of a single copy of FOXP2 leads to a phenotype that is largely restricted to orofacial impairment during articulation and linguistic processing deficits. Why perturbed FOXP2 function affects specific aspects of the developing brain remains elusive. We investigated the role of FOXP2 in neuronal differentiation and found that FOXP2 drives molecular changes consistent with neuronal differentiation in a human model system. We identified a network of FOXP2 regulated genes related to retinoic acid signaling and neuronal differentiation. FOXP2 also produced phenotypic changes associated with neuronal differentiation including increased neurite outgrowth and reduced migration. Crucially, cells expressing FOXP2 displayed increased sensitivity to retinoic acid exposure. This suggests a mechanism by which FOXP2 may be able to increase the cellular differentiation response to environmental retinoic acid cues for specific subsets of neurons in the brain. These data demonstrate that FOXP2 promotes neuronal differentiation by interacting with the retinoic acid signaling pathway and regulates key processes required for normal circuit formation such as neuronal migration and neurite outgrowth. In this way, FOXP2, which is found only in specific subpopulations of neurons in the brain, may drive precise neuronal differentiation patterns and/or control localization and connectivity of these FOXP2 positive cells. PMID:25309332

Animals with a schizophrenia-like phenotype are differentially sensitive to the motivational effects of cannabinoid agonists in conditioned place preference.

PubMed

Gallo, A; Bouchard, C; Rompré, P-P

2014-07-15

Cannabis is the most consumed illicit drug worldwide, but among patients with a diagnosis of schizophrenia, this consumption is higher suggesting that they are differentially sensitive to cannabis. We chose to study this problematic using a neurodevelopmental model of schizophrenia: neonatal ventral hippocampus lesions (NVHL). In a first study, we compared the locomotor response to novelty, a mild stress and two doses of amphetamine (0.75 and 1.5 mg/kg) in sham and NVHL rats at post-natal day 35 (PD35) or 56 (PD56). In a second study, we investigated the valence of the motivational effect of Delta-9-tetrahydrocannabinnol (THC, 0.5 mg/kg, i.p.) and the cannabinoid receptor agonist, WIN55,212-2 (WIN, 1 mg/kg, i.p.), using the conditioned place preference paradigm; we used a biased procedure that comprised 12 days of testing with 3 paired-conditioning. The effects of this dose of WIN were also measured on locomotor activity. Results confirmed that the adult NVHL animals displayed a stronger locomotor response to the two doses of amphetamine, but not to novelty and a mild stress. In adult NVHL, but not sham animals, WIN stimulated locomotor activity and produced a conditioned place aversion. At the dose tested, THC tended to produce an aversion in adult sham but not NVHL animals. Taken together these findings show that adult animals with a schizophrenia-like phenotype are differentially sensitive to the motivational effect of cannabinoids. Copyright © 2014 Elsevier B.V. All rights reserved.

76 FR 29006 - In the Matter of Certain Motion-Sensitive Sound Effects Devices and Image Display Devices and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-19

... Effects Devices and Image Display Devices and Components and Products Containing Same; Notice of... United States after importation of certain motion-sensitive sound effects devices and image display... devices and image display devices and components and products containing same that infringe one or more of...

Fibronectin is a survival factor for differentiated osteoblasts

NASA Technical Reports Server (NTRS)

Globus, R. K.; Doty, S. B.; Lull, J. C.; Holmuhamedov, E.; Humphries, M. J.; Damsky, C. H.

1998-01-01

The skeletal extracellular matrix produced by osteoblasts contains the glycoprotein fibronectin, which regulates the adhesion, differentiation and function of various adherent cells. Interactions with fibronectin are required for osteoblast differentiation in vitro, since fibronectin antagonists added to cultures of immature fetal calvarial osteoblasts inhibit their progressive differentiation. To determine if fibronectin plays a unique role in fully differentiated osteoblasts, cultures that had already formed mineralized nodules in vitro were treated with fibronectin antagonists. Fibronectin antibodies caused >95% of the cells in the mature cultures to display characteristic features of apoptosis (nuclear condensation, apoptotic body formation, DNA laddering) within 24 hours. Cells appeared to acquire sensitivity to fibronectin antibody-induced apoptosis as a consequence of differentiation, since antibodies failed to kill immature cells and the first cells killed were those associated with mature nodules. Intact plasma fibronectin, as well as fragments corresponding to the amino-terminal, cell-binding, and carboxy-terminal domains of fibronectin, independently induced apoptosis of mature (day-13), but not immature (day-4), osteoblasts. Finally, transforming growth factor-beta1 partially protected cells from the apoptotic effects of fibronectin antagonists. Thus, in the course of maturation cultured osteoblasts switch from depending on fibronectin for differentiation to depending on fibronectin for survival. These data suggest that fibronectin, together with transforming growth factor-beta1, may affect bone formation, in part by regulating the survival of osteoblasts.

Transient Exposure to Ethanol during Zebrafish Embryogenesis Results in Defects in Neuronal Differentiation: An Alternative Model System to Study FASD

PubMed Central

Joya, Xavier; Garcia-Algar, Oscar; Vall, Oriol; Pujades, Cristina

2014-01-01

Background The exposure of the human embryo to ethanol results in a spectrum of disorders involving multiple organ systems, including the impairment of the development of the central nervous system (CNS). In spite of the importance for human health, the molecular basis of prenatal ethanol exposure remains poorly understood, mainly to the difficulty of sample collection. Zebrafish is now emerging as a powerful organism for the modeling and the study of human diseases. In this work, we have assessed the sensitivity of specific subsets of neurons to ethanol exposure during embryogenesis and we have visualized the sensitive embryonic developmental periods for specific neuronal groups by the use of different transgenic zebrafish lines. Methodology/Principal Findings In order to evaluate the teratogenic effects of acute ethanol exposure, we exposed zebrafish embryos to ethanol in a given time window and analyzed the effects in neurogenesis, neuronal differentiation and brain patterning. Zebrafish larvae exposed to ethanol displayed small eyes and/or a reduction of the body length, phenotypical features similar to the observed in children with prenatal exposure to ethanol. When neuronal populations were analyzed, we observed a clear reduction in the number of differentiated neurons in the spinal cord upon ethanol exposure. There was a decrease in the population of sensory neurons mainly due to a decrease in cell proliferation and subsequent apoptosis during neuronal differentiation, with no effect in motoneuron specification. Conclusion Our investigation highlights that transient exposure to ethanol during early embryonic development affects neuronal differentiation although does not result in defects in early neurogenesis. These results establish the use of zebrafish embryos as an alternative research model to elucidate the molecular mechanism(s) of ethanol-induced developmental toxicity at very early stages of embryonic development. PMID:25383948

ER-mitochondria contacts control surface glycan expression and sensitivity to killer lymphocytes in glioma stem-like cells.

PubMed

Bassoy, Esen Yonca; Kasahara, Atsuko; Chiusolo, Valentina; Jacquemin, Guillaume; Boydell, Emma; Zamorano, Sebastian; Riccadonna, Cristina; Pellegatta, Serena; Hulo, Nicolas; Dutoit, Valérie; Derouazi, Madiha; Dietrich, Pierre Yves; Walker, Paul R; Martinvalet, Denis

2017-06-01

Glioblastoma is a highly heterogeneous aggressive primary brain tumor, with the glioma stem-like cells (GSC) being more sensitive to cytotoxic lymphocyte-mediated killing than glioma differentiated cells (GDC). However, the mechanism behind this higher sensitivity is unclear. Here, we found that the mitochondrial morphology of GSCs modulates the ER-mitochondria contacts that regulate the surface expression of sialylated glycans and their recognition by cytotoxic T lymphocytes and natural killer cells. GSCs displayed diminished ER-mitochondria contacts compared to GDCs. Forced ER-mitochondria contacts in GSCs increased their cell surface expression of sialylated glycans and reduced their susceptibility to cytotoxic lymphocytes. Therefore, mitochondrial morphology and dynamism dictate the ER-mitochondria contacts in order to regulate the surface expression of certain glycans and thus play a role in GSC recognition and elimination by immune effector cells. Targeting the mitochondrial morphology, dynamism, and contacts with the ER could be an innovative strategy to deplete the cancer stem cell compartment to successfully treat glioblastoma. © 2017 The Authors.

Mextli proteins use both canonical bipartite and novel tripartite binding modes to form eIF4E complexes that display differential sensitivity to 4E-BP regulation

PubMed Central

Peter, Daniel; Weber, Ramona; Köne, Carolin; Chung, Min-Yi; Ebertsch, Linda; Truffault, Vincent; Weichenrieder, Oliver; Igreja, Cátia; Izaurralde, Elisa

2015-01-01

The eIF4E-binding proteins (4E-BPs) are a diverse class of translation regulators that share a canonical eIF4E-binding motif (4E-BM) with eIF4G. Consequently, they compete with eIF4G for binding to eIF4E, thereby inhibiting translation initiation. Mextli (Mxt) is an unusual 4E-BP that promotes translation by also interacting with eIF3. Here we present the crystal structures of the eIF4E-binding regions of the Drosophila melanogaster (Dm) and Caenorhabditis elegans (Ce) Mxt proteins in complex with eIF4E in the cap-bound and cap-free states. The structures reveal unexpected evolutionary plasticity in the eIF4E-binding mode, with a classical bipartite interface for Ce Mxt and a novel tripartite interface for Dm Mxt. Both interfaces comprise a canonical helix and a noncanonical helix that engage the dorsal and lateral surfaces of eIF4E, respectively. Remarkably, Dm Mxt contains a C-terminal auxiliary helix that lies anti-parallel to the canonical helix on the eIF4E dorsal surface. In contrast to the eIF4G and Ce Mxt complexes, the Dm eIF4E–Mxt complexes are resistant to competition by bipartite 4E-BPs, suggesting that Dm Mxt can bind eIF4E when eIF4G binding is inhibited. Our results uncovered unexpected diversity in the binding modes of 4E-BPs, resulting in eIF4E complexes that display differential sensitivity to 4E-BP regulation. PMID:26294658

Explaining Discrepancies in Arrest Rates Between Black and White Male Juveniles

PubMed Central

Fite, Paula J.; Wynn, Porche’; Pardini, Dustin A.

2010-01-01

The authors investigated discrepancies in arrest rates between Black and White male juveniles by examining the role of early risk factors for arrest. Two hypotheses were evaluated: (a) Disproportionate minority arrest is due to increased exposure to early risk factors, and (b) a differential sensitivity to early risk factors contributes to disproportionate minority arrest. The study included 481 Black and White boys who were followed from childhood to early adulthood. A higher incidence of early risk factors accounted for racial differences related to any juvenile arrest, as well as differences in violence- and theft-related arrests. However, increased exposure to early risk factors did not explain race differences in drug-related arrests. Minimal support was found for the hypothesis that a differential sensitivity to risk factors accounts for disproportionate rate of minority male arrests. In sum, most racial discrepancies in juvenile male arrests were accounted for by an increased exposure to childhood risk factors. Specifically, Black boys were more likely to display early conduct problems and low academic achievement and experience poor parent–child communication, peer delinquency, and neighborhood problems, which increased their risk for juvenile arrest. PMID:19803571

A culture system to study oligodendrocyte myelination-processes using engineered nanofibers

PubMed Central

Lee, Seonok; Leach, Michelle K.; Redmond, Stephanie A.; Chong, S.Y. Christin; Mellon, Synthia H.; Tuck, Samuel J.; Feng, Zhang-Qi; Corey, Joseph M.; Chan, Jonah R.

2012-01-01

Current methods for studying central nervous system myelination necessitate permissive axonal substrates conducive for myelin wrapping by oligodendrocytes. We have developed a neuron-free culture system in which electron-spun nanofibers of varying sizes substitute for axons as a substrate for oligodendrocyte myelination, thereby allowing manipulation of the biophysical elements of axonal-oligodendroglial interactions. To investigate axonal regulation of myelination, this system effectively uncouples the role of molecular (inductive) cues from that of biophysical properties of the axon. We use this method to uncover the causation and sufficiency of fiber diameter in the initiation of concentric wrapping by rat oligodendrocytes. We also show that oligodendrocyte precursor cells display sensitivity to the biophysical properties of fiber diameter and initiate membrane ensheathment prior to differentiation. The use of nanofiber scaffolds will enable screening for potential therapeutic agents that promote oligodendrocyte differentiation and myelination as well as provide valuable insight into the processes involved in remyelination. PMID:22796663

Contrast Transmission In Medical Image Display

NASA Astrophysics Data System (ADS)

Pizer, Stephen M.; Zimmerman, John B.; Johnston, R. Eugene

1982-11-01

The display of medical images involves transforming recorded intensities such at CT numbers into perceivable intensities such as combinations of color and luminance. For the viewer to extract the most information about patterns of decreasing and increasing recorded intensity, the display designer must pay attention to three issues: 1) choice of display scale, including its discretization; 2) correction for variations in contrast sensitivity across the display scale due to the observer and the display device (producing an honest display); and 3) contrast enhancement based on the information in the recorded image and its importance, determined by viewing objectives. This paper will present concepts and approaches in all three of these areas. In choosing display scales three properties are important: sensitivity, associability, and naturalness of order. The unit of just noticeable difference (jnd) will be carefully defined. An observer experiment to measure the jnd values across a display scale will be specified. The overall sensitivity provided by a scale as measured in jnd's gives a measure of sensitivity called the perceived dynamic range (PDR). Methods for determining the PDR fran the aforementioned PDR values, and PDR's for various grey and pseudocolor scales will be presented. Methods of achieving sensitivity while retaining associability and naturalness of order with pseudocolor scales will be suggested. For any display device and scale it is useful to compensate for the device and observer by preceding the device with an intensity mapping (lookup table) chosen so that perceived intensity is linear with display-driving intensity. This mapping can be determined from the aforementioned jnd values. With a linearized display it is possible to standardize display devices so that the same image displayed on different devices or scales (e.g. video and hard copy) will be in sane sense perceptually equivalent. Furthermore, with a linearized display, it is possible to design contrast enhancement mappings that optimize the transmission of information from the recorded image to the display-driving signal with the assurance that this information will not then be lost by a -further nonlinear relation between display-driving and perceived intensity. It is suggested that optimal contrast enhancement mappings are adaptive to the local distribution of recorded intensities.

In vitro proliferation and osteogenic differentiation of human dental pulp stem cells in injectable thermo-sensitive chitosan/β-glycerophosphate/hydroxyapatite hydrogel.

PubMed

Chen, Yantian; Zhang, Fengli; Fu, Qiang; Liu, Yong; Wang, Zejian; Qi, Nianmin

2016-09-01

Injectable thermo-sensitive hydrogels have a potential application in bone tissue engineering for their sensitivities and minimal invasive properties. Human dental pulp stem cells have been considered a promising tool for tissue reconstruction. The objective of this study was to investigate the proliferation and osteogenic differentiation of dental pulp stem cells in injectable thermo-sensitive chitosan/β-glycerophosphate/hydroxyapatite hydrogel in vitro. The chitosan /β-glycerophosphate hydrogel and chitosan/β-glycerophosphate/hydroxyapatite hydrogel were prepared using the sol-gel method. The injectability of chitosan /β-glycerophosphate hydrogel and chitosan/β-glycerophosphate/hydroxyapatite hydrogel was measured using a commercial disposable syringe. Scanning electron microscopy was used to observe the inner structure of hydrogels. Then dental pulp stem cells were seeded in chitosan /β-glycerophosphate hydrogel and chitosan/β-glycerophosphate/hydroxyapatite hydrogel, respectively. The growth of dental pulp stem cells was periodically observed under an inverted microscope. The proliferation of dental pulp stem cells was detected by using an Alamar Blue kit, while cell apoptosis was determined by using a Live/Dead Viability/Cytotoxicity kit. The osteogenic differentiations of dental pulp stem cells in chitosan /β-glycerophosphate hydrogel and chitosan/β-glycerophosphate/hydroxyapatite hydrogel were evaluated by alkaline phosphatase activity assay and mRNA expression of osteogenesis gene for 21 days in osteogenic medium. The results indicated that there was no significant difference between chitosan /β-glycerophosphate hydrogel and chitosan/β-glycerophosphate/hydroxyapatite hydrogel in injectability. Cells within the chitosan/β-glycerophosphate/hydroxyapatite hydrogel displayed a typical adherent cell morphology and rapid proliferation with high cellular viability after 14 days of culture. Dental pulp stem cells seeded in chitosan/β-glycerophosphate/hydroxyapatite hydrogels had a higher alkaline phosphatase activity and better up-regulation of gene expression levels of Runx-2, Collagen I, alkaline phosphatase and osteocalcin than in chitosan /β-glycerophosphate hydrogels after osteogenic differentiation. These results demonstrated that the chitosan/β-glycerophosphate/hydroxyapatite hydrogel had excellent cellular compatibility and the superiority in promoting dental pulp stem cells osteogenic differentiation in vitro, showing that the combination of dental pulp stem cells and chitosan/β-glycerophosphate/hydroxyapatite hydrogel has the potential to be used for bone tissue engineering. © The Author(s) 2016.

An Integrated Bioinformatics Approach Identifies Elevated Cyclin E2 Expression and E2F Activity as Distinct Features of Tamoxifen Resistant Breast Tumors

PubMed Central

Huang, Lei; Zhao, Shuangping; Frasor, Jonna M.; Dai, Yang

2011-01-01

Approximately half of estrogen receptor (ER) positive breast tumors will fail to respond to endocrine therapy. Here we used an integrative bioinformatics approach to analyze three gene expression profiling data sets from breast tumors in an attempt to uncover underlying mechanisms contributing to the development of resistance and potential therapeutic strategies to counteract these mechanisms. Genes that are differentially expressed in tamoxifen resistant vs. sensitive breast tumors were identified from three different publically available microarray datasets. These differentially expressed (DE) genes were analyzed using gene function and gene set enrichment and examined in intrinsic subtypes of breast tumors. The Connectivity Map analysis was utilized to link gene expression profiles of tamoxifen resistant tumors to small molecules and validation studies were carried out in a tamoxifen resistant cell line. Despite little overlap in genes that are differentially expressed in tamoxifen resistant vs. sensitive tumors, a high degree of functional similarity was observed among the three datasets. Tamoxifen resistant tumors displayed enriched expression of genes related to cell cycle and proliferation, as well as elevated activity of E2F transcription factors, and were highly correlated with a Luminal intrinsic subtype. A number of small molecules, including phenothiazines, were found that induced a gene signature in breast cancer cell lines opposite to that found in tamoxifen resistant vs. sensitive tumors and the ability of phenothiazines to down-regulate cyclin E2 and inhibit proliferation of tamoxifen resistant breast cancer cells was validated. Our findings demonstrate that an integrated bioinformatics approach to analyze gene expression profiles from multiple breast tumor datasets can identify important biological pathways and potentially novel therapeutic options for tamoxifen-resistant breast cancers. PMID:21789246

DIFFERENTIAL DISPLAY ANALYSES OF THE AMPHIPOD HYALELLA AZTECA EXPOSED TO ETHYNYLESTRADIOL AT THREE DIFFERENT TROPHIC LEVELS

EPA Science Inventory

A study was conducted to determine if differential display could be used to detect differences in gene expression in the amphipod, Hyalella azteca. In a study of synthetic estrogen attenuation in different aquatic media, amphipods were exposed to 20 ng/L 17 a-ethynylestradiol in...

Adolescent and adult rat cortical protein kinase A display divergent responses to acute ethanol exposure

PubMed Central

Gigante, Eduardo D.; Santerre, Jessica L.; Carter, Jenna M.; Werner, David F.

2014-01-01

Adolescent rats display reduced sensitivity to many dysphoria-related effects of alcohol (ethanol) including motor ataxia and sedative hypnosis, but the underlying neurobiological factors that contribute to these differences remain unknown. The cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) pathway, particularly the type II regulatory subunit (RII), has been implicated in ethanol-induced molecular and behavioral responses in adults. Therefore, the current study examined cerebral cortical PKA in adolescent and adult ethanol responses. With the exception of early adolescence, PKA RIIα and RIIβ subunit levels largely did not differ from adult levels in either whole cell lysate or P2 synaptosomal expression. However, following acute ethanol exposure, PKA RIIβ P2 synaptosomal expression and activity were increased in adults, but not in adolescents. Behaviorally, intracerebroventricular administration of the PKA activator Sp-cAMP and inhibitor Rp-cAMP prior to ethanol administration increased adolescent sensitivity to the sedative-hypnotic effects of ethanol compared to controls. Sp-cAMP was ineffective in adults whereas Rp-cAMP suggestively reduced loss of righting reflex (LORR) with paralleled increases in blood ethanol concentrations. Overall, these data suggest that PKA activity modulates the sedative/hypnotic effects of ethanol and may potentially play a wider role in the differential ethanol responses observed between adolescents and adults. PMID:24874150

Differentially expressed genes and proteins upon drought acclimation in tolerant and sensitive genotypes of Coffea canephora

PubMed Central

Marraccini, Pierre; Vinecky, Felipe; Alves, Gabriel S.C.; Ramos, Humberto J.O.; Elbelt, Sonia; Vieira, Natalia G.; Carneiro, Fernanda A.; Sujii, Patricia S.; Alekcevetch, Jean C.; Silva, Vânia A.; DaMatta, Fábio M.; Ferrão, Maria A.G.; Leroy, Thierry; Pot, David; Vieira, Luiz G.E.; da Silva, Felipe R.; Andrade, Alan C.

2012-01-01

The aim of this study was to investigate the molecular mechanisms underlying drought acclimation in coffee plants by the identification of candidate genes (CGs) using different approaches. The first approach used the data generated during the Brazilian Coffee expressed sequence tag (EST) project to select 13 CGs by an in silico analysis (electronic northern). The second approach was based on screening macroarrays spotted with plasmid DNA (coffee ESTs) with separate hybridizations using leaf cDNA probes from drought-tolerant and susceptible clones of Coffea canephora var. Conilon, grown under different water regimes. This allowed the isolation of seven additional CGs. The third approach used two-dimensional gel electrophoresis to identify proteins displaying differential accumulation in leaves of drought-tolerant and susceptible clones of C. canephora. Six of them were characterized by MALDI-TOF-MS/MS (matrix-assisted laser desorption-time of flight-tandem mass spectrometry) and the corresponding proteins were identified. Finally, additional CGs were selected from the literature, and quantitative real-time polymerase chain reaction (qPCR) was performed to analyse the expression of all identified CGs. Altogether, >40 genes presenting differential gene expression during drought acclimation were identified, some of them showing different expression profiles between drought-tolerant and susceptible clones. Based on the obtained results, it can be concluded that factors involved a complex network of responses probably involving the abscisic signalling pathway and nitric oxide are major molecular determinants that might explain the better efficiency in controlling stomata closure and transpiration displayed by drought-tolerant clones of C. canephora. PMID:22511801

Characterization of immortalized human brown and white pre-adipocyte cell models from a single donor

PubMed Central

Andersen, Elise S.; Rasmussen, Nanna E.; Petersen, Louise I.; Pedersen, Steen B.; Richelsen, Bjørn

2017-01-01

Brown adipose tissue with its constituent brown adipocytes is a promising therapeutic target in metabolic disorders due to its ability to dissipate energy and improve systemic insulin sensitivity and glucose homeostasis. The molecular control of brown adipocyte differentiation and function has been extensively studied in mice, but relatively little is known about such regulatory mechanisms in humans, which in part is due to lack of human brown adipose tissue derived cell models. Here, we used retrovirus-mediated overexpression to stably integrate human telomerase reverse transcriptase (TERT) into stromal-vascular cell fractions from deep and superficial human neck adipose tissue biopsies from the same donor. The brown and white pre-adipocyte cell models (TERT-hBA and TERT-hWA, respectively) displayed a stable proliferation rate and differentiation until at least passage 20. Mature TERT-hBA adipocytes expressed higher levels of thermogenic marker genes and displayed a higher maximal respiratory capacity than mature TERT-hWA adipocytes. TERT-hBA adipocytes were UCP1-positive and responded to β-adrenergic stimulation by activating the PKA-MKK3/6-p38 MAPK signaling module and increasing thermogenic gene expression and oxygen consumption. Mature TERT-hWA adipocytes underwent efficient rosiglitazone-induced ‘browning’, as demonstrated by strongly increased expression of UCP1 and other brown adipocyte-enriched genes. In summary, the TERT-hBA and TERT-hWA cell models represent useful tools to obtain a better understanding of the molecular control of human brown and white adipocyte differentiation and function as well as of browning of human white adipocytes. PMID:28957413

Display modes for CT colonography. Part II. Blinded comparison of axial CT and virtual endoscopic and panoramic endoscopic volume-rendered studies.

PubMed

Beaulieu, C F; Jeffrey, R B; Karadi, C; Paik, D S; Napel, S

1999-07-01

To determine the sensitivity of radiologist observers for detecting colonic polyps by using three different data review (display) modes for computed tomographic (CT) colonography, or "virtual colonoscopy." CT colonographic data in a patient with a normal colon were used as base data for insertion of digitally synthesized polyps. Forty such polyps (3.5, 5, 7, and 10 mm in diameter) were randomly inserted in four copies of the base data. Axial CT studies, volume-rendered virtual endoscopic movies, and studies from a three-dimensional mode termed "panoramic endoscopy" were reviewed blindly and independently by two radiologists. Detection improved with increasing polyp size. Trends in sensitivity were dependent on whether all inserted lesions or only visible lesions were considered, because modes differed in how completely the colonic surface was depicted. For both reviewers and all polyps 7 mm or larger, panoramic endoscopy resulted in significantly greater sensitivity (90%) than did virtual endoscopy (68%, P = .014). For visible lesions only, the sensitivities were 85%, 81%, and 60% for one reader and 65%, 62%, and 28% for the other for virtual endoscopy, panoramic endoscopy, and axial CT, respectively. Three-dimensional displays were more sensitive than two-dimensional displays (P < .05). The sensitivity of panoramic endoscopy is higher than that of virtual endoscopy, because the former displays more of the colonic surface. Higher sensitivities for three-dimensional displays may justify the additional computation and review time.

Supersensitive detection and discrimination of enantiomers by dorsal olfactory receptors: evidence for hierarchical odour coding.

PubMed

Sato, Takaaki; Kobayakawa, Reiko; Kobayakawa, Ko; Emura, Makoto; Itohara, Shigeyoshi; Kizumi, Miwako; Hamana, Hiroshi; Tsuboi, Akio; Hirono, Junzo

2015-09-11

Enantiomeric pairs of mirror-image molecular structures are difficult to resolve by instrumental analyses. The human olfactory system, however, discriminates (-)-wine lactone from its (+)-form rapidly within seconds. To gain insight into receptor coding of enantiomers, we compared behavioural detection and discrimination thresholds of wild-type mice with those of ΔD mice in which all dorsal olfactory receptors are genetically ablated. Surprisingly, wild-type mice displayed an exquisite "supersensitivity" to enantiomeric pairs of wine lactones and carvones. They were capable of supersensitive discrimination of enantiomers, consistent with their high detection sensitivity. In contrast, ΔD mice showed selective major loss of sensitivity to the (+)-enantiomers. The resulting 10(8)-fold differential sensitivity of ΔD mice to (-)- vs. (+)-wine lactone matched that observed in humans. This suggests that humans lack highly sensitive orthologous dorsal receptors for the (+)-enantiomer, similarly to ΔD mice. Moreover, ΔD mice showed >10(10)-fold reductions in enantiomer discrimination sensitivity compared to wild-type mice. ΔD mice detected one or both of the (-)- and (+)-enantiomers over a wide concentration range, but were unable to discriminate them. This "enantiomer odour discrimination paradox" indicates that the most sensitive dorsal receptors play a critical role in hierarchical odour coding for enantiomer identification.

Supersensitive detection and discrimination of enantiomers by dorsal olfactory receptors: evidence for hierarchical odour coding

PubMed Central

Sato, Takaaki; Kobayakawa, Reiko; Kobayakawa, Ko; Emura, Makoto; Itohara, Shigeyoshi; Kizumi, Miwako; Hamana, Hiroshi; Tsuboi, Akio; Hirono, Junzo

2015-01-01

Enantiomeric pairs of mirror-image molecular structures are difficult to resolve by instrumental analyses. The human olfactory system, however, discriminates (−)-wine lactone from its (+)-form rapidly within seconds. To gain insight into receptor coding of enantiomers, we compared behavioural detection and discrimination thresholds of wild-type mice with those of ΔD mice in which all dorsal olfactory receptors are genetically ablated. Surprisingly, wild-type mice displayed an exquisite “supersensitivity” to enantiomeric pairs of wine lactones and carvones. They were capable of supersensitive discrimination of enantiomers, consistent with their high detection sensitivity. In contrast, ΔD mice showed selective major loss of sensitivity to the (+)-enantiomers. The resulting 108-fold differential sensitivity of ΔD mice to (−)- vs. (+)-wine lactone matched that observed in humans. This suggests that humans lack highly sensitive orthologous dorsal receptors for the (+)-enantiomer, similarly to ΔD mice. Moreover, ΔD mice showed >1010-fold reductions in enantiomer discrimination sensitivity compared to wild-type mice. ΔD mice detected one or both of the (−)- and (+)-enantiomers over a wide concentration range, but were unable to discriminate them. This “enantiomer odour discrimination paradox” indicates that the most sensitive dorsal receptors play a critical role in hierarchical odour coding for enantiomer identification. PMID:26361056

Apoptosis in differentiating C2C12 muscle cells selectively targets Bcl-2-deficient myotubes

PubMed Central

Schoneich, Christian; Dremina, Elena; Galeva, Nadezhda; Sharov, Victor

2014-01-01

Muscle cell apoptosis accompanies normal muscle development and regeneration, as well as degenerative diseases and aging. C2C12 murine myoblast cells represent a common model to study muscle differentiation. Though it was already shown that myogenic differentiation of C2C12 cells is accompanied by enhanced apoptosis in a fraction of cells, either the cell population sensitive to apoptosis or regulatory mechanisms for the apoptotic response are unclear so far. In the current study we characterize apoptotic phenotypes of different types of C2C12 cells at all stages of differentiation, and report here that myotubes of differentiated C2C12 cells with low levels of anti-apoptotic Bcl-2 expression are particularly vulnerable to apoptosis even though they are displaying low levels of pro-apoptotic proteins Bax, Bak and Bad. In contrast, reserve cells exhibit higher levels of Bcl-2 and high resistance to apoptosis. The transfection of proliferating myoblasts with Bcl-2 prior to differentiation did not protect against spontaneous apoptosis accompanying differentiation of C2C12 cell but led to Bcl-2 overexpression in myotubes and to significant protection from apoptotic cell loss caused by exposure to hydrogen peroxide. Overall, our data advocate for a Bcl-2-dependent mechanism of apoptosis in differentiated muscle cells. However, downstream processes for spontaneous and hydrogen peroxide induced apoptosis are not completely similar. Apoptosis in differentiating myoblasts and myotubes is regulated not through interaction of Bcl-2 with pro-apoptotic Bcl-2 family proteins such as Bax, Bak, and Bad. PMID:24129924

[Identification of genes that are specifically/preferentially expressed in developing cotton fibers by mRNA fluorescence differential display (FDD)].

PubMed

Sun, Jie; Li, Yuan-Li; Wang, Ruo-Hai; Xia, Gui-Xian

2004-01-01

Fluorescence differential display (FDD) technique was used to identify genes that are specifically or preferentially expressed in different developmental stages of cotton fiber cells. One hundred and nine differentially displayed cDNA fragments were isolated using 9, 21 and 27 DPA (days postanthesis) fibers as experimental materials. By a combination of two rounds of reverse Northern hybridization and Northern blot analyses, a number of such cDNA fragments were proved to represent fiber-specific/preferential genes. Sequencing determination and database searching indicated that most of these genes are novel. This work is an important step towards cloning the full-length cDNAs and characterizing the cellular functions of aforementioned genes in fiber development.

High expression of TROP2 characterizes different cell subpopulations in androgen-sensitive and androgen-independent prostate cancer cells.

PubMed

Xie, Jinhan; Mølck, Christina; Paquet-Fifield, Sophie; Butler, Lisa; Sloan, Erica; Ventura, Sabatino; Hollande, Frédéric

2016-07-12

Progression of castration-resistant tumors is frequent in prostate cancer. Current systemic treatments for castration-resistant prostate cancer only produce modest increases in survival time and self-renewing Tumor-Initiating Cells (TICs) are suspected to play an important role in resistance to these treatments. However it remains unclear whether the same TICs display both chemo-resistance and self-renewing abilities throughout progression from early stage lesions to late, castration resistant tumors. Here, we found that treatment of mice bearing LNCaP-derived xenograft tumors with cytotoxic (docetaxel) and anti-androgen (flutamide) compounds enriched for cells that express TROP2, a putative TIC marker. Consistent with a tumor-initiating role, TROP2high cells from androgen-sensitive prostate cancer cell lines displayed an enhanced ability to re-grow in culture following treatment with taxane-based chemotherapy with or without androgen blockade. TROP2 down-regulation in these cells reduced their ability to recur after treatment with docetaxel, in the presence or absence of flutamide. Accordingly, in silico analysis of published clinical data revealed that prostate cancer patients with poor prognosis exhibit significantly elevated TROP2 expression level compared to low-risk patients, particularly in the case of patients diagnosed with early stage tumors. In contrast, in androgen-independent prostate cancer cell lines, TROP2high cells did not exhibit a differential treatment response but were characterized by their high self-renewal ability. Based on these findings we propose that high TROP2 expression identifies distinct cell sub-populations in androgen-sensitive and androgen-independent prostate tumors and that it may be a predictive biomarker for prostate cancer treatment response in androgen-sensitive tumors.

Sensitivity of Physiological Emotional Measures to Odors Depends on the Product and the Pleasantness Ranges Used

PubMed Central

Pichon, Aline M.; Coppin, Géraldine; Cayeux, Isabelle; Porcherot, Christelle; Sander, David; Delplanque, Sylvain

2015-01-01

Emotions are characterized by synchronized changes in several components of an organism. Among them, physiological variations provide energy support for the expression of approach/avoid action tendencies induced by relevant stimuli, while self-reported subjective pleasantness feelings integrate all other emotional components and are plastic. Consequently, emotional responses evoked by odors should be highly differentiated when they are linked to different functions of olfaction (e.g., avoiding environmental hazards). As this differentiation has been observed for contrasted odors (very pleasant or unpleasant), we questioned whether subjective and physiological emotional response indicators could still disentangle subtle affective variations when no clear functional distinction is made (mildly pleasant or unpleasant fragrances). Here, we compared the sensitivity of behavioral and physiological [respiration, skin conductance, facial electromyography (EMG), and heart rate] indicators in differentiating odor-elicited emotions in two situations: when a wide range of odor families was presented (e.g., fruity, animal), covering different functional meanings; or in response to a restricted range of products in one particular family (fragrances). Results show clear differences in physiological indicators to odors that display a wide range of reported pleasantness, but these differences almost entirely vanish when fragrances are used even though their subjective pleasantness still differed. Taken together, these results provide valuable information concerning the ability of classic verbal and psychophysiological measures to investigate subtle differences in emotional reactions to a restricted range of similar olfactory stimuli. PMID:26648888

Prognostic Classifier Based on Genome-Wide DNA Methylation Profiling in Well-Differentiated Thyroid Tumors.

PubMed

Bisarro Dos Reis, Mariana; Barros-Filho, Mateus Camargo; Marchi, Fábio Albuquerque; Beltrami, Caroline Moraes; Kuasne, Hellen; Pinto, Clóvis Antônio Lopes; Ambatipudi, Srikant; Herceg, Zdenko; Kowalski, Luiz Paulo; Rogatto, Silvia Regina

2017-11-01

Even though the majority of well-differentiated thyroid carcinoma (WDTC) is indolent, a number of cases display an aggressive behavior. Cumulative evidence suggests that the deregulation of DNA methylation has the potential to point out molecular markers associated with worse prognosis. To identify a prognostic epigenetic signature in thyroid cancer. Genome-wide DNA methylation assays (450k platform, Illumina) were performed in a cohort of 50 nonneoplastic thyroid tissues (NTs), 17 benign thyroid lesions (BTLs), and 74 thyroid carcinomas (60 papillary, 8 follicular, 2 Hürthle cell, 1 poorly differentiated, and 3 anaplastic). A prognostic classifier for WDTC was developed via diagonal linear discriminant analysis. The results were compared with The Cancer Genome Atlas (TCGA) database. A specific epigenetic profile was detected according to each histological subtype. BTLs and follicular carcinomas showed a greater number of methylated CpG in comparison with NTs, whereas hypomethylation was predominant in papillary and undifferentiated carcinomas. A prognostic classifier based on 21 DNA methylation probes was able to predict poor outcome in patients with WDTC (sensitivity 63%, specificity 92% for internal data; sensitivity 64%, specificity 88% for TCGA data). High-risk score based on the classifier was considered an independent factor of poor outcome (Cox regression, P < 0.001). The methylation profile of thyroid lesions exhibited a specific signature according to the histological subtype. A meaningful algorithm composed of 21 probes was capable of predicting the recurrence in WDTC. Copyright © 2017 Endocrine Society

Assessment of a bedside test for N-terminal pro B-type natriuretic peptide (NT-proBNP) to differentiate cardiac from non-cardiac causes of pleural effusion in cats.

PubMed

Wurtinger, Gabriel; Henrich, Estelle; Hildebrandt, Nicolai; Wiedemann, Nicola; Schneider, Matthias; Hassdenteufel, Esther

2017-12-20

Cats with pleural effusion represent common emergencies in small animal practice. The aim of this prospective study was to investigate the diagnostic ability of a point-of-care ELISA (POC-ELISA) for the measurement of N-terminal pro B-type natriuretic peptide (NT-proBNP) to differentiate cardiac from non-cardiac disease in cats with pleural effusion. The sample material for use of this rapid test was either plasma or diluted pleural effusion. Twenty cats with moderate to severe pleural effusion were prospectively recruited. The cats were grouped into two groups, with or without congestive heart failure (CHF; N-CHF), after complete work-up. Blood and effusion were collected in EDTA tubes. Plasma and pleural effusion supernatants were transferred into stabilizer tubes and frozen. POC-ELISA for NT-proBNP was performed with plasma and diluted effusion (1:1). Quantitative NT-proBNP measurement was performed in plasma and diluted and undiluted effusions. Six cats were assigned to the CHF group. Of the 14 cats in the N-CHF group, 6 had concurrent cardiac abnormalities that were not responsible for the effusion. For the detection of CHF, the test displayed respective sensitivities and specificities of 100% and 79% in plasma and 100% and 86% in diluted pleural fluid. Receiver operating characteristic (ROC) analysis for quantitative NT-proBNP measurement of plasma and diluted and undiluted pleural effusions displayed areas under the curve of 0.98, sensitivities of 100% and specificities of 86%. The optimum cut-off was calculated at 399 pmol/l in plasma and 229 pmol/l in the diluted effusion and 467 pmol/l in the undiluted effusion. POC-ELISA for NT-proBNP in both plasma and diluted pleural effusion was suitable to differentiate cardiac from non-cardiac causes of feline pleural effusion. According to our results, use of pleural effusion is feasible, but dilution of the effusion before measurement seems to improve specificity.

Increased mitochondrial calcium sensitivity and abnormal expression of innate immunity genes precede dopaminergic defects in Pink1-deficient mice.

PubMed

Akundi, Ravi S; Huang, Zhenyu; Eason, Joshua; Pandya, Jignesh D; Zhi, Lianteng; Cass, Wayne A; Sullivan, Patrick G; Büeler, Hansruedi

2011-01-13

PTEN-induced kinase 1 (PINK1) is linked to recessive Parkinsonism (EOPD). Pink1 deletion results in impaired dopamine (DA) release and decreased mitochondrial respiration in the striatum of mice. To reveal additional mechanisms of Pink1-related dopaminergic dysfunction, we studied Ca²+ vulnerability of purified brain mitochondria, DA levels and metabolism and whether signaling pathways implicated in Parkinson's disease (PD) display altered activity in the nigrostriatal system of Pink1⁻/⁻ mice. Purified brain mitochondria of Pink1⁻/⁻ mice showed impaired Ca²+ storage capacity, resulting in increased Ca²+ induced mitochondrial permeability transition (mPT) that was rescued by cyclosporine A. A subpopulation of neurons in the substantia nigra of Pink1⁻/⁻ mice accumulated phospho-c-Jun, showing that Jun N-terminal kinase (JNK) activity is increased. Pink1⁻/⁻ mice 6 months and older displayed reduced DA levels associated with increased DA turnover. Moreover, Pink1⁻/⁻ mice had increased levels of IL-1β, IL-12 and IL-10 in the striatum after peripheral challenge with lipopolysaccharide (LPS), and Pink1⁻/⁻ embryonic fibroblasts showed decreased basal and inflammatory cytokine-induced nuclear factor kappa-β (NF-κB) activity. Quantitative transcriptional profiling in the striatum revealed that Pink1⁻/⁻ mice differentially express genes that (i) are upregulated in animals with experimentally induced dopaminergic lesions, (ii) regulate innate immune responses and/or apoptosis and (iii) promote axonal regeneration and sprouting. Increased mitochondrial Ca²+ sensitivity and JNK activity are early defects in Pink1⁻/⁻ mice that precede reduced DA levels and abnormal DA homeostasis and may contribute to neuronal dysfunction in familial PD. Differential gene expression in the nigrostriatal system of Pink1⁻/⁻ mice supports early dopaminergic dysfunction and shows that Pink1 deletion causes aberrant expression of genes that regulate innate immune responses. While some differentially expressed genes may mitigate neurodegeneration, increased LPS-induced brain cytokine expression and impaired cytokine-induced NF-κB activation may predispose neurons of Pink1⁻/⁻ mice to inflammation and injury-induced cell death.

Digital halftoning methods for selectively partitioning error into achromatic and chromatic channels

NASA Technical Reports Server (NTRS)

Mulligan, Jeffrey B.

1990-01-01

A method is described for reducing the visibility of artifacts arising in the display of quantized color images on CRT displays. The method is based on the differential spatial sensitivity of the human visual system to chromatic and achromatic modulations. Because the visual system has the highest spatial and temporal acuity for the luminance component of an image, a technique which will reduce luminance artifacts at the expense of introducing high-frequency chromatic errors is sought. A method based on controlling the correlations between the quantization errors in the individual phosphor images is explored. The luminance component is greatest when the phosphor errors are positively correlated, and is minimized when the phosphor errors are negatively correlated. The greatest effect of the correlation is obtained when the intensity quantization step sizes of the individual phosphors have equal luminances. For the ordered dither algorithm, a version of the method can be implemented by simply inverting the matrix of thresholds for one of the color components.

Alexithymia and affective verbal behaviour of three groups of patients.

PubMed

Ahrens, S

1985-01-01

The study described in this article was designed to investigate patients' response to affective stimuli on two levels of measurement: one was designed to yield information about cognitive attribution processes whereas the second level was aimed at uncovering deeper, more unconscious responses to the given stimuli. These were displayed as part of an experimental setting, in which three groups were compared: psychosomatic (duodenal ulcer), somatic and psychoneurotic patients. Systematic variation was introduced by showing either of two versions of a short film which differed in the degree of friendliness displayed by the main character. The results show differential effects on the two levels of measurement: in the case of the first level, an interpretation within the framework of current conceptualizations of alexithymia would have been possible, but results for the second level of measurement (utilizing Gottschalk-Gleser content analysis of speech) indicate that psychosomatic patients show the same kind of sensitive response to affective stimuli as patients from the other two groups.

Construction of helper plasmid-mediated dual-display phage for autoantibody screening in serum.

PubMed

Rajaram, Kaushik; Vermeeren, Veronique; Somers, Klaartje; Somers, Veerle; Michiels, Luc

2014-01-01

M13 filamentous bacteriophage has been used in displaying disease-specific antibodies, biomarkers, and peptides. One of the major drawbacks of using phage in diagnostic assays is the aspecific adsorption of proteins leading to a high background signal and decreasing sensitivity. To deal with this, we developed a genetically pure, exchangeable dual-display phage system in which biomarkers and streptavidin-binding protein (SBP) are displayed at opposite ends of the phage. This approach allows for sample purification, using streptavidin-coated magnetic beads resulting in a higher sensitivity of signal detection assays. Our dual-display cassette system approach also allows for easy exchange of both the anchor protein (SBP) and the displayed biomarker. The presented principle is applied for the detection of antibody reactivity against UH-RA.21 which is a good candidate biomarker for rheumatoid arthritis (RA). The applicability of dual-display phage preparation using a helper plasmid system is demonstrated, and its increased sensitivity in phage ELISA assays using patient serum samples is shown.

Perception of biomechanical motions by infants: implementation of various processing constraints.

PubMed

Bertenthal, B I; Proffitt, D R; Kramer, S J

1987-11-01

Geometry informs us that there exist a large number of possible connectivity patterns consistent with a point-light display of a person walking. Yet there is only one pattern consistent with a "stick figure" representation of the human form, and that pattern is uniquely specified by those pairwise connections that remain locally rigid. In this study, sensitivity to local rigidity in biomechanical displays was investigated in 3- and 5-month-old infants. The results of Experiment 1 revealed that by 5 months of age, infants discriminate a locally rigid point-light walker display from one in which local rigidity is perturbed. In Experiment 2 we tested infants' sensitivity to the same stimuli when those stimuli were inverted. Contrary to the preceding experiment, the results revealed no evidence of discrimination. Taken together, these findings suggest that infants are sensitive to local rigidity in biomechanical displays but that this sensitivity is orientation specific. Possible mechanisms for this specificity are discussed in the context of additional constraints on the processing of biomechanical displays.

Female signalling to male song in the domestic canary, Serinus canaria

PubMed Central

Amy, Mathieu; Salvin, Pauline; Naguib, Marc; Leboucher, Gerard

2015-01-01

Most studies on sexual selection focus on male characteristics such as male song in songbirds. Yet female vocalizations in songbirds are growing in interest among behavioural and evolutionary biologists because these vocalizations can reveal the female's preferences for male traits and may affect male display. This study was designed to test whether male song performance influences the different female signals in the domestic canary (Serinus canaria). Female canaries were exposed to three types of song performance, differing in the repetition rate of sexy syllables. This experiment demonstrates that female birds are engaged in multimodal communication during sexual interaction. The results support the copulation solicitation hypothesis for female-specific trills: these trills were positively correlated and had a similar pattern to the copulation solicitation displays; responses were higher to the songs with higher performance and responses decreased with the repetition of the stimulation. Also, we observed a sensitization effect with the repetition of the song of the highest performance for the simple calls. Simple trills and other calls were more frequent during the broadcast of canary songs compared with the heterospecific control songs. The differential use of female signals in response to different song performance reveals a highly differentiated female signalling system which is discussed in light of the role of female traits to understand sexual selection in a broader perspective. PMID:26064577

Mixed chimerism and split tolerance

PubMed Central

Al-Adra, David P.

2011-01-01

Establishing hematopoietic mixed chimerism can lead to donor-specific tolerance to transplanted organs and may eliminate the need for long-term immunosuppressive therapy, while also preventing chronic rejection. In this review, we discuss central and peripheral mechanisms of chimerism induced tolerance. However, even in the long-lasting presence of a donor organ or donor hematopoietic cells, some allogeneic tissues from the same donor can be rejected; a phenomenon known as split tolerance. With the current goal of creating mixed chimeras using clinically feasible amounts of donor bone marrow and with minimal conditioning, split tolerance may become more prevalent and its mechanisms need to be explored. Some predisposing factors that may increase the likelihood of split tolerance are immunogenicity of the graft, certain donor-recipient combinations, prior sensitization, location and type of graft and minimal conditioning chimerism induction protocols. Additionally, split tolerance may occur due to a differential susceptibility of various types of tissues to rejection. The mechanisms involved in a tissue’s differential susceptibility to rejection include the presence of polymorphic tissue-specific antigens and variable sensitivity to indirect pathway effector mechanisms. Finally, we review the clinical attempts at allograft tolerance through the induction of chimerism; studies that are revealing the complex relationship between chimerism and tolerance. This relationship often displays split tolerance, and further research into its mechanisms is warranted. PMID:22509425

Bias magnification in ecologic studies: a methodological investigation

PubMed Central

Webster, Thomas F

2007-01-01

Background As ecologic studies are often inexpensive to conduct, consideration of the magnitude and direction of ecologic biases may be useful in both study design and sensitivity analysis of results. This paper examines three types of ecologic bias: confounding by group, effect measure modification by group, and non-differential exposure misclassification. Methods Bias of the risk difference on the individual and ecologic levels are compared using two-by-two tables, simple equations, and risk diagrams. Risk diagrams provide a convenient way to simultaneously display information from both levels. Results Confounding by group and effect measure modification by group act in the same direction on the individual and group levels, but have larger impact on the latter. The reduction in exposure variance caused by aggregation magnifies the individual level bias due to ignoring groups. For some studies, the magnification factor can be calculated from the ecologic data alone. Small magnification factors indicate little bias beyond that occurring at the individual level. Aggregation is also responsible for the different impacts of non-differential exposure misclassification on individual and ecologic studies. Conclusion The analytical tools developed here are useful in analyzing ecologic bias. The concept of bias magnification may be helpful in designing ecologic studies and performing sensitivity analysis of their results. PMID:17615079

The limit of detection for explosives in spectroscopic differential reflectometry

NASA Astrophysics Data System (ADS)

Dubroca, Thierry; Vishwanathan, Karthik; Hummel, Rolf E.

2011-05-01

In the wake of recent terrorist attacks, such as the 2008 Mumbai hotel explosion or the December 25th 2009 "underwear bomber", our group has developed a technique (US patent #7368292) to apply differential reflection spectroscopy to detect traces of explosives. Briefly, light (200-500 nm) is shone on a surface such as a piece of luggage at an airport. Upon reflection, the light is collected with a spectrometer combined with a CCD camera. A computer processes the data and produces in turn a differential reflection spectrum involving two adjacent areas of the surface. This differential technique is highly sensitive and provides spectroscopic data of explosives. As an example, 2,4,6, trinitrotoluene (TNT) displays strong and distinct features in differential reflectograms near 420 nm. Similar, but distinctly different features are observed for other explosives. One of the most important criteria for explosive detection techniques is the limit of detection. This limit is defined as the amount of explosive material necessary to produce a signal to noise ratio of three. We present here, a method to evaluate the limit of detection of our technique. Finally, we present our sample preparation method and experimental set-up specifically developed to measure the limit of detection for our technology. This results in a limit ranging from 100 nano-grams to 50 micro-grams depending on the method and the set-up parameters used, such as the detector-sample distance.

Development and Optimization of a Fluorescent Differential Display PCR System for Analyzing the Stress Response in Lactobacillus sakei Strains

PubMed Central

Bonomo, Maria Grazia; Sico, Maria Anna; Grieco, Simona; Salzano, Giovanni

2009-01-01

Lactobacillus sakei is widely used as starter in the production process of Italian fermented sausages and its growth and survival are affected by various factors. We studied the differential expression of genome in response to different stresses by the fluorescent differential display (FDD) technique. This study resulted in the development and optimization of an innovative technique, with a high level of reproducibility and quality, which allows the identification of gene expression changes associated with different microbial behaviours under different growth conditions. PMID:22253979

Influence of long-term gravity vector changes on mesenchymal stem cells in vitro

NASA Astrophysics Data System (ADS)

Buravkova, L. B.; Merzlikina, N. V.; Romanov, Yu. A.; Buravkov, S. V.

2005-08-01

In vivo and in vitro studies have identified the bone marrow as the primary source of a multipotential mesenchymal stem cells (MSC) that give rise to progenitors for several mesenchymal tissues, including bone, cartilage, tendon, adipose, muscle and hematopoietic-supporting stroma. It is known that MSC are sensitive to chemical signals and mechanical stimuli. It was also suggested that microgravity may influence on progenitor cells and induce abnormalities in cellular differentiation in muscle and skeletal components leading to the changes in physiological regeneration of these tissues. To prove gravitational sensitivity of MSC, we studied the effects of prolonged clinorotation on cultured human MSC (hMSC) morphology, actin cytoskeleton organization and phenotype. It was found that the proliferation rate was significantly decreased during clinorotation but augmented during recovery. The cell cytoskeleton displayed actin filament thinning and altered morphology at clinorotation. The production of interleukin-6 was increased and expression of surface molecules was modified by simulated microgravity. Observed changes of cultured hMSC behavior suggest the gravitational sensitivity of human stromal progenitor cells.

Articular Cartilage Repair Through Muscle Cell-Based Tissue Engineering

DTIC Science & Technology

2011-03-01

defects display good cell survival and can differentiate into chondrocytes that improve the healing of articular cartilage. We also have observed that... self -renewal to their regenerative capacity after transplantation into the cartilage defects (Technical Objective #1). Next, we will determine the...osteochondral defects display good cell survival and can differentiate into chondrocytes that improve the healing of articular cartilage. We also have

Isolation of diapause-regulated transcripts by differential display from the Colorado potato beetle, and their expression in prediapausing and nondiapausing adults. GenBank. Accessions: FG591137-FG591192

USDA-ARS?s Scientific Manuscript database

Using differential display, 56 putatively diapause regulated transcripts were isolated from the Colorado potato beetle, Leptinotarsa decemlineata. The clones insert sizes range from 114 to 795 bp with mean length of 392 ± SD of 191 bp. Fourteen of the transcripts were confirmed by northern blot anal...

Cell type-specific hypersensitivity to oxidative damage in CSB and XPA mice.

PubMed

de Waard, Harm; de Wit, Jan; Gorgels, Theo G M F; van den Aardweg, Gerard; Andressoo, Jaan Olle; Vermeij, Marcel; van Steeg, Harry; Hoeijmakers, Jan H J; van der Horst, Gijsbertus T J

2003-01-02

Mutations in the CSB gene cause Cockayne syndrome (CS), a rare inherited disorder, characterized by UV-sensitivity, severe neurodevelopmental and progeroid symptoms. CSB functions in the transcription-coupled repair (TCR) sub-pathway of nucleotide excision repair (NER), responsible for the removal of UV-induced and other helix-distorting lesions from the transcribed strand of active genes. Several lines of evidence support the notion that the CSB TCR defect extends to other non-NER type transcription-blocking lesions, notably various kinds of oxidative damage, which may provide an explanation for part of the severe CS phenotype. We used genetically defined mouse models to examine the relationship between the CSB defect and sensitivity to oxidative damage in different cell types and at the level of the intact organism. The main conclusions are: (1) CSB(-/-) mouse embryo fibroblasts (MEFs) exhibit a clear hypersensitivity to ionizing radiation, extending the findings in genetically heterogeneous human CSB fibroblasts to another species. (2) CSB(-/-) MEFs are highly sensitive to paraquat, strongly indicating that the increased cytotoxicity is due to oxidative damage. (3) The hypersenstivity is independent of genetic background and directly related to the CSB defect and is not observed in totally NER-deficient XPA MEFs. (4) Wild type embryonic stem (ES) cells display an increased sensitivity to ionizing radiation compared to fibroblasts. Surprisingly, the CSB deficiency has only a very minor additional effect on ES cell sensitivity to oxidative damage and is comparable to that of an XPA defect, indicating cell type-specific differences in the contribution of TCR and NER to cellular survival. (5) Similar to ES cells, CSB and XPA mice both display a minor sensitivity to whole-body X-ray exposure. This suggests that the response of an intact organism to radiation is largely determined by the sensitivity of stem cells, rather than differentiated cells. These findings establish the role of transcription-coupled repair in resistance to oxidative damage and reveal a cell- and organ-specific impact of this repair pathway to the clinical phenotype of CS and XP.

PCB 136 Atropselectively Alters Morphometric and Functional Parameters of Neuronal Connectivity in Cultured Rat Hippocampal Neurons via Ryanodine Receptor-Dependent Mechanisms

PubMed Central

Yang, Dongren; Kania-Korwel, Izabela; Ghogha, Atefeh; Chen, Hao; Stamou, Marianna; Bose, Diptiman D.; Pessah, Isaac N.; Lehmler, Hans-Joachim; Lein, Pamela J.

2014-01-01

We recently demonstrated that polychlorinated biphenyl (PCB) congeners with multiple ortho chlorine substitutions sensitize ryanodine receptors (RyRs), and this activity promotes Ca2+-dependent dendritic growth in cultured neurons. Many ortho-substituted congeners display axial chirality, and we previously reported that the chiral congener PCB 136 (2,2′,3,3′,6,6′-hexachlorobiphenyl) atropselectively sensitizes RyRs. Here, we test the hypothesis that PCB 136 atropisomers differentially alter dendritic growth and other parameters of neuronal connectivity influenced by RyR activity. (−)-PCB 136, which potently sensitizes RyRs, enhances dendritic growth in primary cultures of rat hippocampal neurons, whereas (+)-PCB 136, which lacks RyR activity, has no effect on dendritic growth. The dendrite-promoting activity of (−)-PCB 136 is observed at concentrations ranging from 0.1 to 100nM and is blocked by pharmacologic RyR antagonism. Neither atropisomer alters axonal growth or cell viability. Quantification of PCB 136 atropisomers in hippocampal cultures indicates that atropselective effects on dendritic growth are not due to differential partitioning of atropisomers into cultured cells. Imaging of hippocampal neurons loaded with Ca2+-sensitive dye demonstrates that (−)-PCB 136 but not (+)-PCB 136 increases the frequency of spontaneous Ca2+ oscillations. Similarly, (−)-PCB 136 but not (+)-PCB 136 increases the activity of hippocampal neurons plated on microelectrode arrays. These data support the hypothesis that atropselective effects on RyR activity translate into atropselective effects of PCB 136 atropisomers on neuronal connectivity, and suggest that the variable atropisomeric enrichment of chiral PCBs observed in the human population may be a significant determinant of individual susceptibility for adverse neurodevelopmental outcomes following PCB exposure. PMID:24385416

Male-specific expression of Sox9 during gonad development of crocodile and mouse is mediated by alternative splicing of its proline-glutamine-alanine rich domain.

PubMed

Agrawal, Raman; Wessely, Oliver; Anand, Amit; Singh, Lalji; Aggarwal, Ramesh K

2009-08-01

The initial trigger for sexual differentiation is regulated by multiple ways during embryonic development. In vertebrates, chromosome-based mechanisms generally known as genetic sex determination are prevalent; however, some species, such as many reptilians, display temperature-dependent sex determination. The Sry-related transcription factor, Sox9, which is expressed by an evolutionary conserved gene, has been shown to be a key player in the process of sex determination. In the present study, we report the identification and expression of crocodile homolog of Sox9 (cpSox9) from the Indian Mugger, Crocodylus palustris. We show that cpSox9 undergoes extensive alternative splicing around the proline-glutamine-alanine rich transactivation domain that results in cpSox9 variants with presumably impaired or reduced transactivation potential. The multiple isoforms were also detected in various embryonic tissues, with some of them displaying a differential expression profile. With respect to sex differentiation, a putative unspliced full-length cpSox9 could be detected only in the genital ridge-adrenal-mesonephros complex of male, but not female embryos during the temperature-sensitive period. Importantly, we further show that this phenomenon was not restricted to the temperature-dependent sex determination species C. palustris, but was also observed in the mouse, a species exhibiting genetic sex determination. Thus, the present study describes, for the first time, a complete coding locus of Sox9 homolog from a temperature-dependent sex determination species. More importantly, we demonstrate an evolutionarily conserved role of alternative splicing resulting in transcriptional diversity and male-sex specific expression of Sox9 during testis development in vertebrates (i.e. irrespective of their underlying sex-determination mechanisms).

Quantitative analysis of proteome extracted from barley crowns grown under different drought conditions

PubMed Central

Vítámvás, Pavel; Urban, Milan O.; Škodáček, Zbynek; Kosová, Klára; Pitelková, Iva; Vítámvás, Jan; Renaut, Jenny; Prášil, Ilja T.

2015-01-01

Barley cultivar Amulet was used to study the quantitative proteome changes through different drought conditions utilizing two-dimensional difference gel electrophoresis (2D-DIGE). Plants were cultivated for 10 days under different drought conditions. To obtain control and differentially drought-treated plants, the soil water content was kept at 65, 35, and 30% of soil water capacity (SWC), respectively. Osmotic potential, water saturation deficit, 13C discrimination, and dehydrin accumulation were monitored during sampling of the crowns for proteome analysis. Analysis of the 2D-DIGE gels revealed 105 differentially abundant spots; most were differentially abundant between the controls and drought-treated plants, and 25 spots displayed changes between both drought conditions. Seventy-six protein spots were successfully identified by tandem mass spectrometry. The most frequent functional categories of the identified proteins can be put into the groups of: stress-associated proteins, amino acid metabolism, carbohydrate metabolism, as well as DNA and RNA regulation and processing. Their possible role in the response of barley to drought stress is discussed. Our study has shown that under drought conditions barley cv. Amulet decreased its growth and developmental rates, displayed a shift from aerobic to anaerobic metabolism, and exhibited increased levels of several protective proteins. Comparison of the two drought treatments revealed plant acclimation to milder drought (35% SWC); but plant damage under more severe drought treatment (30% SWC). The results obtained revealed that cv. Amulet is sensitive to drought stress. Additionally, four spots revealing a continuous and significant increase with decreasing SWC (UDP-glucose 6-dehydrogenase, glutathione peroxidase, and two non-identified) could be good candidates for testing of their protein phenotyping capacity together with proteins that were significantly distinguished in both drought treatments. PMID:26175745

Differential Gene Expression of Longan Under Simulated Acid Rain Stress.

PubMed

Zheng, Shan; Pan, Tengfei; Ma, Cuilan; Qiu, Dongliang

2017-05-01

Differential gene expression profile was studied in Dimocarpus longan Lour. in response to treatments of simulated acid rain with pH 2.5, 3.5, and a control (pH 5.6) using differential display reverse transcription polymerase chain reaction (DDRT-PCR). Results showed that mRNA differential display conditions were optimized to find an expressed sequence tag (EST) related with acid rain stress. The potential encoding products had 80% similarity with a transcription initiation factor IIF of Gossypium raimondii and 81% similarity with a protein product of Theobroma cacao. This fragment is the transcription factor activated by second messenger substances in longan leaves after signal perception of acid rain.

Physiological Plasticity of Neural-Crest-Derived Stem Cells in the Adult Mammalian Carotid Body.

PubMed

Annese, Valentina; Navarro-Guerrero, Elena; Rodríguez-Prieto, Ismael; Pardal, Ricardo

2017-04-18

Adult stem cell plasticity, or the ability of somatic stem cells to cross boundaries and differentiate into unrelated cell types, has been a matter of debate in the last decade. Neural-crest-derived stem cells (NCSCs) display a remarkable plasticity during development. Whether adult populations of NCSCs retain this plasticity is largely unknown. Herein, we describe that neural-crest-derived adult carotid body stem cells (CBSCs) are able to undergo endothelial differentiation in addition to their reported role in neurogenesis, contributing to both neurogenic and angiogenic processes taking place in the organ during acclimatization to hypoxia. Moreover, CBSC conversion into vascular cell types is hypoxia inducible factor (HIF) dependent and sensitive to hypoxia-released vascular cytokines such as erythropoietin. Our data highlight a remarkable physiological plasticity in an adult population of tissue-specific stem cells and could have impact on the use of these cells for cell therapy. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Antineoplastic Effects of PPARγ Agonists, with a Special Focus on Thyroid Cancer.

PubMed

Ferrari, Silvia Martina; Materazzi, Gabriele; Baldini, Enke; Ulisse, Salvatore; Miccoli, Paolo; Antonelli, Alessandro; Fallahi, Poupak

2016-01-01

Peroxisome Proliferator-Activated Receptor-γ (PPARγ) is a ligand-activated nuclear hormone receptor that functions as transcription factor and plays an important role in lipid metabolism and insulin sensitization. Recent studies have shown that PPARγ is overexpressed in many tumor types, including cancers of breast, lung, pancreas, colon, glioblastoma, prostate and thyroid differentiated/anaplastic cancers. These data suggest a role of PPARγ in tumor development and/or progression. PPARγ is emerging as a growth-limiting and differentiation-promoting factor, and it exerts a tumor suppressor role. Moreover, naturally-occurring and synthetic PPARγ agonists promote growth inhibition and apoptosis. Thiazolidinediones (TZDs) are synthetic agonists of PPARγ that were developed to treat type II diabetes. These compounds also display anticancer effects which appear mainly to be independent of their PPARγ agonist activity. Various preclinical and clinical studies strongly suggest a role for TZDs both alone and in combination with existing chemotherapeutic agents, for the treatment of cancer. Differentiation therapy involves the use of agents with the ability to induce differentiation in cells that have lost this ability, i.e. cancer cells, targeting pathways capable of re-activating blocked terminal differentiation programs. PPARγ agonists have been shown to induce differentiation in solid tumors such as thyroid differentiated/ anaplastic cancers and sarcomas. However, emerging data suggest that chronic use of TZDs is associated with increased risk of adverse cardiovascular events. The exploration of newer PPARγ agonists can help in unveiling the underlying mechanisms of these drugs, providing new molecules that are able to treat cancer, without increasing the cardiovascular risk of neoplastic patients.

Monkey pulvinar neurons fire differentially to snake postures.

PubMed

Le, Quan Van; Isbell, Lynne A; Matsumoto, Jumpei; Le, Van Quang; Hori, Etsuro; Tran, Anh Hai; Maior, Rafael S; Tomaz, Carlos; Ono, Taketoshi; Nishijo, Hisao

2014-01-01

There is growing evidence from both behavioral and neurophysiological approaches that primates are able to rapidly discriminate visually between snakes and innocuous stimuli. Recent behavioral evidence suggests that primates are also able to discriminate the level of threat posed by snakes, by responding more intensely to a snake model poised to strike than to snake models in coiled or sinusoidal postures (Etting and Isbell 2014). In the present study, we examine the potential for an underlying neurological basis for this ability. Previous research indicated that the pulvinar is highly sensitive to snake images. We thus recorded pulvinar neurons in Japanese macaques (Macaca fuscata) while they viewed photos of snakes in striking and non-striking postures in a delayed non-matching to sample (DNMS) task. Of 821 neurons recorded, 78 visually responsive neurons were tested with the all snake images. We found that pulvinar neurons in the medial and dorsolateral pulvinar responded more strongly to snakes in threat displays poised to strike than snakes in non-threat-displaying postures with no significant difference in response latencies. A multidimensional scaling analysis of the 78 visually responsive neurons indicated that threat-displaying and non-threat-displaying snakes were separated into two different clusters in the first epoch of 50 ms after stimulus onset, suggesting bottom-up visual information processing. These results indicate that pulvinar neurons in primates discriminate between poised to strike from those in non-threat-displaying postures. This neuronal ability likely facilitates behavioral discrimination and has clear adaptive value. Our results are thus consistent with the Snake Detection Theory, which posits that snakes were instrumental in the evolution of primate visual systems.

Overexpression of a partial fragment of the salt-responsive gene OsNUC1 enhances salt adaptation in transgenic Arabidopsis thaliana and rice (Oryza sativa L.) during salt stress.

PubMed

Sripinyowanich, Siriporn; Chamnanmanoontham, Nontalee; Udomchalothorn, Thanikarn; Maneeprasopsuk, Somporn; Santawee, Panudda; Buaboocha, Teerapong; Qu, Li-Jia; Gu, Hongya; Chadchawan, Supachitra

2013-12-01

The rice (Oryza sativa L.) nucleolin gene, OsNUC1, transcripts were expressed in rice leaves, flowers, seeds and roots but differentially expressed within and between two pairs of salt-sensitive and salt-resistant rice lines when subjected to salt stress. Salt-resistant lines exhibited higher OsNUC1 transcript expression levels than salt-sensitive lines during 0.5% (w/v) NaCl salt stress for 6d. Two sizes of OsNUC1 full-length cDNA were found in the rice genome database and northern blot analysis confirmed their existence in rice tissues. The longer transcript (OsNUC1-L) putatively encodes for a protein with a serine rich N-terminal, RNA recognition motifs in the central domain and a glycine- and arginine-rich repeat in the C-terminal domain, while the shorter one (OsNUC1-S) putatively encodes for the similar protein without the N-terminus. Without salt stress, OsNUC1-L expressing Arabidopsis thaliana Atnuc1-L1 plants displayed a substantial but incomplete revertant phenotype, whereas OsNUC1-S expression only induced a weak effect. However, under 0.5% (w/v) NaCl salt stress they displayed a higher relative growth rate, longer root length and a lower H2O2 level than the wild type plants, suggesting a higher salt resistance. Moreover, they displayed elevated AtSOS1 and AtP5CS1 transcript levels. We propose that OsNUC1-S plays an important role in salt resistance during salt stress, a new role for nucleolin in plants. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

The phenotype of mes-2, mes-3, mes-4 and mes-6, maternal-effect genes required for survival of the germline in Caenorhabditis elegans, is sensitive to chromosome dosage.

PubMed Central

Garvin, C; Holdeman, R; Strome, S

1998-01-01

Mutations in mes-2, mes-3, mes-4, and mes-6 result in maternal-effect sterility: hermaphrodite offspring of mes/mes mothers are sterile because of underproliferation and death of the germ cells, as well as an absence of gametes. Mutant germ cells do not undergo programmed cell death, but instead undergo a necrotic-type death, and their general poor health apparently prevents surviving germ cells from forming gametes. Male offspring of mes mothers display a significantly less severe germline phenotype than their hermaphrodite siblings, and males are often fertile. This differential response of hermaphrodite and male offspring to the absence of mes+ product is a result of their different X chromosome compositions; regardless of their sexual phenotype, XX worms display a more severe germline phenotype than XO worms, and XXX worms display the most severe phenotype. The sensitivity of the mutant phenotype to chromosome dosage, along with the similarity of two MES proteins to chromatin-associated regulators of gene expression in Drosophila, suggest that the essential role of the mes genes is in control of gene expression in the germline. An additional, nonessential role of the mes genes in the soma is suggested by the surprising finding that mutations in the mes genes, like mutations in dosage compensation genes, feminize animals whose male sexual identity is somewhat ambiguous. We hypothesize that the mes genes encode maternally supplied regulators of chromatin structure and gene expression in the germline and perhaps in somatic cells of the early embryo, and that at least some of their targets are on the X chromosomes. PMID:9475730

The reduced local lymph node assay: the impact of group size.

PubMed

Ryan, Cindy A; Chaney, Joel G; Kern, Petra S; Patlewicz, Grace Y; Basketter, David A; Betts, Catherine J; Dearman, Rebecca J; Kimber, Ian; Gerberick, G Frank

2008-05-01

The local lymph node assay (LLNA) is a skin sensitization test that provides animal welfare benefits. To reduce animal usage further, a modified version (rLLNA) was proposed. Conducting the rLLNA as a screening test with a single high dose group and vehicle control differentiated accurately between skin sensitizers and non-sensitizers. This study examined whether a reduction in animal number/group is feasible. Historical data were utilized to examine the impact of conducting the rLLNA with two mice/group. To assess the effect on the stimulation index (SI) 41 datasets with individual animal data derived using five mice/group were analysed. SIs were calculated on all possible combinations of two control and two high dose group disintegrations per minute (dpm) values. For 25 of 33 sensitizer datasets, > 96% of possible dpm combinations resulted in a calculated SI > 3. The lowest percentages of positive SIs were observed with weak allergens when, in the standard LLNA, the mean SIs would have been nearer to the threshold value of 3. The results indicate that moderate, strong and extreme allergens are more likely than weak allergens to be identified as sensitizers when group sizes of two mice are used within the rLLNA. It is concluded that a rLLNA with two mice/group would display decreased sensitivity and is inappropriate for use in hazard identification. Copyright (c) 2007 John Wiley & Sons, Ltd.

Comparison of the antidepressant sertraline on differential depression-like behaviors elicited by restraint stress and repeated corticosterone administration.

PubMed

Ulloa, J L; Castañeda, P; Berríos, C; Díaz-Veliz, G; Mora, S; Bravo, J A; Araneda, K; Menares, C; Morales, P; Fiedler, J L

2010-12-01

Depressive disorder involves emotional, cognitive, autonomic and endocrine alterations and also evidences support the role of stress in the development of this disorder. Because the hypothalamic-pituitary-adrenal axis is involved in the stress response with a concomitant rise in plasma corticoids, the present study compares the antidepressant effects of sertraline (10mg/kg, i.p.) on behavioral changes elicited by (i) restraint stress (2.5h/day for 13days) and (ii) corticosterone injections (30mg/kg, s.c., for 13days). Stressed animals, but not corticosterone-treated animals displayed anxiety behavior and a reduction in the acquisition of a conditioned avoidance response to 25% of control levels (8.0±2.2 vs. 31.7±3.2), being this effect partly sensitive to sertraline. Stressed, but not corticosterone-treated, animals displayed an increased escape failure compared with the control group (24.6%±3.5 vs. 1.6±0.7), an effect partly prevented by sertraline treatment (7.3%±2.0). Both stressed rats and corticosterone-treated rats showed an increase in immobility in the forced swim test, an effect prevented by sertraline. These results suggest that the altered behaviors elicited by stress and corticosterone can be explained by neural modifications that are sensitive to the sertraline antidepressant. Copyright © 2010 Elsevier Inc. All rights reserved.

Intrinsic cardiac nervous system in tachycardia induced heart failure.

PubMed

Arora, Rakesh C; Cardinal, Rene; Smith, Frank M; Ardell, Jeffrey L; Dell'Italia, Louis J; Armour, J Andrew

2003-11-01

The purpose of this study was to test the hypothesis that early-stage heart failure differentially affects the intrinsic cardiac nervous system's capacity to regulate cardiac function. After 2 wk of rapid ventricular pacing in nine anesthetized canines, cardiac and right atrial neuronal function were evaluated in situ in response to enhanced cardiac sensory inputs, stimulation of extracardiac autonomic efferent neuronal inputs, and close coronary arterial administration of neurochemicals that included nicotine. Right atrial neuronal intracellular electrophysiological properties were then evaluated in vitro in response to synaptic activation and nicotine. Intrinsic cardiac nicotine-sensitive, neuronally induced cardiac responses were also evaluated in eight sham-operated, unpaced animals. Two weeks of rapid ventricular pacing reduced the cardiac index by 54%. Intrinsic cardiac neurons of paced hearts maintained their cardiac mechano- and chemosensory transduction properties in vivo. They also responded normally to sympathetic and parasympathetic preganglionic efferent neuronal inputs, as well as to locally administered alpha-or beta-adrenergic agonists or angiotensin II. The dose of nicotine needed to modify intrinsic cardiac neurons was 50 times greater in failure compared with normal preparations. That dose failed to alter monitored cardiovascular indexes in failing preparations. Phasic and accommodating neurons identified in vitro displayed altered intracellular membrane properties compared with control, including decreased membrane resistance, indicative of reduced excitability. Early-stage heart failure differentially affects the intrinsic cardiac nervous system's capacity to regulate cardiodynamics. While maintaining its capacity to transduce cardiac mechano- and chemosensory inputs, as well as inputs from extracardiac autonomic efferent neurons, intrinsic cardiac nicotine-sensitive, local-circuit neurons differentially remodel such that their capacity to influence cardiodynamics becomes obtunded.

Useful information provided by graphic displays of automated cell counter in hematological malignancies.

PubMed

Gupta, Monica; Chauhan, Kriti; Singhvi, Tanvi; Kumari, Manisha; Grover, Rajesh Kumar

2018-01-21

Automated cell counters have become more and more sophisticated with passing years. The numerical and graphic data both provide useful clues for suspecting a diagnosis especially when the workload is very high. We present our experience of useful information provided by graphic displays of an automated cell counter in hematological malignancies in a cancer hospital where a large number of complete blood count (CBC) requests are received either before or during chemotherapy. This study was conducted to assess the usefulness of hematology cell counter, viz. WBC-Diff (WBC differential), WBC/BASO (WBC basophil) and IMI (immature myeloid information) channel scatter plots, and the flaggings generated in various hematological malignancies. The graphic displays have been compiled over a period of 1 year (October 2015-September 2016) from blood samples of various solid and hematological malignancies (approximately 400 per day) received for routine CBC in the laboratory. Approximately 50 000 scattergrams have been analyzed during the study period. The findings were confirmed by peripheral blood smear examination. The scattergram analysis on XE-2100 is very sensitive as well as specific for diagnosing acute leukemia, viz. acute myeloid leukemia, acute lymphoblastic leukemia; chronic myeloproliferative disorders, viz. chronic myeloid leukemia; and chronic lymphoproliferative disorder especially chronic lymphocytic leukemia. It is suggested that the laboratories using the hematology analyzers be aware of graphic display patterns in addition to flaggings generated which provide additional information and give clue toward the diagnosis even before peripheral smear examination. © 2018 Wiley Periodicals, Inc.

Enhanced visualization of inner ear structures

NASA Astrophysics Data System (ADS)

Niemczyk, Kazimierz; Kucharski, Tomasz; Kujawinska, Malgorzata; Bruzgielewicz, Antoni

2004-07-01

Recently surgery requires extensive support from imaging technologies in order to increase effectiveness and safety of operations. One of important tasks is to enhance visualisation of quasi-phase (transparent) 3d structures. Those structures are characterized by very low contrast. It makes differentiation of tissues in field of view very difficult. For that reason the surgeon may be extremly uncertain during operation. This problem is connected with supporting operations of inner ear during which physician has to perform cuts at specific places of quasi-transparent velums. Conventionally during such operations medical doctor views the operating field through stereoscopic microscope. In the paper we propose a 3D visualisation system based on Helmet Mounted Display. Two CCD cameras placed at the output of microscope perform acquisition of stereo pairs of images. The images are processed in real-time with the goal of enhancement of quasi-phased structures. The main task is to create algorithm that is not sensitive to changes in intensity distribution. The disadvantages of existing algorithms is their lack of adaptation to occuring reflexes and shadows in field of view. The processed images from both left and right channels are overlaid on the actual images exported and displayed at LCD's of Helmet Mounted Display. A physician observes by HMD (Helmet Mounted Display) a stereoscopic operating scene with indication of the places of special interest. The authors present the hardware ,procedures applied and initial results of inner ear structure visualisation. Several problems connected with processing of stereo-pair images are discussed.

Google Glass Glare: disability glare produced by a head-mounted visual display.

PubMed

Longley, Chris; Whitaker, David

2016-03-01

Head mounted displays are a type of wearable technology - a market that is projected to expand rapidly over the coming years. Probably the most well known example is the device Google Glass (or 'Glass'). Here we investigate the extent to which the device display can interfere with normal visual function by producing monocular disability glare. Contrast sensitivity was measured in two normally sighted participants, 32 and 52 years of age. Data were recorded for the right eye, the left eye and then again in a binocular condition. Measurements were taken both with and without the Glass in place, across a range of stimulus luminance levels using a two-alternative forced-choice methodology. The device produced a significant reduction in contrast sensitivity in the right eye (>0.5 log units). The level of disability glare increased as stimulus luminance was reduced in a manner consistent with intraocular light scatter, resulting in a veiling retinal illuminance. Sensitivity in the left eye was unaffected. A significant reduction in binocular contrast sensitivity occurred at lower luminance levels due to a loss of binocular summation, although binocular sensitivity was not found to fall below the sensitivity of the better monocular level (binocular inhibition). Head mounted displays such as Google Glass have the potential to cause significant disability glare in the eye exposed to the visual display, particularly under conditions of low luminance. They can also cause a more modest binocular reduction in sensitivity by eliminating the benefits of binocular summation. © 2015 The Authors Ophthalmic & Physiological Optics © 2015 The College of Optometrists.

Expression of cardiac neural crest and heart genes isolated by modified differential display.

PubMed

Martinsen, Brad J; Groebner, Nathan J; Frasier, Allison J; Lohr, Jamie L

2003-08-01

The invasion of the cardiac neural crest (CNC) into the outflow tract (OFT) and subsequent outflow tract septation are critical events during vertebrate heart development. We have performed four modified differential display screens in the chick embryo to identify genes that may be involved in CNC, OFT, secondary heart field, and heart development. The screens included differential display of RNA isolated from three different axial segments containing premigratory cranial neural crest cells; of RNA from distal outflow tract, proximal outflow tract, and atrioventricular tissue of embryonic chick hearts; and of RNA isolated from left and right cranial tissues, including the early heart fields. These screens have resulted in the identification of the five cDNA clones presented here, which are expressed in the cardiac neural crest, outflow tract and developing heart in patterns that are unique in heart development.

Trait motivation moderates neural activation associated with goal pursuit

PubMed Central

Miller, Gregory A.; Warren, Stacie L.; Engels, Anna S.; Crocker, Laura D.; Sutton, Bradley P.; Heller, Wendy

2012-01-01

Research has indicated that regions of left and right dorsolateral prefrontal cortex (DLPFC) are involved in integrating the motivational and executive function processes related to, respectively, approach and avoidance goals. Given that sensitivity to pleasant and unpleasant stimuli is an important feature of conceptualizations of approach and avoidance motivation, it is possible that these regions of DLPFC are preferentially activated by valenced stimuli. The present study tested this hypothesis by using a task in which goal pursuit was threatened by distraction from valenced stimuli while functional magnetic resonance imaging data were collected. The analyses examined whether the impact of trait approach and avoidance motivation on the neural processes associated with executive function differed depending on the valence or arousal level of the distractor stimuli. The present findings support the hypothesis that the regions of DLPFC under investigation are involved in integrating motivational and executive function processes, and they also indicate the involvement of a number of other brain areas in maintaining goal pursuit. However, DLPFC did not display differential sensitivity to valence. PMID:22460723

Trait motivation moderates neural activation associated with goal pursuit.

PubMed

Spielberg, Jeffrey M; Miller, Gregory A; Warren, Stacie L; Engels, Anna S; Crocker, Laura D; Sutton, Bradley P; Heller, Wendy

2012-06-01

Research has indicated that regions of left and right dorsolateral prefrontal cortex (DLPFC) are involved in integrating the motivational and executive function processes related to, respectively, approach and avoidance goals. Given that sensitivity to pleasant and unpleasant stimuli is an important feature of conceptualizations of approach and avoidance motivation, it is possible that these regions of DLPFC are preferentially activated by valenced stimuli. The present study tested this hypothesis by using a task in which goal pursuit was threatened by distraction from valenced stimuli while functional magnetic resonance imaging data were collected. The analyses examined whether the impact of trait approach and avoidance motivation on the neural processes associated with executive function differed depending on the valence or arousal level of the distractor stimuli. The present findings support the hypothesis that the regions of DLPFC under investigation are involved in integrating motivational and executive function processes, and they also indicate the involvement of a number of other brain areas in maintaining goal pursuit. However, DLPFC did not display differential sensitivity to valence.

Extreme sensitivity to ultraviolet light in the fungal pathogen causing white-nose syndrome of bats.

PubMed

Palmer, Jonathan M; Drees, Kevin P; Foster, Jeffrey T; Lindner, Daniel L

2018-01-02

Bat white-nose syndrome (WNS), caused by the fungal pathogen Pseudogymnoascus destructans, has decimated North American hibernating bats since its emergence in 2006. Here, we utilize comparative genomics to examine the evolutionary history of this pathogen in comparison to six closely related nonpathogenic species. P. destructans displays a large reduction in carbohydrate-utilizing enzymes (CAZymes) and in the predicted secretome (~50%), and an increase in lineage-specific genes. The pathogen has lost a key enzyme, UVE1, in the alternate excision repair (AER) pathway, which is known to contribute to repair of DNA lesions induced by ultraviolet (UV) light. Consistent with a nonfunctional AER pathway, P. destructans is extremely sensitive to UV light, as well as the DNA alkylating agent methyl methanesulfonate (MMS). The differential susceptibility of P. destructans to UV light in comparison to other hibernacula-inhabiting fungi represents a potential "Achilles' heel" of P. destructans that might be exploited for treatment of bats with WNS.

Adaptive controller for volumetric display of neuroimaging studies

NASA Astrophysics Data System (ADS)

Bleiberg, Ben; Senseney, Justin; Caban, Jesus

2014-03-01

Volumetric display of medical images is an increasingly relevant method for examining an imaging acquisition as the prevalence of thin-slice imaging increases in clinical studies. Current mouse and keyboard implementations for volumetric control provide neither the sensitivity nor specificity required to manipulate a volumetric display for efficient reading in a clinical setting. Solutions to efficient volumetric manipulation provide more sensitivity by removing the binary nature of actions controlled by keyboard clicks, but specificity is lost because a single action may change display in several directions. When specificity is then further addressed by re-implementing hardware binary functions through the introduction of mode control, the result is a cumbersome interface that fails to achieve the revolutionary benefit required for adoption of a new technology. We address the specificity versus sensitivity problem of volumetric interfaces by providing adaptive positional awareness to the volumetric control device by manipulating communication between hardware driver and existing software methods for volumetric display of medical images. This creates a tethered effect for volumetric display, providing a smooth interface that improves on existing hardware approaches to volumetric scene manipulation.

Ap4A induces apoptosis in human cultured cells.

PubMed

Vartanian, A; Alexandrov, I; Prudowski, I; McLennan, A; Kisselev, L

1999-07-30

Diadenosine oligophosphates (Ap(n)A) have been proposed as intracellular and extracellular signaling molecules in animal cells. The ratio of diadenosine 5',5'''-P1,P3-triphosphate to diadenosine 5',5'''-P1,P4-tetraphosphate (Ap3A/Ap4A) is sensitive to the cellular status and alters when cultured cells undergo differentiation or are treated with interferons. In cells undergoing apoptosis induced by DNA topoisomerase II inhibitor VP16, the concentration of Ap3A decreases significantly while that of Ap4A increases. Here, we have examined the effects of exogenously added Ap3A and Ap4A on apoptosis and morphological differentiation. Penetration of Ap(n)A into cells was achieved by cold shock. Ap4A at 10 microM induced programmed cell death in human HL60, U937 and Jurkat cells and mouse VMRO cells and this effect appeared to require Ap4A breakdown as hydrolysis-resistant analogues of Ap4A were inactive. On its own, Ap3A induced neither apoptosis nor cell differentiation but did display strong synergism with the protein kinase C activators 12-deoxyphorbol-13-O-phenylacetate and 12-deoxyphorbol-13-O-phenylacetate-20-acetate in inducing differentiation of HL60 cells. We propose that Ap4A and Ap3A are physiological antagonists in determination of the cellular status: Ap4A induces apoptosis whereas Ap3A is a co-inductor of differentiation. In both cases, the mechanism of signal transduction remains unknown.

Contrasting eigenvalue and singular-value spectra for lasing and antilasing in a PT -symmetric periodic structure

NASA Astrophysics Data System (ADS)

Ge, Li; Feng, Liang

2017-01-01

It has been proposed and demonstrated that lasing and coherent perfect absorption (CPA or "antilasing") coexist in parity-time (PT ) symmetric photonic systems. In this work we show that the spectral signature of such a CPA laser displayed by the singular value spectrum of the scattering matrix (S ) can be orders of magnitude wider than that displayed by the eigenvalue spectrum of S . Since the former reflects how strongly light can be absorbed or amplified and the latter announces the spontaneous symmetry breaking of S , these contrasting spectral signatures indicate that near perfect absorption and extremely strong amplification can be achieved even in the PT -symmetric phase of S , which is known for and defined by its flux-conserving eigenstates. We also show that these contrasting spectral signatures are accompanied by strikingly different sensitivities to disorder and imperfection, suggesting that the eigenvalue spectrum is potentially suitable for sensing and the singular value spectrum for robust switching. A differential light amplifier may also be devised based on these two spectra.

Extracting Depth From Motion Parallax in Real-World and Synthetic Displays

NASA Technical Reports Server (NTRS)

Hecht, Heiko; Kaiser, Mary K.; Aiken, William; Null, Cynthia H. (Technical Monitor)

1994-01-01

In psychophysical studies on human sensitivity to visual motion parallax (MP), the use of computer displays is pervasive. However, a number of potential problems are associated with such displays: cue conflicts arise when observers accommodate to the screen surface, and observer head and body movements are often not reflected in the displays. We investigated observers' sensitivity to depth information in MP (slant, depth order, relative depth) using various real-world displays and their computer-generated analogs. Angle judgments of real-world stimuli were consistently superior to judgments that were based on computer-generated stimuli. Similar results were found for perceived depth order and relative depth. Perceptual competence of observers tends to be underestimated in research that is based on computer generated displays. Such findings cannot be generalized to more realistic viewing situations.

Dishevelled3 is a novel arginine methyl transferase substrate.

PubMed

Bikkavilli, Rama Kamesh; Avasarala, Sreedevi; Vanscoyk, Michelle; Sechler, Marybeth; Kelley, Nicole; Malbon, Craig C; Winn, Robert A

2012-01-01

Dishevelled, a phosphoprotein scaffold, is a central component in all the Wnt-sensitive signaling pathways. In the present study, we report that Dishevelled is post-translationally modified, both in vitro and in vivo, via arginine methylation. We also show protein arginine methyl transferases 1 and 7 as the key enzymes catalyzing Dishevelled methylation. Interestingly, Wnt3a stimulation of F9 teratocarcinoma cells results in reduced Dishevelled methylation. Similarly, the methylation-deficient mutant of Dishevelled, R271K, displayed spontaneous membrane localization and robust activation of Wnt signaling; suggesting that differential methylation of Dishevelled plays an important role in Wnt signaling. Thus arginine methylation is shown to be an important switch in regulation of Dishevelled function and Wnt signaling.

Melanocortin-1 receptor gene variants affect pain and µ-opioid analgesia in mice and humans

PubMed Central

Mogil, J; Ritchie, J; Smith, S; Strasburg, K; Kaplan, L; Wallace, M; Romberg, R; Bijl, H; Sarton, E; Fillingim, R; Dahan, A

2005-01-01

Background: A recent genetic study in mice and humans revealed the modulatory effect of MC1R (melanocortin-1 receptor) gene variants on κ-opioid receptor mediated analgesia. It is unclear whether this gene affects basal pain sensitivity or the efficacy of analgesics acting at the more clinically relevant µ-opioid receptor. Objective: To characterise sensitivity to pain and µ-opioid analgesia in mice and humans with non-functional melanocortin-1 receptors. Methods: Comparisons of spontaneous mutant C57BL/6-Mc1re/e mice to C57BL/6 wildtype mice, followed by a gene dosage study of pain and morphine-6-glucuronide (M6G) analgesia in humans with MC1R variants. Results: C57BL/6-Mc1re/e mutant mice and human redheads—both with non-functional MC1Rs—display reduced sensitivity to noxious stimuli and increased analgesic responsiveness to the µ-opioid selective morphine metabolite, M6G. In both species the differential analgesia is likely due to pharmacodynamic factors, as plasma levels of M6G are similar across genotype. Conclusions: Genotype at MC1R similarly affects pain sensitivity and M6G analgesia in mice and humans. These findings confirm the utility of cross species translational strategies in pharmacogenetics. PMID:15994880

Abnormal social reward processing in autism as indexed by pupillary responses to happy faces

PubMed Central

2012-01-01

Background Individuals with Autism Spectrum Disorders (ASD) typically show impaired eye contact during social interactions. From a young age, they look less at faces than typically developing (TD) children and tend to avoid direct gaze. However, the reason for this behavior remains controversial; ASD children might avoid eye contact because they perceive the eyes as aversive or because they do not find social engagement through mutual gaze rewarding. Methods We monitored pupillary diameter as a measure of autonomic response in children with ASD (n = 20, mean age = 12.4) and TD controls (n = 18, mean age = 13.7) while they looked at faces displaying different emotions. Each face displayed happy, fearful, angry or neutral emotions with the gaze either directed to or averted from the subjects. Results Overall, children with ASD and TD controls showed similar pupillary responses; however, they differed significantly in their sensitivity to gaze direction for happy faces. Specifically, pupillary diameter increased among TD children when viewing happy faces with direct gaze as compared to those with averted gaze, whereas children with ASD did not show such sensitivity to gaze direction. We found no group differences in fixation that could explain the differential pupillary responses. There was no effect of gaze direction on pupil diameter for negative affect or neutral faces among either the TD or ASD group. Conclusions We interpret the increased pupillary diameter to happy faces with direct gaze in TD children to reflect the intrinsic reward value of a smiling face looking directly at an individual. The lack of this effect in children with ASD is consistent with the hypothesis that individuals with ASD may have reduced sensitivity to the reward value of social stimuli. PMID:22958650

Robotic crabs reveal that female fiddler crabs are sensitive to changes in male display rate.

PubMed

Mowles, Sophie L; Jennions, Michael D; Backwell, Patricia R Y

2018-01-01

Males often produce dynamic, repetitive courtship displays that can be demanding to perform and might advertise male quality to females. A key feature of demanding displays is that they can change in intensity: escalating as a male increases his signalling effort, but de-escalating as a signaller becomes fatigued. Here, we investigated whether female fiddler crabs, Uca mjoebergi , are sensitive to changes in male courtship wave rate. We performed playback experiments using robotic male crabs that had the same mean wave rate, but either escalated, de-escalated or remained constant. Females demonstrated a strong preference for escalating robots, but showed mixed responses to robots that de-escalated ('fast' to 'slow') compared to those that waved at a constant 'medium' rate. These findings demonstrate that females can discern changes in male display rate, and prefer males that escalate, but that females are also sensitive to past display rates indicative of prior vigour. © 2018 The Authors.

Selective voltammetric determination of Cd(II) by using N,S-codoped porous carbon nanofibers.

PubMed

Gao, Sanshuang; Liu, Jing; Luo, Jun; Mamat, Xamxikamar; Sambasivam, Sangaraju; Li, Yongtao; Hu, Xun; Wågberg, Thomas; Hu, Guangzhi

2018-05-05

Porous carbon nanofibers codoped with nitrogen and sulfur (NFs) were prepared by pyrolysis of trithiocyanuric acid, silica nanospheres and polyacrylonitrile (PAN) followed by electrospinning. The NFs were used to modify a glassy carbon electrode (GCE) which then displayed highly sensitive response to traces of Cd(II). Compared to a bare GCE and a Nafion modified GCE, the GCE modified with codoped NFs shows improved sensitivity for Cd(II) in differential pulse anodic sweep voltammetry. The stripping peak current (typically measured at 0.81 V vs. Ag/AgCl) increases linearly in the 2.0-500 μg·L -1 Cd(II) concentration range. This is attributed to the large surface area (109 m 2 ·g -1 ), porous structure, and high fraction of heteroatoms (19 at.% of N and 0.75 at.% of S). The method was applied to the determination of Cd(II) in (spiked) tap water where it gave recoveries that ranged between 96% and 103%. Graphical abstract Schematic of a glassy carbon electrode (GCE) modified with N- and S-codoped porous carbon nanofibers (N,S-PCNFs). This GCE has good selectivity for cadmium ion (Cd 2+ ) which can be determined by differential pulse anodic sweeping voltammetry (DPASV) with a detection limit as low as 0.7 ng·mL -1 .

Preventative effect of an herbal preparation (HemoHIM) on development of airway inflammation in mice via modulation of Th1/2 cells differentiation.

PubMed

Kim, Jong-Jin; Cho, Hyun Wook; Park, Hae-Ran; Jung, Uhee; Jo, Sung-Kee; Yee, Sung-Tae

2013-01-01

HemoHIM, an herbal preparation of three edible herbs (Angelica gigas Nakai, Cnidium officinale Makino, Paeonia japonica Miyabe) is known to increase the Th1 immune response as well as reduce the allergic response in human mast cells. Here, our goal was to determine whether or not HemoHIM could induce Th1 cell differentiation as well as inhibit the development of airway inflammation. To study Th1/Th2 cell differentiation, naive CD4(+) T cells isolated from C57BL/6 mouse spleens were cultured with or without HemoHIM. To examine airway inflammation, C57BL/6 mice were fed HemoHIM for 4 weeks before sensitization and provocation with ovalbumin (OVA). In an in vitro experiment, naive CD4(+) T cells displayed increased Th1 (IFN-γ(+) cell) as well as decreased Th2 (IL-4(+) cell) differentiation in a HemoHIM concentration-dependent manner. Furthermore, in an airway inflammation mice model, eosinophil numbers in BALF, serum levels of OVA-specific IgE and IgG1, and cytokine (IL-4, IL-5, and IL-13) levels in BALF and the supernatant of splenocytes all decreased upon HemoHIM (100 mg/kg body weight) pretreatment (4 weeks). These results show that HemoHIM attenuated allergic airway inflammation in the mouse model through regulation of the Th1/Th2 balance.

Isolation of genes negatively or positively co-expressed with human recombination activating gene 1 (RAG1) by differential display PCR (DD RT-PCR).

PubMed

Verkoczy, L K; Berinstein, N L

1998-10-01

Differential display PCR (DD RT-PCR) has been extensively used for analysis of differential gene expression, but continues to be hampered by technical limitations that impair its effectiveness. In order to isolate novel genes co-expressing with human RAG1, we have developed an effective, multi-tiered screening/purification approach which effectively complements the standard DD RT-PCR methodology. In 'primary' screens, standard DD RT-PCR was used, detecting 22 reproducible differentially expressed amplicons between clonally related cell variants with differential constitutive expression of RAG mRNAs. 'Secondary' screens used differential display (DD) amplicons as probes in low and high stringency northern blotting. Eight of 22 independent DD amplicons detected nine independent differentially expressed transcripts. 'Tertiary' screens used reconfirmed amplicons as probes in northern analysis of multiple RAG-and RAG+sources. Reconfirmed DD amplicons detected six independent RAG co-expressing transcripts. All DD amplicons reconfirmed by northern blot were a heterogeneous mixture of cDNAs, necessitating further purification to isolate single cDNAs prior to subcloning and sequencing. To effectively select the appropriate cDNAs from DD amplicons, we excised and eluted the cDNA(s) directly from regions of prior northern blots in which differentially expressed transcripts were detected. Sequences of six purified cDNA clones specifically detecting RAG co-expressing transcripts included matches to portions of the human RAG2 and BSAP regions and to four novel partial cDNAs (three with homologies to human ESTs). Overall, our results also suggest that even when using clonally related variants from the same cell line in addition to all appropriate internal controls previously reported, further screening and purification steps are still required in order to efficiently and specifically isolate differentially expressed genes by DD RT-PCR.

Increased Mitochondrial Calcium Sensitivity and Abnormal Expression of Innate Immunity Genes Precede Dopaminergic Defects in Pink1-Deficient Mice

PubMed Central

Akundi, Ravi S.; Huang, Zhenyu; Eason, Joshua; Pandya, Jignesh D.; Zhi, Lianteng; Cass, Wayne A.; Sullivan, Patrick G.; Büeler, Hansruedi

2011-01-01

Background PTEN-induced kinase 1 (PINK1) is linked to recessive Parkinsonism (EOPD). Pink1 deletion results in impaired dopamine (DA) release and decreased mitochondrial respiration in the striatum of mice. To reveal additional mechanisms of Pink1-related dopaminergic dysfunction, we studied Ca2+ vulnerability of purified brain mitochondria, DA levels and metabolism and whether signaling pathways implicated in Parkinson's disease (PD) display altered activity in the nigrostriatal system of Pink1−/− mice. Methods and Findings Purified brain mitochondria of Pink1−/− mice showed impaired Ca2+ storage capacity, resulting in increased Ca2+ induced mitochondrial permeability transition (mPT) that was rescued by cyclosporine A. A subpopulation of neurons in the substantia nigra of Pink1−/− mice accumulated phospho-c-Jun, showing that Jun N-terminal kinase (JNK) activity is increased. Pink1−/− mice 6 months and older displayed reduced DA levels associated with increased DA turnover. Moreover, Pink1−/− mice had increased levels of IL-1β, IL-12 and IL-10 in the striatum after peripheral challenge with lipopolysaccharide (LPS), and Pink1−/− embryonic fibroblasts showed decreased basal and inflammatory cytokine-induced nuclear factor kappa-β (NF-κB) activity. Quantitative transcriptional profiling in the striatum revealed that Pink1−/− mice differentially express genes that (i) are upregulated in animals with experimentally induced dopaminergic lesions, (ii) regulate innate immune responses and/or apoptosis and (iii) promote axonal regeneration and sprouting. Conclusions Increased mitochondrial Ca2+ sensitivity and JNK activity are early defects in Pink1−/− mice that precede reduced DA levels and abnormal DA homeostasis and may contribute to neuronal dysfunction in familial PD. Differential gene expression in the nigrostriatal system of Pink1−/− mice supports early dopaminergic dysfunction and shows that Pink1 deletion causes aberrant expression of genes that regulate innate immune responses. While some differentially expressed genes may mitigate neurodegeneration, increased LPS-induced brain cytokine expression and impaired cytokine-induced NF-κB activation may predispose neurons of Pink1−/− mice to inflammation and injury-induced cell death. PMID:21249202

Monkey Pulvinar Neurons Fire Differentially to Snake Postures

PubMed Central

Le, Quan Van; Isbell, Lynne A.; Matsumoto, Jumpei; Le, Van Quang; Hori, Etsuro; Tran, Anh Hai; Maior, Rafael S.; Tomaz, Carlos; Ono, Taketoshi; Nishijo, Hisao

2014-01-01

There is growing evidence from both behavioral and neurophysiological approaches that primates are able to rapidly discriminate visually between snakes and innocuous stimuli. Recent behavioral evidence suggests that primates are also able to discriminate the level of threat posed by snakes, by responding more intensely to a snake model poised to strike than to snake models in coiled or sinusoidal postures (Etting and Isbell 2014). In the present study, we examine the potential for an underlying neurological basis for this ability. Previous research indicated that the pulvinar is highly sensitive to snake images. We thus recorded pulvinar neurons in Japanese macaques (Macaca fuscata) while they viewed photos of snakes in striking and non-striking postures in a delayed non-matching to sample (DNMS) task. Of 821 neurons recorded, 78 visually responsive neurons were tested with the all snake images. We found that pulvinar neurons in the medial and dorsolateral pulvinar responded more strongly to snakes in threat displays poised to strike than snakes in non-threat-displaying postures with no significant difference in response latencies. A multidimensional scaling analysis of the 78 visually responsive neurons indicated that threat-displaying and non-threat-displaying snakes were separated into two different clusters in the first epoch of 50 ms after stimulus onset, suggesting bottom-up visual information processing. These results indicate that pulvinar neurons in primates discriminate between poised to strike from those in non-threat-displaying postures. This neuronal ability likely facilitates behavioral discrimination and has clear adaptive value. Our results are thus consistent with the Snake Detection Theory, which posits that snakes were instrumental in the evolution of primate visual systems. PMID:25479158

On the dependence of information display quality requirements upon human characteristics and pilot/automatics relations

NASA Technical Reports Server (NTRS)

Wilckens, V.

1972-01-01

Present information display concepts for pilot landing guidance are outlined considering manual control as well as substitution of man by fully competent automatics. Display improvements are achieved by compressing the distributed indicators into an accumulative display and thus reducing information scanning. Complete integration of quantitative indications, outer loop information, and real world display in a pictorial information channel geometry constitutes an interface with human ability to differentiate and integrate for optimal manual control of the aircraft.

Evaluation of an Erns-based enzyme-linked immunosorbent assay to distinguish Classical swine fever virus-infected pigs from pigs vaccinated with CP7_E2alf.

PubMed

Pannhorst, Katrin; Fröhlich, Andreas; Staubach, Christoph; Meyer, Denise; Blome, Sandra; Becher, Paul

2015-07-01

Infections with Classical swine fever virus (CSFV) are a major economic threat to pig production. To combat CSF outbreaks and to maintain trade, new marker vaccines were developed that allow differentiation of infected from vaccinated animals (DIVA principle). The chimeric pestivirus CP7_E2alf was shown to be safe and efficacious. Its DIVA strategy is based on the detection of CSFV E(rns)-specific antibodies that are only developed on infection. However, for the new marker vaccine to be considered a valuable control tool, a validated discriminatory assay is needed. One promising candidate is the already commercially available enzyme-linked immunosorbent assay, PrioCHECK CSFV E(rns) ELISA (Prionics BV, Lelystad, The Netherlands). Four laboratories of different European Union member states tested 530 serum samples and country-specific field sera from domestic pigs and wild boar. The ELISA displayed a good robustness. However, based on its reproducibility and repeatability, ranges rather than single values for diagnostic sensitivity and specificity were defined. The ELISA displayed a sensitivity of 90-98% with sera from CSFV-infected domestic pigs. A specificity of 89-96% was calculated with sera from domestic pigs vaccinated once with CP7_E2alf. The ELISA detected CSFV infections in vaccinated domestic pigs with a sensitivity of 82-94%. The sensitivity was lower with sera taken ≤21 days post-challenge indicating that the stage of CSFV infection had a considerable influence on testing. Taken together, the PrioCHECK CSFV E(rns) ELISA can be used for detection of CSFV infections in CP7_E2alf-vaccinated and nonvaccinated domestic pig populations, but should only be applied on a herd basis by testing a defined number of animals. © 2015 The Author(s).

Male specific genes from dioecious white campion identified by fluorescent differential display.

PubMed

Scutt, Charles P; Jenkins, Tom; Furuya, Masaki; Gilmartin, Philip M

2002-05-01

Fluorescent differential display (FDD) has been used to screen for cDNAs that are differentially up-regulated in male flowers of the dioecious plant Silene latifolia in which an X/Y chromosome system of sex determination operates. To adapt FDD to the cloning of large numbers of differential cDNAs, a novel method of confirming the differential expression of these has been devised. FDD gels were Southern electro-blotted and probed with mixtures of individual cDNA clones derived from different FDD product ligation reactions. These Southern blots were then stripped and re-probed with further mixtures of individual cloned FDD products to identify the maximum number of recombinant clones carrying the true differential amplification products. Of 135 differential bands identified by FDD, 56 differential amplification products were confirmed; these represent 23 unique differentially expressed genes as determined by virtual Northern analysis and two genes expressed at or below the level of detection by virtual Northern analysis. These two low expressed genes show bands of hybridization on genomic Southern blots that are specific to male plants, indicating that they are derived from, or closely related to, Y chromosome genes.

Comparative gene expression in sexual and apomictic ovaries of Pennisetum ciliare (L.) Link.

PubMed

Vielle-Calzada, J P; Nuccio, M L; Budiman, M A; Thomas, T L; Burson, B L; Hussey, M A; Wing, R A

1996-12-01

Limited emphasis has been given to the molecular study of apomixis, an asexual method of reproduction where seeds are produced without fertilization. Most buffelgrass (Pennisetum ciliare (L.) Link syn = Cenchrus ciliaris L.) genotypes reproduce by obligate apomixis (apospory); however, rare sexual plants have been recovered. A modified differential display procedure was used to compare gene expression in unpollinated ovaries containing ovules with either sexual or apomictic female gametophytes. The modification incorporated end-labeled poly(A)+ anchored primers as the only isotopic source, and was a reliable and consistent approach for detecting differentially displayed transcripts. Using 20 different decamers and two anchor primers, 2268 cDNA fragments between 200 and 600 bp were displayed. From these, eight reproducible differentially displayed cDNAs were identified and cloned. Based on northern analysis, one cDNA was detected in only the sexual ovaries, two cDNAs in only apomictic ovaries and one cDNA was present in both types of ovaries. Three fragments could not be detected and one fragment was detected in ovaries, stems, and leaves. Comparison of gene expression during sexual and apomictic development in buffelgrass represents a new model system and a strategy for investigating female reproductive development in the angiosperms.

Voltammetric determination of attomolar levels of a sequence derived from the genom of hepatitis B virus by using molecular beacon mediated circular strand displacement and rolling circle amplification.

PubMed

Huang, Shan; Feng, Mengmeng; Li, Jiawen; Liu, Yi; Xiao, Qi

2018-03-03

The authors describe an electrochemical method for the determination of the single-stranded DNA (ssDNA) oligonucleotide with a sequence derived from the genom of hepatitis B virus (HBV). It is making use of circular strand displacement (CSD) and rolling circle amplification (RCA) strategies mediated by a molecular beacon (MB). This ssDNA hybridizes with the loop portion of the MB immobilized on the surface of a gold electrode, while primer DNA also hybridizes with the rest of partial DNA sequences of MB. This triggers the MB-mediated CSD. The RCA is then initiated to produce a long DNA strand with multiple tandem-repeat sequences, and this results in a significant increase of the differential pulse voltammetric response of the electrochemical probe Methylene Blue at a rather low working potential of -0.24 V (vs. Ag/AgCl). Under optimal experimental conditions, the assay displays an ultrahigh sensitivity (with a 2.6 aM detection limit) and excellent selectivity. Response is linear in the 10 to 700 aM DNA concentration range. Graphical abstract Schematic of a voltammetric method for the determination of attomolar levels of target DNA. It is based on molecular beacon mediated circular strand displacement and rolling circle amplification strategies. Under optimal experimental conditions, the assay displays an ultrahigh sensitivity with a 2.6 aM detection limit and excellent selectivity.

Differential DNA methylation profiles of coding and non-coding genes define hippocampal sclerosis in human temporal lobe epilepsy

PubMed Central

Miller-Delaney, Suzanne F.C.; Bryan, Kenneth; Das, Sudipto; McKiernan, Ross C.; Bray, Isabella M.; Reynolds, James P.; Gwinn, Ryder; Stallings, Raymond L.

2015-01-01

Temporal lobe epilepsy is associated with large-scale, wide-ranging changes in gene expression in the hippocampus. Epigenetic changes to DNA are attractive mechanisms to explain the sustained hyperexcitability of chronic epilepsy. Here, through methylation analysis of all annotated C-phosphate-G islands and promoter regions in the human genome, we report a pilot study of the methylation profiles of temporal lobe epilepsy with or without hippocampal sclerosis. Furthermore, by comparative analysis of expression and promoter methylation, we identify methylation sensitive non-coding RNA in human temporal lobe epilepsy. A total of 146 protein-coding genes exhibited altered DNA methylation in temporal lobe epilepsy hippocampus (n = 9) when compared to control (n = 5), with 81.5% of the promoters of these genes displaying hypermethylation. Unique methylation profiles were evident in temporal lobe epilepsy with or without hippocampal sclerosis, in addition to a common methylation profile regardless of pathology grade. Gene ontology terms associated with development, neuron remodelling and neuron maturation were over-represented in the methylation profile of Watson Grade 1 samples (mild hippocampal sclerosis). In addition to genes associated with neuronal, neurotransmitter/synaptic transmission and cell death functions, differential hypermethylation of genes associated with transcriptional regulation was evident in temporal lobe epilepsy, but overall few genes previously associated with epilepsy were among the differentially methylated. Finally, a panel of 13, methylation-sensitive microRNA were identified in temporal lobe epilepsy including MIR27A, miR-193a-5p (MIR193A) and miR-876-3p (MIR876), and the differential methylation of long non-coding RNA documented for the first time. The present study therefore reports select, genome-wide DNA methylation changes in human temporal lobe epilepsy that may contribute to the molecular architecture of the epileptic brain. PMID:25552301

Implementation and Evaluation of a Fully Automated Multiplex Real-Time PCR Assay on the BD Max Platform to Detect and Differentiate Herpesviridae from Cerebrospinal Fluids

PubMed Central

Köller, Thomas; Kurze, Daniel; Lange, Mirjam; Scherdin, Martin; Podbielski, Andreas; Warnke, Philipp

2016-01-01

A fully automated multiplex real-time PCR assay—including a sample process control and a plasmid based positive control—for the detection and differentiation of herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2) and varicella-zoster virus (VZV) from cerebrospinal fluids (CSF) was developed on the BD Max platform. Performance was compared to an established accredited multiplex real time PCR protocol utilizing the easyMAG and the LightCycler 480/II, both very common devices in viral molecular diagnostics. For clinical validation, 123 CSF specimens and 40 reference samples from national interlaboratory comparisons were examined with both methods, resulting in 97.6% and 100% concordance for CSF and reference samples, respectively. Utilizing the BD Max platform revealed sensitivities of 173 (CI 95%, 88–258) copies/ml for HSV1, 171 (CI 95%, 148–194) copies/ml for HSV2 and 84 (CI 95%, 5–163) copies/ml for VZV. Cross reactivity could be excluded by checking 25 common viral, bacterial and fungal human pathogens. Workflow analyses displayed shorter test duration as well as remarkable fewer and easier preparation steps with the potential to reduce error rates occurring when manually assessing patient samples. This protocol allows for a fully automated PCR assay on the BD Max platform for the simultaneously detection of herpesviridae from CSF specimens. Singular or multiple infections due to HSV1, HSV2 and VZV can reliably be differentiated with good sensitivities. Control parameters are included within the assay, thereby rendering its suitability for current quality management requirements. PMID:27092772

Construction of a Lotus japonicus late nodulin expressed sequence tag library and identification of novel nodule-specific genes.

PubMed Central

Szczyglowski, K; Hamburger, D; Kapranov, P; de Bruijn, F J

1997-01-01

A range of novel expressed sequence tags (ESTs) associated with late developmental events during nodule organogenesis in the legume Lotus japonicus were identified using mRNA differential display; 110 differentially displayed polymerase chain reaction products were cloned and analyzed. Of 88 unique cDNAs obtained, 22 shared significant homology to DNA/protein sequences in the respective databases. This group comprises, among others, a nodule-specific homolog of protein phosphatase 2C, a peptide transporter protein, and a nodule-specific form of cytochrome P450. RNA gel-blot analysis of 16 differentially displayed ESTs confirmed their nodule-specific expression pattern. The kinetics of mRNA accumulation of the majority of the ESTs analyzed were found to resemble the expression pattern observed for the L. japonicus leghemoglobin gene. These results indicate that the newly isolated molecular markers correspond to genes induced during late developmental stages of L. japonicus nodule organogenesis and provide important, novel tools for the study of nodulation. PMID:9276951

Gene expression profiling data of Schizosaccharomyces pombe under nitrosative stress using differential display.

PubMed

Biswas, Pranjal; Majumdar, Uddalak; Ghosh, Sanjay

2016-03-01

Excess production of nitric oxide (NO) and reactive nitrogen intermediates (RNIs) causes nitrosative stress on cells. Schizosaccharomyces pombe was used as a model to study nitrosative stress response. In the present data article, we have used differential display to identify the differentially expressed genes in the fission yeast under nitrosative stress conditions. We have used pure NO donor compound detaNONOate at final concentrations of 0.1 mM and 1 mM to treat the cells for 15 min alongside control before studying their gene expression profiles. At both the treated conditions, we identified genes which were commonly repressed while several genes were induced upon both 0.1 mM and 1 mM treatments. The differentially expressed genes were further analyzed in DAVID and categorized into several different pathways.

Quantitative Proteomics Reveals Membrane Protein-Mediated Hypersaline Sensitivity and Adaptation in Halophilic Nocardiopsis xinjiangensis.

PubMed

Zhang, Yao; Li, Yanchang; Zhang, Yongguang; Wang, Zhiqiang; Zhao, Mingzhi; Su, Na; Zhang, Tao; Chen, Lingsheng; Wei, Wei; Luo, Jing; Zhou, Yanxia; Xu, Yongru; Xu, Ping; Li, Wenjun; Tao, Yong

2016-01-04

The genus Nocardiopsis is one of the most dominant Actinobacteria that survives in hypersaline environments. However, the adaptation mechanisms for halophilism are still unclear. Here, we performed isobaric tags for relative and absolute quantification based quantitative proteomics to investigate the functions of the membrane proteome after salt stress. A total of 683 membrane proteins were identified and quantified, of which 126 membrane proteins displayed salt-induced changes in abundance. Intriguingly, bioinformatics analyses indicated that these differential proteins showed two expression patterns, which were further validated by phenotypic changes and functional differences. The majority of ABC transporters, secondary active transporters, cell motility proteins, and signal transduction kinases were up-regulated with increasing salt concentration, whereas cell differentiation, small molecular transporter (ions and amino acids), and secondary metabolism proteins were significantly up-regulated at optimum salinity, but down-regulated or unchanged at higher salinity. The small molecule transporters and cell differentiation-related proteins acted as sensing proteins that played a more important biological role at optimum salinity. However, the ABC transporters for compatible solutes, Na(+)-dependent transporters, and cell motility proteins acted as adaptive proteins that actively counteracted higher salinity stress. Overall, regulation of membrane proteins may provide a major protection strategy against hyperosmotic stress.

Zika virus infection dysregulates human neural stem cell growth and inhibits differentiation into neuroprogenitor cells.

PubMed

Devhare, Pradip; Meyer, Keith; Steele, Robert; Ray, Ratna B; Ray, Ranjit

2017-10-12

The current outbreak of Zika virus-associated diseases in South America and its threat to spread to other parts of the world has emerged as a global health emergency. A strong link between Zika virus and microcephaly exists, and the potential mechanisms associated with microcephaly are under intense investigation. In this study, we evaluated the effect of Zika virus infection of Asian and African lineages (PRVABC59 and MR766) in human neural stem cells (hNSCs). These two Zika virus strains displayed distinct infection pattern and growth rates in hNSCs. Zika virus MR766 strain increased serine 139 phosphorylation of histone H2AX (γH2AX), a known early cellular response proteins to DNA damage. On the other hand, PRVABC59 strain upregulated serine 15 phosphorylation of p53, p21 and PUMA expression. MR766-infected cells displayed poly (ADP-ribose) polymerase (PARP) and caspase-3 cleavage. Interestingly, infection of hNSCs by both strains of Zika virus for 24 h, followed by incubation in astrocyte differentiation medium, induced rounding and cell death. However, astrocytes generated from hNSCs by incubation in differentiation medium when infected with Zika virus displayed minimal cytopathic effect at an early time point. Infected hNSCs incubated in astrocyte differentiating medium displayed PARP cleavage within 24-36 h. Together, these results showed that two distinct strains of Zika virus potentiate hNSC growth inhibition by different mechanisms, but both viruses strongly induce death in early differentiating neuroprogenitor cells even at a very low multiplicity of infection. Our observations demonstrate further mechanistic insights for impaired neuronal homeostasis during active Zika virus infection.

Zika virus infection dysregulates human neural stem cell growth and inhibits differentiation into neuroprogenitor cells

PubMed Central

Devhare, Pradip; Meyer, Keith; Steele, Robert; Ray, Ratna B; Ray, Ranjit

2017-01-01

The current outbreak of Zika virus-associated diseases in South America and its threat to spread to other parts of the world has emerged as a global health emergency. A strong link between Zika virus and microcephaly exists, and the potential mechanisms associated with microcephaly are under intense investigation. In this study, we evaluated the effect of Zika virus infection of Asian and African lineages (PRVABC59 and MR766) in human neural stem cells (hNSCs). These two Zika virus strains displayed distinct infection pattern and growth rates in hNSCs. Zika virus MR766 strain increased serine 139 phosphorylation of histone H2AX (γH2AX), a known early cellular response proteins to DNA damage. On the other hand, PRVABC59 strain upregulated serine 15 phosphorylation of p53, p21 and PUMA expression. MR766-infected cells displayed poly (ADP-ribose) polymerase (PARP) and caspase-3 cleavage. Interestingly, infection of hNSCs by both strains of Zika virus for 24 h, followed by incubation in astrocyte differentiation medium, induced rounding and cell death. However, astrocytes generated from hNSCs by incubation in differentiation medium when infected with Zika virus displayed minimal cytopathic effect at an early time point. Infected hNSCs incubated in astrocyte differentiating medium displayed PARP cleavage within 24–36 h. Together, these results showed that two distinct strains of Zika virus potentiate hNSC growth inhibition by different mechanisms, but both viruses strongly induce death in early differentiating neuroprogenitor cells even at a very low multiplicity of infection. Our observations demonstrate further mechanistic insights for impaired neuronal homeostasis during active Zika virus infection. PMID:29022904

Differential Expression of Immunogenic Proteins on Virulent Mycobacterium tuberculosis Clinical Isolates

PubMed Central

Klepp, Laura; Vazquez, Camila; Rocha, Roxana Valeria; Blanco, Federico Carlos; López, Beatriz; Bigi, Fabiana; Sasiain, María del Carmen

2014-01-01

Molecular epidemiology has revealed that Mycobacterium tuberculosis (Mtb), formerly regarded as highly conserved species, displays a considerable degree of genetic variability that can influence the outcome of the disease as well as the innate and adaptive immune response. Recent studies have demonstrated that Mtb families found worldwide today differ in pathology, transmissibility, virulence, and development of immune response. By proteomic approaches seven proteins that were differentially expressed between a local clinical isolate from Latin-American-Mediterranean (LAM) and from Haarlem (H) lineages were identified. In order to analyze the immunogenic ability, recombinant Rv2241, Rv0009, Rv0407, and Rv2624c proteins were produced for testing specific antibody responses. We found that these proteins induced humoral immune responses in patients with drug-sensitive and drug-resistant tuberculosis with substantial cross-reactivity among the four proteins. Moreover, such reactivity was also correlated with anti-Mtb-cell surface IgM, but not with anti-ManLAM, anti-PPD, or anti-Mtb-surface IgG antibodies. Therefore, the present results describe new Mtb antigens with potential application as biomarkers of TB. PMID:25105140

BRD4 localization to lineage-specific enhancers is associated with a distinct transcription factor repertoire

PubMed Central

Najafova, Zeynab; Tirado-Magallanes, Roberto; Subramaniam, Malayannan; Hossan, Tareq; Schmidt, Geske; Nagarajan, Sankari; Baumgart, Simon J.; Mishra, Vivek Kumar; Bedi, Upasana; Hesse, Eric; Knapp, Stefan; Hawse, John R.; Johnsen, Steven A.

2017-01-01

Proper temporal epigenetic regulation of gene expression is essential for cell fate determination and tissue development. The Bromodomain-containing Protein-4 (BRD4) was previously shown to control the transcription of defined subsets of genes in various cell systems. In this study we examined the role of BRD4 in promoting lineage-specific gene expression and show that BRD4 is essential for osteoblast differentiation. Genome-wide analyses demonstrate that BRD4 is recruited to the transcriptional start site of differentiation-induced genes. Unexpectedly, while promoter-proximal BRD4 occupancy correlated with gene expression, genes which displayed moderate expression and promoter-proximal BRD4 occupancy were most highly regulated and sensitive to BRD4 inhibition. Therefore, we examined distal BRD4 occupancy and uncovered a specific co-localization of BRD4 with the transcription factors C/EBPb, TEAD1, FOSL2 and JUND at putative osteoblast-specific enhancers. These findings reveal the intricacies of lineage specification and provide new insight into the context-dependent functions of BRD4. PMID:27651452

BRD4 localization to lineage-specific enhancers is associated with a distinct transcription factor repertoire.

PubMed

Najafova, Zeynab; Tirado-Magallanes, Roberto; Subramaniam, Malayannan; Hossan, Tareq; Schmidt, Geske; Nagarajan, Sankari; Baumgart, Simon J; Mishra, Vivek Kumar; Bedi, Upasana; Hesse, Eric; Knapp, Stefan; Hawse, John R; Johnsen, Steven A

2017-01-09

Proper temporal epigenetic regulation of gene expression is essential for cell fate determination and tissue development. The Bromodomain-containing Protein-4 (BRD4) was previously shown to control the transcription of defined subsets of genes in various cell systems. In this study we examined the role of BRD4 in promoting lineage-specific gene expression and show that BRD4 is essential for osteoblast differentiation. Genome-wide analyses demonstrate that BRD4 is recruited to the transcriptional start site of differentiation-induced genes. Unexpectedly, while promoter-proximal BRD4 occupancy correlated with gene expression, genes which displayed moderate expression and promoter-proximal BRD4 occupancy were most highly regulated and sensitive to BRD4 inhibition. Therefore, we examined distal BRD4 occupancy and uncovered a specific co-localization of BRD4 with the transcription factors C/EBPb, TEAD1, FOSL2 and JUND at putative osteoblast-specific enhancers. These findings reveal the intricacies of lineage specification and provide new insight into the context-dependent functions of BRD4. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Differential pulse voltammetric determination of acyclovir in pharmaceutical preparations using a pencil graphite electrode.

PubMed

Dilgin, Didem Giray; Karakaya, Serkan

2016-06-01

In this study, a new selective and sensitive voltammetric procedure for determination of acyclovir (ACV) was proposed using a disposable electrode, pencil graphite electrode (PGE). Cyclic and differential pulse voltammograms of ACV were recorded in Britton-Robinson buffer solution containing 0.10 M KCl with pH of 4.0 at PGE. The PGE displayed a very good electrochemical behavior with significant enhancement of the peak current compared to a glassy carbon electrode (GCE). Under experimental conditions, the PGE had a linear response range from 1.0 μM to 100.0 μM ACV with a detection limit of 0.3 μM (based on 3 Sb). Relative standard deviations of 4.8 and 3.6% were obtained for five successive determinations of 10.0 and 50.0 μM ACV, respectively, which indicate acceptable repeatability. This voltammetric method was successfully applied to the direct determination of ACV in real pharmaceutical samples. The effect of various interfering compounds on the ACV peak current was studied. Copyright © 2016 Elsevier B.V. All rights reserved.

A portable fluorescent sensing system using multiple LEDs

NASA Astrophysics Data System (ADS)

Shin, Young-Ho; Barnett, Jonathan Z.; Gutierrez-Wing, M. Teresa; Rusch, Kelly A.; Choi, Jin-Woo

2017-02-01

This paper presents a portable fluorescent sensing system that utilizes different light emitting diode (LED) excitation lights for multiple target detection. In order to identify different analytes, three different wavelengths (385 nm, 448 nm, and 590 nm) of excitation light emitting diodes were used to selectively stimulate the target analytes. A highly sensitive silicon photomultiplier (SiPM) was used to detect corresponding fluorescent signals from each analyte. Based on the unique fluorescent response of each analyte, it is possible to simultaneously differentiate one analyte from the other in a mixture of target analytes. A portable system was designed and fabricated consisting of a display module, battery, data storage card, and sample loading tray into a compact 3D-printed jig. The portable sensor system was demonstrated for quantification and differentiation of microalgae (Chlorella vulgaris) and cyanobacteria (Spirulina) by measuring fluorescent responses of chlorophyll a in microalgae and phycocyanin in cyanobacteria. Obtained results suggest that the developed portable sensor system could be used as a generic fluorescence sensor platform for on-site detection of multiple analytes of interest.

Genetic variance contributes to ingestive processes: a survey of eleven inbred mouse strains for fat (Intralipid) intake.

PubMed

Lewis, Sarah R; Dym, Cheryl; Chai, Christina; Singh, Amreeta; Kest, Benjamin; Bodnar, Richard J

2007-01-30

Genetic variation across inbred and outbred mouse strains have been observed for intake of sweet solutions, salts, bitter tastants and a high-fat diet. Our laboratory recently reported marked strain differences in the amounts and/or percentages of kilocalories of sucrose consumed among 11 inbred and one outbred mouse strains exposed to a wide range of nine sucrose concentrations (0.0001-5%) in two-bottle 24-h preference tests. To assess whether differences in fat intake were similarly associated with genetic variation, the present study examined intake of chow, water and an emulsified fat source (Intralipid) across nine different concentrations (0.00001-5%) in the same 11 inbred and 1 outbred mouse strains using two-bottle 24-h preference tests, which controlled for Intralipid concentration presentation effects, Intralipid and water bottle positions, and measurement of kilocalorie intake consumed as Intralipid or chow. Strains displayed differential increases in Intralipid intake relative to corresponding water with significant effects observed at the seven (BALB/cJ: 0.001% threshold sensitivity), four (AKR/J, C57BL/6J, DBA/2J, SWR/J: 0.5% threshold sensitivity), three (CD-1, C57BL/10J, SJL/J: 1% threshold sensitivity) and two (A/J, CBA/J, C3H/HeJ, 129P3/J: 2% threshold sensitivity) highest concentrations. In assessing the percentage of kilocalories consumed as Intralipid, SWR/J mice consumed significantly more at the three highest concentrations to a greater degree than BALB/cJ, C57BL/6J, CD-1, C3H/HeJ, DBA/J and 129P3/J strains which in turn consumed more than A/J, AKR/J, CBA/J, C57BL/10J and SJL/J mice. Relatively strong (h2 = 0.73-0.79) heritability estimates were obtained for weight-adjusted Intralipid intake at those concentrations (0.001-1%) that displayed the largest strain-specific effects in sensitivity to Intralipid. The identification of strains with diverging abilities to regulate kilocalorie intake when presented with high Intralipid concentrations may lead to the successful mapping of genes related to hedonics and obesity.

Spin-Label CW Microwave Power Saturation and Rapid Passage with Triangular Non-Adiabatic Rapid Sweep (NARS) and Adiabatic Rapid Passage (ARP) EPR Spectroscopy

PubMed Central

Kittell, Aaron W.; Hyde, James S.

2015-01-01

Non-adiabatic rapid passage (NARS) electron paramagnetic resonance (EPR) spectroscopy was introduced by Kittell, A.W., Camenisch, T.G., Ratke, J.J. Sidabras, J.W., Hyde, J.S., 2011 as a general purpose technique to collect the pure absorption response. The technique has been used to improve sensitivity relative to sinusoidal magnetic field modulation, increase the range of inter-spin distances that can be measured under near physiological conditions, and enhance spectral resolution in copper (II) spectra. In the present work, the method is extended to CW microwave power saturation of spin-labeled T4 Lysozyme (T4L). As in the cited papers, rapid triangular sweep of the polarizing magnetic field was superimposed on slow sweep across the spectrum. Adiabatic rapid passage (ARP) effects were encountered in samples undergoing very slow rotational diffusion as the triangular magnetic field sweep rate was increased. The paper reports results of variation of experimental parameters at the interface of adiabatic and non-adiabatic rapid sweep conditions. Comparison of the forward (up) and reverse (down) triangular sweeps is shown to be a good indicator of the presence of rapid passage effects. Spectral turning points can be distinguished from spectral regions between turning points in two ways: differential microwave power saturation and differential passage effects. Oxygen accessibility data are shown under NARS conditions that appear similar to conventional field modulation data. However, the sensitivity is much higher, permitting, in principle, experiments at substantially lower protein concentrations. Spectral displays were obtained that appear sensitive to rotational diffusion in the range of rotational correlation times of 10−3 to 10−7 s in a manner that is analogous to saturation transfer spectroscopy. PMID:25917132

System Collects And Displays Demultiplexed Data

NASA Technical Reports Server (NTRS)

Reschke, Millard F.; Fariss, Julie L.; Kulecz, Walter B.; Paloski, William H.

1992-01-01

Electronic system collects, manipulates, and displays in real time results of manipulation of streams of data transmitted from remote scientific instrumentation. Interface circuit shifts data-and-clock signal from differential logic levels of multiplexer to single-ended logic levels of computer. System accommodates nonstandard data-transmission protocol. Software useful in applications where Macintosh computers used in real-time display and recording of data.

The NETPET Score: Combining FDG and Somatostatin Receptor Imaging for Optimal Management of Patients with Metastatic Well-Differentiated Neuroendocrine Tumors.

PubMed

Hindié, Elif

2017-01-01

Neuroendocrine tumors (NET) are often metastatic at the time of diagnosis. Metastatic well-differentiated (G1/G2) NET may display a wide range of behaviors, ranging from indolent to aggressive, even within apparently homogeneous categories. Thus, selecting the optimal treatment strategy is a challenging task. Somatostatin receptor imaging (SRI) is the standard molecular imaging technique for well-differentiated NET. When performed with 68 Ga-labeled somatostatin analogs (SRI-PET), it offers exquisite sensitivity for disease staging. SRI is also a prerequisite for using targeted radionuclide therapy (e.g. 177 Lu-DOTATATE). 18F-FDG imaging has traditionally been reserved for staging poorly-differentiated G3 neuroendocrine carcinomas. However, recent data showed that FDG imaging has prognostic value in patients with well-differentiated NET: high uptake was associated with an increased risk of early progression while low uptake suggested an indolent tumor. In this issue of the Journal, Chan and colleagues propose a grading system where the results from the combined reading of SRI-PET and FDG-PET are reported as a single parameter, the "NETPET" score. While the scoring system still needs validation, it is clear that time has come to think about FDG and SRI in metastatic NET not as competitors but as complementary imaging modalities. Dual-tracer imaging can be viewed as a way to characterize disease phenotype in the whole-body. Moving from the prognostic value of dual-tracer imaging to a tool that allows for individualized management would require prospective trials. This editorial will argue that dual-tracer FDG-PET and SRI-PET might influence management of patients with well-differentiated metastatic NET and help selecting between different therapy options.

Featured Article: Dexamethasone and rosiglitazone are sufficient and necessary for producing functional adipocytes from mesenchymal stem cells

PubMed Central

Ezquer, Fernando; Espinosa, Maximiliano; Arango-Rodriguez, Martha; Puebla, Carlos; Sobrevia, Luis; Conget, Paulette

2015-01-01

The final product of adipogenesis is a functional adipocyte. This mature cell acquires the necessary machinery for lipid metabolism, loses its proliferation potential, increases its insulin sensitivity, and secretes adipokines. Multipotent mesechymal stromal cells have been recognized as a source of adipocytes both in vivo and in vitro. The in vitro adipogenic differentiation of human MSC (hMSC) has been induced up to now by using a complex stimulus which includes dexamethasone, 3-isobutyl-1-methylxanthine, indomethacin, and insulin (a classical cocktail) and evaluated according to morphological changes. The present work was aimed at demonstrating that the simultaneous activation of dexamethasone’s canonical signaling pathways, through the glucocorticoid receptor and CCAAT-enhancer-binding proteins (C/EBPs) and rosiglitazone through peroxisome proliferator-activated receptor gamma (PPAR-gamma) is sufficient yet necessary for inducing hMSC adipogenic differentiation. It was also ascertained that hMSC exposed just to dexamethasone and rosiglitazone (D&R) differentiated into cells which accumulated neutral lipid droplets, expressed C/EBP-alpha, PPAR-gamma, aP2, lipoprotein lipase, acyl-CoA synthetase, phosphoenolpyruvate carboxykinase, adiponectin, and leptin genes but did not proliferate. Glucose uptake was dose dependent on insulin stimulus and high levels of adipokines were secreted (i.e. displaying not only the morphology but also expressing mature adipocytes’ specific genes and functional characteristics). This work has demonstrated that (i) the activating C/EBPs and PPAR-gamma signaling pathways were sufficient to induce adipogenic differentiation from hMSC, (ii) D&R producing functional adipocytes from hMSC, (iii) D&R induce adipogenic differentiation from mammalian MSC (including those which are refractory to classical adipogenic differentiation stimuli). D&R would thus seem to be a useful tool for MSC characterization, studying adipogenesis pathways and producing functional adipocytes. PMID:25595190

Evaluations of the removal of Varroa destructor in Russian honey bee colonies that display different levels of Varroa Sensitive Hygienic activities

USDA-ARS?s Scientific Manuscript database

The removal of Varroa destructor was assessed in Russian honey bee (RHB) colonies with known levels of Varroa Sensitive Hygienic (VSH) and brood removal activities. The expression of grooming behaviour using individual bees was also measured using three groups of RHB displaying different VSH levels:...

DICER governs characteristics of glioma stem cells and the resulting tumors in xenograft mouse models of glioblastoma.

PubMed

Mansouri, Sheila; Singh, Sanjay; Alamsahebpour, Amir; Burrell, Kelly; Li, Mira; Karabork, Merve; Ekinci, Can; Koch, Elizabeth; Solaroglu, Ihsan; Chang, Jeffery T; Wouters, Bradly; Aldape, Kenneth; Zadeh, Gelareh

2016-08-30

The RNAse III endonuclease DICER is a key regulator of microRNA (miRNA) biogenesis and is frequently decreased in a variety of malignancies. We characterized the role of DICER in glioblastoma (GB), specifically demonstrating its effects on the ability of glioma stem-like cells (GSCs) to form tumors in a mouse model of GB. DICER silencing in GSCs reduced their stem cell characteristics, while tumors arising from these cells were more aggressive, larger in volume, and displayed a higher proliferation index and lineage differentiation. The resulting tumors, however, were more sensitive to radiation treatment. Our results demonstrate that DICER silencing enhances the tumorigenic potential of GSCs, providing a platform for analysis of specific relevant miRNAs and development of potentially novel therapies against GB.

Color matrix display simulation based upon luminance and chromatic contrast sensitivity of early vision

NASA Technical Reports Server (NTRS)

Martin, Russel A.; Ahumada, Albert J., Jr.; Larimer, James O.

1992-01-01

This paper describes the design and operation of a new simulation model for color matrix display development. It models the physical structure, the signal processing, and the visual perception of static displays, to allow optimization of display design parameters through image quality measures. The model is simple, implemented in the Mathematica computer language, and highly modular. Signal processing modules operate on the original image. The hardware modules describe backlights and filters, the pixel shape, and the tiling of the pixels over the display. Small regions of the displayed image can be visualized on a CRT. Visual perception modules assume static foveal images. The image is converted into cone catches and then into luminance, red-green, and blue-yellow images. A Haar transform pyramid separates the three images into spatial frequency and direction-specific channels. The channels are scaled by weights taken from human contrast sensitivity measurements of chromatic and luminance mechanisms at similar frequencies and orientations. Each channel provides a detectability measure. These measures allow the comparison of images displayed on prospective devices and, by that, the optimization of display designs.

Mitochondrial-related gene expression changes are sensitive to agonal-pH state: implications for brain disorders

PubMed Central

Vawter, MP; Tomita, H; Meng, F; Bolstad, B; Li, J; Evans, S; Choudary, P; Atz, M; Shao, L; Neal, C; Walsh, DM; Burmeister, M; Speed, T; Myers, R; Jones, EG; Watson, SJ; Akil, H; Bunney, WE

2010-01-01

Mitochondrial defects in gene expression have been implicated in the pathophysiology of bipolar disorder and schizophrenia. We have now contrasted control brains with low pH versus high pH and showed that 28% of genes in mitochondrial-related pathways meet criteria for differential expression. A majority of genes in the mitochondrial, chaperone and proteasome pathways of nuclear DNA-encoded gene expression were decreased with decreased brain pH, whereas a majority of genes in the apoptotic and reactive oxygen stress pathways showed an increased gene expression with a decreased brain pH. There was a significant increase in mitochondrial DNA copy number and mitochondrial DNA gene expression with increased agonal duration. To minimize effects of agonal-pH state on mood disorder comparisons, two classic approaches were used, removing all subjects with low pH and agonal factors from analysis, or grouping low and high pH as a separate variable. Three groups of potential candidate genes emerged that may be mood disorder related: (a) genes that showed no sensitivity to pH but were differentially expressed in bipolar disorder or major depressive disorder; (b) genes that were altered by agonal-pH in one direction but altered in mood disorder in the opposite direction to agonal-pH and (c) genes with agonal-pH sensitivity that displayed the same direction of changes in mood disorder. Genes from these categories such as NR4A1 and HSPA2 were confirmed with Q-PCR. The interpretation of postmortem brain studies involving broad mitochondrial gene expression and related pathway alterations must be monitored against the strong effect of agonal-pH state. Genes with the least sensitivity to agonal-pH could present a starting point for candidate gene search in neuropsychiatric disorders. PMID:16636682

Differential hypothalamic leptin sensitivity in obese rat offspring exposed to maternal and postnatal intake of chocolate and soft drink.

PubMed

Kjaergaard, M; Nilsson, C; Secher, A; Kildegaard, J; Skovgaard, T; Nielsen, M O; Grove, K; Raun, K

2017-01-16

Intake of high-energy foods and maternal nutrient overload increases the risk of metabolic diseases in the progeny such as obesity and diabetes. We hypothesized that maternal and postnatal intake of chocolate and soft drink will affect leptin sensitivity and hypothalamic astrocyte morphology in adult rat offspring. Pregnant Sprague-Dawley rats were fed ad libitum chow diet only (C) or with chocolate and high sucrose soft drink supplement (S). At birth, litter size was adjusted into 10 male offspring per mother. After weaning, offspring from both dietary groups were assigned to either S or C diet, giving four groups until the end of the experiment at 26 weeks of age. As expected, adult offspring fed the S diet post weaning became obese (body weight: P<0.01, %body fat per kg: P<0.001) and this was due to the reduced energy expenditure (P<0.05) and hypothalamic astrogliosis (P<0.001) irrespective of maternal diet. Interesting, offspring born to S-diet-fed mothers and fed the S diet throughout postnatal life became obese despite lower energy intake than controls (P<0.05). These SS offspring showed increased feed efficiency (P<0.001) and reduced fasting pSTAT3 activity (P<0.05) in arcuate nucleus (ARC) compared with other groups. The findings indicated that the combination of the maternal and postnatal S-diet exposure induced persistent changes in leptin signalling, hence affecting energy balance. Thus, appetite regulation was more sensitive to the effect of leptin than energy expenditure, suggesting differential programming of leptin sensitivity in ARC in SS offspring. Effects of the maternal S diet were normalized when offspring were fed a chow diet after weaning. Maternal intake of chocolate and soft drink had long-term consequences for the metabolic phenotype in the offspring if they continued on the S diet in postnatal life. These offspring displayed obesity despite lowered energy intake associated with alterations in hypothalamic leptin signalling.

Proteomic differential display analysis for TS-1-resistant and -sensitive pancreatic cancer cells using two-dimensional gel electrophoresis and mass spectrometry.

PubMed

Yoshida, Kanako; Kuramitsu, Yasuhiro; Murakami, Kohei; Ryozawa, Shomei; Taba, Kumiko; Kaino, Seiji; Zhang, Xiulian; Sakaida, Isao; Nakamura, Kazuyuki

2011-06-01

TS-1 is an oral anticancer agent containing two biochemical modulators for 5-fluorouracil (5-FU) and tegafur (FT), a metabolically activated prodrug of 5-FU. TS-1 has been recognized as an effective anticancer drug using standard therapies for patients with advanced pancreatic cancer along with gemcitabine. However, a high level of inherent and acquired tumor resistance to TS-1 induces difficulty in the treatment. To identify proteins linked to the TS-1-resistance of pancreatic cancer, we profiled protein expression levels in samples of TS-1-resistant and -sensitive pancreatic cancer cell lines by using two-dimensional gel electrophoresis (2-DE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The cytotoxicity of a 5-FU/5-chloro-2,4-dihydroxypyridine (CDHP) combination towards pancreatic cancer cell lines was evaluated by MTS assay. Panc-1, BxPC-3, MiaPaCa-2 and PK59 showed high sensitivity to the 5-FU/CDHP combination (TS-1-sensitive), whereas PK45p and KLM-1 were much less sensitive (TS-1-resistant). Proteomic analysis showed that eleven spots, including T-complex protein 1 subunit beta, ribonuclease inhibitor, elongation factor 1-delta, peroxiredoxin-2 and superoxide dismutase (Cu-Zn), appeared to be down-regulated, and 29 spots, including hypoxia up-regulated protein 1, lamin-A/C, endoplasmin, fascin and annexin A1, appeared to be up-regulated in TS-1-resistant cells compared with -sensitive cells. These results suggest that the identified proteins showing different expression between TS-1-sensitive and -resistant pancreatic cancer cells possibly relate to TS-1-sensitivity. These findings could be useful to overcome the TS-1-resistance of pancreatic cancer cells.

Isolation of stress responsive Psb A gene from rice (Oryza sativa l.) using differential display.

PubMed

Tyagi, Aruna; Chandra, Arti

2006-08-01

Differential display (DD) experiments were performed on drought-tolerant rice (Oryza sativa L.) genotype N22 to identify both upregulated and downregulated partial cDNAs with respect to moisture stress. DNA polymorphism was detected between drought-stressed and control leaf tissues on the DD gels. A partial cDNA showing differential expression, with respect to moisture stress was isolated from the gel. Northern blotting analysis was performed using this cDNA as a probe and it was observed that mRNA corresponding to this transcript was accumulated to high level in rice leaves under water deficit stress. At the DNA sequence level, the partial cDNA showed homology with psb A gene encoding for Dl protein.

Differentially displayed expressed sequence tags in Melipona scutellaris (Hymenoptera, Apidae, Meliponini) development.

PubMed

Santana, Flávia A; Nunes, Francis M F; Vieira, Carlos U; Machado, Maria Alice M S; Kerr, Warwick E; Silva, Wilson A; Bonetti, Ana Maria

2006-03-01

We have compared gene expression, using the Differential Display Reverse Transcriptase-Polymerase Chain Reaction (DDRT-PCR) technique, by means of mRNA profile in Melipona scutellaris during ontogenetic postembryonic development, in adult worker, and in both Natural and Juvenile Hormone III-induced adult queen. Six, out of the nine ESTs described here, presented differentially expressed in the phases L1 or L2, or even in both of them, suggesting that key mechanisms to the development of Melipona scutellaris are regulated in these stages. The combination HT11G-AP05 revealed in L1 and L2 a product which matches to thioredoxin reductase protein domain in the Clostridium sporogenes, an important protein during cellular oxidoreduction processes. This study represents the first molecular evidence of differential gene expression profiles toward a description of the genetic developmental traits in the genus Melipona.

[Study on screening differentially expressed genes in mice livers by silver staining DD-PCR].

PubMed

Luan, Xin-Hong; Hu, Zhong-Ming; Liu, Wei-Quan; Jiang, Yu; Wang, Kai; Wu, Yong-Kui; Li, Qian-Xue

2005-08-01

To screen swimming-fatigue related genes in mice and lay theoretic basis for researching the molecular mechanism of fatigue. 30 male BALB/c mice (20 +/- 2g) were divided into control group, dipping in water group and swimming-fatigue group respectively. After fatigue for swimming in swimming-fatigue group, with control group and dipping in water group, liver tissues in mice were collected. With improved silver staining mRNA differential display method, the differentially expressed genes in mice livers were screened and evaluated by reversed Northern blot. The positive segments were analyzed homology by BLAST. 7 of DD-ESTs were gained. Two of them only expressed in swimming-fatigue group, two down-regulated expressed, and three up-regulated. One of them was a novel gene and was accepted by GenBank, AY615302. Seven DD-ESTs in swimming-fatigue mice were gained by silver staining mRNA differential display method.

Hunted Woolly Monkeys (Lagothrix poeppigii) Show Threat-Sensitive Responses to Human Presence

PubMed Central

Papworth, Sarah; Milner-Gulland, E. J.; Slocombe, Katie

2013-01-01

Responding only to individuals of a predator species which display threatening behaviour allows prey species to minimise energy expenditure and other costs of predator avoidance, such as disruption of feeding. The threat sensitivity hypothesis predicts such behaviour in prey species. If hunted animals are unable to distinguish dangerous humans from non-dangerous humans, human hunting is likely to have a greater effect on prey populations as all human encounters should lead to predator avoidance, increasing stress and creating opportunity costs for exploited populations. We test the threat sensitivity hypothesis in wild Poeppigi's woolly monkeys (Lagothrix poeppigii) in Yasuní National Park, Ecuador, by presenting human models engaging in one of three behaviours “hunting”, “gathering” or “researching”. These experiments were conducted at two sites with differing hunting pressures. Visibility, movement and vocalisations were recorded and results from two sites showed that groups changed their behaviours after being exposed to humans, and did so in different ways depending on the behaviour of the human model. Results at the site with higher hunting pressure were consistent with predictions based on the threat sensitivity hypothesis. Although results at the site with lower hunting pressure were not consistent with the results at the site with higher hunting pressure, groups at this site also showed differential responses to different human behaviours. These results provide evidence of threat-sensitive predator avoidance in hunted primates, which may allow them to conserve both time and energy when encountering humans which pose no threat. PMID:23614003

Preventative Effect of an Herbal Preparation (HemoHIM) on Development of Airway Inflammation in Mice via Modulation of Th1/2 Cells Differentiation

PubMed Central

Kim, Jong-Jin; Cho, Hyun Wook; Park, Hae-Ran; Jung, Uhee; Jo, Sung-Kee; Yee, Sung-Tae

2013-01-01

HemoHIM, an herbal preparation of three edible herbs (Angelica gigas Nakai, Cnidium officinale Makino, Paeonia japonica Miyabe) is known to increase the Th1 immune response as well as reduce the allergic response in human mast cells. Here, our goal was to determine whether or not HemoHIM could induce Th1 cell differentiation as well as inhibit the development of airway inflammation. To study Th1/Th2 cell differentiation, naive CD4+ T cells isolated from C57BL/6 mouse spleens were cultured with or without HemoHIM. To examine airway inflammation, C57BL/6 mice were fed HemoHIM for 4 weeks before sensitization and provocation with ovalbumin (OVA). In an in vitro experiment, naive CD4+ T cells displayed increased Th1 (IFN-γ+ cell) as well as decreased Th2 (IL-4+ cell) differentiation in a HemoHIM concentration-dependent manner. Furthermore, in an airway inflammation mice model, eosinophil numbers in BALF, serum levels of OVA-specific IgE and IgG1, and cytokine (IL-4, IL-5, and IL-13) levels in BALF and the supernatant of splenocytes all decreased upon HemoHIM (100 mg/kg body weight) pretreatment (4 weeks). These results show that HemoHIM attenuated allergic airway inflammation in the mouse model through regulation of the Th1/Th2 balance. PMID:23844220

Arabidopsis and Tobacco SUPERMAN regulate hormone signalling and mediate cell proliferation and differentiation

PubMed Central

Nibau, Candida; Di Stilio, Verónica S.; Wu, Hen-ming; Cheung, Alice Y.

2011-01-01

Arabidopsis thaliana SUPERMAN (SUP) plays an important role during flower development by maintaining the boundary between stamens and carpels in the inner two whorls. It was proposed that SUP maintains this boundary by regulating cell proliferation in both whorls, as loss-of-function superman mutants produce more stamens at the expense of carpels. However, the cellular mechanism that underlies SUP function remains unknown. Here Arabidopsis or tobacco (Nicotiana tabacum) SUP was overexpressed in tobacco plants to substantiate SUP's role as a regulator of cell proliferation and boundary definition and provide evidence that its biological role may be mediated via hormonal changes. It was found that moderate levels of SUP stimulated cell growth and proliferation, whereas high levels were inhibitory. SUP stimulated auxin- and cytokinin-regulated processes, and cells overexpressing SUP displayed reduced hormone dependency for proliferation and regeneration into plants. SUP also induced proliferation of female traits in the second and third flower whorls and promoted differentiation of petaloid properties in sepals, further supporting a role for SUP as a boundary regulator. Moreover, cytokinin suppressed stamen development and promoted differentiation of carpeloid tissues, suggesting that SUP may regulate male and female development via its effect on cytokinin signalling. Taken together, these observations suggest a model whereby the effect of SUP on cell growth and proliferation involves the modulation of auxin- and cytokinin-regulated processes. Furthermore, differential SUP expression or different sensitivities of different cell types to SUP may determine whether SUP stimulates or suppresses their proliferation. PMID:20980362

Rationale and description of a coordinated cockpit display for aircraft flight management

NASA Technical Reports Server (NTRS)

Baty, D. L.

1976-01-01

The design for aircraft cockpit display systems is discussed in detail. The system consists of a set of three beam penetration color cathode ray tubes (CRT). One of three orthogonal projects of the aircraft's state appears on each CRT which displays different views of the same information. The color feature is included to obtain visual separation of information elements. The colors of red, green and yellow are used to differentiate control, performance and navigation information. Displays are coordinated in information and color.

Ergonomic problems regarding the interactive touch input via screens in onboard and ground-based flight control

NASA Technical Reports Server (NTRS)

Holzhausen, K. P.; Gaertner, K. P.

1985-01-01

A significant problem concerning the integration of display and switching functions is related to the fact that numerous informative data which have to be processed by man must be read from only a few display devices. A satisfactory ergonomic design of integrated display devices and keyboards is in many cases difficult, because not all functions which can be displayed and selected are simultaneously available. A technical solution which provides an integration of display and functional elements on the basis of the highest flexibility is obtained by using a cathode ray tube with a touch-sensitive screen. The employment of an integrated data input/output system is demonstrated for the cases of onboard and ground-based flight control. Ergonomic studies conducted to investigate the suitability of an employment of touch-sensitive screens are also discussed.

Selective production of sealed plasma membrane vesicles from red beet (Beta vulgaris L.) storage tissue.

PubMed

Giannini, J L; Gildensoph, L H; Briskin, D P

1987-05-01

Modification of our previous procedure for the isolation of microsomal membrane vesicles from red beet (Beta vulgaris L.) storage tissue allowed the recovery of sealed membrane vesicles displaying proton transport activity sensitive to both nitrate and orthovanadate. In the absence of a high salt concentration in the homogenization medium, contributions of nitrate-sensitive (tonoplast) and vanadate-sensitive (plasma membrane) proton transport were roughly equal. The addition of 0.25 M KCl to the homogenization medium increased the relative amount of nitrate-inhibited proton transport activity while the addition of 0.25 M KI resulted in proton pumping vesicles displaying inhibition by vanadate but stimulation by nitrate. These effects appeared to result from selective sealing of either plasma membrane or tonoplast membrane vesicles during homogenization in the presence of the two salts. Following centrifugation on linear sucrose gradients it was shown that the nitrate-sensitive, proton-transporting vesicles banded at low density and comigrated with nitrate-sensitive ATPase activity while the vanadate-sensitive, proton-transporting vesicles banded at a much higher density and comigrated with vanadate-sensitive ATPase. The properties of the vanadate-sensitive proton pumping vesicles were further characterized in microsomal membrane fractions produced by homogenization in the presence of 0.25 M KI and centrifugation on discontinuous sucrose density gradients. Proton transport was substrate specific for ATP, displayed a sharp pH optimum at 6.5, and was insensitive to azide but inhibited by N'-N-dicyclohexylcarbodiimide, diethylstilbestrol, and fluoride. The Km of proton transport for Mg:ATP was 0.67 mM and the K0.5 for vanadate inhibition was at about 50 microM. These properties are identical to those displayed by the plasma membrane ATPase and confirm a plasma membrane origin for the vesicles.

Effects of Leucine Supplementation and Serum Withdrawal on Branched-Chain Amino Acid Pathway Gene and Protein Expression in Mouse Adipocytes

PubMed Central

Vivar, Juan C.; Knight, Megan S.; Pointer, Mildred A.; Gwathmey, Judith K.; Ghosh, Sujoy

2014-01-01

The essential branched-chain amino acids (BCAA), leucine, valine and isoleucine, are traditionally associated with skeletal muscle growth and maintenance, energy production, and generation of neurotransmitter and gluconeogenic precursors. Recent evidence from human and animal model studies has established an additional link between BCAA levels and obesity. However, details of the mechanism of regulation of BCAA metabolism during adipogenesis are largely unknown. We interrogated whether the expression of genes and proteins involved in BCAA metabolism are sensitive to the adipocyte differentiation process, and responsive to nutrient stress from starvation or BCAA excess. Murine 3T3-L1 preadipocytes were differentiated to adipocytes under control conditions and under conditions of L-leucine supplementation or serum withdrawal. RNA and proteins were isolated at days 0, 4 and 10 of differentiation to represent pre-differentiation, early differentiation and late differentiation stages. Expression of 16 BCAA metabolism genes was quantified by quantitative real-time PCR. Expression of the protein levels of branched-chain amino acid transaminase 2 (Bcat2) and branched-chain alpha keto acid dehydrogenase (Bckdha) was quantified by immunoblotting. Under control conditions, all genes displayed induction of gene expression during early adipogenesis (Day 4) compared to Day 0. Leucine supplementation resulted in an induction of Bcat2 and Bckdha genes during early and late differentiation. Western blot analysis demonstrated condition-specific concordance between gene and protein expression. Serum withdrawal resulted in undetectable Bcat2 and Bckdha protein levels at all timepoints. These results demonstrate that the expression of genes related to BCAA metabolism are regulated during adipocyte differentiation and influenced by nutrient levels. These results provide additional insights on how BCAA metabolism is associated with adipose tissue function and extends our understanding of the transcriptomic response of this pathway to variations in nutrient availability. PMID:25050624

Use of an Antecedent Analysis and a Force Sensitive Platform to Compare Stereotyped Movements and Motor Tics

ERIC Educational Resources Information Center

Crosland, Kimberly A.; Zarcone, Jennifer R.; Schroeder, Stephen; Zarcane, Troy; Fowler, Stephen

2005-01-01

Stereotyped movements displayed by 6 participants and tics displayed by 6 children were evaluated using an antecedent behavioral analysis and a force sensitive platform. We found that tics occurred more often in an alone condition when compared to high preference toy and play conditions, whereas stereotyped movements were more variable across…

Physical correction filter for improving the optical quality of an image

NASA Technical Reports Server (NTRS)

Lee, S. Y. (Inventor)

1975-01-01

A family of physical correction filters is described. Each filter is designed to correct image content of a photographed scene of limited resolution and includes a first filter element with a pinhole through which light passes to a differential amplifier. A second filter element through which light passes through one or more openings, whose geometric configuration is a function of the cause of the resolution loss included. The light, passing through the second filter element, is also supplied to the differential amplifier whose output is used to activate an optical display or recorder to reproduce a photograph or display of the scene in the original photograph or display of the scene in the original photograph with resolution which is significantly greater than that characterizing the original photograph.

Exercise differentially affects metabolic functions and white adipose tissue in female letrozole- and dihydrotestosterone-induced mouse models of polycystic ovary syndrome.

PubMed

Marcondes, Rodrigo R; Maliqueo, Manuel; Fornes, Romina; Benrick, Anna; Hu, Min; Ivarsson, Niklas; Carlström, Mattias; Cushman, Samuel W; Stenkula, Karin G; Maciel, Gustavo A R; Stener-Victorin, Elisabet

2017-06-15

Here we hypothesized that exercise in dihydrotestosterone (DHT) or letrozole (LET)-induced polycystic ovary syndrome mouse models improves impaired insulin and glucose metabolism, adipose tissue morphology, and expression of genes related to adipogenesis, lipid metabolism, Notch pathway and browning in inguinal and mesenteric fat. DHT-exposed mice had increased body weight, increased number of large mesenteric adipocytes. LET-exposed mice displayed increased body weight and fat mass, decreased insulin sensitivity, increased frequency of small adipocytes and increased expression of genes related to lipolysis in mesenteric fat. In both models, exercise decreased fat mass and inguinal and mesenteric adipose tissue expression of Notch pathway genes, and restored altered mesenteric adipocytes morphology. In conclusion, exercise restored mesenteric adipocytes morphology in DHT- and LET-exposed mice, and insulin sensitivity and mesenteric expression of lipolysis-related genes in LET-exposed mice. Benefits could be explained by downregulation of Notch, and modulation of browning and lipolysis pathways in the adipose tissue. Copyright © 2017 Elsevier B.V. All rights reserved.

Long-range correlations and patterns of recurrence in children and adults' attention to hierarchical displays

PubMed Central

Castillo, Ramon D.; Kloos, Heidi; Holden, John G.; Richardson, Michael J.

2015-01-01

In order to make sense of a scene, a person must pay attention to several levels of nested order, ranging from the most differentiated details of the display to the integrated whole. In adults, research shows that the processes of integration and differentiation have the signature of self-organization. Does the same hold for children? The current study addresses this question with children between 6 and 9 years of age, using two tasks that require attention to hierarchical displays. A group of adults were tested as well, for control purposes. To get at the question of self-organization, reaction times were submitted to a detrended fluctuation analysis and a recurrence quantification analysis. H exponents show a long-range correlations (1/f noise), and recurrence measures (percent determinism, maximum line, entropy, and trend), show a deterministic structure of variability being characteristic of self-organizing systems. Findings are discussed in terms of organism-environment coupling that gives rise to fluid attention to hierarchical displays. PMID:25999862

Dynamic Displays Enhance the Ability to Discriminate Genuine and Posed Facial Expressions of Emotion

PubMed Central

Namba, Shushi; Kabir, Russell S.; Miyatani, Makoto; Nakao, Takashi

2018-01-01

Accurately gauging the emotional experience of another person is important for navigating interpersonal interactions. This study investigated whether perceivers are capable of distinguishing between unintentionally expressed (genuine) and intentionally manipulated (posed) facial expressions attributed to four major emotions: amusement, disgust, sadness, and surprise. Sensitivity to this discrimination was explored by comparing unstaged dynamic and static facial stimuli and analyzing the results with signal detection theory. Participants indicated whether facial stimuli presented on a screen depicted a person showing a given emotion and whether that person was feeling a given emotion. The results showed that genuine displays were evaluated more as felt expressions than posed displays for all target emotions presented. In addition, sensitivity to the perception of emotional experience, or discriminability, was enhanced in dynamic facial displays, but was less pronounced in the case of static displays. This finding indicates that dynamic information in facial displays contributes to the ability to accurately infer the emotional experiences of another person. PMID:29896135

Pacifiplex: an ancestry-informative SNP panel centred on Australia and the Pacific region.

PubMed

Santos, Carla; Phillips, Christopher; Fondevila, Manuel; Daniel, Runa; van Oorschot, Roland A H; Burchard, Esteban G; Schanfield, Moses S; Souto, Luis; Uacyisrael, Jolame; Via, Marc; Carracedo, Ángel; Lareu, Maria V

2016-01-01

The analysis of human population variation is an area of considerable interest in the forensic, medical genetics and anthropological fields. Several forensic single nucleotide polymorphism (SNP) assays provide ancestry-informative genotypes in sensitive tests designed to work with limited DNA samples, including a 34-SNP multiplex differentiating African, European and East Asian ancestries. Although assays capable of differentiating Oceanian ancestry at a global scale have become available, this study describes markers compiled specifically for differentiation of Oceanian populations. A sensitive multiplex assay, termed Pacifiplex, was developed and optimized in a small-scale test applicable to forensic analyses. The Pacifiplex assay comprises 29 ancestry-informative marker SNPs (AIM-SNPs) selected to complement the 34-plex test, that in a combined set distinguish Africans, Europeans, East Asians and Oceanians. Nine Pacific region study populations were genotyped with both SNP assays, then compared to four reference population groups from the HGDP-CEPH human diversity panel. STRUCTURE analyses estimated population cluster membership proportions that aligned with the patterns of variation suggested for each study population's currently inferred demographic histories. Aboriginal Taiwanese and Philippine samples indicated high East Asian ancestry components, Papua New Guinean and Aboriginal Australians samples were predominantly Oceanian, while other populations displayed cluster patterns explained by the distribution of divergence amongst Melanesians, Polynesians and Micronesians. Genotype data from Pacifiplex and 34-plex tests is particularly well suited to analysis of Australian Aboriginal populations and when combined with Y and mitochondrial DNA variation will provide a powerful set of markers for ancestry inference applied to modern Australian demographic profiles. On a broader geographic scale, Pacifiplex adds highly informative data for inferring the ancestry of individuals from Oceanian populations. The sensitivity of Pacifiplex enabled successful genotyping of population samples from 50-year-old serum samples obtained from several Oceanian regions that would otherwise be unlikely to produce useful population data. This indicates tests primarily developed for forensic ancestry analysis also provide an important contribution to studies of populations where useful samples are in limited supply. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Parametric Sensitivity Analysis of Oscillatory Delay Systems with an Application to Gene Regulation.

PubMed

Ingalls, Brian; Mincheva, Maya; Roussel, Marc R

2017-07-01

A parametric sensitivity analysis for periodic solutions of delay-differential equations is developed. Because phase shifts cause the sensitivity coefficients of a periodic orbit to diverge, we focus on sensitivities of the extrema, from which amplitude sensitivities are computed, and of the period. Delay-differential equations are often used to model gene expression networks. In these models, the parametric sensitivities of a particular genotype define the local geometry of the evolutionary landscape. Thus, sensitivities can be used to investigate directions of gradual evolutionary change. An oscillatory protein synthesis model whose properties are modulated by RNA interference is used as an example. This model consists of a set of coupled delay-differential equations involving three delays. Sensitivity analyses are carried out at several operating points. Comments on the evolutionary implications of the results are offered.

Differential Si ring resonators for label-free biosensing

NASA Astrophysics Data System (ADS)

Taniguchi, Tomoya; Yokoyama, Shuhei; Amemiya, Yoshiteru; Ikeda, Takeshi; Kuroda, Akio; Yokoyama, Shin

2016-04-01

Differential Si ring optical resonator sensors have been fabricated. Their detection sensitivity was 10-3-10-2% for sucrose solution, which corresponds to a sensitivity of ˜1.0 ng/ml for prostate-specific antigen (PSA), which is satisfactory for practical use. In the differential sensing the input light is incident to two rings, and one of the outputs is connected to a π phase shifter then the two outputs are merged again. For the differential detection, not only is the common-mode noise canceled, resulting in high sensitivity, but also the temperature stability is much improved. A fluid channel is fabricated so that the detecting liquid flows to the detection ring and the reference liquid flows to the reference ring. We have proposed a method of obtaining a constant sensitivity for the integrated sensors even though the resonance wavelengths of the two rings of the differential sensor are slightly different. It was found that a region exists with a linear relationship between the differential output and the difference in the resonance wavelengths of the two rings. By intentionally differentiating the resonance wavelengths in this linear region, the sensors have a constant sensitivity. Many differential sensors with different ring spaces have been fabricated and the output scattering characteristics were statistically evaluated. As a result, a standard deviation of resonance wavelength σ = 8 × 10-3 nm was obtained for a ring space of 31 µm. From the width of the linear region and the standard deviation, it was estimated from the Gaussian distribution of the resonance wavelength that 93.8% of the devices have the same sensitivity.

Identification of sexually dimorphic gene expression in brain tissue of the fish Leporinus macrocephalus through mRNA differential display and real time PCR analyses.

PubMed

Alves-Costa, Fernanda A; Wasko, A P

2010-03-01

Differentially expressed genes in males and females of vertebrate species generally have been investigated in gonads and, to a lesser extent, in other tissues. Therefore, we attempted to identify sexually dimorphic gene expression in the brains of adult males and females of Leporinus macrocephalus, a gonochoristic fish species that presents a ZZ/ZW sex determination system, throughout a comparative analysis using differential display reverse transcriptase-PCR and real-time PCR. Four cDNA fragments were characterized, representing candidate genes with differential expression between the samples. Two of these fragments presented no significant identity with previously reported gene sequences. The other two fragments, isolated from male specimens, were associated to the gene that codes for the protein APBA2 (amyloid beta (A4) precursor protein-binding, family A, member 2) and to the Rab 37 gene, a member of the Ras oncogene family. The overexpression of these genes has been associated to a greater production of the beta-amyloid protein which, in turns, is the major factor that leads to Alzheimer's disease, and to the development of brain-tumors, respectively. Quantitative RT-PCR analyses revealed a higher Apba2 gene expression in males, thus validating the previous data on differential display. L. macrocephalus may represent an interesting animal model to the understanding of the function of several vertebrate genes, including those involved in neurodegenerative and cancer diseases.

Assessment of oral mucosal lesions with autofluorescence imaging and reflectance spectroscopy.

PubMed

Lalla, Yastira; Matias, Marie Anne T; Farah, Camile S

2016-08-01

The aim of this prospective study was to evaluate the efficacy of a new form of autofluorescence imaging and tissue reflectance spectroscopy (Identafi, DentalEZ) in examining patients with oral mucosal lesions. The authors examined 88 patients with 231 oral mucosal lesions by conventional oral examination (COE) using white-light illumination and ×2.5 magnification loupes, followed by examination using Identafi. The authors noted fluorescence visualization loss, the presence of blanching, and diffuseness of vasculature. They performed incisional biopsies to provide definitive histopathologic diagnosis. Identafi's white light produced lesion visibility and border distinctness equivalent to COE. Identafi's violet light displayed a sensitivity of 12.5% and specificity of 85.4% for detection of oral epithelial dysplasia (OED). The authors noted visible vasculature using the green-amber light in 40.9% of lesions. Identafi's intraoral white light provided detailed visualization of oral mucosal lesions comparable with examination using an extraoral white-light source with magnification. A high level of clinical experience is required to interpret the results of autofluorescence examination as the violet light displayed low sensitivity for detection of OED. The green-amber light provided additional clinical information in relation to underlying vasculature and inflammation of lesions. Examination using Identafi can provide clinicians with more clinical data than a standard COE with yellow incandescent light, but the clinical and optical findings should be interpreted as a whole and not in isolation. Clinicians should use the light features of Identafi in a sequential and differential manner. Copyright © 2016 American Dental Association. Published by Elsevier Inc. All rights reserved.

Scrambled eggs: A highly sensitive molecular diagnostic workflow for Fasciola species specific detection from faecal samples.

PubMed

Calvani, Nichola Eliza Davies; Windsor, Peter Andrew; Bush, Russell David; Šlapeta, Jan

2017-09-01

Fasciolosis, due to Fasciola hepatica and Fasciola gigantica, is a re-emerging zoonotic parasitic disease of worldwide importance. Human and animal infections are commonly diagnosed by the traditional sedimentation and faecal egg-counting technique. However, this technique is time-consuming and prone to sensitivity errors when a large number of samples must be processed or if the operator lacks sufficient experience. Additionally, diagnosis can only be made once the 12-week pre-patent period has passed. Recently, a commercially available coprological antigen ELISA has enabled detection of F. hepatica prior to the completion of the pre-patent period, providing earlier diagnosis and increased throughput, although species differentiation is not possible in areas of parasite sympatry. Real-time PCR offers the combined benefits of highly sensitive species differentiation for medium to large sample sizes. However, no molecular diagnostic workflow currently exists for the identification of Fasciola spp. in faecal samples. A new molecular diagnostic workflow for the highly-sensitive detection and quantification of Fasciola spp. in faecal samples was developed. The technique involves sedimenting and pelleting the samples prior to DNA isolation in order to concentrate the eggs, followed by disruption by bead-beating in a benchtop homogeniser to ensure access to DNA. Although both the new molecular workflow and the traditional sedimentation technique were sensitive and specific, the new molecular workflow enabled faster sample throughput in medium to large epidemiological studies, and provided the additional benefit of speciation. Further, good correlation (R2 = 0.74-0.76) was observed between the real-time PCR values and the faecal egg count (FEC) using the new molecular workflow for all herds and sampling periods. Finally, no effect of storage in 70% ethanol was detected on sedimentation and DNA isolation outcomes; enabling transport of samples from endemic to non-endemic countries without the requirement of a complete cold chain. The commercially-available ELISA displayed poorer sensitivity, even after adjustment of the positive threshold (65-88%), compared to the sensitivity (91-100%) of the new molecular diagnostic workflow. Species-specific assays for sensitive detection of Fasciola spp. enable ante-mortem diagnosis in both human and animal settings. This includes Southeast Asia where there are potentially many undocumented human cases and where post-mortem examination of production animals can be difficult. The new molecular workflow provides a sensitive and quantitative diagnostic approach for the rapid testing of medium to large sample sizes, potentially superseding the traditional sedimentation and FEC technique and enabling surveillance programs in locations where animal and human health funding is limited.

Attention-based long-lasting sensitization and suppression of colors.

PubMed

Tseng, Chia-Huei; Vidnyanszky, Zoltan; Papathomas, Thomas; Sperling, George

2010-02-22

In contrast to the short-duration and quick reversibility of attention, a long-term sensitization to color based on protracted attention in a visual search task was reported by Tseng, Gobell, and Sperling (2004). When subjects were trained for a few hours to search for a red object among colored distracters, sensitivity to red was increased for weeks. This sensitization was quantified using ambiguous motion displays containing isoluminant red-green and texture-contrast gratings, in which the perceived motion-direction depended both on the attended color and on the relative red-green saturation. Such long-term effects could result from either sensitization of the attended color, or suppression of unattended colors, or a combination of the two. Here we unconfound these effects by eliminating one of the paired colors of the motion display from the search task. The other paired color in the motion display can then be either a target or a distracter in the search task. Thereby, we separately measure the effect of attention on sensitizing the target color or suppressing distracter colors. The results indicate that only sensitization of the target color in the search task is statistically significant for the present experimental conditions. We conclude that selective attention to a color in our visual search task caused long-term sensitization to the attended color but not significant long-term suppression of the unattended color. Copyright 2009 Elsevier Ltd. All rights reserved.

Information transmission and detection thresholds in the vestibular nuclei: single neurons vs. population encoding

PubMed Central

Massot, Corentin; Chacron, Maurice J.

2011-01-01

Understanding how sensory neurons transmit information about relevant stimuli remains a major goal in neuroscience. Of particular relevance are the roles of neural variability and spike timing in neural coding. Peripheral vestibular afferents display differential variability that is correlated with the importance of spike timing; regular afferents display little variability and use a timing code to transmit information about sensory input. Irregular afferents, conversely, display greater variability and instead use a rate code. We studied how central neurons within the vestibular nuclei integrate information from both afferent classes by recording from a group of neurons termed vestibular only (VO) that are known to make contributions to vestibulospinal reflexes and project to higher-order centers. We found that, although individual central neurons had sensitivities that were greater than or equal to those of individual afferents, they transmitted less information. In addition, their velocity detection thresholds were significantly greater than those of individual afferents. This is because VO neurons display greater variability, which is detrimental to information transmission and signal detection. Combining activities from multiple VO neurons increased information transmission. However, the information rates were still much lower than those of equivalent afferent populations. Furthermore, combining responses from multiple VO neurons led to lower velocity detection threshold values approaching those measured from behavior (∼2.5 vs. 0.5–1°/s). Our results suggest that the detailed time course of vestibular stimuli encoded by afferents is not transmitted by VO neurons. Instead, they suggest that higher vestibular pathways must integrate information from central vestibular neuron populations to give rise to behaviorally observed detection thresholds. PMID:21307329

Perceptual grouping does not affect multi-attribute decision making if no processing costs are involved.

PubMed

Ettlin, Florence; Bröder, Arndt

2015-05-01

Adaptive strategy selection implies that a decision strategy is chosen based on its fit to the task and situation. However, other aspects, such as the way information is presented, can determine information search behavior; especially when the application of certain strategies over others is facilitated. But are such display effects on multi-attribute decisions also at work when the manipulation does not entail differential costs for different decision strategies? Three Mouselab experiments with hidden information and one eye tracking experiment with an open information board revealed that decision behavior is unaffected by purely perceptual manipulations of the display based on Gestalt principles; that is, based on manipulations that induce no noteworthy processing costs for different information search patterns. We discuss our results in the context of previous findings on display effects; specifically, how the combination of these findings and our results reveal the crucial role of differential processing costs for different strategies for the emergence of display effects. This finding describes a boundary condition of the commonly acknowledged influence of information displays and is in line with the ideas of adaptive strategy selection and cost-benefit tradeoffs. Copyright © 2015. Published by Elsevier B.V.

Imaging dynamic and selective low-complexity domain interactions that control gene transcription.

PubMed

Chong, Shasha; Dugast-Darzacq, Claire; Liu, Zhe; Dong, Peng; Dailey, Gina M; Cattoglio, Claudia; Heckert, Alec; Banala, Sambashiva; Lavis, Luke; Darzacq, Xavier; Tjian, Robert

2018-06-21

Many eukaryotic transcription factors (TFs) contain intrinsically disordered low-complexity domains (LCDs), but how they drive transactivation remains unclear. Here, live-cell single-molecule imaging reveals that TF-LCDs form local high-concentration interaction hubs at synthetic and endogenous genomic loci. TF-LCD hubs stabilize DNA binding, recruit RNA polymerase II (Pol II), and activate transcription. LCD-LCD interactions within hubs are highly dynamic, display selectivity with binding partners, and are differentially sensitive to disruption by hexanediols. Under physiological conditions, rapid and reversible LCD-LCD interactions occur between TFs and the Pol II machinery without detectable phase separation. Our findings reveal fundamental mechanisms underpinning transcriptional control and suggest a framework for developing single-molecule imaging screens for novel drugs targeting gene regulatory interactions implicated in disease. Copyright © 2018, American Association for the Advancement of Science.

Scalable, large area compound array refractive lens for hard X-rays

NASA Astrophysics Data System (ADS)

Reich, Stefan; dos Santos Rolo, Tomy; Letzel, Alexander; Baumbach, Tilo; Plech, Anton

2018-04-01

We demonstrate the fabrication of a 2D Compound Array Refractive Lens (CARL) for multi-contrast X-ray imaging. The CARL consists of six stacked polyimide foils with each displaying a 2D array of lenses with a 65 μm pitch aiming for a sensitivity on sub-micrometer structures with a (few-)micrometer resolution in sensing through phase and scattering contrast at multiple keV. The parabolic lenses are formed by indents in the foils by a paraboloid needle. The ability for fast single-exposure multi-contrast imaging is demonstrated by filming the kinetics of pulsed laser ablation in liquid. The three contrast channels, absorption, differential phase, and scattering, are imaged with a time resolution of 25 μs. By changing the sample-detector distance, it is possible to distinguish between nanoparticles and microbubbles.

The aminoglycoside antibiotic kanamycin damages DNA bases in Escherichia coli: caffeine potentiates the DNA-damaging effects of kanamycin while suppressing cell killing by ciprofloxacin in Escherichia coli and Bacillus anthracis.

PubMed

Kang, Tina Manzhu; Yuan, Jessica; Nguyen, Angelyn; Becket, Elinne; Yang, Hanjing; Miller, Jeffrey H

2012-06-01

The distribution of mutants in the Keio collection of Escherichia coli gene knockout mutants that display increased sensitivity to the aminoglycosides kanamycin and neomycin indicates that damaged bases resulting from antibiotic action can lead to cell death. Strains lacking one of a number of glycosylases (e.g., AlkA, YzaB, Ogt, KsgA) or other specific repair proteins (AlkB, PhrB, SmbC) are more sensitive to these antibiotics. Mutants lacking AlkB display the strongest sensitivity among the glycosylase- or direct lesion removal-deficient strains. This perhaps suggests the involvement of ethenoadenine adducts, resulting from reactive oxygen species and lipid peroxidation, since AlkB removes this lesion. Other sensitivities displayed by mutants lacking UvrA, polymerase V (Pol V), or components of double-strand break repair indicate that kanamycin results in damaged base pairs that need to be removed or replicated past in order to avoid double-strand breaks that saturate the cellular repair capacity. Caffeine enhances the sensitivities of these repair-deficient strains to kanamycin and neomycin. The gene knockout mutants that display increased sensitivity to caffeine (dnaQ, holC, holD, and priA knockout mutants) indicate that caffeine blocks DNA replication, ultimately leading to double-strand breaks that require recombinational repair by functions encoded by recA, recB, and recC, among others. Additionally, caffeine partially protects cells of both Escherichia coli and Bacillus anthracis from killing by the widely used fluoroquinolone antibiotic ciprofloxacin.

Efficient sensitivity analysis method for chaotic dynamical systems

NASA Astrophysics Data System (ADS)

Liao, Haitao

2016-05-01

The direct differentiation and improved least squares shadowing methods are both developed for accurately and efficiently calculating the sensitivity coefficients of time averaged quantities for chaotic dynamical systems. The key idea is to recast the time averaged integration term in the form of differential equation before applying the sensitivity analysis method. An additional constraint-based equation which forms the augmented equations of motion is proposed to calculate the time averaged integration variable and the sensitivity coefficients are obtained as a result of solving the augmented differential equations. The application of the least squares shadowing formulation to the augmented equations results in an explicit expression for the sensitivity coefficient which is dependent on the final state of the Lagrange multipliers. The LU factorization technique to calculate the Lagrange multipliers leads to a better performance for the convergence problem and the computational expense. Numerical experiments on a set of problems selected from the literature are presented to illustrate the developed methods. The numerical results demonstrate the correctness and effectiveness of the present approaches and some short impulsive sensitivity coefficients are observed by using the direct differentiation sensitivity analysis method.

The Connotative Dimensions of Selected Display Typefaces.

ERIC Educational Resources Information Center

Benton, Camille L.

The semantic differential ratings of ten typefaces given by a group of 24 subjects were factor analyzed to discover what connotative meanings laypeople applied to typefaces and how these meanings compared with those of professional typographers. The typefaces, five from general categories and five from novelty categories of display typefaces, were…

Factors Expressed by Murine Embryonic Pancreatic Mesenchyme Enhance Generation of Insulin-Producing Cells From hESCs

PubMed Central

Guo, Tingxia; Landsman, Limor; Li, Na; Hebrok, Matthias

2013-01-01

Islet transplantation has proven to be a successful strategy to restore normoglycemia in patients with type 1 diabetes (T1D). However, the dearth of cadaveric islets available for transplantation hampers the widespread application of this treatment option. Although human embryonic stem cells and induced pluripotent stem cells are capable of generating insulin-producing cells in vitro when provided with the appropriate inductive cues, the insulin-expressing cells that develop behave more like immature β-cells with minimal sensitivity to glucose stimulation. Here, we identify a set of signaling factors expressed in mouse embryonic mesenchyme during the time when foregut and pancreatic progenitors are specified and test their activities during in vitro differentiation of human embryonic stem cells. Several of the identified factors work in concert to expand the pancreatic progenitor pool. Interestingly, transforming growth factor (TGF)-β ligands, most potent in inducing pancreatic progenitors, display strong inhibitory effects on subsequent endocrine cell differentiation. Treatment with TGF-β ligands, followed by the addition of a TGF-β receptor antagonist, dramatically increased the number of insulin-producing cells in vitro, demonstrating the need for dynamic temporal regulation of TGF-β signaling during in vitro differentiation. These studies illustrate the need to precisely mimic the in vivo conditions to fully recapitulate pancreatic lineage specification in vitro. PMID:23305648

Accounting for technical noise in differential expression analysis of single-cell RNA sequencing data.

PubMed

Jia, Cheng; Hu, Yu; Kelly, Derek; Kim, Junhyong; Li, Mingyao; Zhang, Nancy R

2017-11-02

Recent technological breakthroughs have made it possible to measure RNA expression at the single-cell level, thus paving the way for exploring expression heterogeneity among individual cells. Current single-cell RNA sequencing (scRNA-seq) protocols are complex and introduce technical biases that vary across cells, which can bias downstream analysis without proper adjustment. To account for cell-to-cell technical differences, we propose a statistical framework, TASC (Toolkit for Analysis of Single Cell RNA-seq), an empirical Bayes approach to reliably model the cell-specific dropout rates and amplification bias by use of external RNA spike-ins. TASC incorporates the technical parameters, which reflect cell-to-cell batch effects, into a hierarchical mixture model to estimate the biological variance of a gene and detect differentially expressed genes. More importantly, TASC is able to adjust for covariates to further eliminate confounding that may originate from cell size and cell cycle differences. In simulation and real scRNA-seq data, TASC achieves accurate Type I error control and displays competitive sensitivity and improved robustness to batch effects in differential expression analysis, compared to existing methods. TASC is programmed to be computationally efficient, taking advantage of multi-threaded parallelization. We believe that TASC will provide a robust platform for researchers to leverage the power of scRNA-seq. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Accounting for technical noise in differential expression analysis of single-cell RNA sequencing data

PubMed Central

Jia, Cheng; Hu, Yu; Kelly, Derek; Kim, Junhyong

2017-01-01

Abstract Recent technological breakthroughs have made it possible to measure RNA expression at the single-cell level, thus paving the way for exploring expression heterogeneity among individual cells. Current single-cell RNA sequencing (scRNA-seq) protocols are complex and introduce technical biases that vary across cells, which can bias downstream analysis without proper adjustment. To account for cell-to-cell technical differences, we propose a statistical framework, TASC (Toolkit for Analysis of Single Cell RNA-seq), an empirical Bayes approach to reliably model the cell-specific dropout rates and amplification bias by use of external RNA spike-ins. TASC incorporates the technical parameters, which reflect cell-to-cell batch effects, into a hierarchical mixture model to estimate the biological variance of a gene and detect differentially expressed genes. More importantly, TASC is able to adjust for covariates to further eliminate confounding that may originate from cell size and cell cycle differences. In simulation and real scRNA-seq data, TASC achieves accurate Type I error control and displays competitive sensitivity and improved robustness to batch effects in differential expression analysis, compared to existing methods. TASC is programmed to be computationally efficient, taking advantage of multi-threaded parallelization. We believe that TASC will provide a robust platform for researchers to leverage the power of scRNA-seq. PMID:29036714

Sertoli cell androgen receptor expression regulates temporal fetal and adult Leydig cell differentiation, function, and population size.

PubMed

Hazra, Rasmani; Jimenez, Mark; Desai, Reena; Handelsman, David J; Allan, Charles M

2013-09-01

We recently created a mouse model displaying precocious Sertoli cell (SC) and spermatogenic development induced by SC-specific transgenic androgen receptor expression (TgSCAR). Here we reveal that TgSCAR regulates the development, function, and absolute number of Leydig cells (LCs). Total fetal and adult type LC numbers were reduced in postnatal and adult TgSCAR vs control testes, despite normal circulating LH levels. Normal LC to SC ratios found in TgSCAR testes indicate that SC androgen receptor (SCAR)-mediated activity confers a quorum-dependent relationship between total SC and LC numbers. TgSCAR enhanced LC differentiation, shown by elevated ratios of advanced to immature LC types, and reduced LC proliferation in postnatal TgSCAR vs control testes. Postnatal TgSCAR testes displayed up-regulated expression of coupled ligand-receptor transcripts (Amh-Amhr2, Dhh-Ptch1, Pdgfa-Pdgfra) for potential SCAR-stimulated paracrine pathways, which may coordinate LC differentiation. Neonatal TgSCAR testes displayed normal T and dihydrotestosterone levels despite differential changes to steroidogenic gene expression, with down-regulated Star, Cyp11a1, and Cyp17a1 expression contrasting with up-regulated Hsd3b1, Hsd17b3, and Srd5a1 expression. TgSCAR males also displayed elevated postnatal and normal adult serum testosterone levels, despite reduced LC numbers. Enhanced adult-type LC steroidogenic output was revealed by increased pubertal testicular T, dihydrotestosterone, 3α-diol and 3β-diol levels per LC and up-regulated steroidogenic gene (Nr5a1, Lhr, Cyp11a1, Cyp17a1, Hsd3b6, Srd5a1) expression in pubertal or adult TgSCAR vs control males, suggesting regulatory mechanisms maintain androgen levels independently of absolute LC numbers. Our unique gain-of-function TgSCAR model has revealed that SCAR activity controls temporal LC differentiation, steroidogenic function, and population size.

Young Children's Responses to Guilt Displays

ERIC Educational Resources Information Center

Vaish, Amrisha; Carpenter, Malinda; Tomasello, Michael

2011-01-01

Displaying guilt after a transgression serves to appease the victim and other group members, restore interpersonal relationships, and indicate the transgressors' awareness of and desire to conform to the group's norms. We investigated whether and when young children are sensitive to these functions of guilt displays. In Study 1, after 4- and…

The Small-RNA Profiles of Almond (Prunus dulcis Mill.) Reproductive Tissues in Response to Cold Stress.

PubMed

Karimi, Marzieh; Ghazanfari, Farahnaz; Fadaei, Adeleh; Ahmadi, Laleh; Shiran, Behrouz; Rabei, Mohammad; Fallahi, Hossein

2016-01-01

Spring frost is an important environmental stress that threatens the production of Prunus trees. However, little information is available regarding molecular response of these plants to the frost stress. Using high throughput sequencing, this study was conducted to identify differentially expressed miRNAs, both the conserved and the non-conserved ones, in the reproductive tissues of almond tolerant H genotype under cold stress. Analysis of 50 to 58 million raw reads led to identification of 174 unique conserved and 59 novel microRNAs (miRNAs). Differential expression pattern analysis showed that 50 miRNA families were expressed differentially in one or both of almond reproductive tissues (anther and ovary). Out of these 50 miRNA families, 12 and 15 displayed up-regulation and down-regulation, respectively. The distribution of conserved miRNA families indicated that miR482f harbor the highest number of members. Confirmation of miRNAs expression patterns by quantitative real- time PCR (qPCR) was performed in cold tolerant (H genotype) alongside a sensitive variety (Sh12 genotype). Our analysis revealed differential expression for 9 miRNAs in anther and 3 miRNAs in ovary between these two varieties. Target prediction of miRNAs followed by differential expression analysis resulted in identification of 83 target genes, mostly transcription factors. This study comprehensively catalogued expressed miRNAs under different temperatures in two reproductive tissues (anther and ovary). Results of current study and the previous RNA-seq study, which was conducted in the same tissues by our group, provide a unique opportunity to understand the molecular basis of responses of almond to cold stress. The results can also enhance the possibility for gene manipulation to develop cold tolerant plants.

The Small-RNA Profiles of Almond (Prunus dulcis Mill.) Reproductive Tissues in Response to Cold Stress

PubMed Central

Shiran, Behrouz; Rabei, Mohammad; Fallahi, Hossein

2016-01-01

Spring frost is an important environmental stress that threatens the production of Prunus trees. However, little information is available regarding molecular response of these plants to the frost stress. Using high throughput sequencing, this study was conducted to identify differentially expressed miRNAs, both the conserved and the non-conserved ones, in the reproductive tissues of almond tolerant H genotype under cold stress. Analysis of 50 to 58 million raw reads led to identification of 174 unique conserved and 59 novel microRNAs (miRNAs). Differential expression pattern analysis showed that 50 miRNA families were expressed differentially in one or both of almond reproductive tissues (anther and ovary). Out of these 50 miRNA families, 12 and 15 displayed up-regulation and down-regulation, respectively. The distribution of conserved miRNA families indicated that miR482f harbor the highest number of members. Confirmation of miRNAs expression patterns by quantitative real- time PCR (qPCR) was performed in cold tolerant (H genotype) alongside a sensitive variety (Sh12 genotype). Our analysis revealed differential expression for 9 miRNAs in anther and 3 miRNAs in ovary between these two varieties. Target prediction of miRNAs followed by differential expression analysis resulted in identification of 83 target genes, mostly transcription factors. This study comprehensively catalogued expressed miRNAs under different temperatures in two reproductive tissues (anther and ovary). Results of current study and the previous RNA-seq study, which was conducted in the same tissues by our group, provide a unique opportunity to understand the molecular basis of responses of almond to cold stress. The results can also enhance the possibility for gene manipulation to develop cold tolerant plants. PMID:27253370

Changes in functional properties of the caffeine-sensitive Ca2+ store during differentiation of human SH-SY5Y neuroblastoma cells.

PubMed

Riddoch, Fiona C; Brown, Anna M; Rowbotham, Sophie E; Redfern, Christopher P F; Cheek, Timothy R

2007-03-01

We have used single cell fluorescence imaging techniques to examine how functional properties of the caffeine-sensitive Ca(2+) store change during differentiation of a sub-population of caffeine-sensitive SH-SY5Y cells. Application of caffeine (30 mM) 1-10.5 min after a 'priming' depolarisation pulse of 55 mM K(+) revealed that the caffeine-sensitive store in undifferentiated cells remained replete, whereas that in 9-cis retinoic acid (9cRA)-differentiated cells spontaneously dissipated with a t(1/2) of 2.8 min, and was essentially completely depleted approximately 10 min after priming. In 9cRA-differentiated cells that were stimulated with methacholine (10 microM) 1 min after priming, the amplitude, rate of rise and propagation velocity of the Ca(2+) wave in the neurites were all constant, whereas these kinetic parameters all progressively decreased as the wave travelled along the neurites in cells that were stimulated 10 min after priming. Use-dependent block with ryanodine inhibited the global Ca(2+) signal in 9cRA-differentiated cells stimulated with methacholine 1 min after priming (71+/-8%) but not 10 min after priming. Depolarisation was more effective at priming the caffeine-sensitive Ca(2+) store in 9cRA-differentiated cells, which lack a functional store-operated Ca(2+) entry pathway. We conclude that differentiation of caffeine-sensitive SH-SY5Y cells is accompanied by an increase in lability of the caffeine-sensitive Ca(2+) store, and that spontaneous dissipation of Ca(2+) from the store limits the time course of its molecular 'memory' during which it can amplify the hormone-induced Ca(2+) signal by Ca(2+)-induced Ca(2+) release.

Isolation of a pH-Sensitive IgNAR Variable Domain from a Yeast-Displayed, Histidine-Doped Master Library.

PubMed

Könning, Doreen; Zielonka, Stefan; Sellmann, Carolin; Schröter, Christian; Grzeschik, Julius; Becker, Stefan; Kolmar, Harald

2016-04-01

In recent years, engineering of pH-sensitivity into antibodies as well as antibody-derived fragments has become more and more attractive for biomedical and biotechnological applications. Herein, we report the isolation of the first pH-sensitive IgNAR variable domain (vNAR), which was isolated from a yeast-displayed, semi-synthetic master library. This strategy enables the direct identification of pH-dependent binders from a histidine-enriched CDR3 library. Displayed vNAR variants contained two histidine substitutions on average at random positions in their 12-residue CDR3 loop. Upon screening of seven rounds against the proof-of-concept target EpCAM (selection for binding at pH 7.4 and decreased binding at pH 6.0), a single clone was obtained that showed specific and pH-dependent binding as characterized by yeast surface display and biolayer interferometry. Potential applications for such pH-dependent vNAR domains include their employment in tailored affinity chromatography, enabling mild elution protocols. Moreover, utilizing a master library for the isolation of pH-sensitive vNAR variants may be a generic strategy to obtain binding entities with prescribed characteristics for applications in biotechnology, diagnostics, and therapy.

Enhanced Sensitivity to Hyperpolarizing Inhibition in Mesoaccumbal Relative to Nigrostriatal Dopamine Neuron Subpopulations

PubMed Central

2017-01-01

Midbrain dopamine neurons recorded in vivo pause their firing in response to reward omission and aversive stimuli. While the initiation of pauses typically involves synaptic or modulatory input, intrinsic membrane properties may also enhance or limit hyperpolarization, raising the question of how intrinsic conductances shape pauses in dopamine neurons. Using retrograde labeling and electrophysiological techniques combined with computational modeling, we examined the intrinsic conductances that shape pauses evoked by current injections and synaptic stimulation in subpopulations of dopamine neurons grouped according to their axonal projections to the nucleus accumbens or dorsal striatum in mice. Testing across a range of conditions and pulse durations, we found that mesoaccumbal and nigrostriatal neurons differ substantially in rebound properties with mesoaccumbal neurons displaying significantly longer delays to spiking following hyperpolarization. The underlying mechanism involves an inactivating potassium (IA) current with decay time constants of up to 225 ms, and small-amplitude hyperpolarization-activated currents (IH), characteristics that were most often observed in mesoaccumbal neurons. Pharmacological block of IA completely abolished rebound delays and, importantly, shortened synaptically evoked inhibitory pauses, thereby demonstrating the involvement of A-type potassium channels in prolonging pauses evoked by GABAergic inhibition. Therefore, these results show that mesoaccumbal and nigrostriatal neurons display differential responses to hyperpolarizing inhibitory stimuli that favors a higher sensitivity to inhibition in mesoaccumbal neurons. These findings may explain, in part, observations from in vivo experiments that ventral tegmental area neurons tend to exhibit longer aversive pauses relative to SNc neurons. SIGNIFICANCE STATEMENT Our study examines rebound, postburst, and synaptically evoked inhibitory pauses in subpopulations of midbrain dopamine neurons. We show that pauses in dopamine neuron firing, evoked by either stimulation of GABAergic inputs or hyperpolarizing current injections, are enhanced by a subclass of potassium conductances that are recruited at voltages below spike threshold. Importantly, A-type potassium currents recorded in mesoaccumbal neurons displayed substantially slower inactivation kinetics, which, combined with weaker expression of hyperpolarization-activated currents, lengthened hyperpolarization-induced delays in spiking relative to nigrostriatal neurons. These results suggest that input integration differs among dopamine neurons favoring higher sensitivity to inhibition in mesoaccumbal neurons and may partially explain in vivo observations that ventral tegmental area neurons exhibit longer aversive pauses relative to SNc neurons. PMID:28219982

Human sensitivity to vertical self-motion.

PubMed

Nesti, Alessandro; Barnett-Cowan, Michael; Macneilage, Paul R; Bülthoff, Heinrich H

2014-01-01

Perceiving vertical self-motion is crucial for maintaining balance as well as for controlling an aircraft. Whereas heave absolute thresholds have been exhaustively studied, little work has been done in investigating how vertical sensitivity depends on motion intensity (i.e., differential thresholds). Here we measure human sensitivity for 1-Hz sinusoidal accelerations for 10 participants in darkness. Absolute and differential thresholds are measured for upward and downward translations independently at 5 different peak amplitudes ranging from 0 to 2 m/s(2). Overall vertical differential thresholds are higher than horizontal differential thresholds found in the literature. Psychometric functions are fit in linear and logarithmic space, with goodness of fit being similar in both cases. Differential thresholds are higher for upward as compared to downward motion and increase with stimulus intensity following a trend best described by two power laws. The power laws' exponents of 0.60 and 0.42 for upward and downward motion, respectively, deviate from Weber's Law in that thresholds increase less than expected at high stimulus intensity. We speculate that increased sensitivity at high accelerations and greater sensitivity to downward than upward self-motion may reflect adaptations to avoid falling.

Differential Responsiveness of Innate-like IL-17- and IFN-γ-Producing γδ T Cells to Homeostatic Cytokines.

PubMed

Corpuz, Theresa M; Stolp, Jessica; Kim, Hee-Ok; Pinget, Gabriela V; Gray, Daniel H D; Cho, Jae-Ho; Sprent, Jonathan; Webster, Kylie E

2016-01-15

γδ T cells respond to molecules upregulated following infection or cellular stress using both TCR and non-TCR molecules. The importance of innate signals versus TCR ligation varies greatly. Both innate-like IL-17-producing γδ T (γδT-17) and IFN-γ-producing γδ T (γδT-IFNγ) subsets tune the sensitivity of their TCR following thymic development, allowing robust responses to inflammatory cytokines in the periphery. The remaining conventional γδ T cells retain high TCR responsiveness. We determined homeostatic mechanisms that govern these various subsets in the peripheral lymphoid tissues. We found that, although innate-like γδT-17 and γδT-IFNγ cells share elements of thymic development, they diverge when it comes to homeostasis. Both exhibit acute sensitivity to cytokines compared with conventional γδ T cells, but they do not monopolize the same cytokine. γδT-17 cells rely exclusively on IL-7 for turnover and survival, aligning them with NKT17 cells; IL-7 ligation triggers proliferation, as well as promotes survival, upregulating Bcl-2 and Bcl-xL. γδT-IFNγ cells instead depend heavily on IL-15. They display traits analogous to memory CD8(+) T cells and upregulate Bcl-xL and Mcl-1 upon cytokine stimulation. The conventional γδ T cells display low sensitivity to cytokine-alone stimulation and favor IL-7 for their turnover, characteristics reminiscent of naive αβ T cells, suggesting that they may also require tonic TCR signaling for population maintenance. These survival constraints suggest that γδ T cell subsets do not directly compete with each other for cytokines, but instead fall into resource niches with other functionally similar lymphocytes. Copyright © 2016 by The American Association of Immunologists, Inc.

The functional organization of the left STS: a large scale meta-analysis of PET and fMRI studies of healthy adults

PubMed Central

Liebenthal, Einat; Desai, Rutvik H.; Humphries, Colin; Sabri, Merav; Desai, Anjali

2014-01-01

The superior temporal sulcus (STS) in the left hemisphere is functionally diverse, with sub-areas implicated in both linguistic and non-linguistic functions. However, the number and boundaries of distinct functional regions remain to be determined. Here, we present new evidence, from meta-analysis of a large number of positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) studies, of different functional specificity in the left STS supporting a division of its middle to terminal extent into at least three functional areas. The middle portion of the left STS stem (fmSTS) is highly specialized for speech perception and the processing of language material. The posterior portion of the left STS stem (fpSTS) is highly versatile and involved in multiple functions supporting semantic memory and associative thinking. The fpSTS responds to both language and non-language stimuli but the sensitivity to non-language material is greater. The horizontal portion of the left STS stem and terminal ascending branches (ftSTS) display intermediate functional specificity, with the anterior-dorsal ascending branch (fatSTS) supporting executive functions and motor planning and showing greater sensitivity to language material, and the horizontal stem and posterior-ventral ascending branch (fptSTS) supporting primarily semantic processing and displaying greater sensitivity to non-language material. We suggest that the high functional specificity of the left fmSTS for speech is an important means by which the human brain achieves exquisite affinity and efficiency for native speech perception. In contrast, the extreme multi-functionality of the left fpSTS reflects the role of this area as a cortical hub for semantic processing and the extraction of meaning from multiple sources of information. Finally, in the left ftSTS, further functional differentiation between the dorsal and ventral aspect is warranted. PMID:25309312

Differential display detects host nucleic acid motifs altered in scrapie-infected brain.

PubMed

Lathe, Richard; Harris, Alyson

2009-09-25

The transmissible spongiform encephalopathies (TSEs) including scrapie have been attributed to an infectious protein or prion. Infectivity is allied to conversion of the endogenous nucleic-acid-binding protein PrP to an infectious modified form known as PrP(sc). The protein-only theory does not easily explain the enigmatic properties of the agent including strain variation. It was previously suggested that a short nucleic acid, perhaps host-encoded, might contribute to the pathoetiology of the TSEs. No candidate host molecules that might explain transmission of strain differences have yet been put forward. Differential display is a robust technique for detecting nucleic acid differences between two populations. We applied this technique to total nucleic acid preparations from scrapie-infected and control brain. Independent RNA preparations from eight normal and eight scrapie-infected (strain 263K) hamster brains were randomly amplified and visualized in parallel. Though the nucleic acid patterns were generally identical in scrapie-infected versus control brain, some rare bands were differentially displayed. Molecular species consistently overrepresented (or underrepresented) in all eight infected brain samples versus all eight controls were excised from the display, sequenced, and assembled into contigs. Only seven ros contigs (RNAs over- or underrepresented in scrapie) emerged, representing <4 kb from the transcriptome. All contained highly stable regions of secondary structure. The most abundant scrapie-only ros sequence was homologous to a repetitive transposable element (LINE; long interspersed nuclear element). Other ros sequences identified cellular RNA 7SL, clathrin heavy chain, visinin-like protein-1, and three highly specific subregions of ribosomal RNA (ros1-3). The ribosomal ros sequences accurately corresponded to LINE; retrotransposon insertion sites in ribosomal DNA (p<0.01). These differential motifs implicate specific host RNAs in the pathoetiology of the TSEs.

An accuracy evaluation of clinical, arthrometric, and stress-sonographic acute ankle instability examinations.

PubMed

Wiebking, Ulrich; Pacha, Tarek Omar; Jagodzinski, Michael

2015-03-01

Ankle sprain injuries, often due to lateral ligamentous injury, are the most common sports traumatology conditions. Correct diagnoses require an understanding of the assessment tools with a high degree of diagnostic accuracy. Obviously, there are still no clear consensuses or standard methods to differentiate between a ligament tear and an ankle sprain. In addition to clinical assessments, stress sonography, arthrometer and other methods are often performed simultaneously. These methods are often costly, however, and their accuracy is controversial. The aim of this study was to investigate three different measurement tools that can be used after a lateral ligament lesion of the ankle with injury of the anterior talofibular ligament to determine their diagnostic accuracy. Thirty patients were recruited for this study. The mean patient age was 35±14 years. There were 15 patients with a ligamentous rupture and 15 patients with an ankle sprain. We quantified two devices and one clinical assessment by which we calculated the sensitivity and specifity: Stress sonography according to Hoffmann, an arthrometer to investigate the 100N talar drawer and maximum manual testing and the clinical assessment of the anterior drawer test. A high resolution sonography was used as the gold standard. The ultrasound-assisted gadgetry according to Hoffmann, with a 3mm cut-off value, displayed a sensitivity of 0.27 and a specificity of 0.87. Using a 3.95mm cut-off value, the arthrometer displayed a sensitivity of 0.8 and a specificity of 0.4. The clinical investigation sensitivities and specificities were 0.93 and 0.67, respectively. Different assessment methods for ankle rupture diagnoses are suggested in the literature; however, these methods lack reliable data to set investigation standards. Clinical examination under adequate analgesia seems to remains the most reliable tool to investigate ligamentous ankle lesions. Further clinical studies with higher case numbers are necessary, however, to evaluate these findings and to measure the reliability. Copyright © 2014 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.

Development of an Automatic Differentiation Version of the FPX Rotor Code

NASA Technical Reports Server (NTRS)

Hu, Hong

1996-01-01

The ADIFOR2.0 automatic differentiator is applied to the FPX rotor code along with the grid generator GRGN3. The FPX is an eXtended Full-Potential CFD code for rotor calculations. The automatic differentiation version of the code is obtained, which provides both non-geometry and geometry sensitivity derivatives. The sensitivity derivatives via automatic differentiation are presented and compared with divided difference generated derivatives. The study shows that automatic differentiation method gives accurate derivative values in an efficient manner.

NLRP7 affects trophoblast lineage differentiation, binds to overexpressed YY1 and alters CpG methylation

USDA-ARS?s Scientific Manuscript database

Maternal-effect mutations in NLRP7 cause rare biparentally inherited hydatidiform moles (BiHMs), abnormal pregnancies containing hypertrophic vesicular trophoblast but no embryo. BiHM trophoblasts display abnormal DNA methylation patterns affecting maternally methylated germline differentially methy...

Small-molecule-directed, efficient generation of retinal pigment epithelium from human pluripotent stem cells.

PubMed

Maruotti, Julien; Sripathi, Srinivas R; Bharti, Kapil; Fuller, John; Wahlin, Karl J; Ranganathan, Vinod; Sluch, Valentin M; Berlinicke, Cynthia A; Davis, Janine; Kim, Catherine; Zhao, Lijun; Wan, Jun; Qian, Jiang; Corneo, Barbara; Temple, Sally; Dubey, Ramin; Olenyuk, Bogdan Z; Bhutto, Imran; Lutty, Gerard A; Zack, Donald J

2015-09-01

Age-related macular degeneration (AMD) is associated with dysfunction and death of retinal pigment epithelial (RPE) cells. Cell-based approaches using RPE-like cells derived from human pluripotent stem cells (hPSCs) are being developed for AMD treatment. However, most efficient RPE differentiation protocols rely on complex, stepwise treatments and addition of growth factors, whereas small-molecule-only approaches developed to date display reduced yields. To identify new compounds that promote RPE differentiation, we developed and performed a high-throughput quantitative PCR screen complemented by a novel orthogonal human induced pluripotent stem cell (hiPSC)-based RPE reporter assay. Chetomin, an inhibitor of hypoxia-inducible factors, was found to strongly increase RPE differentiation; combination with nicotinamide resulted in conversion of over one-half of the differentiating cells into RPE. Single passage of the whole culture yielded a highly pure hPSC-RPE cell population that displayed many of the morphological, molecular, and functional characteristics of native RPE.

Small-molecule–directed, efficient generation of retinal pigment epithelium from human pluripotent stem cells

PubMed Central

Maruotti, Julien; Sripathi, Srinivas R.; Bharti, Kapil; Fuller, John; Wahlin, Karl J.; Ranganathan, Vinod; Sluch, Valentin M.; Berlinicke, Cynthia A.; Davis, Janine; Kim, Catherine; Zhao, Lijun; Wan, Jun; Qian, Jiang; Corneo, Barbara; Temple, Sally; Dubey, Ramin; Olenyuk, Bogdan Z.; Bhutto, Imran; Lutty, Gerard A.; Zack, Donald J.

2015-01-01

Age-related macular degeneration (AMD) is associated with dysfunction and death of retinal pigment epithelial (RPE) cells. Cell-based approaches using RPE-like cells derived from human pluripotent stem cells (hPSCs) are being developed for AMD treatment. However, most efficient RPE differentiation protocols rely on complex, stepwise treatments and addition of growth factors, whereas small-molecule–only approaches developed to date display reduced yields. To identify new compounds that promote RPE differentiation, we developed and performed a high-throughput quantitative PCR screen complemented by a novel orthogonal human induced pluripotent stem cell (hiPSC)-based RPE reporter assay. Chetomin, an inhibitor of hypoxia-inducible factors, was found to strongly increase RPE differentiation; combination with nicotinamide resulted in conversion of over one-half of the differentiating cells into RPE. Single passage of the whole culture yielded a highly pure hPSC-RPE cell population that displayed many of the morphological, molecular, and functional characteristics of native RPE. PMID:26269569

Task-dependent color discrimination

NASA Technical Reports Server (NTRS)

Poirson, Allen B.; Wandell, Brian A.

1990-01-01

When color video displays are used in time-critical applications (e.g., head-up displays, video control panels), the observer must discriminate among briefly presented targets seen within a complex spatial scene. Color-discrimination threshold are compared by using two tasks. In one task the observer makes color matches between two halves of a continuously displayed bipartite field. In a second task the observer detects a color target in a set of briefly presented objects. The data from both tasks are well summarized by ellipsoidal isosensitivity contours. The fitted ellipsoids differ both in their size, which indicates an absolute sensitivity difference, and orientation, which indicates a relative sensitivity difference.

IR sensitive photorefractive polymers, the first updateable holographic three-dimensional display

NASA Astrophysics Data System (ADS)

Tay, Savas

This work presents recent advances in the development of infra-red sensitive photorefractive polymers, and updateable near real-time holographic 3D displays based on photorefractive polymers. Theoretical and experimental techniques used for design, fabrication and characterization of photorefractive polymers are outlined. Materials development and technical advances that made possible the use of photorefractive polymers for infra-red free-space optical communications, and 3D holographic displays are presented. Photorefractive polymers are dynamic holographic materials that allow recording of highly efficient reversible holograms. The longest operation wavelength for a photorefractive polymer before this study has been 950nm, far shorter than 1550nm, the wavelength of choice for optical communications and medical imaging. The polymers shown here were sensitized using two-photon absorption, a third order nonlinear effect, beyond the linear absorption spectrum of organic dyes, and reach 40% diffraction efficiency with a 35ms response time at this wavelength. As a consequence of two-photon absorption sensitization they exhibit non-destructive readout, which is an important advantage for applications that require high signal-to-noise ratios. Holographic 3D displays provide highly realistic images without the need for special eyewear, making them valuable tools for applications that require "situational awareness" such as medical, industrial and military imaging. Current commercially available holographic 3D displays employ photopolymers that lack image updating capability, resulting in their restricted use and high cost per 3D image. The holographic 3D display shown here employs photorefractive polymers with nearly 100% diffraction efficiency and fast writing time, hours of image persistence, rapid erasure and large area, a combination of properties that has not been shown before. The 3D display is based on stereography and utilizes world's largest photorefractive devices (4x4 inch in size). It can be recorded within a few minutes, viewed for several hours without the need for refreshing and can be completely erased and updated with new images when desired, thusly comprising the first updateable holographic 3D display with memory, suitable for practical use.

Induced pluripotent stem cell-derived limbal epithelial cells (LiPSC) as a cellular alternative for in vitro ocular toxicity testing.

PubMed

Aberdam, Edith; Petit, Isabelle; Sangari, Linda; Aberdam, Daniel

2017-01-01

Induced pluripotent stem cells hold great potential to produce unlimited amount of differentiated cells as cellular source for regenerative medicine but also for in vitro drug screening and cytotoxicity tests. Ocular toxicity testing is mandatory to evaluate the risks of drugs and cosmetic products before their application to human patients by preventing eye irritation or insult. Since the global ban to use animals, many human-derived alternatives have been proposed, from ex-vivo enucleated postmortem cornea, primary corneal cell culture and immortalized corneal epithelial cell lines. All of them share limitations for their routine use. Using an improved protocol, we derived limbal epithelial cells from human induced pluripotent stem cells, named LiPSC, that are able to be passaged and differentiate further into corneal epithelial cells. Comparative RT-qPCR, immunofluorescence staining, flow cytometry analysis and zymography assays demonstrate that LiPSC are morphologically and molecularly similar to the adult stem cells. Moreover, contrary to HCE, LiPSC and primary limbal cells display similarly sensitive to cytotoxicity treatment among passages. Our data strongly suggest that LiPSC could become a powerful alternative cellular model for cosmetic and drug tests.

Induced pluripotent stem cell-derived limbal epithelial cells (LiPSC) as a cellular alternative for in vitro ocular toxicity testing

PubMed Central

Aberdam, Edith; Petit, Isabelle; Sangari, Linda

2017-01-01

Induced pluripotent stem cells hold great potential to produce unlimited amount of differentiated cells as cellular source for regenerative medicine but also for in vitro drug screening and cytotoxicity tests. Ocular toxicity testing is mandatory to evaluate the risks of drugs and cosmetic products before their application to human patients by preventing eye irritation or insult. Since the global ban to use animals, many human-derived alternatives have been proposed, from ex-vivo enucleated postmortem cornea, primary corneal cell culture and immortalized corneal epithelial cell lines. All of them share limitations for their routine use. Using an improved protocol, we derived limbal epithelial cells from human induced pluripotent stem cells, named LiPSC, that are able to be passaged and differentiate further into corneal epithelial cells. Comparative RT-qPCR, immunofluorescence staining, flow cytometry analysis and zymography assays demonstrate that LiPSC are morphologically and molecularly similar to the adult stem cells. Moreover, contrary to HCE, LiPSC and primary limbal cells display similarly sensitive to cytotoxicity treatment among passages. Our data strongly suggest that LiPSC could become a powerful alternative cellular model for cosmetic and drug tests. PMID:28640863

Thyroid Hormone Differentially Modulates Warburg Phenotype in Breast Cancer Cells

PubMed Central

Suhane, Sonal; Ramanujan, V Krishnan

2011-01-01

Sustenance of cancer cells in vivo critically depends on a variety of genetic and metabolic adaptations. Aerobic glycolysis or Warburg effect has been a defining biochemical hallmark of transformed cells for more than five decades although a clear molecular basis of this observation is emerging only in recent years. In this study, we present our findings that thyroid hormone exerts its non-genomic and genomic actions in two model human breast cancer cell lines differentially. By laying a clear foundation for experimentally monitoring the Warburg phenotype in living cancer cells, we demonstrate that thyroid hormone-induced modulation of bioenergetic profiles in these two model cell lines depends on the degree of Warburg phenotype that they display. Further we also show that thyroid hormone can sensitize mitochondria in aggressive, triple-negative breast cancer cells favorably to increase the chemotherapeutic efficacy in these cells. Even though the role of thyroid hormone in modulating mitochondrial metabolism has been known, the current study accentuates the critical role it plays in modulating Warburg phenotype in breast cancer cells. The clinical significance of this finding is the possibility to devise strategies for metabolically modulating aggressive triple-negative tumors so as to enhance their chemosensitivity in vivo. PMID:21945435

Psychophysical contrast calibration

PubMed Central

To, Long; Woods, Russell L; Goldstein, Robert B; Peli, Eli

2013-01-01

Electronic displays and computer systems offer numerous advantages for clinical vision testing. Laboratory and clinical measurements of various functions and in particular of (letter) contrast sensitivity require accurately calibrated display contrast. In the laboratory this is achieved using expensive light meters. We developed and evaluated a novel method that uses only psychophysical responses of a person with normal vision to calibrate the luminance contrast of displays for experimental and clinical applications. Our method combines psychophysical techniques (1) for detection (and thus elimination or reduction) of display saturating nonlinearities; (2) for luminance (gamma function) estimation and linearization without use of a photometer; and (3) to measure without a photometer the luminance ratios of the display’s three color channels that are used in a bit-stealing procedure to expand the luminance resolution of the display. Using a photometer we verified that the calibration achieved with this procedure is accurate for both LCD and CRT displays enabling testing of letter contrast sensitivity to 0.5%. Our visual calibration procedure enables clinical, internet and home implementation and calibration verification of electronic contrast testing. PMID:23643843

Investigation of the mechanism for phthalate-induced toxicity during male sexual differentiation in the rat

EPA Science Inventory

Male rats exposed to phthalate esters during sexual differentiation (GDI4-GDI8) display various developmental abnormalities of the reproductive tract that are manifested later in adult life. Induction of these malformations is associated with declines in fetal testicular testoste...

Investigation of the mechanism for phthalate-induced toxicity during male sexual differentiation in the rat.

EPA Science Inventory

Male rats exposed to phthalate esters during sexual differentiation (GDI4-GDI8) display various reproductive developmental abnormalities later in adult life which are associated with declines in fetal testicular testosterone (T) production and insulin-like three hormone (lnsl-3...

The Conditioning of Counter Empathy toward In-Group and Out-Group Members.

ERIC Educational Resources Information Center

Englis, Basil G.

Research has shown that observers' vicarious emotional reactions to an in-group member's facial display of pleasure and pain are highly differentiated and empathetic, while responses to the expressive displays of an out-group member are relatively undifferentiated and indifferent. This study examines the effects of perceived group membership on…

Central and Peripheral Vision Loss Differentially Affects Contextual Cueing in Visual Search

ERIC Educational Resources Information Center

Geringswald, Franziska; Pollmann, Stefan

2015-01-01

Visual search for targets in repeated displays is more efficient than search for the same targets in random distractor layouts. Previous work has shown that this contextual cueing is severely impaired under central vision loss. Here, we investigated whether central vision loss, simulated with gaze-contingent displays, prevents the incidental…

Oligo-dT anchored cDNA-SCoT: a novel differential display method for analyzing differential gene expression in response to several stress treatments in mango (Mangifera indica L.).

PubMed

Luo, Cong; He, Xin-Hua; Hu, Ying; Yu, Hai-xia; Ou, Shi-Jin; Fang, Zhong-Bin

2014-09-15

Differential display is a powerful technique for analyzing differences in gene expression. Oligo-dT cDNAstart codon targeted marker (cDNA-SCoT) technique is a novel, simple, cheap, rapid, and efficient method for differential gene expression research. In the present study, the oligo-dT anchored cDNA-SCoT technique was exploited to identify differentially expressed genes during several stress treatments in mango. A total of 37 primers combined with oligo-dT anchor primers 3side amplified approximately 150 fragments of 150 bp to 1500 bp in length. Up to 100 fragments were differentially expressed among the stress treatments and control samples, among which 92 were obtained and sequenced. Out of the 92 transcript derived fragments (TDFs), 70% were highly homologous to known genes, and 30% encoded unclassified proteins with unknown functions. The expression pattern of nine genes with known functions involved in several abiotic stresses in other species was confirmed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) under cold (4 °C), salinity (NaCl), polyethylene glycol (PEG, MW 6000), and heavy metal treatments in leaves and stems at different time points (0, 24, 48, and 72 h). The expression patterns of the genes (TDF4, TDF7, TDF23, TDF45, TDF49, TDF50, TDF57, TDF91 and TDF92) that had direct or indirect relationships with cold, salinity, drought and heavy metal stress response were analyzed through qRT-PCR. The possible roles of these genes are discussed. This study suggests that the oligo-dT anchored cDNA-SCoT differential display method is a useful tool to serve as an initial step for characterizing transcriptional changes induced by abiotic stresses and provide gene information for further study and application in genetic improvement and breeding in mango. Copyright © 2014 Elsevier B.V. All rights reserved.

Differential solute gas response in ionic-liquid-based QCM arrays: elucidating design factors responsible for discriminative explosive gas sensing.

PubMed

Rehman, Abdul; Hamilton, Andrew; Chung, Alfred; Baker, Gary A; Wang, Zhe; Zeng, Xiangqun

2011-10-15

An eight-sensor array coupling a chemoselective room-temperature ionic liquid (RTIL) with quartz crystal microbalance (QCM) transduction is presented in this work in order to demonstrate the power of this approach in differentiating closely related analytes in sensory devices. The underlying mechanism behind the specific sensory response was explored by (i) studying mass loading and viscoelasticity effects of the sensing layers, predominantly through variation in damping impedance, the combination of which determines the sensitivity; (ii) creation of a solvation model based on Abraham's solvation descriptors which reveals the fact that polarizability and lipophilicity are the main factors influencing the dissolution of gas analytes into the RTILs; and (iii) determination of enthalpy and entropy values for the studied interactions and comparison via a simulation model, which is also effective for pattern discrimination, in order to establish a foundation for the analytical scientist as well as inspiration for synthetic pathways and innovative research into next-generation sensory approaches. The reported sensors displayed an excellent sensitivity with detection limit of <0.2%, fast response and recovery, and a workable temperature range of 27-55 °C and even higher. Linear discriminant analysis (LDA) showed a discrimination accuracy of 86-92% for nitromethane and 1-ethyl-2-nitrobenzene, 71% for different mixtures of nitromethane, and 100% for these analytes when thermodynamic parameters were used as input data. We envisage applications to detecting other nitroaromatics and security-related gas targets, and high-temperature or real-time situations where manual access is restricted, opening up new horizons in chemical sensing. © 2011 American Chemical Society

The regulatory network of ThbZIP1 in response to abscisic acid treatment

PubMed Central

Ji, Xiaoyu; Liu, Guifeng; Liu, Yujia; Nie, Xianguang; Zheng, Lei; Wang, Yucheng

2015-01-01

Previously, a bZIP transcription factor from Tamarix hispida, ThbZIP1, was characterized: plants overexpressing ThbZIP1 displayed improved salt stress tolerance but were sensitive to abscisic acid (ABA). In the current study, we further characterized the regulatory network of ThbZIP1 and the mechanism of ABA sensitivity mediated by ThbZIP1. An ABF transcription factor from T. hispida, ThABF1, directly regulates the expression of ThbZIP1. Microarray analysis identified 1662 and 1609 genes that were respectively significantly upregulated or downregulated by ThbZIP1 when exposed to ABA. Gene ontology (GO) analysis showed that the processes including “response to stimulus,” “catalytic activity,” “binding function,” and “metabolic process” were highly altered in ThbZIP1 expressing plants exposed to ABA. The gene expression in ThbZIP1 transformed plants were compared between exposed to ABA and salt on the genome scale. Genes differentially regulated by both salt and ABA treatment only accounted for 9.75% of total differentially regulated genes. GO analysis showed that structural molecule activity, organelle part, membrane-enclosed lumen, reproduction, and reproductive process are enhanced by ABA but inhibited by salt stress. Conversely, immune system and multi-organism process were improved by salt but inhibited by ABA. Transcription regulator activity, enzyme regulator activity, and developmental process were significantly altered by ABA but were not affected by salt stress. Our study provides insights into how ThbZIP1 mediates ABA and salt stress response at the molecular level. PMID:25713576

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

Liao, Haitao, E-mail: liaoht@cae.ac.cn

The direct differentiation and improved least squares shadowing methods are both developed for accurately and efficiently calculating the sensitivity coefficients of time averaged quantities for chaotic dynamical systems. The key idea is to recast the time averaged integration term in the form of differential equation before applying the sensitivity analysis method. An additional constraint-based equation which forms the augmented equations of motion is proposed to calculate the time averaged integration variable and the sensitivity coefficients are obtained as a result of solving the augmented differential equations. The application of the least squares shadowing formulation to the augmented equations results inmore » an explicit expression for the sensitivity coefficient which is dependent on the final state of the Lagrange multipliers. The LU factorization technique to calculate the Lagrange multipliers leads to a better performance for the convergence problem and the computational expense. Numerical experiments on a set of problems selected from the literature are presented to illustrate the developed methods. The numerical results demonstrate the correctness and effectiveness of the present approaches and some short impulsive sensitivity coefficients are observed by using the direct differentiation sensitivity analysis method.« less

Am80 induces neuronal differentiation via increased tropomyosin-related kinase B expression in a human neuroblastoma SH-SY5Y cell line.

PubMed

Shiohira, Hideo; Kitaoka, Akira; Enjoji, Munechika; Uno, Tsukasa; Nakashima, Manabu

2012-01-01

Am80, a synthetic retinoid, has been used in differentiation therapy for acute promyelocytic leukemia (APL). All-trans retinoic acid (ATRA) as one of natural retinoid has been also used to treat APL. ATRA treatment causes neuronal differentiation by inducing tropomyosin-related kinase B (TrkB) expression and increasing the sensitivity to brain-derived neurotrophic factor (BDNF), a TrkB ligand. In the present study, we investigated the effects of Am80 on neuronal differentiation, BDNF sensitivity and TrkB expression in human neuroblastoma SH-SY5Y cells. Treatment with Am80 induced morphological differentiation of neurite outgrowth and increased the expression of GAP43 mRNA, a neuronal differentiation marker. Additionally, TrkB protein was also increased, and exogenous BDNF stimulation after treatment with Am80 induced greater neurite outgrowth than without BDNF treatment. These results suggest that Am80 induced neuronal differentiation by increasing TrkB expression and BDNF sensitivity.

Patterns of neural activity associated with differential acute locomotor stimulation to cocaine and methamphetamine in adolescent versus adult male C57BL/6J mice

PubMed Central

Zombeck, Jonathan A.; Lewicki, Aaron D.; Patel, Kevin; Gupta, Tripta; Rhodes, Justin S.

2009-01-01

Adolescence is a time period when major changes occur in the brain with long-term consequences for behavior. One ramification is altered responses to drugs of abuse, but the specific brain mechanisms and implications for mental health are poorly understood. Here, we used a mouse model in which adolescents display dramatically reduced sensitivity to the acute locomotor stimulating effects of cocaine and methamphetamine. The goal was to identify key brain regions or circuits involved in the differential behavior. Male adolescent (PN 30–35) and young adult (PN 69–74) C57BL/6J mice were administered an intraperitoneal injection of cocaine (0, 15, 30 mg/kg) or methamphetamine (0, 2, 4 mg/kg) and euthanized 90 minutes later. Locomotor activity was monitored continuously in the home cage by video tracking. Immunohistochemical detection of Fos protein was used to quantify neuronal activation in 16 different brain regions. As expected, adolescents were less sensitive to the locomotor stimulating effects of cocaine and methamphetamine as indicated by a rightward shift in the dose response relationship. After a saline injection, adolescents showed similar levels of Fos as adults in all regions except the dorsal and lateral caudate where levels were lower in adolescents. Cocaine and methamphetamine dose dependently increased Fos in all brain regions sampled in both adolescents and adults, but Fos levels were similar in both age groups for a majority of regions and doses. Locomotor activity was correlated with Fos in several brain areas within adolescent and adult groups, and adolescents had a significantly greater induction of Fos for a given amount of locomotor activity in key brain regions including the caudate where they showed reduced Fos under baseline conditions. Future research will identify the molecular and cellular events that are responsible for the differential psychostimulant-induced patterns of brain activation and behavior observed in adolescent versus adult mice. PMID:19932887

Quantification of Dynamic Morphological Drug Responses in 3D Organotypic Cell Cultures by Automated Image Analysis

PubMed Central

Härmä, Ville; Schukov, Hannu-Pekka; Happonen, Antti; Ahonen, Ilmari; Virtanen, Johannes; Siitari, Harri; Åkerfelt, Malin; Lötjönen, Jyrki; Nees, Matthias

2014-01-01

Glandular epithelial cells differentiate into complex multicellular or acinar structures, when embedded in three-dimensional (3D) extracellular matrix. The spectrum of different multicellular morphologies formed in 3D is a sensitive indicator for the differentiation potential of normal, non-transformed cells compared to different stages of malignant progression. In addition, single cells or cell aggregates may actively invade the matrix, utilizing epithelial, mesenchymal or mixed modes of motility. Dynamic phenotypic changes involved in 3D tumor cell invasion are sensitive to specific small-molecule inhibitors that target the actin cytoskeleton. We have used a panel of inhibitors to demonstrate the power of automated image analysis as a phenotypic or morphometric readout in cell-based assays. We introduce a streamlined stand-alone software solution that supports large-scale high-content screens, based on complex and organotypic cultures. AMIDA (Automated Morphometric Image Data Analysis) allows quantitative measurements of large numbers of images and structures, with a multitude of different spheroid shapes, sizes, and textures. AMIDA supports an automated workflow, and can be combined with quality control and statistical tools for data interpretation and visualization. We have used a representative panel of 12 prostate and breast cancer lines that display a broad spectrum of different spheroid morphologies and modes of invasion, challenged by a library of 19 direct or indirect modulators of the actin cytoskeleton which induce systematic changes in spheroid morphology and differentiation versus invasion. These results were independently validated by 2D proliferation, apoptosis and cell motility assays. We identified three drugs that primarily attenuated the invasion and formation of invasive processes in 3D, without affecting proliferation or apoptosis. Two of these compounds block Rac signalling, one affects cellular cAMP/cGMP accumulation. Our approach supports the growing needs for user-friendly, straightforward solutions that facilitate large-scale, cell-based 3D assays in basic research, drug discovery, and target validation. PMID:24810913

An enzymatically-sensitized sequential and concentric energy transfer relay self-assembled around semiconductor quantum dots

NASA Astrophysics Data System (ADS)

Samanta, Anirban; Walper, Scott A.; Susumu, Kimihiro; Dwyer, Chris L.; Medintz, Igor L.

2015-04-01

The ability to control light energy within de novo nanoscale structures and devices will greatly benefit their continuing development and ultimate application. Ideally, this control should extend from generating the light itself to its spatial propagation within the device along with providing defined emission wavelength(s), all in a stand-alone modality. Here we design and characterize macromolecular nanoassemblies consisting of semiconductor quantum dots (QDs), several differentially dye-labeled peptides and the enzyme luciferase which cumulatively demonstrate many of these capabilities by engaging in multiple-sequential energy transfer steps. To create these structures, recombinantly-expressed luciferase and the dye-labeled peptides were appended with a terminal polyhistidine sequence allowing for controlled ratiometric self-assembly around the QDs via metal-affinity coordination. The QDs serve to provide multiple roles in these structures including as central assembly platforms or nanoscaffolds along with acting as a potent energy harvesting and transfer relay. The devices are activated by addition of coelenterazine H substrate which is oxidized by luciferase producing light energy which sensitizes the central 625 nm emitting QD acceptor by bioluminescence resonance energy transfer (BRET). The sensitized QD, in turn, acts as a relay and transfers the energy to a first peptide-labeled Alexa Fluor 647 acceptor dye displayed on its surface. This dye then transfers energy to a second red-shifted peptide-labeled dye acceptor on the QD surface through a second concentric Förster resonance energy transfer (FRET) process. Alexa Fluor 700 and Cy5.5 are both tested in the role of this terminal FRET acceptor. Photophysical analysis of spectral profiles from the resulting sequential BRET-FRET-FRET processes allow us to estimate the efficiency of each of the transfer steps. Importantly, the efficiency of each step within this energy transfer cascade can be controlled to some extent by the number of enzymes/peptides displayed on the QD. Further optimization of the energy transfer process(es) along with potential applications of such devices are finally discussed.The ability to control light energy within de novo nanoscale structures and devices will greatly benefit their continuing development and ultimate application. Ideally, this control should extend from generating the light itself to its spatial propagation within the device along with providing defined emission wavelength(s), all in a stand-alone modality. Here we design and characterize macromolecular nanoassemblies consisting of semiconductor quantum dots (QDs), several differentially dye-labeled peptides and the enzyme luciferase which cumulatively demonstrate many of these capabilities by engaging in multiple-sequential energy transfer steps. To create these structures, recombinantly-expressed luciferase and the dye-labeled peptides were appended with a terminal polyhistidine sequence allowing for controlled ratiometric self-assembly around the QDs via metal-affinity coordination. The QDs serve to provide multiple roles in these structures including as central assembly platforms or nanoscaffolds along with acting as a potent energy harvesting and transfer relay. The devices are activated by addition of coelenterazine H substrate which is oxidized by luciferase producing light energy which sensitizes the central 625 nm emitting QD acceptor by bioluminescence resonance energy transfer (BRET). The sensitized QD, in turn, acts as a relay and transfers the energy to a first peptide-labeled Alexa Fluor 647 acceptor dye displayed on its surface. This dye then transfers energy to a second red-shifted peptide-labeled dye acceptor on the QD surface through a second concentric Förster resonance energy transfer (FRET) process. Alexa Fluor 700 and Cy5.5 are both tested in the role of this terminal FRET acceptor. Photophysical analysis of spectral profiles from the resulting sequential BRET-FRET-FRET processes allow us to estimate the efficiency of each of the transfer steps. Importantly, the efficiency of each step within this energy transfer cascade can be controlled to some extent by the number of enzymes/peptides displayed on the QD. Further optimization of the energy transfer process(es) along with potential applications of such devices are finally discussed. Electronic supplementary information (ESI) available: This material includes control experimental data and select deconvoluted spectra. See DOI: 10.1039/c5nr00828j

Comparison of workload measures on computer-generated primary flight displays

NASA Technical Reports Server (NTRS)

Nataupsky, Mark; Abbott, Terence S.

1987-01-01

Four Air Force pilots were used as subjects to assess a battery of subjective and physiological workload measures in a flight simulation environment in which two computer-generated primary flight display configurations were evaluated. A high- and low-workload task was created by manipulating flight path complexity. Both SWAT and the NASA-TLX were shown to be effective in differentiating the high and low workload path conditions. Physiological measures were inconclusive. A battery of workload measures continues to be necessary for an understanding of the data. Based on workload, opinion, and performance data, it is fruitful to pursue research with a primary flight display and a horizontal situation display integrated into a single display.

Differential Endocannabinoid Regulation of Extinction in Appetitive and Aversive Barnes Maze Tasks

ERIC Educational Resources Information Center

Harloe, John P.; Thorpe, Andrew J.; Lichtman, Aron H.

2008-01-01

CB[subscript 1] receptor-compromised animals show profound deficits in extinguishing learned behavior from aversive conditioning tasks, but display normal extinction learning in appetitive operant tasks. However, it is difficult to discern whether the differential involvement of the endogenous cannabinoid system on extinction results from the…

Real-time analysis of dual-display phage immobilization and autoantibody screening using quartz crystal microbalance with dissipation monitoring.

PubMed

Rajaram, Kaushik; Losada-Pérez, Patricia; Vermeeren, Veronique; Hosseinkhani, Baharak; Wagner, Patrick; Somers, Veerle; Michiels, Luc

2015-01-01

Over the last three decades, phage display technology has been used for the display of target-specific biomarkers, peptides, antibodies, etc. Phage display-based assays are mostly limited to the phage ELISA, which is notorious for its high background signal and laborious methodology. These problems have been recently overcome by designing a dual-display phage with two different end functionalities, namely, streptavidin (STV)-binding protein at one end and a rheumatoid arthritis-specific autoantigenic target at the other end. Using this dual-display phage, a much higher sensitivity in screening specificities of autoantibodies in complex serum sample has been detected compared to single-display phage system on phage ELISA. Herein, we aimed to develop a novel, rapid, and sensitive dual-display phage to detect autoantibodies presence in serum samples using quartz crystal microbalance with dissipation monitoring as a sensing platform. The vertical functionalization of the phage over the STV-modified surfaces resulted in clear frequency and dissipation shifts revealing a well-defined viscoelastic signature. Screening for autoantibodies using antihuman IgG-modified surfaces and the dual-display phage with STV magnetic bead complexes allowed to isolate the target entities from complex mixtures and to achieve a large response as compared to negative control samples. This novel dual-display strategy can be a potential alternative to the time consuming phage ELISA protocols for the qualitative analysis of serum autoantibodies and can be taken as a departure point to ultimately achieve a point of care diagnostic system.

Method and apparatus for reflection mode imaging

NASA Technical Reports Server (NTRS)

Heyser, Richard C. (Inventor); Rooney, James A. (Inventor)

1989-01-01

A volume is scanned with a raster scan about a center of rotation using a transmitter/receiver at a selected range while gating a range window on the receiver with a selected range differential. The received signals are then demodulated to obtain signals representative of a property within the volume being scanned such as the density of a tumor. The range is varied until the entire volume has been scanned at all ranges to be displayed. An imaging display is synchronously scanned together with the raster scan to display variations of the property on the display. A second transmitter/receiver with associated equipment may be offset from the first and variations displayed from each of the transmitter/receivers on its separate display. The displays may then be combined stereoscopically to provide a three-dimensional image representative of variations of the property.

Efficient iodine-free dye-sensitized solar cells employing truxene-based organic dyes.

PubMed

Zong, Xueping; Liang, Mao; Chen, Tao; Jia, Jiangnan; Wang, Lina; Sun, Zhe; Xue, Song

2012-07-07

Two new truxene-based organic sensitizers (M15 and M16) featuring high extinction coefficients were synthesized for dye-sensitized solar cells employing cobalt electrolyte. The M16-sensitized device displays a 7.6% efficiency at an irradiation of AM1.5 full sunlight.

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

Rajalin, Ann-Marie; Pollock, Hanna; Aarnisalo, Piia, E-mail: piia.aarnisalo@helsinki.fi

The orphan nuclear receptor estrogen-related receptor-{alpha} (ERR{alpha}) has been reported to have both a positive and a negative regulatory role in osteoblastic and adipocytic differentiation. We have studied the role of ERR{alpha} in osteoblastic and adipogenic differentiation of mesenchymal stem cells. Bone marrow mesenchymal stem cells were isolated from ERR{alpha} deficient mice and their differentiation capacities were compared to that of the wild-type cells. ERR{alpha} deficient cultures displayed reduced cellular proliferation, osteoblastic differentiation, and mineralization. In the complementary experiment, overexpression of ERR{alpha} in MC3T3-E1 cells increased the expression of osteoblastic markers and mineralization. Alterations in the expression of bone sialoproteinmore » (BSP) may at least partially explain the effects on mineralization as BSP expression was reduced in ERR{alpha} deficient MSCs and enhanced upon ERR{alpha} overexpression in MC3T3-E1 cells. Furthermore, a luciferase reporter construct driven by the BSP promoter was efficiently transactivated by ERR{alpha}. Under adipogenic conditions, ERR{alpha} deficient cultures displayed reduced adipocytic differentiation. Our data thus propose a positive role for ERR{alpha} in osteoblastic and adipocytic differentiation. The variability in the results yielded in the different studies implies that ERR{alpha} may play different roles in bone under different physiological conditions.« less

An interactive editor for definition of touch-sensitive zones for a graphic display

NASA Technical Reports Server (NTRS)

Monroe, Burt L., III; Jones, Denise R.

1987-01-01

In the continuing effort to develop more efficient man-machine communications methods, touch displays have shown potential as straightforward input systems. The development of software necessary to handle such systems, however, can become tedious. In order to reduce the need for redundant programming, a touch editor has been developed which allows a programmer to interactively define touch-sensitive areas for a graphic display. The information produced during the editing process is written to a data file, which can be accessed easily when needed by an application program. This paper outlines the structure, logic, and use of the editor, as well as the hardware with which it is presently compatible.

How Interactive Is the Interactive Whiteboard?

ERIC Educational Resources Information Center

Quashie, Valerie

2009-01-01

An interactive whiteboard (IWB) is simply a surface onto which a computer screen can be displayed, via a projector. It is touch-sensitive and lets one use a pen like a mouse, controlling the computer from the board itself. Everything that can be displayed on a computer can be displayed onto the whiteboard and, if the computer is linked to speakers…

Infants Perceive Human Point-Light Displays as Solid Forms

ERIC Educational Resources Information Center

Moore, Derek G.; Goodwin, Julia E.; George, Rachel; Axelsson, Emma L.; Braddick, Fleur M. B.

2007-01-01

While five-month-old infants show orientation-specific sensitivity to changes in the motion and occlusion patterns of human point-light displays, it is not known whether infants are capable of binding a human representation to these displays. Furthermore, it has been suggested that infants do not encode the same physical properties for humans and…

Theoretical foundations for traditional and generalized sensitivity functions for nonlinear delay differential equations.

PubMed

Banks, H Thomas; Robbins, Danielle; Sutton, Karyn L

2013-01-01

In this paper we present new results for differentiability of delay systems with respect to initial conditions and delays. After motivating our results with a wide range of delay examples arising in biology applications, we further note the need for sensitivity functions (both traditional and generalized sensitivity functions), especially in control and estimation problems. We summarize general existence and uniqueness results before turning to our main results on differentiation with respect to delays, etc. Finally we discuss use of our results in the context of estimation problems.

Interactions among aging, gender, and gonadectomy effects upon naloxone hypophagia in rats.

PubMed

Islam, A K; Beczkowska, I W; Bodnar, R J

1993-11-01

The present study examined the dose-dependent (0.25-5 mg/kg) effects of systemic naloxone upon deprivation-induced intake and high-fat intake as functions of age (4, 8, 14, and 20 months), gender, and gonadectomy in rats. Significant increases in body weight were observed as functions of age and gonadectomy. Whereas aging significantly reduced basal deprivation-induced intake, it generally failed to alter basal high-fat intake. Whereas age, gender, and gonadectomy failed to alter the decreases in deprivation-induced intake following low (0.25-2.5 mg/kg) naloxone doses, sham males displayed significantly greater age-related and gender-related inhibition following the 5 mg/kg dose of naloxone. Young gonadectomized rats displayed significant increases in naloxone's inhibition of deprivation-induced intake as well. More dramatic changes occurred in naloxone's inhibition of high-fat intake. Naloxone's potency increased in sham female rats as a function of age, and decreased in sham males and ovariectomized females as a function of age. Whereas sham males and ovariectomized females were most sensitive to naloxone's inhibition of high-fat intake at young ages, sham females were most sensitive at older ages. These data indicate that effects of age, gender, and gonadectomy upon naloxone-induced hypophagia dissociate as a function of the type of intake. Because selective opioid antagonist studies demonstrate that deprivation-induced intake is mediated by the mu1 receptor and high-fat intake is mediated by kappa and mu2 receptors, it is postulated that the differential effects of aging, gender, and gonadectomy variables upon opioid mediation of the two forms of intake may reflect their interaction with different opioid receptor subtypes.

Biochemical and physiological processes associated with the differential ozone response in ozone-tolerant and sensitive soybean genotypes

USDA-ARS?s Scientific Manuscript database

Biochemical and physiological traits of two soybean [Glycine max (L.) Merr.] genotypes that differ in sensitivity to ozone (O3) were investigated to determine the possible basis for the differential response. Fiskeby III (O3-tolerant) and Mandarin (Ottawa) (O3-sensitive) were grown in a greenhouse ...

The perception of subjective contours and neon color spreading figures in young infants.

PubMed

Kavsek, Michael

2009-02-01

The goal of the present habituation-dishabituation study was to explore sensitivity to subjective contours and neon color spreading patterns in infants. The first experiment was a replication of earlier investigations that showed evidence that even young infants are capable of perceiving subjective contours. Participants 4 months of age were habituated to a subjective Kanizsa square and were tested afterward for their ability to differentiate between the subjective square and a nonsubjective pattern that was constructed by rotating some of the inducing elements. Data analysis indicated a significant preference for the nonsubjective pattern. A control condition ensured that this result was not generated by the difference in figural symmetry or by the local differences between the test displays. In the second experiment, infant perception of a neon color spreading display was analyzed. Again, 4-month-old infants could discriminate between the illusory figure and a nonillusory pattern. Furthermore, infants in a control group did not respond to the difference in symmetry and the local differences between two nonillusory targets. Overall, the results show that young infants respond to illusory figures that are generated by either implicit T-junctions (Experiment 1) or implicit X-junctions (Experiment 2). The findings are interpreted against the background of the neurophysiological model proposed by Grossberg and Mingolla (1985).

Continuous microfluidic assortment of interactive ligands (CMAIL)

NASA Astrophysics Data System (ADS)

Hsiao, Yi-Hsing; Huang, Chao-Yang; Hu, Chih-Yung; Wu, Yen-Yu; Wu, Chung-Hsiun; Hsu, Chia-Hsien; Chen, Chihchen

2016-08-01

Finding an interactive ligand-receptor pair is crucial to many applications, including the development of monoclonal antibodies. Biopanning, a commonly used technique for affinity screening, involves a series of washing steps and is lengthy and tedious. Here we present an approach termed continuous microfluidic assortment of interactive ligands, or CMAIL, for the screening and sorting of antigen-binding single-chain variable antibody fragments (scFv) displayed on bacteriophages (phages). Phages carrying native negative charges on their coat proteins were electrophoresed through a hydrogel matrix functionalized with target antigens under two alternating orthogonal electric fields. During the weak horizontal electric field phase, phages were differentially swept laterally depending on their affinity for the antigen, and all phages were electrophoresed down to be collected during the strong vertical electric field phase. Phages of different affinity were spatially separated, allowing the continuous operation. More than 105 CFU (colony forming unit) antigen-interacting phages were isolated with ~100% specificity from a phage library containing 3 × 109 individual members within 40 minutes of sorting using CMAIL. CMAIL is rapid, sensitive, specific, and does not employ washing, elution or magnetic beads. In conclusion, we have developed an efficient and cost-effective method for isolating and sorting affinity reagents involving phage display.

Novel porphyrin conjugates with a potent photodynamic antitumor effect: differential efficacy of mono- and bis-beta-cyclodextrin derivatives in vitro and in vivo.

PubMed

Kralova, Jarmila; Synytsya, Alla; Pouckova, Pavla; Koc, Michal; Dvorak, Michal; Kral, Vladimir

2006-01-01

In the present study we investigated the photosensitizing properties of two novel mono- and bis-cyclodextrin tetrakis (pentafluorophenyl) porphyrin derivatives in several tumor cell lines and in BALB/c mice bearing subcutaneously transplanted syngeneic mouse mammary carcinoma 4T1. Both studied sensitizers were localized mainly in lysosomes and were found to induce cell death by triggering apoptosis in human leukemic cells HL-60. In 4T1 and other cell lines both apoptotic and necrotic modes of cell death occurred depending on drug and light doses. Mono-cyclodextrin porphyrin derivative P(beta-CD)1 exhibited stronger in vitro phototoxic effect than bis-cyclodextrin derivative P(beta-CD)2. However, in vivo P(beta-CD)2 displayed faster tumor uptake with maximal accumulation 6 h after application, leading to complete and prolonged elimination of subcutaneous tumors within 3 days after irradiation (100 J cm(-2)). In contrast, P(beta-CD)1 uptake was slower (48 h) and the reduction of tumor mass was only transient, reaching the maximum at the 12 h interval when a favorable tumor-to-skin ratio appeared. Thus, P(beta-CD)2 represents a new photosensitizing drug displaying fast and selective tumor uptake, strong antitumor activity and fast elimination from the body.

Intracellularly Induced Cyclophilins Play an Important Role in Stress Adaptation and Virulence of Brucella abortus

PubMed Central

García Fernández, Lucía; DelVecchio, Vito G.; Briones, Gabriel

2013-01-01

Brucella is an intracellular bacterial pathogen that causes the worldwide zoonotic disease brucellosis. Brucella virulence relies on its ability to transition to an intracellular lifestyle within host cells. Thus, this pathogen must sense its intracellular localization and then reprogram gene expression for survival within the host cell. A comparative proteomic investigation was performed to identify differentially expressed proteins potentially relevant for Brucella intracellular adaptation. Two proteins identified as cyclophilins (CypA and CypB) were overexpressed in the intracellular environment of the host cell in comparison to laboratory-grown Brucella. To define the potential role of cyclophilins in Brucella virulence, a double-deletion mutant was constructed and its resulting phenotype was characterized. The Brucella abortus ΔcypAB mutant displayed increased sensitivity to environmental stressors, such as oxidative stress, pH, and detergents. In addition, the B. abortus ΔcypAB mutant strain had a reduced growth rate at lower temperature, a phenotype associated with defective expression of cyclophilins in other microorganisms. The B. abortus ΔcypAB mutant also displays reduced virulence in BALB/c mice and defective intracellular survival in HeLa cells. These findings suggest that cyclophilins are important for Brucella virulence and survival in the host cells. PMID:23230297

Synergetic signal amplification of multi-walled carbon nanotubes-Fe3O4 hybrid and trimethyloctadecylammonium bromide as a highly sensitive detection platform for tetrabromobisphenol A

PubMed Central

Zhou, Feng; Wang, Yue; Wu, Wei; Jing, Tao; Mei, Surong; Zhou, Yikai

2016-01-01

In this work, we fabricated an electrochemical sensor based on trimethyloctadecylammonium bromide and multi-walled carbon nanotubes-Fe3O4 hybrid (TOAB/MWCNTs-Fe3O4) for sensitive detection of tetrabromobisphenol A (TBBPA). The nanocomposite was characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM) and Fourier transform infrared spectroscopy (FT-IR) techniques. The electrochemical behaviors of TBBPA on TOAB/MWCNTs-Fe3O4 composite film modified glassy carbon electrode (GCE) were investigated by cyclic voltammetry (CV), differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS) method. The experimental results indicated that the incorporation of MWCNTs-Fe3O4 with TOAB greatly enhanced the electrochemical response of TBBPA. This fabricated sensor displayed excellent analytical performance for TBBPA detection over a range from 3.0 nM to 1000.0 nM with a detection limit of 0.73 nM (S/N = 3). Moreover, the proposed electrochemical sensor exhibited good reproducibility and stability, and could be successfully applied to detect TBBPA in water samples with satisfactory results. PMID:27897238

Highly sensitive and selective detection of dopamine based on hollow gold nanoparticles-graphene nanocomposite modified electrode.

PubMed

Zhu, Wencai; Chen, Ting; Ma, Xuemei; Ma, Houyi; Chen, Shenhao

2013-11-01

Highly dispersed hollow gold-graphene (HAu-G) nanocomposites were synthesized by a two-step method. The immobilization of hollow gold nanoparticles (HAu NPs) onto the surface of graphene sheets was achieved by mixing an aqueous solution of HAu NPs with a poly(N-vinylpyrrolidone)-functionalized graphene dispersion at room temperature. A glassy carbon electrode (GCE) was modified with the nanocomposites, and the as-prepared modified electrode displayed high electrocatalytic activity and extraordinary electronic transport properties. Amperometric detection of dopamine (DA) performed with the HAu-G modified electrode exhibits a good linearity between 0.08 and 600 μM with a low detection limit of 0.05 μM (S/N=3) and also possesses good reproducibility and operational stability. The interference of ascorbic acid (AA) and uric acid (UA) can be excluded when using differential pulse voltammetric technique. In addition, this type of modified electrode can also be applied to the determination of DA content in dopamine hydrochloride injection. It is obvious that the HAu-G modified electrode provides a new way to detect dopamine sensitively and selectively. Copyright © 2013 Elsevier B.V. All rights reserved.

Search for methylation-sensitive amplification polymorphisms associated with the mantled variant phenotype in oil palm (Elaeis guineensis Jacq).

PubMed

Jaligot, E; Beulé, T; Baurens, F-C; Billotte, N; Rival, A

2004-02-01

The methylation-sensitive amplification polymorphism (MSAP) technique has been employed on somatic embryo-derived oil palms (Elaeis guineensis Jacq.) to identify methylation polymorphisms correlated with the "mantled" somaclonal variation. The variant phenotype displays an unstable feminization of male organs in both male and female flowers. Using MSAP, the methylation status of CCGG sites was compared in three normal versus three mantled regenerants sampled in clonal populations obtained through somatic embryogenesis from four genotypically distinct mother palms. Overall, 64 selective primer combinations were used and they have amplified 23 markers exhibiting a differential methylation pattern between the two phenotypes. Our results indicate that CCGG sites are poorly affected by the considerable decrease in global DNA methylation that has been previously associated with the mantled phenotype. Each of the 23 markers isolated in the present study could discriminate between the two phenotypes only when they were from the same genetic origin. This result hampers at the moment the direct use of MSAP markers for the early detection of variants, even though valuable information on putative target sequences will be obtained from a further characterization of these polymorphic markers.

( sup 3 H)opipramol labels a novel binding site and sigma receptors in rat brain membranes

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

Ferris, C.D.; Hirsch, D.J.; Brooks, B.P.

1991-02-01

Opipramol (OP), a clinically effective antidepressant with a tricyclic structure, is inactive as an inhibitor of biogenic amine uptake. ({sup 3}H)Opipramol binds saturably to rat brain membranes (apparent KD = 4 nM, Bmax = 3 pmol/mg of protein). ({sup 3}H)Opipramol binding can be differentiated into haloperidol-sensitive and -resistant components, with Ki values for haloperidol of 1 nM (Bmax = 1 pmol/mg of protein) and 350 nM (Bmax = 1.9 pmol/mg of protein), respectively. The drug specificity of the haloperidol-sensitive component is the same as that of sigma receptors labeled with (+)-({sup 3}H)3-(3-hydroxyphenyl)-N-(1-propyl)piperdine. The haloperidol-resistant component does not correspond to anymore » known neurotransmitter receptor or uptake recognition site. It displays high affinity for phenothiazines and related structures such as perphenazine, clopenthixol, and flupenthixol, whose potencies are comparable to that of opipramol. Because certain of these drugs are more potent at the haloperidol-resistant opipramol site than in exerting any other action, it is possible that this opipramol-selective site may mediate their therapeutic effects.« less

Electrochemical determination of L-phenylalanine at polyaniline modified carbon electrode based on β-cyclodextrin incorporated carbon nanotube composite material and imprinted sol-gel film.

PubMed

Hu, Yu-fang; Zhang, Zhao-hui; Zhang, Hua-bin; Luo, Li-juan; Yao, Shou-zhuo

2011-04-15

A sensitive and selective electrochemical sensor based on a polyaniline modified carbon electrode for the determination of L-phenylalanine has been proposed by utilizing β-cyclodextrin (β-CD) incorporated multi-walled carbon nanotube (MWNT) and imprinted sol-gel film. The electrochemical behavior of the sensor towards L-phenylalanine was investigated by cyclic voltammetry (CV), differential pulse voltammetry (DPV), and amperometric i-t curve. The surface morphologies of layer-by-layer assembly electrodes were displayed by scanning electron microscope (SEM). The response mechanism of the imprinted sensor for L-phenylalanine was based on the inclusion interaction of β-CD and molecular recognition capacity of the imprinted film for L-phenylalanine. A linear calibration plot was obtained covering the concentration range from 5.0 × 10(-7) to 1.0 × 10(-4) mol L(-1) with a detection limit of 1.0 × 10(-9) mol L(-1). With excellent sensitivity, selectivity, stability, reproducibility and recovery, the electrochemical imprinted sensor was used to detect L-phenylalanine in blood plasma samples successfully. Copyright © 2011 Elsevier B.V. All rights reserved.

An electrocatalytic oxidation and voltammetric method using a chemically reduced graphene oxide film for the determination of caffeic acid.

PubMed

Vilian, A T Ezhil; Chen, Shen-Ming; Chen, Ying-Hui; Ali, M Ajmal; Al-Hemaid, Fahad M A

2014-06-01

The present work describes the characterization of a chemically reduced graphene oxide (CRGO) modified glassy carbon electrode (GCE) for electrochemical investigation of caffeic acid (CA). Cyclic voltammetry (CV), differential pulse voltammetry (DPV), amperometry, and electrochemical impedance spectroscopy (EIS) techniques were used to characterize the properties of the electrode. There was an obvious enhancement of the current response and a decreased over potential for the oxidation of CA. The interfacial electron transfer rate of CA was studied by EIS. Under optimal conditions, the CRGO displayed a linear response range of 1×10(-8) to 8×10(-4) M and the detection limit was 2×10(-9) M (S/N=3), with a sensitivity of 192.21 μA mM(-1) cm(-2) at an applied potential of +0.2V (vs. Ag/AgCl reference), which suggests that the CRGO is a promising sensing materials for the electrochemical investigation of CA. The results showed the good sensitivity, selectivity and high reproducibility of the CRGO modified electrode. Moreover, this modified electrode was further applied to investigate the CA in real samples of wine with satisfactory results. Copyright © 2014 Elsevier Inc. All rights reserved.

Defining the computational structure of the motion detector in Drosophila

PubMed Central

Clark, Damon A.; Bursztyn, Limor; Horowitz, Mark; Schnitzer, Mark J.; Clandinin, Thomas R.

2011-01-01

SUMMARY Many animals rely on visual motion detection for survival. Motion information is extracted from spatiotemporal intensity patterns on the retina, a paradigmatic neural computation. A phenomenological model, the Hassenstein-Reichardt Correlator (HRC), relates visual inputs to neural and behavioral responses to motion, but the circuits that implement this computation remain unknown. Using cell-type specific genetic silencing, minimal motion stimuli, and in vivo calcium imaging, we examine two critical HRC inputs. These two pathways respond preferentially to light and dark moving edges. We demonstrate that these pathways perform overlapping but complementary subsets of the computations underlying the HRC. A numerical model implementing differential weighting of these operations displays the observed edge preferences. Intriguingly, these pathways are distinguished by their sensitivities to a stimulus correlation that corresponds to an illusory percept, “reverse phi”, that affects many species. Thus, this computational architecture may be widely used to achieve edge selectivity in motion detection. PMID:21689602

[Autoantibodies as biomarkers].

PubMed

Tron, François

2014-01-01

Activation and differentiation of autoreactive B-lymphocytes lead to the production of autoantibodies, which are thus the direct consequence of the autoimmune process. They often constitute biomarkers of autoimmune diseases and are measured by tests displaying various diagnosis sensitivity and specificity. Autoantibody titers can be correlated to the disease activity and certain autoantibody populations associated with particular clinical manifestations or tissue lesions. The demonstration that autoantibodies appear years before the onset of autoimmune diseases indicates that their presence in healthy individuals may be a predictive marker of the occurrence of disease. Certain autoantibodies could also be predictive markers of a therapeutic response to biologics and of the occurrence of side effects as well. Thus, autoantibodies are useful tools in the diagnosis and the management of patients with organ specific or non-organ specific autoimmune diseases at different steps of the autoimmune process. Copyright © 2013. Published by Elsevier Masson SAS.

Transgene-free human induced pluripotent stem cell line (HS5-SV.hiPS) generated from cesarean scar-derived fibroblasts.

PubMed

Rungsiwiwut, Ruttachuk; Pavarajarn, Wipawee; Numchaisrika, Pranee; Virutamasen, Pramuan; Pruksananonda, Kamthorn

2016-01-01

Transgene-free human HS5-SV.hiPS line was generated from human cesarean scar-derived fibroblasts using temperature-sensitive Sendai virus vectors carrying Oct4, Sox2, cMyc and Klf4 exogenous transcriptional factors. The viral constructs were eliminated from HS5-SV.hiPS line through heat treatment. Transgene-free HS5-SV.hiPS cells expressed pluripotent associated transcription factors Oct4, Nanog, Sox2, Rex1 and surface markers SSEA-4, TRA-1-60 and OCT4. HS5-SV.hiPS cells formed embryoid bodies and differentiated into three embryonic germ layers in vivo. HS5-SV.hiPS cells maintained their normal karyotype (46, XX) after culture for extended period. HS5-SV.hiPS displayed the similar pattern of DNA fingerprinting to the parenteral scar-derived fibroblasts. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Delayed match-to-sample early performance decrement in monkeys after $sup 60$Co irradiation

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

Bruner, A.; Bogo, V.; Jones, R.K.

1975-07-01

Sixteen monkeys were trained on a delayed match-to-sample task (DMTS) based on shock avoidance and irradiated with single, whole-body exposures of from 396 to 2000 rad $sup 60$Co (midbody dose) at between 163 and 233 rad/min. Pre- to post-irradiation performance changes were assessed using a penalty-scaling measure which differentially weighted incorrect responses, response omissions, and error-omission sequences. Thirteen of the animals displayed early performance decrement, including five incapacitations, at lower doses (less than 1000 rad) than heretofore found effective. This was considered a function of task complexity, measurement sensitivity, and gamma effectiveness. The minimum effective midbody dose for inducing decrementmore » using the DMTS task was estimated to be on the order of 500 rad. The nature of early, transient performance decrement seems to reflect more of an inability to perform than an inability to perform correctly. (auth)« less

Item Analysis and Differential Item Functioning of a Brief Conduct Problem Screen

ERIC Educational Resources Information Center

Wu, Johnny; King, Kevin M.; Witkiewitz, Katie; Racz, Sarah Jensen; McMahon, Robert J.

2012-01-01

Research has shown that boys display higher levels of childhood conduct problems than girls, and Black children display higher levels than White children, but few studies have tested for scalar equivalence of conduct problems across gender and race. The authors conducted a 2-parameter item response theory (IRT) model to examine item…

Gene expression during ovarian differentiation in parasitic and non-parasitic lampreys: implications for fecundity and life history types.

PubMed

Spice, Erin K; Whyard, Steven; Docker, Margaret F

2014-11-01

Lampreys diverged from the jawed vertebrate lineage approximately 500million years ago. Lampreys undergo sex differentiation much later than most other vertebrates, and ovarian differentiation occurs several years before testicular differentiation. The genetic basis of lamprey sex differentiation is of particular interest both because of the phylogenetic importance of lampreys and because of their unusual pattern of sex differentiation. As well, differences between parasitic and non-parasitic lampreys may first become evident at ovarian differentiation. However, nothing is known about the genetic basis of ovarian differentiation in lampreys. This study examined potential differences in gene expression before, during, and after ovarian differentiation in parasitic chestnut lamprey Ichthyomyzon castaneus and non-parasitic northern brook lamprey Ichthyomyzonfossor. Eight target genes (17β-hydroxysteroid dehydrogenase, germ cell-less, estrogen receptor β, insulin-like growth factor 1 receptor, daz-associated protein 1, cytochrome c oxidase subunit III, Wilms' tumour suppressor protein 1, and dehydrocholesterol reductase 7) were examined. Northern brook lamprey displayed higher expression of cytochrome c oxidase subunit III, whereas chestnut lamprey displayed higher expression of insulin-like growth factor 1 receptor; these genes may be involved in apoptosis and oocyte growth, respectively. Presumptive male larvae had higher expression of Wilms' tumour suppressor protein 1, which may be involved in the undifferentiated gonad and/or later testicular development. Differentiated females had higher expression of 17β hydroxysteroid dehydrogenase and daz-associated protein 1, which may be involved in female development. This study is the first to identify genes that may be involved in ovarian differentiation and fecundity in lampreys. Copyright © 2014 Elsevier Inc. All rights reserved.

Formation of pH-sensitive cationic liposomes from a binary mixture of monoalkylated primary amine and cholesterol.

PubMed

Cui, Zhong-Kai; Bouisse, Anne; Cottenye, Nicolas; Lafleur, Michel

2012-09-25

It has been shown that mixtures of monoalkylated amphiphiles and sterols can form liquid-ordered (lo) lamellar phases. These bilayers can be extruded using conventional methods to obtain large unilamellar vesicles (LUVs) that have very low permeability and a specific response to a given stimulus. For example, pH variations can trigger the release from LUVs formed with palmitic acid and sterols. In the present work, the possibility to form non phospholipid liposomes with mixtures of stearylamine (SA) and cholesterol (Chol) was investigated. The phase behavior of these mixtures was characterized by differential scanning calorimetry, infrared, and (2)H NMR spectroscopy. It is found that this particular mixture can form a lo lamellar phase that is pH-sensitive as the system undergoes a transition from a lo phase to a solid state when pH is increased from 5.5 to 12. LUVs have been successfully extruded from equimolar SA/Chol mixtures. Release experiments as a function of time revealed the relatively low permeability of these systems. The fact that the stability of these liposomes is pH dependent implies that these LUVs display an interesting potential as new cationic carriers for pH-triggered release. This is the first report of non phospholipid liposomes with high sterol content combining an overall positive charge and pH-sensitivity.

A practical toxicity bioassay for vicine and convicine levels in faba bean (Vicia faba).

PubMed

Getachew, Fitsum; Vandenberg, Albert; Smits, Judit

2018-04-02

Faba bean (Vicia faba) vicine and convicine (V-C) aglycones (divicine and isouramil respectively) provoke an acute hemolytic anemia called favism in individuals with a glucose-6-phosphate dehydrogenase (G6PD) enzyme defect in their red blood cells. Geneticists/plant breeders are working with faba bean to decrease V-C levels to improve public acceptance of this high-protein pulse crop. Here, we present a fast and simple ex vivo in vitro bioassay for V-C toxicity testing of faba bean or faba bean food products. We have shown that 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU)-treated (i.e., sensitized) normal red blood cells, like G6PD-defective blood, displayed (i) continuous glutathione (GSH) depletion with no regeneration as incubation time and the dose of aglycones increased, (ii) progressive accumulation of denatured hemoglobin products into high molecular weight (HMW) proteins with increased aglycone dose, (iii) both band 3 membrane proteins and hemichromes, in HMW protein aggregates. We have also demonstrated that sensitized red blood cells can effectively differentiate various levels of toxicity among faba bean varieties through the two hemolysis biomarkers: GSH depletion and HMW clumping. BCNU-sensitized red blood cells provide an ideal model for favism blood, to assess and compare the toxicity of faba bean varieties and their food products. © 2018 Society of Chemical Industry. © 2018 Society of Chemical Industry.

14-3-3 σ Expression Effects G2/M Response to Oxygen and Correlates with Ovarian Cancer Metastasis

PubMed Central

Ravi, Dashnamoorthy; Chen, Yidong; Karia, Bijal; Brown, Adam; Gu, Ting Ting; Li, Jie; Carey, Mark S.; Hennessy, Bryan T.; Bishop, Alexander J. R.

2011-01-01

Background In vitro cell culture experiments with primary cells have reported that cell proliferation is retarded in the presence of ambient compared to physiological O2 levels. Cancer is primarily a disease of aberrant cell proliferation, therefore, studying cancer cells grown under ambient O2 may be undesirable. To understand better the impact of O2 on the propagation of cancer cells in vitro, we compared the growth potential of a panel of ovarian cancer cell lines under ambient (21%) or physiological (3%) O2. Principal Findings Our observations demonstrate that similar to primary cells, many cancer cells maintain an inherent sensitivity to O2, but some display insensitivity to changes in O2 concentration. Further analysis revealed an association between defective G2/M cell cycle transition regulation and O2 insensitivity resultant from overexpression of 14-3-3 σ. Targeting 14-3-3 σ overexpression with RNAi restored O2 sensitivity in these cell lines. Additionally, we found that metastatic ovarian tumors frequently overexpress 14-3-3 σ, which in conjunction with phosphorylated RB, results in poor prognosis. Conclusions Cancer cells show differential proliferative sensitivity to changes in O2 concentration. Although a direct link between O2 insensitivity and metastasis was not determined, this investigation showed that an O2 insensitive phenotype in cancer cells to correlate with metastatic tumor progression. PMID:21249227

Toward a 3D model of human brain development for studying gene/environment interactions

PubMed Central

2013-01-01

This project aims to establish and characterize an in vitro model of the developing human brain for the purpose of testing drugs and chemicals. To accurately assess risk, a model needs to recapitulate the complex interactions between different types of glial cells and neurons in a three-dimensional platform. Moreover, human cells are preferred over cells from rodents to eliminate cross-species differences in sensitivity to chemicals. Previously, we established conditions to culture rat primary cells as three-dimensional aggregates, which will be humanized and evaluated here with induced pluripotent stem cells (iPSCs). The use of iPSCs allows us to address gene/environment interactions as well as the potential of chemicals to interfere with epigenetic mechanisms. Additionally, iPSCs afford us the opportunity to study the effect of chemicals during very early stages of brain development. It is well recognized that assays for testing toxicity in the developing brain must consider differences in sensitivity and susceptibility that arise depending on the time of exposure. This model will reflect critical developmental processes such as proliferation, differentiation, lineage specification, migration, axonal growth, dendritic arborization and synaptogenesis, which will probably display differences in sensitivity to different types of chemicals. Functional endpoints will evaluate the complex cell-to-cell interactions that are affected in neurodevelopment through chemical perturbation, and the efficacy of drug intervention to prevent or reverse phenotypes. The model described is designed to assess developmental neurotoxicity effects on unique processes occurring during human brain development by leveraging human iPSCs from diverse genetic backgrounds, which can be differentiated into different cell types of the central nervous system. Our goal is to demonstrate the feasibility of the personalized model using iPSCs derived from individuals with neurodevelopmental disorders caused by known mutations and chromosomal aberrations. Notably, such a human brain model will be a versatile tool for more complex testing platforms and strategies as well as research into central nervous system physiology and pathology. PMID:24564953

Differential hypothalamic leptin sensitivity in obese rat offspring exposed to maternal and postnatal intake of chocolate and soft drink

PubMed Central

Kjaergaard, M; Nilsson, C; Secher, A; Kildegaard, J; Skovgaard, T; Nielsen, M O; Grove, K; Raun, K

2017-01-01

Background/objective: Intake of high-energy foods and maternal nutrient overload increases the risk of metabolic diseases in the progeny such as obesity and diabetes. We hypothesized that maternal and postnatal intake of chocolate and soft drink will affect leptin sensitivity and hypothalamic astrocyte morphology in adult rat offspring. Methods: Pregnant Sprague-Dawley rats were fed ad libitum chow diet only (C) or with chocolate and high sucrose soft drink supplement (S). At birth, litter size was adjusted into 10 male offspring per mother. After weaning, offspring from both dietary groups were assigned to either S or C diet, giving four groups until the end of the experiment at 26 weeks of age. Results: As expected, adult offspring fed the S diet post weaning became obese (body weight: P<0.01, %body fat per kg: P<0.001) and this was due to the reduced energy expenditure (P<0.05) and hypothalamic astrogliosis (P<0.001) irrespective of maternal diet. Interesting, offspring born to S-diet-fed mothers and fed the S diet throughout postnatal life became obese despite lower energy intake than controls (P<0.05). These SS offspring showed increased feed efficiency (P<0.001) and reduced fasting pSTAT3 activity (P<0.05) in arcuate nucleus (ARC) compared with other groups. The findings indicated that the combination of the maternal and postnatal S-diet exposure induced persistent changes in leptin signalling, hence affecting energy balance. Thus, appetite regulation was more sensitive to the effect of leptin than energy expenditure, suggesting differential programming of leptin sensitivity in ARC in SS offspring. Effects of the maternal S diet were normalized when offspring were fed a chow diet after weaning. Conclusions: Maternal intake of chocolate and soft drink had long-term consequences for the metabolic phenotype in the offspring if they continued on the S diet in postnatal life. These offspring displayed obesity despite lowered energy intake associated with alterations in hypothalamic leptin signalling. PMID:28092346

ADC as a useful diagnostic tool for differentiating benign and malignant vertebral bone marrow lesions and compression fractures: a systematic review and meta-analysis.

PubMed

Suh, Chong Hyun; Yun, Seong Jong; Jin, Wook; Lee, Sun Hwa; Park, So Young; Ryu, Chang-Woo

2018-07-01

To assess the sensitivity and specificity of quantitative assessment of the apparent diffusion coefficient (ADC) for differentiating benign and malignant vertebral bone marrow lesions (BMLs) and compression fractures (CFs) METHODS: An electronic literature search of MEDLINE and EMBASE was conducted. Bivariate modelling and hierarchical summary receiver operating characteristic modelling were performed to evaluate the diagnostic performance of ADC for differentiating vertebral BMLs. Subgroup analysis was performed for differentiating benign and malignant vertebral CFs. Meta-regression analyses according to subject, study and diffusion-weighted imaging (DWI) characteristics were performed. Twelve eligible studies (748 lesions, 661 patients) were included. The ADC exhibited a pooled sensitivity of 0.89 (95% confidence interval [CI] 0.80-0.94) and a pooled specificity of 0.87 (95% CI 0.78-0.93) for differentiating benign and malignant vertebral BMLs. In addition, the pooled sensitivity and specificity for differentiating benign and malignant CFs were 0.92 (95% CI 0.82-0.97) and 0.91 (95% CI 0.87-0.94), respectively. In the meta-regression analysis, the DWI slice thickness was a significant factor affecting heterogeneity (p < 0.01); thinner slice thickness (< 5 mm) showed higher specificity (95%) than thicker slice thickness (81%). Quantitative assessment of ADC is a useful diagnostic tool for differentiating benign and malignant vertebral BMLs and CFs. • Quantitative assessment of ADC is useful in differentiating vertebral BMLs. • Quantitative ADC assessment for BMLs had sensitivity of 89%, specificity of 87%. • Quantitative ADC assessment for CFs had sensitivity of 92%, specificity of 91%. • The specificity is highest (95%) with thinner (< 5 mm) DWI slice thickness.

Scrambled eggs: A highly sensitive molecular diagnostic workflow for Fasciola species specific detection from faecal samples

PubMed Central

Calvani, Nichola Eliza Davies; Windsor, Peter Andrew; Bush, Russell David

2017-01-01

Background Fasciolosis, due to Fasciola hepatica and Fasciola gigantica, is a re-emerging zoonotic parasitic disease of worldwide importance. Human and animal infections are commonly diagnosed by the traditional sedimentation and faecal egg-counting technique. However, this technique is time-consuming and prone to sensitivity errors when a large number of samples must be processed or if the operator lacks sufficient experience. Additionally, diagnosis can only be made once the 12-week pre-patent period has passed. Recently, a commercially available coprological antigen ELISA has enabled detection of F. hepatica prior to the completion of the pre-patent period, providing earlier diagnosis and increased throughput, although species differentiation is not possible in areas of parasite sympatry. Real-time PCR offers the combined benefits of highly sensitive species differentiation for medium to large sample sizes. However, no molecular diagnostic workflow currently exists for the identification of Fasciola spp. in faecal samples. Methodology/Principal findings A new molecular diagnostic workflow for the highly-sensitive detection and quantification of Fasciola spp. in faecal samples was developed. The technique involves sedimenting and pelleting the samples prior to DNA isolation in order to concentrate the eggs, followed by disruption by bead-beating in a benchtop homogeniser to ensure access to DNA. Although both the new molecular workflow and the traditional sedimentation technique were sensitive and specific, the new molecular workflow enabled faster sample throughput in medium to large epidemiological studies, and provided the additional benefit of speciation. Further, good correlation (R2 = 0.74–0.76) was observed between the real-time PCR values and the faecal egg count (FEC) using the new molecular workflow for all herds and sampling periods. Finally, no effect of storage in 70% ethanol was detected on sedimentation and DNA isolation outcomes; enabling transport of samples from endemic to non-endemic countries without the requirement of a complete cold chain. The commercially-available ELISA displayed poorer sensitivity, even after adjustment of the positive threshold (65–88%), compared to the sensitivity (91–100%) of the new molecular diagnostic workflow. Conclusions/Significance Species-specific assays for sensitive detection of Fasciola spp. enable ante-mortem diagnosis in both human and animal settings. This includes Southeast Asia where there are potentially many undocumented human cases and where post-mortem examination of production animals can be difficult. The new molecular workflow provides a sensitive and quantitative diagnostic approach for the rapid testing of medium to large sample sizes, potentially superseding the traditional sedimentation and FEC technique and enabling surveillance programs in locations where animal and human health funding is limited. PMID:28915255

Human platelet lysate is a successful alternative serum supplement for propagation of monocyte-derived dendritic cells.

PubMed

Švajger, Urban

2017-04-01

Clinical protocols for dendritic cell (DC) generation from monocytes require the use of animal serum-free supplements. Serum-free media can also require up to 1% of serum supplementation. In addition, recommendations based on the 3Rs (Refinement, Reduction, Replacement) principle also recommend the use of non-animal sera in in vitro studies. The aim of this study was to explore the potential use of platelet lysate (PL) for generation of optimally differentiated DCs from monocytes. Cells were isolated from buffy coats from healthy volunteers using immunomagnetic selection. DCs were differentiated in RPMI1640 supplemented with either 10% fetal bovine serum (FBS), 10% AB serum or 10% PL with the addition of granulocyte monocyte colony stimulating factor and interleukin-4. Generated DCs were assessed for their morphology, viability, endocytotic capacity, surface phenotype (immature, mature and tolerogenic DCs) and activation of important signaling pathways. DC function was evaluated on the basis of their allostimulatory capacity, cytokine profile and ability to induce different T-helper subsets. DCs generated with PL displayed normal viability, morphology and endocytotic capacity. Their differentiation and maturation phenotype was comparable to FBS-cultured DCs. They showed functional plasticity and up-regulated tolerogenic markers in response to their environment. PL-cultured mature DCs displayed unhindered allostimulatory potential and the capacity to induce Th1 responses. The use of PL allowed for activation of crucial signaling proteins associated with DC differentiation and maturation. This study demonstrates for the first time that human PL represents a successful alternative to FBS in differentiation of DCs from monocytes. DCs display the major phenotypic and functional characteristics compared with existing culture protocols. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Cell-Adhesive Matrices Composed of RGD Peptide-Displaying M13 Bacteriophage/Poly(lactic-co-glycolic acid) Nanofibers Beneficial to Myoblast Differentiation.

PubMed

Shin, Yong Cheol; Lee, Jong Ho; Jin, Linhua; Kim, Min Jeong; Kim, Chuntae; Hong, Suck Won; Oh, Jin Woo; Han, Dong-Wook

2015-10-01

Recently, there has been considerable effort to develop suitable scaffolds for tissue engineering applications. Cell adhesion is a prerequisite for cells to survive. In nature, the extracellular matrix (ECM) plays this role. Therefore, an ideal scaffold should be structurally similar to the natural ECM and have biocompatibility and biodegradability. In addition, the scaffold should have biofunctionality, which provides the potent ability to enhance the cellular behaviors, such as adhesion, proliferation and differentiation. This study concentrates on fabricating cell-adhesive matrices composed of RGD peptide-displaying M13 bacteriophage (RGD-M13 phage) and poly(lactic-co-glycolic acid, PLGA) nanofibers. Long rod-shaped M13 bacteriophages are non-toxic and can express many desired proteins on their surface. A genetically engineered M13 phage was constructed to display RGD peptides on its surface. PLGA is a biodegradable polymer with excellent biocompatibility and suitable physicochemical property for adhesive matrices. In this study, RGD-M13 phage/PLGA hybrid nanofiber matrices were fabricated by electrospinning. The physicochemical properties of these matrices were characterized by scanning electron microscopy, atomic force microscopy, Raman spectroscopy, and contact angle measurement. In addition, the cellular behaviors, such as the initial attachment, proliferation and differentiation, were analyzed by a CCK-8 assay and immunofluorescence staining to evaluate the potential application of these matrices to tissue engineering scaffolds. The RGD-M13 phage/PLGA nanofiber matrices could enhance the cellular behaviors and promote the differentiation of C2C12 myoblasts. These results suggest that the RGD-M13 phage/PLGA nanofiber matrices are beneficial to myoblast differentiation and can serve as effective tissue engineering scaffolds.

Protective laser beam viewing device

DOEpatents

Neil, George R.; Jordan, Kevin Carl

2012-12-18

A protective laser beam viewing system or device including a camera selectively sensitive to laser light wavelengths and a viewing screen receiving images from the laser sensitive camera. According to a preferred embodiment of the invention, the camera is worn on the head of the user or incorporated into a goggle-type viewing display so that it is always aimed at the area of viewing interest to the user and the viewing screen is incorporated into a video display worn as goggles over the eyes of the user.

Touchscreen everywhere: on transferring a normal planar surface to a touch-sensitive display.

PubMed

Dai, Jingwen; Chung, Chi-Kit Ronald

2014-08-01

We address how a human-computer interface with small device size, large display, and touch-input facility can be made possible by a mere projector and camera. The realization is through the use of a properly embedded structured light sensing scheme that enables a regular light-colored table surface to serve the dual roles of both a projection screen and a touch-sensitive display surface. A random binary pattern is employed to code structured light in pixel accuracy, which is embedded into the regular projection display in a way that the user perceives only regular display but not the structured pattern hidden in the display. With the projection display on the table surface being imaged by a camera, the observed image data, plus the known projection content, can work together to probe the 3-D workspace immediately above the table surface, like deciding if there is a finger present and if the finger touches the table surface, and if so, at what position on the table surface the contact is made. All the decisions hinge upon a careful calibration of the projector-camera-table surface system, intelligent segmentation of the hand in the image data, and exploitation of the homography mapping existing between the projector's display panel and the camera's image plane. Extensive experimentation including evaluation of the display quality, hand segmentation accuracy, touch detection accuracy, trajectory tracking accuracy, multitouch capability and system efficiency are shown to illustrate the feasibility of the proposed realization.

Testing for Nonuniform Differential Item Functioning with Multiple Indicator Multiple Cause Models

ERIC Educational Resources Information Center

Woods, Carol M.; Grimm, Kevin J.

2011-01-01

In extant literature, multiple indicator multiple cause (MIMIC) models have been presented for identifying items that display uniform differential item functioning (DIF) only, not nonuniform DIF. This article addresses, for apparently the first time, the use of MIMIC models for testing both uniform and nonuniform DIF with categorical indicators. A…

Analysis and testing of numerical formulas for the initial value problem

NASA Technical Reports Server (NTRS)

Brown, R. L.; Kovach, K. R.; Popyack, J. L.

1980-01-01

Three computer programs for evaluating and testing numerical integration formulas used with fixed stepsize programs to solve initial value systems of ordinary differential equations are described. A program written in PASCAL SERIES, takes as input the differential equations and produces a FORTRAN subroutine for the derivatives of the system and for computing the actual solution through recursive power series techniques. Both of these are used by STAN, a FORTRAN program that interactively displays a discrete analog of the Liapunov stability region of any two dimensional subspace of the system. The derivatives may be used by CLMP, a FORTRAN program, to test the fixed stepsize formula against a good numerical result and interactively display the solutions.

Differential computation method used to calibrate the angle-centroid relationship in coaxial reverse Hartmann test

NASA Astrophysics Data System (ADS)

Li, Xinji; Hui, Mei; Zhao, Zhu; Liu, Ming; Dong, Liquan; Kong, Lingqin; Zhao, Yuejin

2018-05-01

A differential computation method is presented to improve the precision of calibration for coaxial reverse Hartmann test (RHT). In the calibration, the accuracy of the distance measurement greatly influences the surface shape test, as demonstrated in the mathematical analyses. However, high-precision absolute distance measurement is difficult in the calibration. Thus, a differential computation method that only requires the relative distance was developed. In the proposed method, a liquid crystal display screen successively displayed two regular dot matrix patterns with different dot spacing. In a special case, images on the detector exhibited similar centroid distributions during the reflector translation. Thus, the critical value of the relative displacement distance and the centroid distributions of the dots on the detector were utilized to establish the relationship between the rays at certain angles and the detector coordinates. Experiments revealed the approximately linear behavior of the centroid variation with the relative displacement distance. With the differential computation method, we increased the precision of traditional calibration 10-5 rad root mean square. The precision of the RHT was increased by approximately 100 nm.

The underlying process of early ecological and genetic differentiation in a facultative mutualistic Sinorhizobium meliloti population.

PubMed

Toro, Nicolás; Villadas, Pablo J; Molina-Sánchez, María Dolores; Navarro-Gómez, Pilar; Vinardell, José M; Cuesta-Berrio, Lidia; Rodríguez-Carvajal, Miguel A

2017-04-06

The question of how genotypic and ecological units arise and spread in natural microbial populations remains controversial in the field of evolutionary biology. Here, we investigated the early stages of ecological and genetic differentiation in a highly clonal sympatric Sinorhizobium meliloti population. Whole-genome sequencing revealed that a large DNA region of the symbiotic plasmid pSymB was replaced in some isolates with a similar synteny block carrying densely clustered SNPs and displaying gene acquisition and loss. Two different versions of this genomic island of differentiation (GID) generated by multiple genetic exchanges over time appear to have arisen recently, through recombination in a particular clade within this population. In addition, these isolates display resistance to phages from the same geographic region, probably due to the modification of surface components by the acquired genes. Our results suggest that an underlying process of early ecological and genetic differentiation in S. meliloti is primarily triggered by acquisition of genes that confer resistance to soil phages within particular large genomic DNA regions prone to recombination.

Generalised optical differentiation wavefront sensor: a sensitive high dynamic range wavefront sensor.

PubMed

Haffert, S Y

2016-08-22

Current wavefront sensors for high resolution imaging have either a large dynamic range or a high sensitivity. A new kind of wavefront sensor is developed which can have both: the Generalised Optical Differentiation wavefront sensor. This new wavefront sensor is based on the principles of optical differentiation by amplitude filters. We have extended the theory behind linear optical differentiation and generalised it to nonlinear filters. We used numerical simulations and laboratory experiments to investigate the properties of the generalised wavefront sensor. With this we created a new filter that can decouple the dynamic range from the sensitivity. These properties make it suitable for adaptive optic systems where a large range of phase aberrations have to be measured with high precision.

Infant temperamental reactivity, maternal and grandparental sensitivity: Differential susceptibility for behavior problems in China.

PubMed

Xing, Shufen; Zhou, Quan; Archer, Marc; Yue, Jianhong; Wang, Zhengyan

2016-10-01

The differential susceptibility hypothesis suggests that children's innate characteristics and their rearing experiences interact differentially during development. Recently, the study of interactions between infants' temperament and rearing experiences has become a research hotspot. In China, grandparental care is a very common phenomenon, with many infants taken care of by grandparents while mothers are out for work. To investigate whether the associations between maternal and grandmaternal sensitivity, and behavior problems were moderated by infant temperamental reactivity, while the infants were raised by both their mothers and grandmothers. A total of 71 infants (average age of 17.6months), their mothers and grandmothers were included in this study. Maternal sensitivity and grandmaternal sensitivity were assessed with the Maternal Behavior Q-sort-Chinese Version, infants' temperamental reactivity was measured with Carey's Toddler Temperament Questionnaire-Chinese Revision, and infants' behavior problems were measured with the Infant-Toddler Social and Emotional Assessment-Chinese Version. Maternal sensitivity significantly predicted infants' impulsivity and aggression. Infants' temperamental reactivity moderated the effect of maternal sensitivity on infants' general anxiety. In addition, infant temperamental reactivity moderated the impact of grandmaternal sensitivity on infants' separation distress. Our results support the differential susceptibility hypothesis to some extent. Infants with high temperamental reactivity not only suffer more from low maternal and grandmaternal sensitivity, but also benefit more from high maternal and grandmaternal sensitivity as compared to those infants with low temperamental reactivity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Regulation, cell differentiation and protein-based inheritance.

PubMed

Malagnac, Fabienne; Silar, Philippe

2006-11-01

Recent research using fungi as models provide new insight into the ability of regulatory networks to generate cellular states that are sufficiently stable to be faithfully transmitted to daughter cells, thereby generating epigenetic inheritance. Such protein-based inheritance is driven by infectious factors endowed with properties usually displayed by prions. We emphasize the contribution of regulatory networks to the emerging properties displayed by cells.

Spatialized audio improves call sign recognition during multi-aircraft control.

PubMed

Kim, Sungbin; Miller, Michael E; Rusnock, Christina F; Elshaw, John J

2018-07-01

We investigated the impact of a spatialized audio display on response time, workload, and accuracy while monitoring auditory information for relevance. The human ability to differentiate sound direction implies that spatial audio may be used to encode information. Therefore, it is hypothesized that spatial audio cues can be applied to aid differentiation of critical versus noncritical verbal auditory information. We used a human performance model and a laboratory study involving 24 participants to examine the effect of applying a notional, automated parser to present audio in a particular ear depending on information relevance. Operator workload and performance were assessed while subjects listened for and responded to relevant audio cues associated with critical information among additional noncritical information. Encoding relevance through spatial location in a spatial audio display system--as opposed to monophonic, binaural presentation--significantly reduced response time and workload, particularly for noncritical information. Future auditory displays employing spatial cues to indicate relevance have the potential to reduce workload and improve operator performance in similar task domains. Furthermore, these displays have the potential to reduce the dependence of workload and performance on the number of audio cues. Published by Elsevier Ltd.

Differential effects of psychopathy and antisocial personality disorder symptoms on cognitive and fear processing in female offenders.

PubMed

Anton, Marja E; Baskin-Sommers, Arielle R; Vitale, Jennifer E; Curtin, John J; Newman, Joseph P

2012-12-01

Psychopathy and antisocial personality disorder (APD) have long been considered important risk factors for criminal behavior and incarceration. However, little is known about the psychobiological underpinnings that give rise to the disinhibited behavior of female offenders. Using an instructed fear-conditioning paradigm and a sample of incarcerated female offenders, we manipulated attentional focus and cognitive load to characterize and differentiate between the dysfunctional cognitive and affective processes associated with these syndromes. We used fear-potentiated startle (FPS) and event-related potentials as measures of affective and cognitive processing, respectively. After controlling for APD symptoms, psychopathic women displayed greater FPS while attending directly to threat-relevant stimuli and displayed less FPS while performing a demanding task that directed attention to threat-irrelevant information. Conversely, controlling for psychopathy, women with high APD symptoms displayed less overall FPS, especially when instructed to focus on threat-relevant stimuli. However, as the demands on cognitive resources increased, they displayed greater FPS. For both psychopathy and APD, analysis of the event-related potentials qualified these findings and further specified the abnormal cognitive processes associated with these two syndromes. Overall, simultaneous analysis of psychopathy and APD revealed distinct patterns of cognitive processing and fear reactivity.

First- and Second-Order Sensitivity Analysis of a P-Version Finite Element Equation Via Automatic Differentiation

NASA Technical Reports Server (NTRS)

Hou, Gene

1998-01-01

Sensitivity analysis is a technique for determining derivatives of system responses with respect to design parameters. Among many methods available for sensitivity analysis, automatic differentiation has been proven through many applications in fluid dynamics and structural mechanics to be an accurate and easy method for obtaining derivatives. Nevertheless, the method can be computational expensive and can require a high memory space. This project will apply an automatic differentiation tool, ADIFOR, to a p-version finite element code to obtain first- and second- order then-nal derivatives, respectively. The focus of the study is on the implementation process and the performance of the ADIFOR-enhanced codes for sensitivity analysis in terms of memory requirement, computational efficiency, and accuracy.

Differential display cloning of a novel rat cDNA (RNB6) that shows high expression in the neonatal brain revealed a member of Ena/VASP family.

PubMed

Ohta, S; Mineta, T; Kimoto, M; Tabuchi, K

1997-08-18

We have used the differential display method to identify genes that control the neural cell development in CNS. Screening of the differential display bands that showed higher expression at neonate than at adult age enabled us to identify a novel rat cDNA (RNB6) coding for a protein of 393 amino acid residues. Database search revealed this gene as a rat homologue of the murine EVL, a member of Ena/VASP protein family that is implicated to be involved in the control of cell motility through actin filament assembly by their GP5 motifs. Although the precise characterization of EVL was not reported, our Northern blot and immunoblot analyses demonstrated that RNB6 expression in the brain gradually increases during embryonic development, reaches maximum at postnatal day 1 and decreases thereafter. Studies of tissue distribution revealed the expression of RNB6 not only in the brain but also in the spleen, thymus and testis. Histochemical analyses showed that RNB6 protein is mainly expressed in neurons and may be expressed in neural fibers. Our analyses suggest that RNB6 is critically involved in the development of CNS probably through the control of neural cell motility and/or including neuronal fiber extension.

Flying by Ear: Blind Flight with a Music-Based Artificial Horizon

NASA Technical Reports Server (NTRS)

Simpson, Brian D.; Brungart, Douglas S.; Dallman, Ronald C.; Yasky, Richard J., Jr.; Romigh, Griffin

2008-01-01

Two experiments were conducted in actual flight operations to evaluate an audio artificial horizon display that imposed aircraft attitude information on pilot-selected music. The first experiment examined a pilot's ability to identify, with vision obscured, a change in aircraft roll or pitch, with and without the audio artificial horizon display. The results suggest that the audio horizon display improves the accuracy of attitude identification overall, but differentially affects response time across conditions. In the second experiment, subject pilots performed recoveries from displaced aircraft attitudes using either standard visual instruments, or, with vision obscured, the audio artificial horizon display. The results suggest that subjects were able to maneuver the aircraft to within its safety envelope. Overall, pilots were able to benefit from the display, suggesting that such a display could help to improve overall safety in general aviation.

Development of a One-Step Multiplex PCR Assay for Differential Detection of Major Mycobacterium Species

PubMed Central

Chae, Hansong; Han, Seung Jung; Kim, Su-Young; Ki, Chang-Seok; Huh, Hee Jae; Yong, Dongeun

2017-01-01

ABSTRACT The prevalence of tuberculosis continues to be high, and nontuberculous mycobacterial (NTM) infection has also emerged worldwide. Moreover, differential and accurate identification of mycobacteria to the species or subspecies level is an unmet clinical need. Here, we developed a one-step multiplex PCR assay using whole-genome analysis and bioinformatics to identify novel molecular targets. The aims of this assay were to (i) discriminate between the Mycobacterium tuberculosis complex (MTBC) and NTM using rv0577 or RD750, (ii) differentiate M. tuberculosis (M. tuberculosis) from MTBC using RD9, (iii) selectively identify the widespread M. tuberculosis Beijing genotype by targeting mtbk_20680, and (iv) simultaneously detect five clinically important NTM (M. avium, M. intracellulare, M. abscessus, M. massiliense, and M. kansasii) by targeting IS1311, DT1, mass_3210, and mkan_rs12360. An initial evaluation of the multiplex PCR assay using reference strains demonstrated 100% specificity for the targeted Mycobacterium species. Analytical sensitivity ranged from 1 to 10 pg for extracted DNA and was 103 and 104 CFU for pure cultures and nonhomogenized artificial sputum cultures, respectively, of the targeted species. The accuracy of the multiplex PCR assay was further evaluated using 55 reference strains and 94 mycobacterial clinical isolates. Spoligotyping, multilocus sequence analysis, and a commercial real-time PCR assay were employed as standard assays to evaluate the multiplex PCR assay with clinical M. tuberculosis and NTM isolates. The PCR assay displayed 100% identification agreement with the standard assays. Our multiplex PCR assay is a simple, convenient, and reliable technique for differential identification of MTBC, M. tuberculosis, M. tuberculosis Beijing genotype, and major NTM species. PMID:28659320

Genome-wide identification of heat stress-responsive small RNAs in tall fescue (Festuca arundinacea) by high-throughput sequencing.

PubMed

Li, Huiying; Hu, Tao; Amombo, Erick; Fu, Jinmin

2017-06-01

MicroRNAs (miRNAs) play vital roles in the adaptive response of plants to various abiotic and biotic stresses. Tall fescue (Festuca arundinacea Schreb.) is a major cool-season forage and turf grass species which is severely influenced by heat stress. To unravel possible heat stress-responsive miRNAs, high-throughput sequencing was employed for heat-tolerant PI578718 and heat-sensitive PI234881 genotypes growing in presence and absence of heat stress (40°C for 36h). By searching against the miRBase database, among 1421 reference monocotyledon miRNAs, more than 850 were identified in all samples. Among these miRNAs, 1.46% and 2.29% were differentially expressed in PI234881 and PI578718 under heat stress, respectively, and most of them were down-regulated. In addition, a total of 170 novel miRNAs belonging to 145 miRNA families were identified. Furthermore, putative targets of differentially expressed miRNAs were predicted. The regulation of selected miRNAs by heat stress was revalidated through quantitative reverse transcription PCR (qRT-PCR) analysis. Most of these miRNAs shared similar expression patterns; however, some showed distinct expression patterns under heat stress, with their putative targets displaying different transcription levels. This is the first genome-wide miRNA identification in tall fescue. miRNAs specific to PI578718, or those that exhibited differential expression profiles between the two genotypes under high temperature, were probably associated with the variation in thermotolerance of tall fescue. The differentially expressed miRNAs between these two tall fescue genotypes and their putative targeted genes will provide essential information for further study on miRNAs mediating heat response and facilitate to improve turf grass breeding. Copyright © 2017. Published by Elsevier GmbH.

Development of a One-Step Multiplex PCR Assay for Differential Detection of Major Mycobacterium Species.

PubMed

Chae, Hansong; Han, Seung Jung; Kim, Su-Young; Ki, Chang-Seok; Huh, Hee Jae; Yong, Dongeun; Koh, Won-Jung; Shin, Sung Jae

2017-09-01

The prevalence of tuberculosis continues to be high, and nontuberculous mycobacterial (NTM) infection has also emerged worldwide. Moreover, differential and accurate identification of mycobacteria to the species or subspecies level is an unmet clinical need. Here, we developed a one-step multiplex PCR assay using whole-genome analysis and bioinformatics to identify novel molecular targets. The aims of this assay were to (i) discriminate between the Mycobacterium tuberculosis complex (MTBC) and NTM using rv0577 or RD750, (ii) differentiate M. tuberculosis ( M. tuberculosis ) from MTBC using RD9, (iii) selectively identify the widespread M. tuberculosis Beijing genotype by targeting mtbk_20680 , and (iv) simultaneously detect five clinically important NTM ( M. avium , M. intracellulare , M. abscessus , M. massiliense , and M. kansasii ) by targeting IS 1311 , DT1, mass_3210 , and mkan_rs12360 An initial evaluation of the multiplex PCR assay using reference strains demonstrated 100% specificity for the targeted Mycobacterium species. Analytical sensitivity ranged from 1 to 10 pg for extracted DNA and was 10 3 and 10 4 CFU for pure cultures and nonhomogenized artificial sputum cultures, respectively, of the targeted species. The accuracy of the multiplex PCR assay was further evaluated using 55 reference strains and 94 mycobacterial clinical isolates. Spoligotyping, multilocus sequence analysis, and a commercial real-time PCR assay were employed as standard assays to evaluate the multiplex PCR assay with clinical M. tuberculosis and NTM isolates. The PCR assay displayed 100% identification agreement with the standard assays. Our multiplex PCR assay is a simple, convenient, and reliable technique for differential identification of MTBC, M. tuberculosis , M. tuberculosis Beijing genotype, and major NTM species. Copyright © 2017 American Society for Microbiology.

Sigmoid stenosis caused by diverticulitis vs. carcinoma: usefulness of sonographic features for their differentiation in the emergency setting.

PubMed

Ripollés, Tomás; Martínez-Pérez, María Jesús; Gómez Valencia, Diana Patricia; Vizuete, José; Martín, Gregorio

2015-10-01

To retrospectively evaluate the accuracy of ultrasound as a diagnostic method for differentiating acute diverticulitis from colon cancer in patients with sigmoid colon stenosis. Ultrasound examinations of 91 consecutive patients with sigmoid stenosis (50 diverticulitis and 41 colon cancers) were reviewed by two trained radiologists. Sixty-five (71%) patients presented with acute abdominal symptoms. Thirteen sonographic criteria retrieved from the literature were evaluated to differentiate benign from malignant strictures. A score including all parameters which showed significant differences between benign vs. malignant was built. Sensitivity, specificity, accuracy, and positive or negative predictive values of each sonographic sign, the overall diagnosis, and sonographic score were calculated. Loss of the bowel wall stratification was the most reliable criteria for the diagnosis of malignancy (92% and 94% of sensitivity and specificity, respectively), and the best inter-radiologist agreement (κ = 0.848). Adjacent lymph nodes were the most specific feature (98%) for colon cancer, but its sensitivity was low. Global assessment could differentiate both diseases with high sensitivity (92-94.9%) and specificity (98-100%). Sonographic score >3 enabled differentiation of carcinoma from diverticulitis with 95% sensitivity and 92-94% specificity, with an area under the ROC curve of 0.98-0.987. There were no significant differences in the results between patients with acute and nonacute abdominal symptoms. The combination of several morphological sonographic findings using a score can differentiate most cases of diverticulitis from colon carcinoma in sigmoid strictures.

Impact of stirred suspension bioreactor culture on the differentiation of murine embryonic stem cells into cardiomyocytes.

PubMed

Shafa, Mehdi; Krawetz, Roman; Zhang, Yuan; Rattner, Jerome B; Godollei, Anna; Duff, Henry J; Rancourt, Derrick E

2011-12-14

Embryonic stem cells (ESCs) can proliferate endlessly and are able to differentiate into all cell lineages that make up the adult organism. Under particular in vitro culture conditions, ESCs can be expanded and induced to differentiate into cardiomyocytes in stirred suspension bioreactors (SSBs). However, in using these systems we must be cognizant of the mechanical forces acting upon the cells. The effect of mechanical forces and shear stress on ESC pluripotency and differentiation has yet to be clarified. The purpose of this study was to investigate the impact of the suspension culture environment on ESC pluripotency during cardiomyocyte differentiation. Murine D3-MHC-neo(r) ESCs formed embyroid bodies (EBs) and differentiated into cardiomyocytes over 25 days in static culture and suspension bioreactors. G418 (Geneticin) was used in both systems from day 10 to enrich for cardiomyocytes by eliminating non-resistant, undifferentiated cells. Treatment of EBs with 1 mM ascorbic acid and 0.5% dimethyl sulfoxide from day 3 markedly increased the number of beating EBs, which displayed spontaneous and cadenced contractile beating on day 11 in the bioreactor. Our results showed that the bioreactor differentiated cells displayed the characteristics of fully functional cardiomyocytes. Remarkably, however, our results demonstrated that the bioreactor differentiated ESCs retained their ability to express pluripotency markers, to form ESC-like colonies, and to generate teratomas upon transplantation, whereas the cells differentiated in adherent culture lost these characteristics. This study demonstrates that although cardiomyocyte differentiation can be achieved in stirred suspension bioreactors, the addition of medium enhancers is not adequate to force complete differentiation as fluid shear forces appear to maintain a subpopulation of cells in a transient pluripotent state. The development of successful ESC differentiation protocols within suspension bioreactors demands a more complete understanding of the impacts of shear forces on the regulation of pluripotency and differentiation in pluripotent stem cells.

Impact of stirred suspension bioreactor culture on the differentiation of murine embryonic stem cells into cardiomyocytes

PubMed Central

2011-01-01

Background Embryonic stem cells (ESCs) can proliferate endlessly and are able to differentiate into all cell lineages that make up the adult organism. Under particular in vitro culture conditions, ESCs can be expanded and induced to differentiate into cardiomyocytes in stirred suspension bioreactors (SSBs). However, in using these systems we must be cognizant of the mechanical forces acting upon the cells. The effect of mechanical forces and shear stress on ESC pluripotency and differentiation has yet to be clarified. The purpose of this study was to investigate the impact of the suspension culture environment on ESC pluripotency during cardiomyocyte differentiation. Results Murine D3-MHC-neor ESCs formed embyroid bodies (EBs) and differentiated into cardiomyocytes over 25 days in static culture and suspension bioreactors. G418 (Geneticin) was used in both systems from day 10 to enrich for cardiomyocytes by eliminating non-resistant, undifferentiated cells. Treatment of EBs with 1 mM ascorbic acid and 0.5% dimethyl sulfoxide from day 3 markedly increased the number of beating EBs, which displayed spontaneous and cadenced contractile beating on day 11 in the bioreactor. Our results showed that the bioreactor differentiated cells displayed the characteristics of fully functional cardiomyocytes. Remarkably, however, our results demonstrated that the bioreactor differentiated ESCs retained their ability to express pluripotency markers, to form ESC-like colonies, and to generate teratomas upon transplantation, whereas the cells differentiated in adherent culture lost these characteristics. Conclusions This study demonstrates that although cardiomyocyte differentiation can be achieved in stirred suspension bioreactors, the addition of medium enhancers is not adequate to force complete differentiation as fluid shear forces appear to maintain a subpopulation of cells in a transient pluripotent state. The development of successful ESC differentiation protocols within suspension bioreactors demands a more complete understanding of the impacts of shear forces on the regulation of pluripotency and differentiation in pluripotent stem cells. PMID:22168552

Virus activated artificial ECM induces the osteoblastic differentiation of mesenchymal stem cells without osteogenic supplements

PubMed Central

Wang, Jianglin; Wang, Lin; Li, Xin; Mao, Chuanbin

2013-01-01

Biochemical and topographical features of an artificial extracellular matrix (aECM) can direct stem cell fate. However, it is difficult to vary only the biochemical cues without changing nanotopography to study their unique role. We took advantage of two unique features of M13 phage, a non-toxic nanofiber-like virus, to generate a virus-activated aECM with constant ordered ridge/groove nanotopography but displaying different fibronectin-derived peptides (RGD, its synergy site PHSRN, and a combination of RGD and PHSRN). One feature is the self-assembly of phage into a ridge/groove structure, another is the ease of genetically surface-displaying a peptide. We found that the unique ridge/groove nanotopography and the display of RGD and PHSRN could induce the osteoblastic differentiation of mesenchymal stem cells (MSCs) without any osteogenic supplements. The aECM formed through self-assembly and genetic engineering of phage can be used to understand the role of peptide cues in directing stem cell behavior while keeping nanotopography constant. PMID:23393624

The Effects of Testlets on Reliability and Differential Item Functioning

ERIC Educational Resources Information Center

Teker, Gulsen Tasdelen; Dogan, Nuri

2015-01-01

Reliability and differential item functioning (DIF) analyses were conducted on testlets displaying local item dependence in this study. The data set employed in the research was obtained from the answers given by 1,500 students to the 20 items included in six testlets given in English Proficiency Exam by the School of Foreign Languages of a state…

Simvastatin and Dipentyl Phthalate Display Different Mechanisms of Action but Exhibit Dose Additive Effects on Fetal Testicular Testosterone Production in Sprague Dawley Rats

EPA Science Inventory

Sex differentiation of the male reproductive tract in mammals is driven, in part, by fetal androgen production. In utero exposure to some phthalate esters (PEs) alters fetal Leydig cell differentiation, reducing the expression of several genes associated with steroid synthesis/tr...

AHA classification of coronary and carotid atherosclerotic plaques by grating-based phase-contrast computed tomography.

PubMed

Hetterich, Holger; Webber, Nicole; Willner, Marian; Herzen, Julia; Birnbacher, Lorenz; Hipp, Alexander; Marschner, Mathias; Auweter, Sigrid D; Habbel, Christopher; Schüller, Ulrich; Bamberg, Fabian; Ertl-Wagner, Birgit; Pfeiffer, Franz; Saam, Tobias

2016-09-01

To evaluate the potential of grating-based phase-contrast computed-tomography (gb-PCCT) to classify human carotid and coronary atherosclerotic plaques according to modified American Heart Association (AHA) criteria. Experiments were carried out at a laboratory-based set-up consisting of X-ray tube (40 kVp), grating-interferometer and detector. Eighteen human carotid and coronary artery specimens were examined. Histopathology served as the standard of reference. Vessel cross-sections were classified as AHA lesion type I/II, III, IV/V, VI, VII or VIII plaques by two independent reviewers blinded to histopathology. Conservative measurements of diagnostic accuracies for the detection and differentiation of plaque types were evaluated. A total of 127 corresponding gb-PCCT/histopathology sections were analyzed. Based on histopathology, lesion type I/II was present in 12 (9.5 %), III in 18 (14.2 %), IV/V in 38 (29.9 %), VI in 16 (12.6 %), VII in 34 (26.8 %) and VIII in 9 (7.0 %) cross-sections. Sensitivity, specificity and positive and negative predictive value were ≥0.88 for most analyzed plaque types with a good level of agreement (Cohen's kappa = 0.90). Overall, results were better in carotid (kappa = 0.97) than in coronary arteries (kappa = 0.85). Inter-observer agreement was high with kappa = 0.85, p < 0.0001. These results indicate that gb-PCCT can reliably classify atherosclerotic plaques according to modified AHA criteria with excellent agreement to histopathology. • Different atherosclerotic plaque types display distinct morphological features in phase-contrast CT. • Phase-contrast CT can detect and differentiate AHA plaque types. • Calcifications caused streak artefacts and reduced sensitivity in type VI lesions. • Overall agreement was higher in carotid than in coronary arteries.

Differential behavioural and endocrine responses of common voles (Microtus arvalis) to nest predators and resource competitors.

PubMed

Liesenjohann, Monique; Liesenjohann, Thilo; Palme, Rupert; Eccard, Jana Anja

2013-09-08

Adaptive behavioural strategies promoting co-occurrence of competing species are known to result from a sympatric evolutionary past. Strategies should be different for indirect resource competition (exploitation, e.g., foraging and avoidance behaviour) than for direct interspecific interference (e.g., aggression, vigilance, and nest guarding). We studied the effects of resource competition and nest predation in sympatric small mammal species using semi-fossorial voles and shrews, which prey on vole offspring during their sensitive nestling phase. Experiments were conducted in caged outdoor enclosures. Focus common vole mothers (Microtus arvalis) were either caged with a greater white-toothed shrew (Crocidura russula) as a potential nest predator, with an herbivorous field vole (Microtus agrestis) as a heterospecific resource competitor, or with a conspecific resource competitor. We studied behavioural adaptations of vole mothers during pregnancy, parturition, and early lactation, specifically modifications of the burrow architecture and activity at burrow entrances. Further, we measured pre- and postpartum faecal corticosterone metabolites (FCMs) of mothers to test for elevated stress hormone levels. Only in the presence of the nest predator were prepartum FCMs elevated, but we found no loss of vole nestlings and no differences in nestling body weight in the presence of the nest predator or the heterospecific resource competitor. Although the presence of both the shrew and the field vole induced prepartum modifications to the burrow architecture, only nest predators caused an increase in vigilance time at burrow entrances during the sensitive nestling phase. Voles displayed an adequate behavioural response for both resource competitors and nest predators. They modified burrow architecture to improve nest guarding and increased their vigilance at burrow entrances to enhance offspring survival chances. Our study revealed differential behavioural adaptations to resource competitors and nest predators.

Differential behavioural and endocrine responses of common voles (Microtus arvalis) to nest predators and resource competitors

PubMed Central

2013-01-01

Background Adaptive behavioural strategies promoting co-occurrence of competing species are known to result from a sympatric evolutionary past. Strategies should be different for indirect resource competition (exploitation, e.g., foraging and avoidance behaviour) than for direct interspecific interference (e.g., aggression, vigilance, and nest guarding). We studied the effects of resource competition and nest predation in sympatric small mammal species using semi-fossorial voles and shrews, which prey on vole offspring during their sensitive nestling phase. Experiments were conducted in caged outdoor enclosures. Focus common vole mothers (Microtus arvalis) were either caged with a greater white-toothed shrew (Crocidura russula) as a potential nest predator, with an herbivorous field vole (Microtus agrestis) as a heterospecific resource competitor, or with a conspecific resource competitor. Results We studied behavioural adaptations of vole mothers during pregnancy, parturition, and early lactation, specifically modifications of the burrow architecture and activity at burrow entrances. Further, we measured pre- and postpartum faecal corticosterone metabolites (FCMs) of mothers to test for elevated stress hormone levels. Only in the presence of the nest predator were prepartum FCMs elevated, but we found no loss of vole nestlings and no differences in nestling body weight in the presence of the nest predator or the heterospecific resource competitor. Although the presence of both the shrew and the field vole induced prepartum modifications to the burrow architecture, only nest predators caused an increase in vigilance time at burrow entrances during the sensitive nestling phase. Conclusion Voles displayed an adequate behavioural response for both resource competitors and nest predators. They modified burrow architecture to improve nest guarding and increased their vigilance at burrow entrances to enhance offspring survival chances. Our study revealed differential behavioural adaptations to resource competitors and nest predators. PMID:24010574

Clinical Concentrations of Local Anesthetics Bupivacaine and Lidocaine Differentially Inhibit Human Kir2.x Inward Rectifier K+ Channels.

PubMed

Nakahira, Kei; Oshita, Kensuke; Itoh, Masayuki; Takano, Makoto; Sakaguchi, Yoshiro; Ishihara, Keiko

2016-04-01

Inward rectifier K channels of the Kir2.x subfamily are widely expressed in neuronal tissues, controlling neuronal excitability. Previous studies reported that local anesthetics (LAs) do not affect Kir2 channels. However, the effects have not been studied at large concentrations used in regional anesthesia. This study used the patch-clamp technique to examine the effects of bupivacaine and lidocaine on Kir2.1, Kir2.2, and Kir2.3 channels expressed in human embryonic kidney 293 cells. When applied extracellularly in whole-cell recordings, both LAs inhibited Kir2.x currents in a voltage-independent manner. Inhibition with bupivacaine was slow and irreversible, whereas that with lidocaine was fast and reversible. Kir2.3 displayed a greater sensitivity to bupivacaine than Kir2.1 and Kir2.2 (50% inhibitory concentrations at approximately 5 minutes, 0.6 vs 8-10 mM), whereas their sensitivities to lidocaine were similar (50% inhibitory concentrations, 1.5-2.7 mM). Increases in the charged/neutral ratio of the LAs at an acidic extracellular pH attenuated their inhibitory effects, and a permanently charged lidocaine derivative QX-314 exhibited no effects when applied extracellularly. Inside-out experiments demonstrated that inhibition of Kir2.1 with cytoplasmic lidocaine and QX-314 was rapid and reversible, whereas that induced by bupivacaine was slow and irreversible. Furthermore, dose-inhibition relations for the charged form of bupivacaine and lidocaine obtained at different cytoplasmic pHs could be approximated by a single relation for each LA. The results indicate that both LAs at clinical concentrations equilibrated rapidly with the intracellular milieu, differentially inhibiting Kir2.x channel function from the cytoplasmic side.

Relative contribution of Na+/K+ homeostasis, photochemical efficiency and antioxidant defense system to differential salt tolerance in cotton (Gossypium hirsutum L.) cultivars.

PubMed

Wang, Ning; Qiao, Wenqing; Liu, Xiaohong; Shi, Jianbin; Xu, Qinghua; Zhou, Hong; Yan, Gentu; Huang, Qun

2017-10-01

In this study, the role of specific components of different coping strategies to salt load were identified. A pot experiment was conducted with four cotton (Gossypium hirsutum L.) cultivars (differing in salt-sensitivity) under salinity stress. Based on observed responses in growth performance and physiological characteristics, CZ91 was the most tolerant of the four cultivars, followed by cultivars CCRI44 and CCRI49, with Z571 being much more sensitive to salt stress. To perform this tolerant response, they implement different adaptative mechanisms to cope with salt-stress. The superior salt tolerance of CZ91 was conferred by at least three complementary physiological mechanisms: its ability to regulate K + and Na + transport more effectively, its higher photochemical efficiency and better antioxidant defense capacity. However, only one or a few specific components of these defense systems play crucial roles in moderately salt tolerant CCRI44 and CCRI49. Lower ROS load in CCRI44 may be attributed to simultaneous induction of antioxidant defenses by maintaining an unusually high level of SOD, and higher activities of CAT, APX, and POD during salt stress. CCRI49 could reduce the excess generation of ROS not only by maintaining a higher selective absorption of K + over Na + in roots across the membranes through SOS1, AKT1, and HAK5, but also by displaying higher excess-energy dissipation (e.g., higher ETR, P R and qN) during salt stress. Overall, our data provide a mechanistic explanation for differential salt stress tolerance among these cultivars and shed light on the different strategies employed by cotton cultivars to minimize the ill effects of stress. Copyright © 2017. Published by Elsevier Masson SAS.

Estrogenic exposure affects metamorphosis and alters sex ratios in the northern leopard frog (Rana pipiens): identifying critically vulnerable periods of development.

PubMed

Hogan, Natacha S; Duarte, Paula; Wade, Michael G; Lean, David R S; Trudeau, Vance L

2008-05-01

During the transformation from larval tadpole to juvenile frog, there are critical periods of metamorphic development and sex differentiation that may be particularly sensitive to endocrine disruption. The aim of the present study was to identify sensitive developmental periods for estrogenic endocrine disruption in the northern leopard frog (Rana pipiens) using short, targeted exposures to the synthetic estrogen, ethinylestradiol (EE2). Post-hatch tadpoles (Gosner stage 27) were exposed over five distinct periods of metamorphosis: early (stage 27-30), mid (stage 30-36), early and mid (stage 27-36), late (stage 36-42), and the entire metamorphic period (chronic; stage 27-42). For each period, animals were sampled immediately following the EE2 exposure and at metamorphic climax (stage 42). The effects of EE2 on metamorphic development and sex differentiation were assessed through measures of length, weight, developmental stage, days to metamorphosis, sex ratios and incidence of gonadal intersex. Our results show that tadpoles exposed to EE2 during mid-metamorphosis were developmentally delayed immediately following exposure and took 2 weeks longer to reach metamorphic climax. In the unexposed groups, there was low proportion (0.15) of intersex tadpoles at stage 30 and gonads appeared to be morphologically distinct (male and female) in all individuals by stage 36. Tadpoles exposed early in development displayed a strong female-biased sex ratio compared to the controls. Moreover, these effects were also seen at metamorphic climax, approximately 2-3 months after the exposure period, demonstrating that transient early life-stage exposure to estrogen can induce effects on the reproductive organs that persist into the beginning of adult life-stages.

Adaptation of a Simple Microfluidic Platform for High-Dimensional Quantitative Morphological Analysis of Human Mesenchymal Stromal Cells on Polystyrene-Based Substrates.

PubMed

Lam, Johnny; Marklein, Ross A; Jimenez-Torres, Jose A; Beebe, David J; Bauer, Steven R; Sung, Kyung E

2017-12-01

Multipotent stromal cells (MSCs, often called mesenchymal stem cells) have garnered significant attention within the field of regenerative medicine because of their purported ability to differentiate down musculoskeletal lineages. Given the inherent heterogeneity of MSC populations, recent studies have suggested that cell morphology may be indicative of MSC differentiation potential. Toward improving current methods and developing simple yet effective approaches for the morphological evaluation of MSCs, we combined passive pumping microfluidic technology with high-dimensional morphological characterization to produce robust tools for standardized high-throughput analysis. Using ultraviolet (UV) light as a modality for reproducible polystyrene substrate modification, we show that MSCs seeded on microfluidic straight channel devices incorporating UV-exposed substrates exhibited morphological changes that responded accordingly to the degree of substrate modification. Substrate modification also effected greater morphological changes in MSCs seeded at a lower rather than higher density within microfluidic channels. Despite largely comparable trends in morphology, MSCs seeded in microscale as opposed to traditional macroscale platforms displayed much higher sensitivity to changes in substrate properties. In summary, we adapted and qualified microfluidic cell culture platforms comprising simple straight channel arrays as a viable and robust tool for high-throughput quantitative morphological analysis to study cell-material interactions.

Detection of hepatitis B virus core antigen by phage display mediated TaqMan real-time immuno-PCR.

PubMed

Monjezi, Razieh; Tan, Sheau Wei; Tey, Beng Ti; Sieo, Chin Chin; Tan, Wen Siang

2013-01-01

The core antigen (HBcAg) of hepatitis B virus (HBV) is one of the markers for the identification of the viral infection. The main purpose of this study was to develop a TaqMan real-time detection assay based on the concept of phage display mediated immuno-PCR (PD-IPCR) for the detection of HBcAg. PD-IPCR combines the advantages of immuno-PCR (IPCR) and phage display technology. IPCR integrates the versatility of enzyme-linked immunosorbent assay (ELISA) with the sensitivity and signal generation power of PCR. Whereas, phage display technology exploits the physical association between the displayed peptide and the encoding DNA within the same phage particle. In this study, a constrained peptide displayed on the surface of an M13 recombinant bacteriophage that interacts tightly with HBcAg was applied as a diagnostic reagent in IPCR. The phage displayed peptide and its encoding DNA can be used to replace monoclonal antibody (mAb) and chemically bound DNA, respectively. This method is able to detect as low as 10ng of HBcAg with 10(8)pfu/ml of the recombinant phage which is about 10,000 times more sensitive than the phage-ELISA. The PD-IPCR provides an alternative means for the detection of HBcAg in human serum samples. Copyright © 2012 Elsevier B.V. All rights reserved.

Aclacinomycin A Sensitizes K562 Chronic Myeloid Leukemia Cells to Imatinib through p38MAPK-Mediated Erythroid Differentiation

PubMed Central

Liu, Fu-Hwa; Huang, Yu-Wen; Huang, Huei-Mei

2013-01-01

Expression of oncogenic Bcr-Abl inhibits cell differentiation of hematopoietic stem/progenitor cells in chronic myeloid leukemia (CML). Differentiation therapy is considered to be a new strategy for treating this type of leukemia. Aclacinomycin A (ACM) is an antitumor antibiotic. Previous studies have shown that ACM induced erythroid differentiation of CML cells. In this study, we investigate the effect of ACM on the sensitivity of human CML cell line K562 to Bcr-Abl specific inhibitor imatinib (STI571, Gleevec). We first determined the optimal concentration of ACM for erythroid differentiation but not growth inhibition and apoptosis in K562 cells. Then, pretreatment with this optimal concentration of ACM followed by a minimally toxic concentration of imatinib strongly induced growth inhibition and apoptosis compared to that with simultaneous co-treatment, indicating that ACM-induced erythroid differentiation sensitizes K562 cells to imatinib. Sequential treatment with ACM and imatinib induced Bcr-Abl down-regulation, cytochrome c release into the cytosol, and caspase-3 activation, as well as decreased Mcl-1 and Bcl-xL expressions, but did not affect Fas ligand/Fas death receptor and procaspase-8 expressions. ACM/imatinib sequential treatment-induced apoptosis was suppressed by a caspase-9 inhibitor and a caspase-3 inhibitor, indicating that the caspase cascade is involved in this apoptosis. Furthermore, we demonstrated that ACM induced erythroid differentiation through the p38 mitogen-activated protein kinase (MAPK) pathway. The inhibition of erythroid differentiation by p38MAPK inhibitor SB202190, p38MAPK dominant negative mutant or p38MAPK shRNA knockdown, reduced the ACM/imatinib sequential treatment-mediated growth inhibition and apoptosis. These results suggest that differentiated K562 cells induced by ACM-mediated p38MAPK pathway become more sensitive to imatinib and result in down-regulations of Bcr-Abl and anti-apoptotic proteins, growth inhibition and apoptosis. These results provided a potential management by which ACM might have a crucial impact on increasing sensitivity of CML cells to imatinib in the differentiation therapeutic approaches. PMID:23613979

Aclacinomycin A sensitizes K562 chronic myeloid leukemia cells to imatinib through p38MAPK-mediated erythroid differentiation.

PubMed

Lee, Yueh-Lun; Chen, Chih-Wei; Liu, Fu-Hwa; Huang, Yu-Wen; Huang, Huei-Mei

2013-01-01

Expression of oncogenic Bcr-Abl inhibits cell differentiation of hematopoietic stem/progenitor cells in chronic myeloid leukemia (CML). Differentiation therapy is considered to be a new strategy for treating this type of leukemia. Aclacinomycin A (ACM) is an antitumor antibiotic. Previous studies have shown that ACM induced erythroid differentiation of CML cells. In this study, we investigate the effect of ACM on the sensitivity of human CML cell line K562 to Bcr-Abl specific inhibitor imatinib (STI571, Gleevec). We first determined the optimal concentration of ACM for erythroid differentiation but not growth inhibition and apoptosis in K562 cells. Then, pretreatment with this optimal concentration of ACM followed by a minimally toxic concentration of imatinib strongly induced growth inhibition and apoptosis compared to that with simultaneous co-treatment, indicating that ACM-induced erythroid differentiation sensitizes K562 cells to imatinib. Sequential treatment with ACM and imatinib induced Bcr-Abl down-regulation, cytochrome c release into the cytosol, and caspase-3 activation, as well as decreased Mcl-1 and Bcl-xL expressions, but did not affect Fas ligand/Fas death receptor and procaspase-8 expressions. ACM/imatinib sequential treatment-induced apoptosis was suppressed by a caspase-9 inhibitor and a caspase-3 inhibitor, indicating that the caspase cascade is involved in this apoptosis. Furthermore, we demonstrated that ACM induced erythroid differentiation through the p38 mitogen-activated protein kinase (MAPK) pathway. The inhibition of erythroid differentiation by p38MAPK inhibitor SB202190, p38MAPK dominant negative mutant or p38MAPK shRNA knockdown, reduced the ACM/imatinib sequential treatment-mediated growth inhibition and apoptosis. These results suggest that differentiated K562 cells induced by ACM-mediated p38MAPK pathway become more sensitive to imatinib and result in down-regulations of Bcr-Abl and anti-apoptotic proteins, growth inhibition and apoptosis. These results provided a potential management by which ACM might have a crucial impact on increasing sensitivity of CML cells to imatinib in the differentiation therapeutic approaches.

Cloning and Characterizing Genes Involved in Monoterpene Induced Mammary Tumor Regression

DTIC Science & Technology

1998-05-01

Monoterpene -induced/repressed genes were identified in regressing rat mammary carcinomas treated with dietary limonene using a newly developed method...termed subtractive display. The subtractive display screen identified 42 monoterpene -induced genes comprising 9 known genes and 33 unidentified genes...as well as 58 monoterpene -repressed genes comprising 1 known gene and 57 unidentified genes. Several of the identified differentially expressed

Volcano plots in analyzing differential expressions with mRNA microarrays.

PubMed

Li, Wentian

2012-12-01

A volcano plot displays unstandardized signal (e.g. log-fold-change) against noise-adjusted/standardized signal (e.g. t-statistic or -log(10)(p-value) from the t-test). We review the basic and interactive use of the volcano plot and its crucial role in understanding the regularized t-statistic. The joint filtering gene selection criterion based on regularized statistics has a curved discriminant line in the volcano plot, as compared to the two perpendicular lines for the "double filtering" criterion. This review attempts to provide a unifying framework for discussions on alternative measures of differential expression, improved methods for estimating variance, and visual display of a microarray analysis result. We also discuss the possibility of applying volcano plots to other fields beyond microarray.

A subjective evaluation of high-chroma color with wide color-gamut display

NASA Astrophysics Data System (ADS)

Kishimoto, Junko; Yamaguchi, Masahiro; Ohyama, Nagaaki

2009-01-01

Displays tends to expand its color gamut, such as multi-primary color display, Adobe RGB and so on. Therefore displays got possible to display high chroma colors. However sometimes, we feel unnatural some for the image which only expanded chroma. Appropriate gamut mapping method to expand color gamut is not proposed very much. We are attempting preferred expanded color reproduction on wide color gamut display utilizing high chroma colors effectively. As a first step, we have conducted an experiment to investigate the psychological effect of color schemes including highly saturated colors. We used the six-primary-color projector that we have developed for the presentation of test colors. The six-primary-color projector's gamut volume in CIELAB space is about 1.8 times larger than the normal RGB projector. We conducted a subjective evaluation experiment using the SD (Semantic Differential) technique to find the quantitative psychological effect of high chroma colors.

Real-time synthetic vision cockpit display for general aviation

NASA Astrophysics Data System (ADS)

Hansen, Andrew J.; Smith, W. Garth; Rybacki, Richard M.

1999-07-01

Low cost, high performance graphics solutions based on PC hardware platforms are now capable of rendering synthetic vision of a pilot's out-the-window view during all phases of flight. When coupled to a GPS navigation payload the virtual image can be fully correlated to the physical world. In particular, differential GPS services such as the Wide Area Augmentation System WAAS will provide all aviation users with highly accurate 3D navigation. As well, short baseline GPS attitude systems are becoming a viable and inexpensive solution. A glass cockpit display rendering geographically specific imagery draped terrain in real-time can be coupled with high accuracy (7m 95% positioning, sub degree pointing), high integrity (99.99999% position error bound) differential GPS navigation/attitude solutions to provide both situational awareness and 3D guidance to (auto) pilots throughout en route, terminal area, and precision approach phases of flight. This paper describes the technical issues addressed when coupling GPS and glass cockpit displays including the navigation/display interface, real-time 60 Hz rendering of terrain with multiple levels of detail under demand paging, and construction of verified terrain databases draped with geographically specific satellite imagery. Further, on-board recordings of the navigation solution and the cockpit display provide a replay facility for post-flight simulation based on live landings as well as synchronized multiple display channels with different views from the same flight. PC-based solutions which integrate GPS navigation and attitude determination with 3D visualization provide the aviation community, and general aviation in particular, with low cost high performance guidance and situational awareness in all phases of flight.

Training for Night Operations - Research Challenges and Opportunities

DTIC Science & Technology

2012-08-08

Training and Simulation Conference Exhibits and Visuals by Type ……………..……... 1 Figure 2: Radiant Sensitivity of Intensifiers Currently Used in Night Vision...wavelengths across Figure 2. Radiant Sensitivity of Intensifiers the entire radiant sensitivity band. In either case, in order to be Currently...the projector/display technology and NVGs used. NVGs are very sensitive to any light within their band of radiant sensitivity . The intensifier

Watching the clock

PubMed Central

Fetterman, J. Gregor; Killeen, Peter R.; Hall, Scott

2008-01-01

Four rats and four pigeons were monitored while performing retrospective timing tasks. All animals displayed collateral behaviors which could have mediated their temporal judgements. Statistical analysis made a good case for such mediation in the case of two pigeons performing on a spatially-differentiated response, but not for the two responding on a color-differentiated response. For the rats, all of which performed on a spatially-differentiated task, prediction of their temporal judgements was always better if based on collateral activity than if based on the passage of time. PMID:19701487

Differential Susceptibility in Spillover Between Interparental Conflict and Maternal Parenting Practices: Evidence for OXTR and 5-HTT Genes

PubMed Central

Sturge-Apple, Melissa L.; Cicchetti, Dante; Davies, Patrick T.; Suor, Jennifer H.

2012-01-01

Guided by the affective spillover hypothesis and the differential susceptibility to environmental influence frameworks, the present study examined how associations between interparental conflict and mothers’ parenting practices were moderated by serotonin transporter (5-HTT) and oxytocin receptor (OXTR) genes. A sample of 201 mothers and their two-year old child participated in a laboratory-based research assessment. Results supported differential susceptibility hypotheses within spillover frameworks. With respect to OXTR rs53576, mothers with the GG genotype showed greater differential maternal sensitivity across varying levels of interparental conflict. Mothers with one or two copies of the 5-HTTLPR S allele demonstrated differential susceptibility for both sensitive and harsh/punitive caregiving behaviors. Finally, analyses examined whether maternal depressive symptoms and emotional closeness to their child mediated the moderating effects. Findings suggest that maternal emotional closeness with their child indirectly linked OXTR with maternal sensitivity. The results highlight how molecular genetics may explain heterogeneity in spillover models with differential implications for specific parenting behaviors. Implications for clinicians and therapists working with maritally distressed parents are discussed. PMID:22563705

Altered sensitivity to ellagic acid in neuroblastoma cells undergoing differentiation with 12-O-tetradecanoylphorbol-13-acetate and all-trans retinoic acid.

PubMed

Alfredsson, Christina Fjæraa; Rendel, Filip; Liang, Qui-Li; Sundström, Birgitta E; Nånberg, Eewa

2015-12-01

Ellagic acid has previously been reported to induce reduced proliferation and activation of apoptosis in several tumor cell lines including our own previous data from non-differentiated human neuroblastoma SH-SY5Y cells. The aim of this study was now to investigate if in vitro differentiation with the phorbol ester 12-O- tetradecanoylphorbol-13-acetate or the vitamin A derivative all-trans retinoic acid altered the sensitivity to ellagic acid in SH-SY5Y cells. The methods used were cell counting and LDH-assay for evaluation of cell number and cell death, flow cytometric analysis of SubG1- and TUNEL-analysis for apoptosis and western blot for expression of apoptosis-associated proteins. In vitro differentiation was shown to reduce the sensitivity to ellagic acid with respect to cell detachment, loss of viability and activation of apoptosis. The protective effect was phenotype-specific and most prominent in all-trans retinoic acid-differentiated cultures. Differentiation-dependent up-regulation of Bcl-2 and integrin expression is introduced as possible protective mechanisms. The presented data also point to a positive correlation between proliferative activity and sensitivity to ellagic-acid-induced cell detachment. In conclusion, the presented data emphasize the need to consider degree of neuronal differentiation and phenotype of neuroblastoma cells when discussing a potential pharmaceutical application of ellagic acid in tumor treatment. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Nannocystin A: an Elongation Factor 1 Inhibitor from Myxobacteria with Differential Anti-Cancer Properties.

PubMed

Krastel, Philipp; Roggo, Silvio; Schirle, Markus; Ross, Nathan T; Perruccio, Francesca; Aspesi, Peter; Aust, Thomas; Buntin, Kathrin; Estoppey, David; Liechty, Brigitta; Mapa, Felipa; Memmert, Klaus; Miller, Howard; Pan, Xuewen; Riedl, Ralph; Thibaut, Christian; Thomas, Jason; Wagner, Trixie; Weber, Eric; Xie, Xiaobing; Schmitt, Esther K; Hoepfner, Dominic

2015-08-24

Cultivation of myxobacteria of the Nannocystis genus led to the isolation and structure elucidation of a class of novel cyclic lactone inhibitors of elongation factor 1. Whole genome sequence analysis and annotation enabled identification of the putative biosynthetic cluster and synthesis process. In biological assays the compounds displayed anti-fungal and cytotoxic activity. Combined genetic and proteomic approaches identified the eukaryotic translation elongation factor 1α (EF-1α) as the primary target for this compound class. Nannocystin A (1) displayed differential activity across various cancer cell lines and EEF1A1 expression levels appear to be the main differentiating factor. Biochemical and genetic evidence support an overlapping binding site of 1 with the anti-cancer compound didemnin B on EF-1α. This myxobacterial chemotype thus offers an interesting starting point for further investigations of the potential of therapeutics targeting elongation factor 1. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Schistosoma mansoni: resistant specific infection-induced gene expression in Biomphalaria glabrata identified by fluorescent-based differential display.

PubMed

Lockyer, Anne E; Noble, Leslie R; Rollinson, David; Jones, Catherine S

2004-01-01

The freshwater tropical snail Biomphalaria glabrata is an intermediate host for Schistosoma mansoni, the causative agent of human intestinal schistosomiasis, and strains differ in their susceptibility to parasite infection. Changes in gene expression in response to parasite infection have been simultaneously examined in a susceptible strain (NHM1742) and a resistant strain (NHM1981) using a newly developed fluorescent-based differential display method. Such RNA profiling techniques allow the examination of changes in gene expression in response to parasite infection, without requiring previous sequence knowledge, or selecting candidate genes that may be involved in the complex neuroendocrine or defence systems of the snail. Thus, novel genes may be identified. Ten transcripts were initially identified, present only in the profiles derived from snails of the resistant strain when exposed to infection. The differential expression of five of these genes, including HSP70 and several novel transcripts with one containing at least two globin-like domains, has been confirmed by semi-quantitative RT-PCR.

Sensitivity and specificity of monochromatic photography of the ocular fundus in differentiating optic nerve head drusen and optic disc oedema: optic disc drusen and oedema.

PubMed

Gili, Pablo; Flores-Rodríguez, Patricia; Yangüela, Julio; Orduña-Azcona, Javier; Martín-Ríos, María Dolores

2013-03-01

Evaluation of the efficacy of monochromatic photography of the ocular fundus in differentiating optic nerve head drusen (ONHD) and optic disc oedema (ODE). Sixty-six patients with ONHD, 31 patients with ODE and 70 healthy subjects were studied. Colour and monochromatic fundus photography with different filters (green, red and autofluorescence) were performed. The results were analysed blindly by two observers. The sensitivity, specificity and interobserver agreement (k) of each test were assessed. Colour photography offers 65.5 % sensitivity and 100 % specificity for the diagnosis of ONHD. Monochromatic photography improves sensitivity and specificity and provides similar results: green filter (71.20 % sensitivity, 96.70 % specificity), red filter (80.30 % sensitivity, 96.80 % specificity), and autofluorescence technique (87.8 % sensitivity, 100 % specificity). The interobserver agreement was good with all techniques used: autofluorescence (k = 0.957), green filter (k = 0.897), red filter (k = 0.818) and colour (k = 0.809). Monochromatic fundus photography permits ONHD and ODE to be differentiated, with good sensitivity and very high specificity. The best results were obtained with autofluorescence and red filter study.

Constructing a High-Sensitivity, Computer-Interfaced, Differential Thermal Analysis Device for Teaching and Research

ERIC Educational Resources Information Center

Martinez, L. M.; Videa, M.; Mederos, F.; Mesquita, J.

2007-01-01

The construction of a new highly-sensitive, computer-interfaced, differential thermal analysis (DTA) device, used for gathering different information about the chemical reactions, is described. The instrument provides a better understanding about the phase transitions, phase diagrams and many more concepts to the students.

Examining Differential Item Functions of Different Item Ordered Test Forms According to Item Difficulty Levels

ERIC Educational Resources Information Center

Çokluk, Ömay; Gül, Emrah; Dogan-Gül, Çilem

2016-01-01

The study aims to examine whether differential item function is displayed in three different test forms that have item orders of random and sequential versions (easy-to-hard and hard-to-easy), based on Classical Test Theory (CTT) and Item Response Theory (IRT) methods and bearing item difficulty levels in mind. In the correlational research, the…

Automatic differentiation for design sensitivity analysis of structural systems using multiple processors

NASA Technical Reports Server (NTRS)

Nguyen, Duc T.; Storaasli, Olaf O.; Qin, Jiangning; Qamar, Ramzi

1994-01-01

An automatic differentiation tool (ADIFOR) is incorporated into a finite element based structural analysis program for shape and non-shape design sensitivity analysis of structural systems. The entire analysis and sensitivity procedures are parallelized and vectorized for high performance computation. Small scale examples to verify the accuracy of the proposed program and a medium scale example to demonstrate the parallel vector performance on multiple CRAY C90 processors are included.

Diagnostic utility of hepatocyte nuclear factor 1-beta immunoreactivity in endometrial carcinomas: lack of specificity for endometrial clear cell carcinoma.

PubMed

Fadare, Oluwole; Liang, Sharon X

2012-12-01

Hepatocyte nuclear factor 1-beta (HNF1β) has recently emerged as a relatively sensitive and specific marker for ovarian clear cell carcinoma. The purpose of this study is to assess the diagnostic utility of this marker for endometrial clear cell carcinoma. Immunohistochemical analysis was performed on 75 endometrial tissues using a goat polyclonal antibody raised against a peptide mapping at the C-terminus of human HNF1β protein. The 75 cases included 15 clear cell carcinomas, 20 endometrioid carcinomas, 15 endometrial serous carcinomas/uterine papillary serous carcinomas, 20 cases of normal endometrium, 2 cases of clear cell metaplasia, and 3 cases of Arias Stella reaction. Staining interpretations were based on a semiquantitative scoring system, a 0 to 12+ continuous numerical scale that was derived by multiplying the extent of staining (0 to 4+ scale) by the intensity of staining (0 to 3+ scale) for each case. HNF1β expression was found to be present in a wide spectrum of tissues. Twenty-seven (54%) of the 50 carcinomas displayed at least focal nuclear HNF1β expression, including 11 (73%) of 15, 9 (60%) of 15, and 7 (35%) of 20 clear cell, serous, and endometrioid carcinomas, respectively. The average nuclear staining scores for clear cell carcinomas, endometrioid carcinomas, and serous carcinomas were 5.2, 1.4, and 4.1, respectively. Clear cell carcinomas and endometrioid carcinomas displayed statistically significant differences regarding their nuclear staining scores (P = 0.0027), but clear cell carcinomas and endometrial serous carcinomas did not (P = 0.45). The calculated sensitivity of any nuclear HNF1β expression in classifying a carcinoma as being of the clear cell histotype was 73%, whereas the specificity was 54%. Nineteen of 20 normal endometrium samples displayed at least focal nuclear expression of HNF1β, and this expression was often diffuse. The 5 cases of benign histologic mimics of clear cell carcinomas (Arias Stella reaction and clear cell metaplasia) displayed some degree of HNF1β immunoreactivity, with an average nuclear staining score of 7.3. We conclude that although HNF1β is frequently expressed in clear cell carcinomas, it should be used with caution as a diagnostic marker because of its lack of specificity. It neither distinguishes endometrial serous carcinomas from clear cell carcinomas nor clear cell carcinomas from its benign mimics. The greatest diagnostic utility of HNF1β expression may be in a supportive evidentiary role favoring clear cell carcinoma when the principal differential diagnostic consideration is endometrioid carcinoma.

Differentiated human midbrain-derived neural progenitor cells express excitatory strychnine-sensitive glycine receptors containing α2β subunits.

PubMed

Wegner, Florian; Kraft, Robert; Busse, Kathy; Härtig, Wolfgang; Ahrens, Jörg; Leffler, Andreas; Dengler, Reinhard; Schwarz, Johannes

2012-01-01

Human fetal midbrain-derived neural progenitor cells (NPCs) may deliver a tissue source for drug screening and regenerative cell therapy to treat Parkinson's disease. While glutamate and GABA(A) receptors play an important role in neurogenesis, the involvement of glycine receptors during human neurogenesis and dopaminergic differentiation as well as their molecular and functional characteristics in NPCs are largely unknown. Here we investigated NPCs in respect to their glycine receptor function and subunit expression using electrophysiology, calcium imaging, immunocytochemistry, and quantitative real-time PCR. Whole-cell recordings demonstrate the ability of NPCs to express functional strychnine-sensitive glycine receptors after differentiation for 3 weeks in vitro. Pharmacological and molecular analyses indicate a predominance of glycine receptor heteromers containing α2β subunits. Intracellular calcium measurements of differentiated NPCs suggest that glycine evokes depolarisations mediated by strychnine-sensitive glycine receptors and not by D-serine-sensitive excitatory glycine receptors. Culturing NPCs with additional glycine, the glycine-receptor antagonist strychnine, or the Na(+)-K(+)-Cl(-) co-transporter 1 (NKCC1)-inhibitor bumetanide did not significantly influence cell proliferation and differentiation in vitro. These data indicate that NPCs derived from human fetal midbrain tissue acquire essential glycine receptor properties during neuronal maturation. However, glycine receptors seem to have a limited functional impact on neurogenesis and dopaminergic differentiation of NPCs in vitro.

Differentiated Human Midbrain-Derived Neural Progenitor Cells Express Excitatory Strychnine-Sensitive Glycine Receptors Containing α2β Subunits

PubMed Central

Wegner, Florian; Kraft, Robert; Busse, Kathy; Härtig, Wolfgang; Ahrens, Jörg; Leffler, Andreas; Dengler, Reinhard; Schwarz, Johannes

2012-01-01

Background Human fetal midbrain-derived neural progenitor cells (NPCs) may deliver a tissue source for drug screening and regenerative cell therapy to treat Parkinson’s disease. While glutamate and GABAA receptors play an important role in neurogenesis, the involvement of glycine receptors during human neurogenesis and dopaminergic differentiation as well as their molecular and functional characteristics in NPCs are largely unknown. Methodology/Principal Findings Here we investigated NPCs in respect to their glycine receptor function and subunit expression using electrophysiology, calcium imaging, immunocytochemistry, and quantitative real-time PCR. Whole-cell recordings demonstrate the ability of NPCs to express functional strychnine-sensitive glycine receptors after differentiation for 3 weeks in vitro. Pharmacological and molecular analyses indicate a predominance of glycine receptor heteromers containing α2β subunits. Intracellular calcium measurements of differentiated NPCs suggest that glycine evokes depolarisations mediated by strychnine-sensitive glycine receptors and not by D-serine-sensitive excitatory glycine receptors. Culturing NPCs with additional glycine, the glycine-receptor antagonist strychnine, or the Na+-K+-Cl− co-transporter 1 (NKCC1)-inhibitor bumetanide did not significantly influence cell proliferation and differentiation in vitro. Conclusions/Significance These data indicate that NPCs derived from human fetal midbrain tissue acquire essential glycine receptor properties during neuronal maturation. However, glycine receptors seem to have a limited functional impact on neurogenesis and dopaminergic differentiation of NPCs in vitro. PMID:22606311

76 FR 35910 - Notice of Receipt of Complaint; Solicitation of Comments Relating to the Public Interest

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-20

... Motion-Sensitive Sound Effects Devices and Image Display Devices and Components and Products Containing... sale within the United States after importation of certain motion- sensitive sound devices and image...

Abnormal Social Reward Responses in Anorexia Nervosa: An fMRI Study.

PubMed

Via, Esther; Soriano-Mas, Carles; Sánchez, Isabel; Forcano, Laura; Harrison, Ben J; Davey, Christopher G; Pujol, Jesús; Martínez-Zalacaín, Ignacio; Menchón, José M; Fernández-Aranda, Fernando; Cardoner, Narcís

2015-01-01

Patients with anorexia nervosa (AN) display impaired social interactions, implicated in the development and prognosis of the disorder. Importantly, social behavior is modulated by reward-based processes, and dysfunctional at-brain-level reward responses have been involved in AN neurobiological models. However, no prior evidence exists of whether these neural alterations would be equally present in social contexts. In this study, we conducted a cross-sectional social-judgment functional magnetic resonance imaging (fMRI) study of 20 restrictive-subtype AN patients and 20 matched healthy controls. Brain activity during acceptance and rejection was investigated and correlated with severity measures (Eating Disorder Inventory -EDI-2) and with personality traits of interest known to modulate social behavior (The Sensitivity to Punishment and Sensitivity to Reward Questionnaire). Patients showed hypoactivation of the dorsomedial prefrontal cortex (DMPFC) during social acceptance and hyperactivation of visual areas during social rejection. Ventral striatum activation during rejection was positively correlated in patients with clinical severity scores. During acceptance, activation of the frontal opercula-anterior insula and dorsomedial/dorsolateral prefrontal cortices was differentially associated with reward sensitivity between groups. These results suggest an abnormal motivational drive for social stimuli, and involve overlapping social cognition and reward systems leading to a disruption of adaptive responses in the processing of social reward. The specific association of reward-related regions with clinical and psychometric measures suggests the putative involvement of reward structures in the maintenance of pathological behaviors in AN.

Spatial and velocity statistics of inertial particles in turbulent flows

NASA Astrophysics Data System (ADS)

Bec, J.; Biferale, L.; Cencini, M.; Lanotte, A. S.; Toschi, F.

2011-12-01

Spatial and velocity statistics of heavy point-like particles in incompressible, homogeneous, and isotropic three-dimensional turbulence is studied by means of direct numerical simulations at two values of the Taylor-scale Reynolds number Reλ ~ 200 and Reλ ~ 400, corresponding to resolutions of 5123 and 20483 grid points, respectively. Particles Stokes number values range from St ≈ 0.2 to 70. Stationary small-scale particle distribution is shown to display a singular -multifractal- measure, characterized by a set of generalized fractal dimensions with a strong sensitivity on the Stokes number and a possible, small Reynolds number dependency. Velocity increments between two inertial particles depend on the relative weight between smooth events - where particle velocity is approximately the same of the fluid velocity-, and caustic contributions - when two close particles have very different velocities. The latter events lead to a non-differentiable small-scale behaviour for the relative velocity. The relative weight of these two contributions changes at varying the importance of inertia. We show that moments of the velocity difference display a quasi bi-fractal-behavior and that the scaling properties of velocity increments for not too small Stokes number are in good agreement with a recent theoretical prediction made by K. Gustavsson and B. Mehlig arXiv: 1012.1789v1 [physics.flu-dyn], connecting the saturation of velocity scaling exponents with the fractal dimension of particle clustering.

Differential effects of psychopathy and antisocial personality disorder symptoms on cognitive and fear processing in female offenders

PubMed Central

Anton, Marja E.; Vitale, Jennifer E.; Curtin, John J.; Newman, Joseph P.

2012-01-01

Psychopathy and antisocial personality disorder (APD) have long been considered important risk factors for criminal behavior and incarceration. However, little is known about the psychobiological underpinnings that give rise to the disinhibited behavior of female offenders. Using an instructed fear-conditioning paradigm and a sample of incarcerated female offenders, we manipulated attentional focus and cognitive load to characterize and differentiate between the dysfunctional cognitive and affective processes associated with these syndromes. We used fear-potentiated startle (FPS) and event-related potentials as measures of affective and cognitive processing, respectively. After controlling for APD symptoms, psychopathic women displayed greater FPS while attending directly to threat-relevant stimuli and displayed less FPS while performing a demanding task that directed attention to threat-irrelevant information. Conversely, controlling for psychopathy, women with high APD symptoms displayed less overall FPS, especially when instructed to focus on threat-relevant stimuli. However, as the demands on cognitive resources increased, they displayed greater FPS. For both psychopathy and APD, analysis of the event-related potentials qualified these findings and further specified the abnormal cognitive processes associated with these two syndromes. Overall, simultaneous analysis of psychopathy and APD revealed distinct patterns of cognitive processing and fear reactivity. PMID:22886692

Isolation and hepatocyte differentiation of mesenchymal stem cells from porcine bone marrow--"surgical waste" as a novel MSC source.

PubMed

Brückner, S; Tautenhahn, H-M; Winkler, S; Stock, P; Jonas, S; Dollinger, M; Christ, B

2013-06-01

Mesenchymal stem cells (MSC) isolated from bone marrow and differentiated into hepatocyte-like cells have increasingly gained attention for clinical cell therapy of liver diseases because of their high regenerative capacity. They are available from bone marrow aspirates of the os coxae after puncture of the crista iliaca or from bone marrow "surgical waste" gained from amputations or knee and hip operations. Thus, the aim of the study was to demonstrate whether these pBM-MSC (porcine bone marrow-derived mesenchymal stem cells) displayed mesenchymal features and hepatocyte differentiation potential. MSC were isolated either from crista iliaca punctures or after sampling and collagenase digestion of bone marrow from the os femoris. Mesenchymal features were assessed by flow cytometry for specific surface antigens and their ability to differentiate into at least 3 lineages. Functional properties, such as urea or glycogen synthesis and cytochrome P450 activity, as well as the cell morphology were examined during hepatocyte differentiation. pBM-MSC from both sources lacked the hematopoietic markers CD14 and CD45 but expressed the typical mesenchymal markers CD44, CD29, CD90, and CD105. Both cell types could differentiate into adipocyte, osteocyte, and hepatocyte lineages. After hepatocyte differentiation, CD105 expression decreased significantly and cells changed morphology from fibroblastoid into polygonal, displaying significantly increased glycogen storage, urea synthesis, and cytochrome activity. pBM-MSC from various sources were identical in respect to their mesenchymal features and their hepatocyte differentiation potential. Hence, long bones might be a particularly useful resource to isolate bone marrow mesenchymal stem cells for transplantation. Copyright © 2013 Elsevier Inc. All rights reserved.

Differences in sensitivity to parenting depending on child temperament: A meta-analysis.

PubMed

Slagt, Meike; Dubas, Judith Semon; Deković, Maja; van Aken, Marcel A G

2016-10-01

Several models of individual differences in environmental sensitivity postulate increased sensitivity of some individuals to either stressful (diathesis-stress), supportive (vantage sensitivity), or both environments (differential susceptibility). In this meta-analysis we examine whether children vary in sensitivity to parenting depending on their temperament, and if so, which model can best be used to describe this sensitivity pattern. We tested whether associations between negative parenting and negative or positive child adjustment as well as between positive parenting and positive or negative child adjustment would be stronger among children higher on putative sensitivity markers (difficult temperament, negative emotionality, surgency, and effortful control). Longitudinal studies with children up to 18 years (k = 105 samples from 84 studies, Nmean = 6,153) that reported on a parenting-by-temperament interaction predicting child adjustment were included. We found 235 independent effect sizes for associations between parenting and child adjustment. Results showed that children with a more difficult temperament (compared with those with a more easy temperament) were more vulnerable to negative parenting, but also profited more from positive parenting, supporting the differential susceptibility model. Differences in susceptibility were expressed in externalizing and internalizing problems and in social and cognitive competence. Support for differential susceptibility for negative emotionality was, however, only present when this trait was assessed during infancy. Surgency and effortful control did not consistently moderate associations between parenting and child adjustment, providing little support for differential susceptibility, diathesis-stress, or vantage sensitivity models. Finally, parenting-by-temperament interactions were more pronounced when parenting was assessed using observations compared to questionnaires. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Involvement of the DNA mismatch repair system in cisplatin sensitivity of testicular germ cell tumours.

PubMed

Rudolph, Christiane; Melau, Cecilie; Nielsen, John E; Vile Jensen, Kristina; Liu, Dekang; Pena-Diaz, Javier; Rajpert-De Meyts, Ewa; Rasmussen, Lene Juel; Jørgensen, Anne

2017-08-01

Testicular germ cell tumours (TGCT) are highly sensitive to cisplatin-based chemotherapy, but patients with tumours containing differentiated teratoma components are less responsive to this treatment. The cisplatin sensitivity in TGCT has previously been linked to the embryonic phenotype in the majority of tumours, although the underlying mechanism largely remains to be elucidated. The aim of this study was to investigate the role of the DNA mismatch repair (MMR) system in the cisplatin sensitivity of TGCT. The expression pattern of key MMR proteins, including MSH2, MSH6, MLH1 and PMS2, were investigated during testis development and in the pathogenesis of TGCT, including germ cell neoplasia in situ (GCNIS). The TGCT-derived cell line NTera2 was differentiated using retinoic acid (10 μM, 6 days) after which MMR protein expression and activity, as well as cisplatin sensitivity, were investigated in both undifferentiated and differentiated cells. Finally, the expression of MSH2 was knocked down by siRNA in NTera2 cells after which the effect on cisplatin sensitivity was examined. MMR proteins were expressed in proliferating cells in the testes, while in malignant germ cells MMR protein expression was found to coincide with the expression of the pluripotency factor OCT4, with no or low expression in the more differentiated yolk sac tumours, choriocarcinomas and teratomas. In differentiated NTera2 cells we found a significantly (p < 0.05) lower expression of the MMR and pluripotency factors, as well as a reduced MMR activity and cisplatin sensitivity, compared to undifferentiated NTera2 cells. Also, we found that partial knockdown of MSH2 expression in undifferentiated NTera2 cells resulted in a significantly (p < 0.001) reduced cisplatin sensitivity. This study reports, for the first time, expression of the MMR system in fetal gonocytes, from which GCNIS cells are derived. Our findings in primary TGCT specimens and TGCT-derived cells suggest that a reduced sensitivity to cisplatin in differentiated TGCT components could result from a reduced expression of MMR proteins, in particular MSH2 and MLH1, which are involved in the recognition of cisplatin adducts and in activation of the DNA damage response pathway to initiate apoptosis.

Non-binary Colour Modulation for Display Device Based on Phase Change Materials.

PubMed

Ji, Hong-Kai; Tong, Hao; Qian, Hang; Hui, Ya-Juan; Liu, Nian; Yan, Peng; Miao, Xiang-Shui

2016-12-19

A reflective-type display device based on phase change materials is attractive because of its ultrafast response time and high resolution compared with a conventional display device. This paper proposes and demonstrates a unique display device in which multicolour changing can be achieved on a single device by the selective crystallization of double layer phase change materials. The optical contrast is optimized by the availability of a variety of film thicknesses of two phase change layers. The device exhibits a low sensitivity to the angle of incidence, which is important for display and colour consistency. The non-binary colour rendering on a single device is demonstrated for the first time using optical excitation. The device shows the potential for ultrafast display applications.

A DsbA-Deficient Periplasm Enables Functional Display of a Protein with Redox-Sensitive Folding on M13 Phage.

PubMed

Chen, Minyong; Samuelson, James C

2016-06-14

The requirements for target protein folding in M13 phage display are largely underappreciated. Here we chose Fbs1, a carbohydrate binding protein, as a model to address this issue. Importantly, folding of Fbs1 is impaired in an oxidative environment. Fbs1 can be displayed on M13 phage using the SRP or Sec pathway. However, the displayed Fbs1 protein is properly folded only when Fbs1 is translocated via the SRP pathway and displayed using Escherichia coli cells with a DsbA-negative periplasm. This study indicates M13 phage display may be improved using a system specifically designed according to the folding requirements of each target protein.

Quantification of color vision using a tablet display.

PubMed

Chacon, Alicia; Rabin, Jeff; Yu, Dennis; Johnston, Shawn; Bradshaw, Timothy

2015-01-01

Accurate color vision is essential for optimal performance in aviation and space environments using nonredundant color coding to convey critical information. Most color tests detect color vision deficiency (CVD) but fail to diagnose type or severity of CVD, which are important to link performance to occupational demands. The computer-based Cone Contrast Test (CCT) diagnoses type and severity of CVD. It is displayed on a netbook computer for clinical application, but a more portable version may prove useful for deployments, space and aviation cockpits, as well as accident and sports medicine settings. Our purpose was to determine if the CCT can be conducted on a tablet display (Windows 8, Microsoft, Seattle, WA) using touch-screen response input. The CCT presents colored letters visible only to red (R), green (G), and blue (B) sensitive retinal cones to determine the lowest R, G, and B cone contrast visible to the observer. The CCT was measured in 16 color vision normals (CVN) and 16 CVDs using the standard netbook computer and a Windows 8 tablet display calibrated to produce equal color contrasts. Both displays showed 100% specificity for confirming CVN and 100% sensitivity for detecting CVD. In CVNs there was no difference between scores on netbook vs. tablet displays. G cone CVDs showed slightly lower G cone CCT scores on the tablet. CVD can be diagnosed with a tablet display. Ease-of-use, portability, and complete computer capabilities make tablets ideal for multiple settings, including aviation, space, military deployments, accidents and rescue missions, and sports vision. Chacon A, Rabin J, Yu D, Johnston S, Bradshaw T. Quantification of color vision using a tablet display.

The utility of a classificatory decision tree approach to assist clinical differentiation of melancholic and non-melancholic depression.

PubMed

Parker, G; McCraw, S; Hadzi-Pavlovic, D

2015-07-15

Studies suggest that differentiating melancholic from non-melancholic depressive disorders is advanced by use of illness course as well as symptom variables but, in practice, potentially differentiating variables are generally positioned as having equal value. Judging that differentiating features are more likely to vary in their signal intensity, we sought to determine the number of features required to effect differentiation and their hierarchical order. The 24-item clinician-rated Sydney Melancholia Prototype Index (SMPI-CR) was completed for 364 unipolar depressed patients. The sample was divided into two cohorts according to the recruitment period. An RPART classification tree analysis identified the most discriminating SMPI items in the development sample of 197 patients, and examined the sensitivity and specificity of the diagnostic decisions, then sought to replicate findings in a validation sample of 169 patients. Independent analyses of putative SMPI items identified only seven items as required to discriminate those with clinically-diagnosed melancholic or non-melancholic depression when the conditions were examined separately. An RPART analysis considering differentiation of melancholic and non-melancholic depression in the total samples retained five of those items in the classification tree, three of which were non-symptom items, and with 92% sensitivity and 80% specificity in the development sample. This reduced item set showed 93% sensitivity and 82% specificity in the validation sample. Our clinical judgment of melancholic or non-melancholic depression may not correspond with the clinical logic employed by other clinicians. Only five SMPI items were required to derive a succinct and efficient decision tree, comprising high sensitivity and specificity in differentiating melancholic and non-melancholic depression. Current study findings provide an empirical model that could enrich clinicians׳ approach to differentiating melancholic and non-melancholic depression. Copyright © 2015 Elsevier B.V. All rights reserved.

c-FLIP is involved in erythropoietin-mediated protection of erythroid-differentiated cells from TNF-alpha-induced apoptosis.

PubMed

Vittori, Daniela; Vota, Daiana; Callero, Mariana; Chamorro, María E; Nesse, Alcira

2010-05-04

The TNF-alpha (tumour necrosis factor) affects a wide range of biological activities, such as cell proliferation and apoptosis. Cell life or death responses to this cytokine might depend on cell conditions. This study focused on the modulation of factors that would affect the sensitivity of erythroid-differentiated cells to TNF-alpha. Hemin-differentiated K562 cells showed higher sensitivity to TNF-induced apoptosis than undifferentiated cells. At the same time, hemin-induced erythroid differentiation reduced c-FLIP (cellular FLICE-inhibitory protein) expression. However, this negative effect was prevented by prior treatment with Epo (erythropoietin), which allowed the cell line to maintain c-FLIP levels. On the other hand, erythroid-differentiated UT-7 cells - dependent on Epo for survival - showed resistance to TNF-alpha pro-apoptotic action. Only after the inhibition of PI3K (phosphatidylinositol-3 kinase)-mediated pathways, which was accompanied by negative c-FLIP modulation and increased erythroid differentiation, were UT-7 cells sensitive to TNF-alpha-triggered apoptosis. In summary, erythroid differentiation might deregulate the balance between growth promotion and death signals induced by TNF-alpha, depending on cell type and environmental conditions. The role of c-FLIP seemed to be critical in the protection of erythroid-differentiated cells from apoptosis or in the determination of their sensitivity to TNF-mediated programmed cell death. Epo, which for the first time was found to be involved in the prevention of c-FLIP down-regulation, proved to have an anti-apoptotic effect against the pro-inflammatory factor. The identification of signals related to cell life/death switching would have significant implications in the control of proliferative diseases and would contribute to the understanding of mechanisms underlying the anaemia associated with inflammatory processes.

A highly sensitive and selective electrochemical sensor for determination of Cr(VI) in the presence of Cr(III) using modified multi-walled carbon nanotubes/quercetin screen-printed electrode.

PubMed

Sadeghi, Susan; Garmroodi, Aziz

2013-12-01

A novel screen-printed carbon electrode modified with quercetin/multi-walled carbon nanotubes was fabricated for determination of Cr(VI) in the presence of excess of Cr(III) without any pretreatment. The method is based on accumulation of the quercetin-Cr(III) complex generated in situ from Cr(VI) at the modified electrode surface in an open circuit followed by differential pulse voltammetry detection. The new method allowed selective determination of Cr(VI) in the presence of Cr(III). The influence of various parameters affecting the adsorptive stripping voltammetry performance was investigated. Under the optimum conditions, the calibration plot was found to be linear in the Cr(VI) concentration range from 1.0 to 200 μmol(-1) with a limit of detection(S/N=3) of 0.3 μmol L(-1). The relative standard deviation (RSD%) of seven replicates of the current measurements for a 50 μmol(-1) of Cr(VI) solution was 3.0%. The developed electrode displayed a very low or no sensitivity to alkali, alkali-earth and transition metal cations and was successfully applied for the determination of Cr(VI) in drinking water samples. © 2013.

Neuraminidase Subtyping of Avian Influenza Viruses with PrimerHunter-Designed Primers and Quadruplicate Primer Pools

PubMed Central

Huang, Yanyan; Khan, Mazhar; Măndoiu, Ion I.

2013-01-01

We have previously developed a software package called PrimerHunter to design primers for PCR-based virus subtyping. In this study, 9 pairs of primers were designed with PrimerHunter and successfully used to differentiate the 9 neuraminidase (NA) genes of avian influenza viruses (AIVs) in multiple PCR-based assays. Furthermore, primer pools were designed and successfully used to decrease the number of reactions needed for NA subtyping from 9 to 4. The quadruplicate primer-pool method is cost-saving, and was shown to be suitable for the NA subtyping of both cultured AIVs and uncultured AIV swab samples. The primers selected for this study showed excellent sensitivity and specificity in NA subtyping by RT-PCR, SYBR green-based Real-time PCR and Real-time RT-PCR methods. AIV RNA of 2 to 200 copies (varied by NA subtypes) could be detected by these reactions. No unspecific amplification was displayed when detecting RNAs of other avian infectious viruses such as Infectious bronchitis virus, Infectious bursal disease virus and Newcastle disease virus. In summary, this study introduced several sensitive and specific PCR-based assays for NA subtyping of AIVs and also validated again the effectiveness of the PrimerHunter tool for the design of subtyping primers. PMID:24312367

An rK28-Based Immunoenzymatic Assay for the Diagnosis of Canine Visceral Leishmaniasis in Latin America

PubMed Central

Lauricella, Marta Alicia; Maidana, Cristina Graciela; Frias, Victoria Fragueiro; Romagosa, Carlo M.; Negri, Vanesa; Benedetti, Ruben; Sinagra, Angel J.; Luna, Concepcion; Tartaglino, Lilian; Laucella, Susana; Reed, Steven G.; Riarte, Adelina R.

2016-01-01

Direct observation of Leishmania parasites in tissue aspirates has shown low sensitivity for the detection of canine visceral leishmaniasis (VL). Therefore in the last quarter century immunoenzymatic tests have been developed to improve diagnosis. The purpose of this study was to develop a fast recombinant K28 antigen, naked-eye qualitative enzyme-linked immunosorbent assay (VL Ql-ELISA) and a quantitative version (VL Qt-ELISA), and to display it in a kit format, whose cutoff value (0.156) was selected as the most adequate one to differentiate reactive from nonreactive samples. Considering 167 cases and 300 controls, sensitivity was 91% for both assays and specificity was 100% and 98.7% in Ql-ELISA and Qt-ELISA, respectively. Positive predictive values were 100% and 97.4% for Ql-ELISA and Qt-ELISA, respectively, and negative predictive values were 95.2% for both ELISAs. Reagent stability, reliability studies, including periodic repetitions and retest of samples, cutoff selection, and comparison of rK28 ELISAs with rK39 immunochromatographic test, were the international criteria that supported the quality in both kits. The performance of both ELISA kits in this work confirmed their validity and emphasized their usefulness for low-to-medium complexity laboratories. PMID:27162270

A Posteriori Finite Element Bounds for Sensitivity Derivatives of Partial-Differential-Equation Outputs. Revised

NASA Technical Reports Server (NTRS)

Lewis, Robert Michael; Patera, Anthony T.; Peraire, Jaume

1998-01-01

We present a Neumann-subproblem a posteriori finite element procedure for the efficient and accurate calculation of rigorous, 'constant-free' upper and lower bounds for sensitivity derivatives of functionals of the solutions of partial differential equations. The design motivation for sensitivity derivative error control is discussed; the a posteriori finite element procedure is described; the asymptotic bounding properties and computational complexity of the method are summarized; and illustrative numerical results are presented.

How to reinforce perception of depth in single two-dimensional pictures

NASA Technical Reports Server (NTRS)

Nagata, S.

1989-01-01

The physical conditions of the display of single 2-D pictures, which produce images realistically, were studied by using the characteristics of the intake of the information for visual depth perception. Depth sensitivity, which is defined as the ratio of viewing distance to depth discrimination threshold, was introduced in order to evaluate the availability of various cues for depth perception: binocular parallax, motion parallax, accommodation, convergence, size, texture, brightness, and air-perspective contrast. The effects of binocular parallax in different conditions, the depth sensitivity of which is greatest at a distance of up to about 10 m, were studied with the new versatile stereoscopic display. From these results, four conditions to reinforce the perception of depth in single pictures were proposed, and these conditions are met by the old viewing devices and the new high-definition and wide television displays.

Testing environment shape differentially modulates baseline and nicotine-induced changes in behavior: Sex differences, hypoactivity, and behavioral sensitization.

PubMed

Illenberger, J M; Mactutus, C F; Booze, R M; Harrod, S B

2018-02-01

In those who use nicotine, the likelihood of dependence, negative health consequences, and failed treatment outcomes differ as a function of gender. Women may be more sensitive to learning processes driven by repeated nicotine exposure that influence conditioned approach and craving. Sex differences in nicotine's influence over overt behaviors (i.e. hypoactivity or behavioral sensitization) can be examined using passive drug administration models in male and female rats. Following repeated intravenous (IV) nicotine injections, behavioral sensitization is enhanced in female rats compared to males. Nonetheless, characteristics of the testing environment also mediate rodent behavior following drug administration. The current experiment used a within-subjects design to determine if nicotine-induced changes in horizontal activity, center entries, and rearing displayed by male and female rats is detected when behavior was recorded in round vs. square chambers. Behaviors were recorded from each group (males-round: n=19; males-square: n=18; females-square: n=19; and females-round: n=19) immediately following IV injection of saline, acute nicotine, and repeated nicotine (0.05mg/kg/injection). Prior to nicotine treatment, sex differences were apparent only in round chambers. Following nicotine administration, the order of magnitude for the chamber that provided enhanced detection of hypoactivity or sensitization was contingent upon both the dependent measure under examination and the animal's biological sex. As such, round and square testing chambers provide different, and sometimes contradictory, accounts of how male and female rats respond to nicotine treatment. It is possible that a central mechanism such as stress or cue sensitivity is impacted by both drug exposure and environment to drive the sex differences observed in the current experiment. Until these complex relations are better understood, experiments considering sex differences in drug responses should balance characteristics of the testing environment to provide a complete interpretation of drug-induced changes to behavior. Copyright © 2018 Elsevier Inc. All rights reserved.

Relative sensitivity of developmental and immune parameters in juvenile versus adult male rats after exposure to di(2-ethylhexyl) phthalate

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

Tonk, Elisa C.M., E-mail: ilse.tonk@rivm.nl; Laboratory for Health Protection Research, National Institute for Public Health and the Environment; Verhoef, Aart

The developing immune system displays a relatively high sensitivity as compared to both general toxicity parameters and to the adult immune system. In this study we have performed such comparisons using di(2-ethylhexyl) phthalate (DEHP) as a model compound. DEHP is the most abundant phthalate in the environment and perinatal exposure to DEHP has been shown to disrupt male sexual differentiation. In addition, phthalate exposure has been associated with immune dysfunction as evidenced by effects on the expression of allergy. Male wistar rats were dosed with corn oil or DEHP by gavage from postnatal day (PND) 10–50 or PND 50–90 atmore » doses between 1 and 1000 mg/kg/day. Androgen-dependent organ weights showed effects at lower dose levels in juvenile versus adult animals. Immune parameters affected included TDAR parameters in both age groups, NK activity in juvenile animals and TNF-α production by adherent splenocytes in adult animals. Immune parameters were affected at lower dose levels compared to developmental parameters. Overall, more immune parameters were affected in juvenile animals compared to adult animals and effects were observed at lower dose levels. The results of this study show a relatively higher sensitivity of juvenile versus adult rats. Furthermore, they illustrate the relative sensitivity of the developing immune system in juvenile animals as compared to general toxicity and developmental parameters. This study therefore provides further argumentation for performing dedicated developmental immune toxicity testing as a default in regulatory toxicology. -- Highlights: ► In this study we evaluate the relative sensitivities for DEHP induced effects. ► Results of this study demonstrate the age-dependency of DEHP toxicity. ► Functional immune parameters were more sensitive than structural immune parameters. ► Immune parameters were affected at lower dose levels than developmental parameters. ► Findings demonstrate the susceptibility of the developing immune system for DEHP.« less

Absolute Position Sensing Based on a Robust Differential Capacitive Sensor with a Grounded Shield Window

PubMed Central

Bai, Yang; Lu, Yunfeng; Hu, Pengcheng; Wang, Gang; Xu, Jinxin; Zeng, Tao; Li, Zhengkun; Zhang, Zhonghua; Tan, Jiubin

2016-01-01

A simple differential capacitive sensor is provided in this paper to measure the absolute positions of length measuring systems. By utilizing a shield window inside the differential capacitor, the measurement range and linearity range of the sensor can reach several millimeters. What is more interesting is that this differential capacitive sensor is only sensitive to one translational degree of freedom (DOF) movement, and immune to the vibration along the other two translational DOFs. In the experiment, we used a novel circuit based on an AC capacitance bridge to directly measure the differential capacitance value. The experimental result shows that this differential capacitive sensor has a sensitivity of 2 × 10−4 pF/μm with 0.08 μm resolution. The measurement range of this differential capacitive sensor is 6 mm, and the linearity error are less than 0.01% over the whole absolute position measurement range. PMID:27187393

Investigation of a redox-sensitive predictive model of mouse embryonic stem cells differentiation using quantitative nuclease protection assays and glutathione redox status

EPA Science Inventory

Investigation of a redox-sensitive predictive model of mouse embryonic stem cell differentiation via quantitative nuclease protection assays and glutathione redox status Chandler KJ,Hansen JM, Knudsen T,and Hunter ES 1. U.S. Environmental Protection Agency, Research Triangl...

Child Differential Sensitivity to Parental Self-Efficacy Improvement: A Micro-Trial Perspective

ERIC Educational Resources Information Center

Mouton, Bénédicte; Loop, Laurie; Stievenart, Marie; Roskam, Isabelle

2018-01-01

This study investigates the hypothesis of a child differential sensitivity to parenting improvement. One hundred and fourteen parents of preschoolers participated in two parenting micro-trials aiming to increase parental self-efficacy in view of improving child behavior. The first micro-trial took place in a short-term laboratory experiment; the…

Increased adipogenic conversion of muscle satellite cells in obese Zucker rats.

PubMed

Scarda, A; Franzin, C; Milan, G; Sanna, M; Dal Prà, C; Pagano, C; Boldrin, L; Piccoli, M; Trevellin, E; Granzotto, M; Gamba, P; Federspil, G; De Coppi, P; Vettor, R

2010-08-01

Visceral and intermuscular adipose tissue (IMAT) depots account for most obesity-related metabolic and cardiovascular complications. Muscle satellite cells (SCs) are mesenchymal stem cells giving rise to myotubes and also to adipocytes, suggesting their possible contribution to IMAT origin and expansion. We investigated the myogenic differentiation of SCs and the adipogenic potential of both preadipocytes and SCs from genetically obese Zucker rats (fa/fa), focusing on the role of Wnt signaling in these differentiation processes. SCs were isolated by single-fiber technique from flexor digitorum brevis muscle and preadipocytes were extracted from subcutaneous adipose tissue (AT). Morphological features and gene expression profile were evaluated during in vitro myogenesis and adipogenesis. Wingless-type MMTV integration site family member 10b (Wnt10b) expression was quantified by quantitative PCR in skeletal muscle and AT. We did not observe any difference in the proliferation rate and in the myogenic differentiation of SCs from obese and lean rats. However, a decreased insulin-induced glucose uptake was present in myotubes originating from fa/fa rats. Under adipogenic conditions, preadipocytes and SCs of obese animals displayed an enhanced adipogenesis. Wnt10b expression was reduced in obese rats in both muscle and AT. Our data suggest that the increase in different fat depots including IMAT and the reduced muscle insulin sensitivity, the major phenotypical alteration of obese Zucker rats, could be ascribed to an intrinsic defect, either genetically determined or acquired, still present in both muscle and fat precursors. The involvement of Wnt10b as a regulator of both adipogenesis and muscle-to-fat conversion is suggested.

Differential polarization laser scanning microscopy: biological applications

NASA Astrophysics Data System (ADS)

Steinbach, G.; Besson, F.; Pomozi, I.; Garab, G.

2005-09-01

With the aid of a differential polarization (DP) apparatus, developed in our laboratory and attached to our laser scanning confocal microscope, we can measure the magnitude and spatial distribution of 8 different DP quantities: linear and circular dichroism (LD&CD), linear and circular anisotropy of the emission (R and CPL, confocal), fluorescence detected dichroisms (FDLD&FDCD, confocal), linear birefringence (LB), and the degree of polarization of fluorescence emission (P, confocal). The attachment uses high frequency modulation and subsequent demodulation, via lock-in amplifier, of the detected intensity values, and records and displays pixel-by-pixel the measured DP quantity. These microscopic DP data carry important physical information on the molecular architecture of anisotropically organized samples. Microscopic DP measurements are thought to be of particular importance in biology. In most biological samples anisotropy is difficult to determine with conventional, macroscopic DP measurements and microscopic variations are of special significance. In this paper, we describe the method of LB imaging. Using magnetically oriented isolated chloroplasts trapped in polyacrylamide gel, we demonstrate that LB can be determined with high sensitivity and good spatial resolution. Granal thylakoid membranes in edge-aligned orientation exhibited strong LB, with large variations in its sign and magnitude. In face-aligned position LB was considerably weaker, and tended to vanish when averaged for the whole image. The strong local variations are attributed to the inherent heterogeneity of the membranes, i.e. to their internal differentiation into multilamellar, stacked membranes (grana), and single thylakoids (stroma membranes). Further details and applications of our DP-LSM will be published elsewhere.

Evaluation of ultraviolet radiation, ozone and aerosol interactions in the troposphere using automatic differentiation. Final report

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

Carmichael, G.R.; Potra, F.

1998-10-06

A major goal of this research was to quantify the interactions between UVR, ozone and aerosols. One method of quantification was to calculate sensitivity coefficients. A novel aspect of this work was the use of Automatic Differentiation software to calculate the sensitivities. The authors demonstrated the use of ADIFOR for the first time in a dimensional framework. Automatic Differentiation was used to calculate such quantities as: sensitivities of UV-B fluxes to changes in ozone and aerosols in the stratosphere and the troposphere; changes in ozone production/destruction rates to changes in UV-B flux; aerosol properties including loading, scattering properties (including relativemore » humidity effects), and composition (mineral dust, soot, and sulfate aerosol, etc.). The combined radiation/chemistry model offers an important test of the utility of Automatic Differentiation as a tool in atmospheric modeling.« less

Laser-evoked potentials mediated by mechano-insensitive nociceptors in human skin.

PubMed

Dusch, M; van der Ham, J; Weinkauf, B; Benrath, J; Rukwied, R; Ringkamp, M; Schmelz, M; Treede, R-D; Baumgärtner, U

2016-05-01

Laser-evoked potentials (LEP) were assessed after peripheral nerve block of the lateral femoral cutaneous nerve (LFCN) in healthy volunteers from partially anesthetized skin areas to differentially stimulate mechano-insensitive nociceptors. An ultrasound-guided nerve block of the LFCN was performed in 12 healthy male subjects with Ropivacain 1%. After 30 min, the nerve block induced significantly larger anesthetic areas to mechanical stimuli than to electrical stimuli revealing an area of differential sensitivity. LEPs, reaction times and pain ratings were recorded in response to the laser stimuli of (1) completely anesthetic skin, (2) mechano-insensitive, but electrically excitable skin ('differential sensitivity'), (3) normal skin. LEP latencies in the area of differential sensitivity were increased compared to unaffected skin (228 ± 8.5 ms, vs. 181 ± 3.6 ms, p < 0.01) and LEP amplitudes were reduced (14.8 ± 1.2 μV vs. 24.6 ± 1.7 μV, p < 0.01). Correspondingly, psychophysically assessed response latencies in the differentially anesthetic skin were increased (649 ms vs. 427 ms, p < 0.01) and pain ratings reduced (1.5/10 vs. 5/10 NRS, p < 0.01). The increase in LEP latency suggests that mechano-insensitive heat-sensitive Aδ nociceptors (MIA, type II) have a slower conduction velocity or higher utilization time than mechano-sensitive type II Aδ nociceptors. Moreover, widely branched, slowly conducting and mechano-insensitive branches of Aδ nociceptors can explain our finding. LEPs in the differentially anesthetized skin provide specific information about a mechanically insensitive but heat-sensitive subpopulation of Aδ nociceptors. These findings support the concept that A-fibre nociceptors exhibit a similar degree of modality specificity as C-fibre nociceptors. © 2015 European Pain Federation - EFIC®

Monolithic integration of a resonant tunneling diode and a quantum well semiconductor laser

NASA Astrophysics Data System (ADS)

Grave, I.; Kan, S. C.; Griffel, G.; Wu, S. W.; Sa'Ar, A.

1991-01-01

A monolithic integration of a double barrier AlAs/GaAs resonant tunneling diode and a GaAs/AlGaAs quantum well laser is reported. Negative differential resistance and negative differential optical response are observed at room temperature. The device displays bistable electrical and optical characteristics which are voltage controlled. Operation as a two-state optical memory is demonstrated.

Evaluating a Tablet Application and Differential Reinforcement to Increase Eye Contact in Children with Autism

ERIC Educational Resources Information Center

Jeffries, Tricia; Crosland, Kimberly; Miltenberger, Raymond

2016-01-01

We tested the effectiveness of a tablet application and differential reinforcement to increase eye contact in 3 children with autism. The application required the child to look at a picture of a person's face and identify the number displayed in the person's eyes. Eye contact was assessed immediately after training, 1 hr after training, and in a…

Group-Specific Effects of Matching Subtest Contamination on the Identification of Differential Item Functioning

ERIC Educational Resources Information Center

Keiffer, Elizabeth Ann

2011-01-01

A differential item functioning (DIF) simulation study was conducted to explore the type and level of impact that contamination had on type I error and power rates in DIF analyses when the suspect item favored the same or opposite group as the DIF items in the matching subtest. Type I error and power rates were displayed separately for the…

Comparison of global brain gene expression profiles between inbred long-sleep and inbred short-sleep mice by high-density gene array hybridization.

PubMed

Xu, Y; Ehringer, M; Yang, F; Sikela, J M

2001-06-01

Inbred long-sleep (ILS) and short-sleep (ISS) mice show significant central nervous system-mediated differences in sleep time for sedative dose of ethanol and are frequently used as a rodent model for ethanol sensitivity. In this study, we have used complementary DNA (cDNA) array hybridization methodology to identify genes that are differentially expressed between the brains of ILS and ISS mice. To carry out this analysis, we used both the gene discovery array (GDA) and the Mouse GEM 1 Microarray. GDA consists of 18,378 nonredundant mouse cDNA clones on a single nylon filter. Complex probes were prepared from total brain mRNA of ILS or ISS mice by using reverse transcription and 33P labeling. The labeled probes were hybridized in parallel to the gene array filters. Data from GDA experiments were analyzed with SQL-Plus and Oracle 8. The GEM microarray includes 8,730 sequence-verified clones on a glass chip. Two fluorescently labeled probes were used to hybridize a microarray simultaneously. Data from GEM experiments were analyzed by using the GEMTools software package (Incyte). Differentially expressed genes identified from each method were confirmed by relative quantitative reverse transcription-polymerase chain reaction (RT-PCR). A total of 41 genes or expressed sequence tags (ESTs) display significant expression level differences between brains of ILS and ISS mice after GDA, GEM1 hybridization, and quantitative RT-PCR confirmation. Among them, 18 clones were expressed higher in ILS mice, and 23 clones were expressed higher in ISS mice. The individual gene or EST's function and mapping information have been analyzed. This study identified 41 genes that are differentially expressed between brains of ILS and ISS mice. Some of them may have biological relevance in mediation of phenotypic variation between ILS and ISS mice for ethanol sensitivity. This study also demonstrates that parallel gene expression comparison with high-density cDNA arrays is a rapid and efficient way to discover potential genes and pathways involved in alcoholism and alcohol-related physiologic processes.

Sensitivity to Lateral Information on a Perceptual Word Identification Task in French Third and Fifth Graders

ERIC Educational Resources Information Center

Khelifi, Rachid; Sparrow, Laurent; Casalis, Severine

2012-01-01

This study aimed at examining sensitivity to lateral linguistic and nonlinguistic information in third and fifth grade readers. A word identification task with a threshold was used, and targets were displayed foveally with or without distractors. Sensitivity to lateral information was inferred from the deterioration of the rate of correct word…

The Sensitivity of Precocious Child Writers: More Evidence of the Double-Edged Sword

ERIC Educational Resources Information Center

Edmunds, Alan L.; Edmunds, Gail

2014-01-01

This article provides further evidence of the often observed sensitive nature displayed by children who are gifted. It also addresses the positive and negative effects that this sensitivity can have on these individuals. Earlier, the authors explored this concept through an analysis of the works and life experiences of Geoffrey, aged 9, a prolific…

Differential susceptibility in spillover between interparental conflict and maternal parenting practices: evidence for OXTR and 5-HTT genes.

PubMed

Sturge-Apple, Melissa L; Cicchetti, Dante; Davies, Patrick T; Suor, Jennifer H

2012-06-01

Guided by the affective spillover hypothesis and the differential susceptibility to environmental influence frameworks, the present study examined how associations between interparental conflict and mothers' parenting practices were moderated by serotonin transporter (5-HTT) and oxytocin receptor (OXTR) genes. A sample of 201 mothers and their 2-year old child participated in a laboratory-based research assessment. Results supported differential susceptibility hypotheses within spillover frameworks. With respect to OXTR rs53576, mothers with the GG genotype showed greater differential maternal sensitivity across varying levels of interparental conflict. Mothers with one or two copies of the 5-HTTLPR S allele demonstrated differential susceptibility for both sensitive and harsh/punitive caregiving behaviors. Finally, analyses examined whether maternal depressive symptoms and emotional closeness to their child mediated the moderating effects. Findings suggest that maternal emotional closeness with their child indirectly linked OXTR with maternal sensitivity. The results highlight how molecular genetics may explain heterogeneity in spillover models with differential implications for specific parenting behaviors. Implications for clinicians and therapists working with maritally distressed parents are discussed. PsycINFO Database Record (c) 2012 APA, all rights reserved.

Contrast sensitivity function in stereoscopic viewing of Gabor patches on a medical polarized three-dimensional stereoscopic display

NASA Astrophysics Data System (ADS)

Rousson, Johanna; Haar, Jérémy; Santal, Sarah; Kumcu, Asli; Platiša, Ljiljana; Piepers, Bastian; Kimpe, Tom; Philips, Wilfried

2016-03-01

While three-dimensional (3-D) imaging systems are entering hospitals, no study to date has explored the luminance calibration needs of 3-D stereoscopic diagnostic displays and if they differ from two-dimensional (2-D) displays. Since medical display calibration incorporates the human contrast sensitivity function (CSF), we first assessed the 2-D CSF for benchmarking and then examined the impact of two image parameters on the 3-D stereoscopic CSF: (1) five depth plane (DP) positions (between DP: -171 and DP: 2853 mm), and (2) three 3-D inclinations (0 deg, 45 deg, and 60 deg around the horizontal axis of a DP). Stimuli were stereoscopic images of a vertically oriented 2-D Gabor patch at one of seven frequencies ranging from 0.4 to 10 cycles/deg. CSFs were measured for seven to nine human observers with a staircase procedure. The results indicate that the 2-D CSF model remains valid for a 3-D stereoscopic display regardless of the amount of disparity between the stereo images. We also found that the 3-D CSF at DP≠0 does not differ from the 3-D CSF at DP=0 for DPs and disparities which allow effortless binocular fusion. Therefore, the existing 2-D medical luminance calibration algorithm remains an appropriate tool for calibrating polarized stereoscopic medical displays.

A comparison of kinesthetic-tactual and visual displays via a critical tracking task. [for aircraft control

NASA Technical Reports Server (NTRS)

Jagacinski, R. J.; Miller, D. P.; Gilson, R. D.

1979-01-01

The feasibility of using the critical tracking task to evaluate kinesthetic-tactual displays was examined. The test subjects were asked to control a first-order unstable system with a continuously decreasing time constant by using either visual or tactual unidimensional displays. The results indicate that the critical tracking task is both a feasible and a reliable methodology for assessing tactual tracking. Further, that the critical tracking methodology is as sensitive and valid a measure of tactual tracking as visual tracking is demonstrated by the approximately equal effects of quickening for the tactual and visual displays.

Optimum viewing distance for target acquisition

NASA Astrophysics Data System (ADS)

Holst, Gerald C.

2015-05-01

Human visual system (HVS) "resolution" (a.k.a. visual acuity) varies with illumination level, target characteristics, and target contrast. For signage, computer displays, cell phones, and TVs a viewing distance and display size are selected. Then the number of display pixels is chosen such that each pixel subtends 1 min-1. Resolution of low contrast targets is quite different. It is best described by Barten's contrast sensitivity function. Target acquisition models predict maximum range when the display pixel subtends 3.3 min-1. The optimum viewing distance is nearly independent of magnification. Noise increases the optimum viewing distance.

Reward sensitivity predicts ice cream-related attentional bias assessed by inattentional blindness.

PubMed

Li, Xiaoming; Tao, Qian; Fang, Ya; Cheng, Chen; Hao, Yangyang; Qi, Jianjun; Li, Yu; Zhang, Wei; Wang, Ying; Zhang, Xiaochu

2015-06-01

The cognitive mechanism underlying the association between individual differences in reward sensitivity and food craving is unknown. The present study explored the mechanism by examining the role of reward sensitivity in attentional bias toward ice cream cues. Forty-nine college students who displayed high level of ice cream craving (HICs) and 46 who displayed low level of ice cream craving (LICs) performed an inattentional blindness (IB) task which was used to assess attentional bias for ice cream. In addition, reward sensitivity and coping style were assessed by the Behavior Inhibition System/Behavior Activation System Scales and Simplified Coping Style Questionnaire. Results showed significant higher identification rate of the critical stimulus in the HICs than LICs, suggesting greater attentional bias for ice cream in the HICs. It was indicated that attentional bias for food cues persisted even under inattentional condition. Furthermore, a significant correlation was found between the attentional bias and reward sensitivity after controlling for coping style, and reward sensitivity predicted attentional bias for food cues. The mediation analyses showed that attentional bias mediated the relationship between reward sensitivity and food craving. Those findings suggest that the association between individual differences in reward sensitivity and food craving may be attributed to attentional bias for food-related cues. Copyright © 2015 Elsevier Ltd. All rights reserved.

Accuracy of computed tomographic features in differentiating intestinal tuberculosis from Crohn's disease: a systematic review with meta-analysis.

PubMed

Kedia, Saurabh; Sharma, Raju; Sreenivas, Vishnubhatla; Madhusudhan, Kumble Seetharama; Sharma, Vishal; Bopanna, Sawan; Pratap Mouli, Venigalla; Dhingra, Rajan; Yadav, Dawesh Prakash; Makharia, Govind; Ahuja, Vineet

2017-04-01

Abdominal computed tomography (CT) can noninvasively image the entire gastrointestinal tract and assess extraintestinal features that are important in differentiating Crohn's disease (CD) and intestinal tuberculosis (ITB). The present meta-analysis pooled the results of all studies on the role of CT abdomen in differentiating between CD and ITB. We searched PubMed and Embase for all publications in English that analyzed the features differentiating between CD and ITB on abdominal CT. The features included comb sign, necrotic lymph nodes, asymmetric bowel wall thickening, skip lesions, fibrofatty proliferation, mural stratification, ileocaecal area, long segment, and left colonic involvements. Sensitivity, specificity, positive and negative likelihood ratios, and diagnostic odds ratio (DOR) were calculated for all the features. Symmetric receiver operating characteristic curve was plotted for features present in >3 studies. Heterogeneity and publication bias was assessed and sensitivity analysis was performed by excluding studies that compared features on conventional abdominal CT instead of CT enterography (CTE). We included 6 studies (4 CTE, 1 conventional abdominal CT, and 1 CTE+conventional abdominal CT) involving 417 and 195 patients with CD and ITB, respectively. Necrotic lymph nodes had the highest diagnostic accuracy (sensitivity, 23%; specificity, 100%; DOR, 30.2) for ITB diagnosis, and comb sign (sensitivity, 82%; specificity, 81%; DOR, 21.5) followed by skip lesions (sensitivity, 86%; specificity, 74%; DOR, 16.5) had the highest diagnostic accuracy for CD diagnosis. On sensitivity analysis, the diagnostic accuracy of other features excluding asymmetric bowel wall thickening remained similar. Necrotic lymph nodes and comb sign on abdominal CT had the best diagnostic accuracy in differentiating CD and ITB.

Evaluating a tablet application and differential reinforcement to increase eye contact in children with autism.

PubMed

Jeffries, Tricia; Crosland, Kimberly; Miltenberger, Raymond

2016-03-01

We tested the effectiveness of a tablet application and differential reinforcement to increase eye contact in 3 children with autism. The application required the child to look at a picture of a person's face and identify the number displayed in the person's eyes. Eye contact was assessed immediately after training, 1 hr after training, and in a playroom. The tablet application was not effective; however, differential reinforcement was effective for all participants. © 2015 Society for the Experimental Analysis of Behavior.

Cardiac Subsarcolemmal and Interfibrillar Mitochondria Display Distinct Responsiveness to Protection by Diazoxide

PubMed Central

Holmuhamedov, Ekhson L.; Oberlin, Andrew; Short, Kevin; Terzic, Andre; Jahangir, Arshad

2012-01-01

Objective Cardiac subsarcolemmal (SSM) and interfibrillar (IFM) mitochondrial subpopulations possess distinct biochemical properties and differ with respect to their protein and lipid compositions, capacities for respiration and protein synthesis, and sensitivity to metabolic challenge, yet their responsiveness to mitochondrially active cardioprotective therapeutics has not been characterized. This study assessed the differential responsiveness of the two mitochondrial subpopulations to diazoxide, a cardioprotective agent targeting mitochondria. Methods Mitochondrial subpopulations were freshly isolated from rat ventricles and their morphologies assessed by electron microscopy and enzymatic activities determined using standard biochemical protocols with a plate reader. Oxidative phosphorylation was assessed from State 3 respiration using succinate as a substrate. Calcium dynamics and the status of Ca2+-dependent mitochondrial permeability transition (MPT) pore and mitochondrial membrane potential were assessed using standard Ca2+ and TPP+ ion-selective electrodes. Results Compared to IFM, isolated SSM exhibited a higher sensitivity to Ca2+ overload-mediated inhibition of adenosine triphosphate (ATP) synthesis with decreased ATP production (from 375±25 to 83±15 nmol ATP/min/mg protein in SSM, and from 875±39 to 583±45 nmol ATP/min/mg protein in IFM). In addition, SSM exhibited reduced Ca2+-accumulating capacity as compared to IFM (230±13 vs. 450±46 nmol Ca2+/mg protein in SSM and IFM, respectively), suggestive of increased Ca2+ sensitivity of MPT pore opening. Despite enhanced susceptibility to stress, SSM were more responsive to the protective effect of diazoxide (100 μM) against Ca2+ overload-mediated inhibition of ATP synthesis (67% vs. 2% in SSM and IFM, respectively). Conclusion These results provide evidence for the distinct sensitivity of cardiac SSM and IFM toward Ca2+-dependent metabolic stress and the protective effect of diazoxide on mitochondrial energetics. PMID:22973464

Mechanisms underlying differential food allergy response to heated egg.

PubMed

Martos, Gustavo; Lopez-Exposito, Ivan; Bencharitiwong, Ramon; Berin, M Cecilia; Nowak-Węgrzyn, Anna

2011-04-01

Egg white proteins are usually subjected to heating, making them edible for the majority of children with egg allergy. We sought to investigate the underlying mechanisms responsible for the reduced allergenicity displayed by heat-treated egg white allergens. C3H/HeJ mice were orally sensitized with ovalbumin (OVA) or ovomucoid and challenged with native or heated proteins to evaluate their allergenicity. Immunoreactivity was assessed by immunoblotting using sera from children with egg allergy. In vitro gastrointestinal digestion of native and heated OVA and ovomucoid was studied by SDS-PAGE and liquid chromatography. Intestinal uptake of intact native and heated OVA and ovomucoid by human intestinal epithelial (Caco-2) cells was investigated. Rat basophil leukemia cells passively sensitized with mouse serum and human basophils passively sensitized with serum from children with egg allergy were used to assess the effector cell activation by heated, digested, and transported OVA and ovomucoid. Heated OVA and ovomucoid did not induce symptoms of anaphylaxis in sensitized mice when administered orally. Heating did not completely destroy IgE-binding capacity of OVA or ovomucoid but enhanced in vitro digestibility of OVA. Digestion of both OVA and ovomucoid diminished mediator release in rat basophil leukemia assay and basophil activation. Heating of allergens prevented transport across human intestinal epithelial cells in a form capable of triggering basophil activation or T-cell activation. Heat treatment reduces allergenicity of OVA and ovomucoid. This is partially a result of the enhanced gastrointestinal digestibility of heated OVA and the inability of heated OVA or ovomucoid to be absorbed in a form capable of triggering basophils. Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Isotopic diversity indices: how sensitive to food web structure?

PubMed

Brind'Amour, Anik; Dubois, Stanislas F

2013-01-01

Recently revisited, the concept of niche ecology has lead to the formalisation of functional and trophic niches using stable isotope ratios. Isotopic diversity indices (IDI) derived from a set of measures assessing the dispersion/distribution of points in the δ-space were recently suggested and increasingly used in the literature. However, three main critics emerge from the use of these IDI: 1) they fail to account for the isotopic sources overlap, 2) some indices are highly sensitive to the number of species and/or the presence of rare species, and 3) the lack of standardization prevents any spatial and temporal comparisons. Using simulations we investigated the ability of six commonly used IDI to discriminate among different trophic food web structures, with a focus on the first two critics. We tested the sensitivity of the IDI to five food web structures along a gradient of sources overlap, varying from two distinct food chains with differentiated sources to two superimposed food chains sharing two sources. For each of the food web structure we varied the number of species (from 10 to 100 species) and the type of species feeding behaviour (i.e. random or selective feeding). Values of IDI were generally larger in food webs with distinct basal sources and tended to decrease as the superimposition of the food chains increased. This was more pronounced when species displayed food preferences in comparison to food webs where species fed randomly on any prey. The number of species composing the food web also had strong effects on the metrics, including those that were supposedly less sensitive to small sample size. In all cases, computing IDI on food webs with low numbers of species always increases the uncertainty of the metrics. A threshold of ~20 species was detected above which several metrics can be safely used.

Differential Efficacy of Ketamine in the Acute versus Chronic Stages of Complex Regional Pain Syndrome in Mice

PubMed Central

Tajerian, Maral; Leu, David; Yang, Phillip; Huang, Ting Ting; Kingery, Wade S; Clark, J David

2015-01-01

Background Complex regional pain syndrome (CRPS) is a painful, disabling and often chronic condition, where many patients transition from an acute phase with prominent peripheral neurogenic inflammation to a chronic phase with evident central nervous system (CNS) changes. Ketamine is a centrally-acting agent believed to work through blockade of N-methyl-D-aspartate (NMDA) receptors and is being increasingly used for the treatment of refractory CRPS, although the basis for the drug’s effects and efficacy at different stages of the syndrome remain unclear. Methods We used a mouse model of CRPS (n=8–12/group) involving tibia fracture/cast immobilization to test the efficacy of ketamine (2 mg/kg/day; 7 days) or vehicle infusion during acute (3weeks [3w] post-fracture) and chronic (7w post-fracture) stages. Results Acute phase fracture mice displayed elevated limb temperature, edema and nociceptive sensitization that were not reduced by ketamine. Fracture mice treated with ketamine during the chronic phase showed reduced nociceptive sensitization that persisted beyond completion of the infusion. During this chronic phase, ketamine also reduced latent nociceptive sensitization and improved motor function at 18 weeks post-fracture. No side effects of the infusions were identified. These behavioral changes were associated with altered spinal astrocyte activation and expression of pain-related proteins including NMDA receptor 2b (NR2b), Ca2+/calmodulin-dependent protein kinase ii (CaMK2), and brain-derived neurotrophic factor (BNDF). Conclusions Collectively, these results demonstrate that ketamine is efficacious in the chronic, but not acute stages of CRPS, suggesting that the centrally-acting drug is relatively ineffective in early CRPS when peripheral mechanisms are more critical for supporting nociceptive sensitization. PMID:26492479

Arrestin-2 and arrestin-3 differentially modulate locomotor responses and sensitization to amphetamine.

PubMed

Zurkovsky, Lilia; Sedaghat, Katayoun; Ahmed, M Rafiuddin; Gurevich, Vsevolod V; Gurevich, Eugenia V

2017-07-15

Arrestins play a prominent role in shutting down signaling via G protein-coupled receptors. In recent years, a signaling role for arrestins independent of their function in receptor desensitization has been discovered. Two ubiquitously expressed arrestin isoforms, arrestin-2 and arrestin-3, perform similarly in the desensitization process and share many signaling functions, enabling them to substitute for one another. However, signaling roles specific to each isoform have also been described. Mice lacking arrestin-3 (ARR3KO) were reported to show blunted acute responsiveness to the locomotor stimulatory effect of amphetamine (AMPH). It has been suggested that mice with deletion of arrestin-2 display a similar phenotype. Here we demonstrate that the AMPH-induced locomotion of male ARR3KO mice is reduced over the 7-day treatment period and during AMPH challenge after a 7-day withdrawal. The data are consistent with impaired locomotor sensitization to AMPH and suggest a role for arrestin-3-mediated signaling in the sensitization process. In contrast, male ARR2KO mice showed enhanced early responsiveness to AMPH and the lack of further sensitization, suggesting a role for impaired receptor desensitization. The comparison of mice possessing one allele of arrestin-3 and no arrestin-2 with ARR2KO littermates revealed reduced activity of the former line, consistent with a contribution of arrestin-3-mediated signaling to AMPH responses. Surprisingly, ARR3KO mice with one arrestin-2 allele showed significantly reduced locomotor responses to AMPH combined with lower novelty-induced locomotion, as compared to the ARR3KO line. These data suggest that one allele of arrestin-2 is unable to support normal locomotor behavior due to signaling and/or developmental defects. Copyright © 2017 Elsevier Ltd. All rights reserved.

Anomalous uptake and circulatory characteristics of the plant-based small RNA MIR2911.

PubMed

Yang, Jian; Hotz, Tremearne; Broadnax, LaCassidy; Yarmarkovich, Mark; Elbaz-Younes, Ismail; Hirschi, Kendal D

2016-06-02

Inconsistent detection of plant-based dietary small RNAs in circulation has thwarted the use of dietary RNA therapeutics. Here we demonstrate mice consuming diets rich in vegetables displayed enhanced serum levels of the plant specific small RNA MIR2911. Differential centrifugation, size-exclusion chromatography, and proteinase K treatment of plant extracts suggest this RNA resides within a proteinase K-sensitive complex. Plant derived MIR2911 was more bioavailable than the synthetic RNA. Furthermore, MIR2911 exhibited unusual digestive stability compared with other synthetic plant microRNAs. The characteristics of circulating MIR2911 were also unusual as it was not associated with exosomes and fractionated as a soluble complex that was insensitive to proteinase K treatment, consistent with MIR2911 being stabilized by modifications conferred by the host. These results indicate that intrinsic stability and plant-based modifications orchestrate consumer uptake of this anomalous plant based small RNA and invite revisiting plant-based microRNA therapeutic approaches.

Homogeneous Combinations of ASD-ADHD Traits and Their Cognitive and Behavioral Correlates in a Population-Based Sample.

PubMed

van der Meer, Jolanda M J; Lappenschaar, Martijn G A; Hartman, Catharina A; Greven, Corina U; Buitelaar, Jan K; Rommelse, Nanda N J

2017-07-01

Autism Spectrum Disorders (ASD) and ADHD are assumed to be the extreme manifestations of continuous heterogeneous traits that frequently co-occur. This study aims to identify subgroups of children with distinct ASD-ADHD trait profiles in the general population, using measures sensitive across both trait continua, and show how these subgroups differ in cognitive functioning. We examined 378 children (6-13 years) from a population-based sample. Latent class analyses (LCA) detected three concordant classes with low (10.1%), medium (54.2%), or high (13.2%) scores on both traits, and two discordant classes with more ADHD than ASD characteristics (ADHD > ASD, 18.3%) and vice versa (ASD > ADHD, 4.2%). Findings suggest that ASD and ADHD traits usually are strongly related in the unaffected population, and that a minority of children displays atypical discordant trait profiles characterized by differential visual-spatial functioning. This dissociation suggests that heterogeneity in ASD and ADHD is rooted in heterogeneity in the lower unaffected end of the distribution.

Anomalous uptake and circulatory characteristics of the plant-based small RNA MIR2911

PubMed Central

Yang, Jian; Hotz, Tremearne; Broadnax, LaCassidy; Yarmarkovich, Mark; Elbaz-Younes, Ismail; Hirschi, Kendal D.

2016-01-01

Inconsistent detection of plant-based dietary small RNAs in circulation has thwarted the use of dietary RNA therapeutics. Here we demonstrate mice consuming diets rich in vegetables displayed enhanced serum levels of the plant specific small RNA MIR2911. Differential centrifugation, size-exclusion chromatography, and proteinase K treatment of plant extracts suggest this RNA resides within a proteinase K-sensitive complex. Plant derived MIR2911 was more bioavailable than the synthetic RNA. Furthermore, MIR2911 exhibited unusual digestive stability compared with other synthetic plant microRNAs. The characteristics of circulating MIR2911 were also unusual as it was not associated with exosomes and fractionated as a soluble complex that was insensitive to proteinase K treatment, consistent with MIR2911 being stabilized by modifications conferred by the host. These results indicate that intrinsic stability and plant-based modifications orchestrate consumer uptake of this anomalous plant based small RNA and invite revisiting plant-based microRNA therapeutic approaches. PMID:27251858

Defining the computational structure of the motion detector in Drosophila.

PubMed

Clark, Damon A; Bursztyn, Limor; Horowitz, Mark A; Schnitzer, Mark J; Clandinin, Thomas R

2011-06-23

Many animals rely on visual motion detection for survival. Motion information is extracted from spatiotemporal intensity patterns on the retina, a paradigmatic neural computation. A phenomenological model, the Hassenstein-Reichardt correlator (HRC), relates visual inputs to neural activity and behavioral responses to motion, but the circuits that implement this computation remain unknown. By using cell-type specific genetic silencing, minimal motion stimuli, and in vivo calcium imaging, we examine two critical HRC inputs. These two pathways respond preferentially to light and dark moving edges. We demonstrate that these pathways perform overlapping but complementary subsets of the computations underlying the HRC. A numerical model implementing differential weighting of these operations displays the observed edge preferences. Intriguingly, these pathways are distinguished by their sensitivities to a stimulus correlation that corresponds to an illusory percept, "reverse phi," that affects many species. Thus, this computational architecture may be widely used to achieve edge selectivity in motion detection. Copyright © 2011 Elsevier Inc. All rights reserved.

Tubulin-isotype analysis of two grass species-resistant to dinitroaniline herbicides.

PubMed

Waldin, T R; Ellis, J R; Hussey, P J

1992-09-01

Trifluralin-resistant biotypes of Eleusine indica (L.) Gaertn. (goosegrass) and Setaria viridis (L.) Beauv. (green foxtail) exhibit cross-resistance to other dinitroaniline herbicides. Since microtubules are considered the primary target site for dinitroaniline herbicides we investigated whether the differential sensitivity of resistant and susceptible biotypes of these species results from modified tubulin polypeptides. One-dimensional and two-dimensional polyacrylamide gel electrophoresis combined with immunoblotting using well-characterised anti-tubulin monoclonal antibodies were used to display the family of tubulin isotypes in each species. Seedlings of E. indica exhibited four β-tubulin isotypes and one α-tubulin isotype, whereas those of S. viridis exhibited two β-tubulin and two α-tubulin isotypes. Comparison of the susceptible and resistant biotypes within each species revealed no differences in electrophoretic properties of the multiple tubulin isotypes. These results provide no evidence that resistance to dinitroaniline herbicides is associated with a modified tubulin polypeptide in these biotypes of E. indica or S. viridis.

Direct observation of ligand transfer and bond formation in cytochrome c oxidase by using mid-infrared chirped-pulse upconversion

PubMed Central

Treuffet, Johanne; Kubarych, Kevin J.; Lambry, Jean-Christophe; Pilet, Eric; Masson, Jean-Baptiste; Martin, Jean-Louis; Vos, Marten H.; Joffre, Manuel; Alexandrou, Antigoni

2007-01-01

We have implemented the recently demonstrated technique of chirped-pulse upconversion of midinfrared femtosecond pulses into the visible in a visible pump–midinfrared probe experiment for high-resolution, high-sensitivity measurements over a broad spectral range. We have succeeded in time-resolving the CO ligand transfer process from the heme Fe to the neighboring CuB atom in the bimetallic active site of mammalian cytochrome c oxidase, which was known to proceed in <1 ps, using the full CO vibrational signature of Fe–CO bond breaking and CuB–CO bond formation. Our differential transmission results show a delayed onset of the appearance of the CuB-bound species (200 fs), followed by a 450-fs exponential rise. Trajectories calculated by using molecular-dynamics simulations with a Morse potential for the CuB–C interaction display a similar behavior. Both experimental and calculated data strongly suggest a ballistic contribution to the transfer process. PMID:17895387

[Glucose-monitoring neurons of the medial ventrolateral prefrontal (orbitofrontal) cortex are involved in the maintenance of homeostasis].

PubMed

Szabó, István; Hormay, Edina; Csetényi, Bettina; Nagy, Bernadett; Karádi, Zoltán

2017-05-01

The medial orbitofrontal cortex is involved in the regulation of feeding and metabolism. Little is known, however, about the role of local glucose-monitoring neurons in these processes, and our knowledge is also poor about characteristics of these cells. The functional significance of these chemosensory neurons was to be elucidated. Electrophysiology, by the multibarreled microelectrophoretic technique, and metabolic investigations, after streptozotocin induced selective destruction of the chemosensory neurons, were employed. Fifteen percent of the neurons responded to glucose, and these chemosensory cells displayed differential neurotransmitter and taste sensitivities. In acute glucose tolerance test, at the 30th and 60th minutes, blood glucose level in the streptozotocin-treated rats was significantly higher than that in the controls. The plasma triglyceride concentrations were also higher in the streptozotocin-treated group. Glucose-monitoring neurons of the medial orbitofrontal cortex integrate internal and external environmental signals, and monitor metabolic processes, thus, are indispensable to maintain the healthy homeostasis. Orv Hetil. 2017; 158(18): 692-700.

Flavor release measurement from gum model system.

PubMed

Ovejero-López, Isabel; Haahr, Anne-Mette; van den Berg, Frans; Bredie, Wender L P

2004-12-29

Flavor release from a mint-flavored chewing gum model system was measured by atmospheric pressure chemical ionization mass spectroscopy (APCI-MS) and sensory time-intensity (TI). A data analysis method for handling the individual curves from both methods is presented. The APCI-MS data are ratio-scaled using the signal from acetone in the breath of subjects. Next, APCI-MS and sensory TI curves are smoothed by low-pass filtering. Principal component analysis of the individual curves is used to display graphically the product differentiation by APCI-MS or TI signals. It is shown that differences in gum composition can be measured by both instrumental and sensory techniques, providing comparable information. The peppermint oil level (0.5-2% w/w) in the gum influenced both the retronasal concentration and the perceived peppermint flavor. The sweeteners' (sorbitol or xylitol) effect is less apparent. Sensory adaptation and sensitivity differences of human perception versus APCI-MS detection might explain the divergence between the two dynamic measurement methods.

Long-term culture and cryopreservation does not affect the stability and functionality of human embryonic stem cell-derived hepatocyte-like cells.

PubMed

Mandal, Arundhati; Raju, Sheena; Viswanathan, Chandra

2016-02-01

Human embryonic stem cells (hESCs) are predicted to be an unlimited source of hepatocytes which can pave the way for applications such as cell replacement therapies or as a model of human development or even to predict the hepatotoxicity of drug compounds. We have optimized a 23-d differentiation protocol to generate hepatocyte-like cells (HLCs) from hESCs, obtaining a relatively pure population which expresses the major hepatic markers and is functional and mature. The stability of the HLCs in terms of hepato-specific marker expression and functionality was found to be intact even after an extended period of in vitro culture and cryopreservation. The hESC-derived HLCs have shown the capability to display sensitivity and an alteration in the level of CYP enzyme upon drug induction. This illustrates the potential of such assays in predicting the hepatotoxicity of a drug compound leading to advancement of pharmacology.

Thymocyte Maturation Is Regulated by the Activity of the Helix-Loop-Helix Protein, E47

PubMed Central

Bain, Gretchen; Quong, Melanie W.; Soloff, Rachel S.; Hedrick, Stephen M.; Murre, Cornelis

1999-01-01

The E2A proteins, E12 and E47, are required for progression through multiple developmental pathways, including early B and T lymphopoiesis. Here, we provide in vitro and in vivo evidence demonstrating that E47 activity regulates double-positive thymocyte maturation. In the absence of E47 activity, positive selection of both major histocompatibility complex (MHC) class I– and class II–restricted T cell receptors (TCRs) is perturbed. Additionally, development of CD8 lineage T cells in an MHC class I–restricted TCR transgenic background is sensitive to the dosage of E47. Mice deficient for E47 display an increase in production of mature CD4 and CD8 lineage T cells. Furthermore, ectopic expression of an E2A inhibitor helix-loop-helix protein, Id3, promotes the in vitro differentiation of an immature T cell line. These results demonstrate that E2A functions as a regulator of thymocyte positive selection. PMID:10587351

Shape, color, and the other-race effect in the infant brain

PubMed Central

Balas, Benjamin; Westerlund, Alissa; Hung, Katherine; Nelson, Charles A.

2015-01-01

The “other-race” effect describes the phenomenon in which faces are difficult to distinguish from one another if they belong to an ethnic or racial group to which the observer has had little exposure. Adult observers typically display multiple forms of recognition error for other-race faces, and infants exhibit behavioral evidence of a developing other-race effect at about 9 months of age. The neural correlates of the adult other-race effect have been identified using ERPs and fMRI, but the effects of racial category on infants’ neural response to face stimuli have to date not been described. We examine two distinct components of the infant ERP response to human faces and demonstrate through the use of computer-generated “hybrid” faces that the observed other-race effect is not the result of low-level sensitivity to 3D shape and color differences between the stimuli. Rather, differential processing depends critically on the joint encoding of race-specific features. PMID:21676108

Clinical diagnostic of pleural effusions using a high-speed viscosity measurement method

NASA Astrophysics Data System (ADS)

Hurth, Cedric; Klein, Katherine; van Nimwegen, Lena; Korn, Ronald; Vijayaraghavan, Krishnaswami; Zenhausern, Frederic

2011-08-01

We present a novel bio-analytical method to discriminate between transudative and exudative pleural effusions based on a high-speed video analysis of a solid glass sphere impacting a liquid. Since the result depends on the solution viscosity, it can ultimately replace the battery of biochemical assays currently used. We present results obtained on a series of 7 pleural effusions obtained from consenting patients by analyzing both the splash observed after the glass impactor hits the liquid surface, and in a configuration reminiscent of the drop ball viscometer with added sensitivity and throughput provided by the high-speed camera. The results demonstrate distinction between the pleural effusions and good correlation with the fluid chemistry analysis to accurately differentiate exudates and transudates for clinical purpose. The exudative effusions display a viscosity around 1.39 ± 0.08 cP whereas the transudative effusion was measured at 0.89 ± 0.09 cP, in good agreement with previous reports.

The selective PI3Kα inhibitor BYL719 as a novel therapeutic option for neuroendocrine tumors: Results from multiple cell line models

PubMed Central

Rentsch, Jakob; Freitag, Helma; Detjen, Katharina; Briest, Franziska; Möbs, Markus; Weissmann, Victoria; Siegmund, Britta; Auernhammer, Christoph J.; Aristizabal Prada, Elke Tatjana; Lauseker, Michael; Grossman, Ashley; Exner, Samantha; Fischer, Christian; Grötzinger, Carsten

2017-01-01

Background/Aims The therapeutic options for metastatic neuroendocrine tumors (NETs) are limited. As PI3K signaling is often activated in NETs, we have assessed the effects of selective PI3Kp110α inhibition by the novel agent BYL719 on cell viability, colony formation, apoptosis, cell cycle, signaling pathways, differentiation and secretion in pancreatic (BON-1, QGP-1) and pulmonary (H727) NET cell lines. Methods Cell viability was investigated by WST-1 assay, colony formation by clonogenic assay, apoptosis by caspase3/7 assay, the cell cycle by FACS, cell signaling by Western blot analysis, expression of chromogranin A and somatostatin receptors 1/2/5 by RT-qPCR, and chromogranin A secretion by ELISA. Results BYL719 dose-dependently decreased cell viability and colony formation with the highest sensitivity in BON-1, followed by H727, and lowest sensitivity in QGP-1 cells. BYL719 induced apoptosis and G0/G1 cell cycle arrest associated with increased p27 expression. Western blots showed inhibition of PI3K downstream targets to a varying degree in the different cell lines, but IGF1R activation. The most sensitive BON-1 cells displayed a significant, and H727 cells a non-significant, GSK3 inhibition after BYL719 treatment, but these effects do not appear to be mediated through the IGF1R. In contrast, the most resistant QGP-1 cells showed no GSK3 inhibition, but a modest activation, which would partially counteract the other anti-proliferative effects. Accordingly, BYL719 enhanced neuroendocrine differentiation with the strongest effect in BON-1, followed by H727 cells indicated by induction of chromogranin A and somatostatin receptor 1/2 mRNA-synthesis, but not in QGP-1 cells. In BON-1 and QGP-1 cells, the BYL719/everolimus combination was synergistic through simultaneous AKT/mTORC1 inhibition, and significantly increased somatostatin receptor 2 transcription compared to each drug separately. Conclusion Our results suggest that the agent BYL719 could be a novel therapeutic approach to the treatment of NETs that may sensitize NET cells to somatostatin analogs, and that if there is resistance to its action this may be overcome by combination with everolimus. PMID:28800359

The selective PI3Kα inhibitor BYL719 as a novel therapeutic option for neuroendocrine tumors: Results from multiple cell line models.

PubMed

Nölting, Svenja; Rentsch, Jakob; Freitag, Helma; Detjen, Katharina; Briest, Franziska; Möbs, Markus; Weissmann, Victoria; Siegmund, Britta; Auernhammer, Christoph J; Aristizabal Prada, Elke Tatjana; Lauseker, Michael; Grossman, Ashley; Exner, Samantha; Fischer, Christian; Grötzinger, Carsten; Schrader, Jörg; Grabowski, Patricia

2017-01-01

The therapeutic options for metastatic neuroendocrine tumors (NETs) are limited. As PI3K signaling is often activated in NETs, we have assessed the effects of selective PI3Kp110α inhibition by the novel agent BYL719 on cell viability, colony formation, apoptosis, cell cycle, signaling pathways, differentiation and secretion in pancreatic (BON-1, QGP-1) and pulmonary (H727) NET cell lines. Cell viability was investigated by WST-1 assay, colony formation by clonogenic assay, apoptosis by caspase3/7 assay, the cell cycle by FACS, cell signaling by Western blot analysis, expression of chromogranin A and somatostatin receptors 1/2/5 by RT-qPCR, and chromogranin A secretion by ELISA. BYL719 dose-dependently decreased cell viability and colony formation with the highest sensitivity in BON-1, followed by H727, and lowest sensitivity in QGP-1 cells. BYL719 induced apoptosis and G0/G1 cell cycle arrest associated with increased p27 expression. Western blots showed inhibition of PI3K downstream targets to a varying degree in the different cell lines, but IGF1R activation. The most sensitive BON-1 cells displayed a significant, and H727 cells a non-significant, GSK3 inhibition after BYL719 treatment, but these effects do not appear to be mediated through the IGF1R. In contrast, the most resistant QGP-1 cells showed no GSK3 inhibition, but a modest activation, which would partially counteract the other anti-proliferative effects. Accordingly, BYL719 enhanced neuroendocrine differentiation with the strongest effect in BON-1, followed by H727 cells indicated by induction of chromogranin A and somatostatin receptor 1/2 mRNA-synthesis, but not in QGP-1 cells. In BON-1 and QGP-1 cells, the BYL719/everolimus combination was synergistic through simultaneous AKT/mTORC1 inhibition, and significantly increased somatostatin receptor 2 transcription compared to each drug separately. Our results suggest that the agent BYL719 could be a novel therapeutic approach to the treatment of NETs that may sensitize NET cells to somatostatin analogs, and that if there is resistance to its action this may be overcome by combination with everolimus.

Evidence that the Dictyostelium Dd-STATa protein is a repressor that regulates commitment to stalk cell differentiation and is also required for efficient chemotaxis.

PubMed

Mohanty, S; Jermyn, K A; Early, A; Kawata, T; Aubry, L; Ceccarelli, A; Schaap, P; Williams, J G; Firtel, R A

1999-08-01

Dd-STATa is a structural and functional homologue of the metazoan STAT (Signal Transducer and Activator of Transcription) proteins. We show that Dd-STATa null cells exhibit several distinct developmental phenotypes. The aggregation of Dd-STATa null cells is delayed and they chemotax slowly to a cyclic AMP source, suggesting a role for Dd-STATa in these early processes. In Dd-STATa null strains, slug-like structures are formed but they have an aberrant pattern of gene expression. In such slugs, ecmB/lacZ, a marker that is normally specific for cells on the stalk cell differentiation pathway, is expressed throughout the prestalk region. Stalk cell differentiation in Dictyostelium has been proposed to be under negative control, mediated by repressor elements present in the promoters of stalk cell-specific genes. Dd-STATa binds these repressor elements in vitro and the ectopic expression of ecmB/lacZ in the null strain provides in vivo evidence that Dd-STATa is the repressor protein that regulates commitment to stalk cell differentiation. Dd-STATa null cells display aberrant behavior in a monolayer assay wherein stalk cell differentiation is induced using the stalk cell morphogen DIF. The ecmB gene, a general marker for stalk cell differentiation, is greatly overinduced by DIF in Dd-STATa null cells. Also, Dd-STATa null cells are hypersensitive to DIF for expression of ST/lacZ, a marker for the earliest stages in the differentiation of one of the stalk cell sub-types. We suggest that both these manifestations of DIF hypersensitivity in the null strain result from the balance between activation and repression of the promoter elements being tipped in favor of activation when the repressor is absent. Paradoxically, although Dd-STATa null cells are hypersensitive to the inducing effects of DIF and readily form stalk cells in monolayer assay, the Dd-STATa null cells show little or no terminal stalk cell differentiation within the slug. Dd-STATa null slugs remain developmentally arrested for several days before forming very small spore masses supported by a column of apparently undifferentiated cells. Thus, complete stalk cell differentiation appears to require at least two events: a commitment step, whereby the repression exerted by Dd-STATa is lifted, and a second step that is blocked in a Dd-STATa null organism. This latter step may involve extracellular cAMP, a known repressor of stalk cell differentiation, because Dd-STATa null cells are abnormally sensitive to the inhibitory effects of extracellular cyclic AMP.

A novel helper phage enabling construction of genome-scale ORF-enriched phage display libraries.

PubMed

Gupta, Amita; Shrivastava, Nimisha; Grover, Payal; Singh, Ajay; Mathur, Kapil; Verma, Vaishali; Kaur, Charanpreet; Chaudhary, Vijay K

2013-01-01

Phagemid-based expression of cloned genes fused to the gIIIP coding sequence and rescue using helper phages, such as VCSM13, has been used extensively for constructing large antibody phage display libraries. However, for randomly primed cDNA and gene fragment libraries, this system encounters reading frame problems wherein only one of 18 phages display the translated foreign peptide/protein fused to phagemid-encoded gIIIP. The elimination of phages carrying out-of-frame inserts is vital in order to improve the quality of phage display libraries. In this study, we designed a novel helper phage, AGM13, which carries trypsin-sensitive sites within the linker regions of gIIIP. This renders the phage highly sensitive to trypsin digestion, which abolishes its infectivity. For open reading frame (ORF) selection, the phagemid-borne phages are rescued using AGM13, so that clones with in-frame inserts express fusion proteins with phagemid-encoded trypsin-resistant gIIIP, which becomes incorporated into the phages along with a few copies of AGM13-encoded trypsin-sensitive gIIIP. In contrast, clones with out-of-frame inserts produce phages carrying only AGM13-encoded trypsin-sensitive gIIIP. Trypsin treatment of the phage population renders the phages with out-of-frame inserts non-infectious, whereas phages carrying in-frame inserts remain fully infectious and can hence be enriched by infection. This strategy was applied efficiently at a genome scale to generate an ORF-enriched whole genome fragment library from Mycobacterium tuberculosis, in which nearly 100% of the clones carried in-frame inserts after selection. The ORF-enriched libraries were successfully used for identification of linear and conformational epitopes for monoclonal antibodies specific to mycobacterial proteins.

What is shared, what is different? Core relational themes and expressive displays of eight positive emotions.

PubMed

Campos, Belinda; Shiota, Michelle N; Keltner, Dacher; Gonzaga, Gian C; Goetz, Jennifer L

2013-01-01

Understanding positive emotions' shared and differentiating features can yield valuable insight into the structure of positive emotion space and identify emotion states, or aspects of emotion states, that are most relevant for particular psychological processes and outcomes. We report two studies that examined core relational themes (Study 1) and expressive displays (Study 2) for eight positive emotion constructs--amusement, awe, contentment, gratitude, interest, joy, love, and pride. Across studies, all eight emotions shared one quality: high positive valence. Distinctive core relational theme and expressive display patterns were found for four emotions--amusement, awe, interest, and pride. Gratitude was associated with a distinct core relational theme but not an expressive display. Joy and love were each associated with a distinct expressive display but their core relational themes also characterised pride and gratitude, respectively. Contentment was associated with a distinct expressive display but not a core relational theme. The implications of this work for the study of positive emotion are discussed.

Endothelial glucocorticoid receptor promoter methylation according to dexamethasone sensitivity

PubMed Central

Mata-Greenwood, Eugenia; Jackson, P Naomi; Pearce, William J; Zhang, Lubo

2016-01-01

We have previously shown that in vitro sensitivity to dexamethasone (DEX) stimulation in human endothelial cells is positively regulated by the glucocorticoid receptor (NR3C1, GR). The present study determined the role of differential GR transcriptional regulation in glucocorticoid sensitivity. We studied 25 human umbilical vein endothelial cells (HUVECs) that had been previously characterized as DEX-sensitive (n = 15), or resistant (n = 10). Real-time PCR analysis of GR 5′UTR mRNA isoforms showed that all HUVECs expressed isoforms 1B, 1C, 1D, 1F, and 1H, and isoforms 1B and 1C were predominantly expressed. DEX-resistant cells expressed higher basal levels of the 5′UTR mRNA isoforms 1C and 1D, but lower levels of the 5′UTR mRNA isoform 1F than DEX-sensitive cells. DEX treatment significantly decreased GRα and GR-1C mRNA isoform expression in DEX-resistant cells only. Reporter luciferase assays indicated that differential GR mRNA isoform expression was not due to differential promoter usage between DEX-sensitive and DEX-resistant cells. Analysis of promoter methylation, however, showed that DEX-sensitive cells have higher methylation levels of promoter 1D and lower methylation levels of promoter 1F than DEX-resistant cells. Treatment with 5-aza-2-deoxycytidine abolished the differential 5′UTR mRNA isoform expression between DEX-sensitive and DEX-resistant cells. Finally, both GRα overexpression and 5-aza-2-deoxycytidine treatment eliminated the differences between sensitivity groups to DEX-mediated downregulation of endothelial nitric oxide synthase (NOS3), and upregulation of plasminogen activator inhibitor 1 (SERPINE1). In sum, human endothelial GR 5′UTR mRNA expression is regulated by promoter methylation with DEX-sensitive and DEX-resistant cells having different GR promoter methylation patterns. PMID:26242202

Differentiation of Symbiotic Cells and Endosymbionts in Medicago truncatula Nodulation Are Coupled to Two Transcriptome-Switches

PubMed Central

Maunoury, Nicolas; Redondo-Nieto, Miguel; Bourcy, Marie; Van de Velde, Willem; Alunni, Benoit; Laporte, Philippe; Durand, Patricia; Agier, Nicolas; Marisa, Laetitia; Vaubert, Danièle; Delacroix, Hervé; Duc, Gérard; Ratet, Pascal; Aggerbeck, Lawrence; Kondorosi, Eva; Mergaert, Peter

2010-01-01

The legume plant Medicago truncatula establishes a symbiosis with the nitrogen-fixing bacterium Sinorhizobium meliloti which takes place in root nodules. The formation of nodules employs a complex developmental program involving organogenesis, specific cellular differentiation of the host cells and the endosymbiotic bacteria, called bacteroids, as well as the specific activation of a large number of plant genes. By using a collection of plant and bacterial mutants inducing non-functional, Fix− nodules, we studied the differentiation processes of the symbiotic partners together with the nodule transcriptome, with the aim of unravelling links between cell differentiation and transcriptome activation. Two waves of transcriptional reprogramming involving the repression and the massive induction of hundreds of genes were observed during wild-type nodule formation. The dominant features of this “nodule-specific transcriptome” were the repression of plant defense-related genes, the transient activation of cell cycle and protein synthesis genes at the early stage of nodule development and the activation of the secretory pathway along with a large number of transmembrane and secretory proteins or peptides throughout organogenesis. The fifteen plant and bacterial mutants that were analyzed fell into four major categories. Members of the first category of mutants formed non-functional nodules although they had differentiated nodule cells and bacteroids. This group passed the two transcriptome switch-points similarly to the wild type. The second category, which formed nodules in which the plant cells were differentiated and infected but the bacteroids did not differentiate, passed the first transcriptome switch but not the second one. Nodules in the third category contained infection threads but were devoid of differentiated symbiotic cells and displayed a root-like transcriptome. Nodules in the fourth category were free of bacteria, devoid of differentiated symbiotic cells and also displayed a root-like transcriptome. A correlation thus exists between the differentiation of symbiotic nodule cells and the first wave of nodule specific gene activation and between differentiation of rhizobia to bacteroids and the second transcriptome wave in nodules. The differentiation of symbiotic cells and of bacteroids may therefore constitute signals for the execution of these transcriptome-switches. PMID:20209049

Programming for energy monitoring/display system in multicolor lidar system research

NASA Technical Reports Server (NTRS)

Alvarado, R. C., Jr.; Allen, R. J.

1982-01-01

The Z80 microprocessor based computer program that directs and controls the operation of the six channel energy monitoring/display system that is a part of the NASA Multipurpose Airborne Differential Absorption Lidar (DIAL) system is described. The program is written in the Z80 assembly language and is located on EPROM memories. All source and assembled listings of the main program, five subroutines, and two service routines along with flow charts and memory maps are included. A combinational block diagram shows the interfacing (including port addresses) between the six power sensors, displays, front panel controls, the main general purpose minicomputer, and this dedicated microcomputer system.

Diagnosing and Mapping Pulmonary Emphysema on X-Ray Projection Images: Incremental Value of Grating-Based X-Ray Dark-Field Imaging

PubMed Central

Meinel, Felix G.; Schwab, Felix; Schleede, Simone; Bech, Martin; Herzen, Julia; Achterhold, Klaus; Auweter, Sigrid; Bamberg, Fabian; Yildirim, Ali Ö.; Bohla, Alexander; Eickelberg, Oliver; Loewen, Rod; Gifford, Martin; Ruth, Ronald; Reiser, Maximilian F.; Pfeiffer, Franz; Nikolaou, Konstantin

2013-01-01

Purpose To assess whether grating-based X-ray dark-field imaging can increase the sensitivity of X-ray projection images in the diagnosis of pulmonary emphysema and allow for a more accurate assessment of emphysema distribution. Materials and Methods Lungs from three mice with pulmonary emphysema and three healthy mice were imaged ex vivo using a laser-driven compact synchrotron X-ray source. Median signal intensities of transmission (T), dark-field (V) and a combined parameter (normalized scatter) were compared between emphysema and control group. To determine the diagnostic value of each parameter in differentiating between healthy and emphysematous lung tissue, a receiver-operating-characteristic (ROC) curve analysis was performed both on a per-pixel and a per-individual basis. Parametric maps of emphysema distribution were generated using transmission, dark-field and normalized scatter signal and correlated with histopathology. Results Transmission values relative to water were higher for emphysematous lungs than for control lungs (1.11 vs. 1.06, p<0.001). There was no difference in median dark-field signal intensities between both groups (0.66 vs. 0.66). Median normalized scatter was significantly lower in the emphysematous lungs compared to controls (4.9 vs. 10.8, p<0.001), and was the best parameter for differentiation of healthy vs. emphysematous lung tissue. In a per-pixel analysis, the area under the ROC curve (AUC) for the normalized scatter value was significantly higher than for transmission (0.86 vs. 0.78, p<0.001) and dark-field value (0.86 vs. 0.52, p<0.001) alone. Normalized scatter showed very high sensitivity for a wide range of specificity values (94% sensitivity at 75% specificity). Using the normalized scatter signal to display the regional distribution of emphysema provides color-coded parametric maps, which show the best correlation with histopathology. Conclusion In a murine model, the complementary information provided by X-ray transmission and dark-field images adds incremental diagnostic value in detecting pulmonary emphysema and visualizing its regional distribution as compared to conventional X-ray projections. PMID:23555692

Diagnosing and mapping pulmonary emphysema on X-ray projection images: incremental value of grating-based X-ray dark-field imaging.

PubMed

Meinel, Felix G; Schwab, Felix; Schleede, Simone; Bech, Martin; Herzen, Julia; Achterhold, Klaus; Auweter, Sigrid; Bamberg, Fabian; Yildirim, Ali Ö; Bohla, Alexander; Eickelberg, Oliver; Loewen, Rod; Gifford, Martin; Ruth, Ronald; Reiser, Maximilian F; Pfeiffer, Franz; Nikolaou, Konstantin

2013-01-01

To assess whether grating-based X-ray dark-field imaging can increase the sensitivity of X-ray projection images in the diagnosis of pulmonary emphysema and allow for a more accurate assessment of emphysema distribution. Lungs from three mice with pulmonary emphysema and three healthy mice were imaged ex vivo using a laser-driven compact synchrotron X-ray source. Median signal intensities of transmission (T), dark-field (V) and a combined parameter (normalized scatter) were compared between emphysema and control group. To determine the diagnostic value of each parameter in differentiating between healthy and emphysematous lung tissue, a receiver-operating-characteristic (ROC) curve analysis was performed both on a per-pixel and a per-individual basis. Parametric maps of emphysema distribution were generated using transmission, dark-field and normalized scatter signal and correlated with histopathology. Transmission values relative to water were higher for emphysematous lungs than for control lungs (1.11 vs. 1.06, p<0.001). There was no difference in median dark-field signal intensities between both groups (0.66 vs. 0.66). Median normalized scatter was significantly lower in the emphysematous lungs compared to controls (4.9 vs. 10.8, p<0.001), and was the best parameter for differentiation of healthy vs. emphysematous lung tissue. In a per-pixel analysis, the area under the ROC curve (AUC) for the normalized scatter value was significantly higher than for transmission (0.86 vs. 0.78, p<0.001) and dark-field value (0.86 vs. 0.52, p<0.001) alone. Normalized scatter showed very high sensitivity for a wide range of specificity values (94% sensitivity at 75% specificity). Using the normalized scatter signal to display the regional distribution of emphysema provides color-coded parametric maps, which show the best correlation with histopathology. In a murine model, the complementary information provided by X-ray transmission and dark-field images adds incremental diagnostic value in detecting pulmonary emphysema and visualizing its regional distribution as compared to conventional X-ray projections.

Simulator study of conventional general aviation instrument displays in path-following tasks with emphasis on pilot-induced oscillations

NASA Technical Reports Server (NTRS)

Adams, J. J.

1980-01-01

A study of the use of conventional general aviation instruments by general aviation pilots in a six degree of freedom, fixed base simulator was conducted. The tasks performed were tracking a VOR radial and making an ILS approach to landing. A special feature of the tests was that the sensitivity of the displacement indicating instruments (the RMI, CDI, and HSI) was kept constant at values corresponding to 5 n. mi. and 1.25 n. mi. from the station. Both statistical and pilot model analyses of the data were made. The results show that performance in path following improved with increases in display sensitivity up to the highest sensitivity tested. At this maximum test sensitivity, which corresponds to the sensitivity existing at 1.25 n. mi. for the ILS glide slope transmitter, tracking accuracy was no better than it was at 5 n. mi. from the station and the pilot aircraft system exhibited a marked reduction in damping. In some cases, a pilot induced, long period unstable oscillation occurred.

System for the diagnosis and monitoring of coronary artery disease, acute coronary syndromes, cardiomyopathy and other cardiac conditions

NASA Technical Reports Server (NTRS)

Schlegel, Todd T. (Inventor); Arenare, Brian (Inventor)

2008-01-01

Cardiac electrical data are received from a patient, manipulated to determine various useful aspects of the ECG signal, and displayed and stored in a useful form using a computer. The computer monitor displays various useful information, and in particular graphically displays various permutations of reduced amplitude zones and kurtosis that increase the rapidity and accuracy of cardiac diagnoses. New criteria for reduced amplitude zones are defined that enhance the sensitivity and specificity for detecting cardiac abnormalities.

Tribbles 3 inhibits brown adipocyte differentiation and function by suppressing insulin signaling

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

Jeong, Ha-Won; Choi, Ran Hee; McClellan, Jamie L.

Recent studies have demonstrated that adult humans have substantial amounts of functioning brown adipose tissue (BAT). Since BAT has been implicated as an anti-obese and anti-diabetic tissue, it is important to understand the signaling molecules that regulate BAT function. There has been a link between insulin signaling and BAT metabolism as deletion or pharmaceutical inhibition of insulin signaling impairs BAT differentiation and function. Tribbles 3 (TRB3) is a pseudo kinase that has been shown to regulate metabolism and insulin signaling in multiple tissues but the role of TRB3 in BAT has not been studied. In this study, we found thatmore » TRB3 expression was present in BAT and overexpression of TRB3 in brown preadipocytes impaired differentiation and decreased expression of BAT markers. Furthermore, TRB3 overexpression resulted in significantly lower oxygen consumption rates for basal and proton leakage, indicating decreased BAT activity. Based on previous studies showing that deletion or pharmaceutical inhibition of insulin signaling impairs BAT differentiation and function, we assessed insulin signaling in brown preadipocytes and BAT in vivo. Overexpression of TRB3 in cells impaired insulin-stimulated IRS1 and Akt phosphorylation, whereas TRB3KO mice displayed improved IRS1 and Akt phosphorylation. Finally, deletion of IRS1 abolished the function of TRB3 to regulate BAT differentiation and metabolism. These data demonstrate that TRB3 inhibits insulin signaling in BAT, resulting in impaired differentiation and function. - Highlights: • TRB3 is expressed in brown adipose tissue and its expression is increased during differentiation. • Overexpression of TRB3 inhibits differentiation and its activity. • Overexpression of TRB3 in brown preadipocytes inhibits insulin signaling. • TRB3KO mice displays improved insulin signaling in brown adipose tissue. • Insulin signaling is required for the effects of TRB3 to regulate brown adipose tissue differentiation and activity.« less

VINCLOZOLIN (V) TREATMENT INDUCES REPRODUCTIVE MALFORMATIONS AND INFERTILITY IN F1 MALE RATS WHEN ADMINISTERED DURING SEXUAL BUT NOT GONADAL DIFFERENTIATION. THE EFFECTS ARE NOT TRANSMITTED TO THE SUBSEQUENT GENERATIONS.

EPA Science Inventory

V produces adverse reproductive effects in male rats when administered during sexual differentiation by acting as an androgen-antagonist. It was recently reported that four generations of SD rats, derived from dams dosed via ip injection GD8-15 with 100 mg V/kg/day, displayed pro...

Identification of Powdery Mildew Responsive Genes in Hevea brasiliensis through mRNA Differential Display

PubMed Central

Li, Xiang; Bi, Zhenghong; Di, Rong; Liang, Peng; He, Qiguang; Liu, Wenbo; Miao, Weiguo; Zheng, Fucong

2016-01-01

Powdery mildew is an important disease of rubber trees caused by Oidium heveae B. A. Steinmann. As far as we know, none of the resistance genes related to powdery mildew have been isolated from the rubber tree. There is little information available at the molecular level regarding how a rubber tree develops defense mechanisms against this pathogen. We have studied rubber tree mRNA transcripts from the resistant RRIC52 cultivar by differential display analysis. Leaves inoculated with the spores of O. heveae were collected from 0 to 120 hpi in order to identify pathogen-regulated genes at different infection stages. We identified 78 rubber tree genes that were differentially expressed during the plant–pathogen interaction. BLAST analysis for these 78 ESTs classified them into seven functional groups: cell wall and membrane pathways, transcription factor and regulatory proteins, transporters, signal transduction, phytoalexin biosynthesis, other metabolism functions, and unknown functions. The gene expression for eight of these genes was validated by qRT-PCR in both RRIC52 and the partially susceptible Reyan 7-33-97 cultivars, revealing the similar or differential changes of gene expressions between these two cultivars. This study has improved our overall understanding of the molecular mechanisms of rubber tree resistance to powdery mildew. PMID:26840302

Resolving quandaries: basaloid adenoid cystic carcinoma or breast cylindroma? The role of massively parallel sequencing.

PubMed

Fusco, Nicola; Colombo, Pierre-Emmanuel; Martelotto, Luciano G; De Filippo, Maria R; Piscuoglio, Salvatore; Ng, Charlotte K Y; Lim, Raymond S; Jacot, William; Vincent-Salomon, Anne; Reis-Filho, Jorge S; Weigelt, Britta

2016-01-01

The aims of this study were to perform a whole-exome sequencing analysis of a breast cylindroma and to investigate the role of molecular analyses in the differentiation between breast cylindroma, a benign tumour that displays MYB expression, and CYLD gene mutations, and its main differential diagnosis, the breast solid-basaloid adenoid cystic carcinoma, a malignant tumour that is characterized by the presence of the MYB-NFIB fusion gene and MYB overexpression. A 66-year-old female underwent quadrantectomy after an irregular dense shadow was discovered in the right breast at the screening mammogram. Histologically, the tumour displayed features suggestive of a solid-basaloid variant of adenoid cystic carcinoma with a differential diagnosis of cylindroma. Fluorescence in situ hybridization, reverse transcription-polymerase chain reaction, immunohistochemistry and whole-exome sequencing revealed absence of the MYB-NFIB fusion gene, low levels of MYB protein expression and a clonal somatic CYLD splice site mutation associated with loss of heterozygosity of the wild-type allele. The results of the histological, immunohistochemical and molecular analyses were consistent with a diagnosis of breast cylindroma, providing a proof-of-principle that the integration of histopathological and molecular approaches can help to differentiate between a low-malignant potential and a benign breast tumour of triple-negative phenotype. © 2015 John Wiley & Sons Ltd.

Ecotypic differentiation and phenotypic plasticity combine to enhance the invasiveness of the most widespread daisy in Chile, Leontodon saxatilis.

PubMed

Martín-Forés, Irene; Avilés, Marta; Acosta-Gallo, Belén; Breed, Martin F; Del Pozo, Alejandro; de Miguel, José M; Sánchez-Jardón, Laura; Castro, Isabel; Ovalle, Carlos; Casado, Miguel A

2017-05-08

Dispersal and reproductive traits of successful plant invaders are expected to undergo strong selection during biological invasions. Numerous Asteraceae are invasive and display dimorphic fruits within a single flower head, resulting in differential dispersal pathways - wind-dispersed fruits vs. non-dispersing fruits. We explored ecotypic differentiation and phenotypic plasticity of seed output and fruit dimorphisms in exotic Chilean and native Spanish populations of Leontodon saxatilis subsp. rothii. We collected flower heads from populations in Spain and Chile along a rainfall gradient. Seeds from all populations were planted in reciprocal transplant trials in Spain and Chile to explore their performance in the native and invasive range. We scored plant biomass, reproductive investment and fruit dimorphism. We observed strong plasticity, where plants grown in the invasive range had much greater biomass, flower head size and seed output, with a higher proportion of wind-dispersed fruits, than those grown in the native range. We also observed a significant ecotype effect, where the exotic populations displayed higher proportions of wind-dispersed fruits than native populations. Together, these patterns reflect a combination of phenotypic plasticity and ecotypic differentiation, indicating that Leontodon saxatilis has probably increased propagule pressure and dispersal distances in its invasive range to enhance its invasiveness.

Evaluating linguistic equivalence of patient-reported outcomes in a cancer clinical trial.

PubMed

Hahn, Elizabeth A; Bode, Rita K; Du, Hongyan; Cella, David

2006-01-01

In order to make meaningful cross-cultural or cross-linguistic comparisons of health-related quality of life (HRQL) or to pool international research data, it is essential to create unbiased measures that can detect clinically important differences. When HRQL scores differ between cultural/linguistic groups, it is important to determine whether this reflects real group differences, or is the result of systematic measurement variability. To investigate the linguistic measurement equivalence of a cancer-specific HRQL questionnaire, and to conduct a sensitivity analysis of treatment differences in HRQL in a clinical trial. Patients with newly diagnosed chronic myelogenous leukemia (n = 1049) completed serial HRQL assessments in an international Phase III trial. Two types of differential item functioning (uniform and non-uniform) were evaluated using item response theory and classical test theory approaches. A sensitivity analysis was conducted to compare HRQL between treatment arms using items without evidence of differential functioning. Among 27 items, nine (33%) did not exhibit any evidence of differential functioning in both linguistic comparisons (English versus French, English versus German). Although 18 items functioned differently, there was no evidence of systematic bias. In a sensitivity analysis, adjustment for differential functioning affected the magnitude, but not the direction or interpretation of clinical trial treatment arm differences. Sufficient sample sizes were available for only three of the eight language groups. Identification of differential functioning in two-thirds of the items suggests that current psychometric methods may be too sensitive. Enhanced methodologies are needed to differentiate trivial from substantive differential item functioning. Systematic variability in HRQL across different groups can be evaluated for its effect upon clinical trial results; a practice recommended when data are pooled across cultural or linguistic groups to make conclusions about treatment effects.

Ratiometric near infrared luminescent thermometer based on lanthanide metal-organic frameworks

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

Yue, Dan; Zhang, Jun; Zhao, Dian

2016-09-15

A near infrared luminescent MOFs thermometer (Nd{sub 0.676}Yb{sub 0.324}BTC) was prepared via a simple solvothermal method using Ln{sup 3+} (Ln=Nd, Yb) ions and 1, 3, 5-benznenetricarboxylic acid (H{sub 3}BTC), and characterized by PXRD, TGA, ICP, and photoluminescence (PL) spectrum. These results indicate that the Nd{sub 0.676}Yb{sub 0.324}BTC displays high relative sensitivity and excellent repeatability in the physiological temperature range (288–323 K), and the maximum relative sensitivity is determined to be 1.187% K{sup −1} at 323 K. These NIR luminescent MOFs may have potential applications in physiological temperature sensing. - Graphical abstract: A near infrared luminescent MOFs thermometer (Nd{sub 0.054}Yb{sub 0.946}BTCmore » ) displays high relative sensitivity and excellent repeatability in the physiological temperature range (288–323 K). Display Omitted - Highlights: • A ratiometric near infrared luminescent MOFs thermometer (Nd{sub 0.676}Yb{sub 0.324}BTC) was prepared via a simple solvothermal method. • The maximum relative sensitivity of Nd{sub 0.676}Yb{sub 0.324}BTC is determined to be 1.187% K{sup −1} at 323 K. • Nd{sub 0.676}Yb{sub 0.324}BTC showed excellent repeatability in the physiological temperature range (288–323 K).« less

Computer Corner: Computer Graphics for the Vibrating String.

ERIC Educational Resources Information Center

Smith, David A.; Cunningham, R. Stephen

1986-01-01

Computer graphics are used to display the sum of the first few terms of the series solution for the problem of the vibrating string frequently discussed in introductory courses on differential equations. (MNS)

Differential item functioning by sex and race in the Hogan Personality Inventory.

PubMed

Sheppard, Richard; Han, Kyunghee; Colarelli, Stephen M; Dai, Guangdong; King, Daniel W

2006-12-01

The authors examined measurement bias in the Hogan Personality Inventory by investigating differential item functioning (DIF) across sex and two racial groups (Caucasian and Black). The sample consisted of 1,579 Caucasians (1,023 men, 556 women) and 523 Blacks (321 men, 202 women) who were applying for entry-level, unskilled jobs in factories. Although the group mean differences were trivial, more than a third of the items showed DIF by sex (38.4%) and by race (37.3%). A content analysis of potentially biased items indicated that the themes of items displaying DIF were slightly more cohesive for sex than for race. The authors discuss possible explanations for differing clustering tendencies of items displaying DIF and some practical and theoretical implications of DIF in the development and interpretation of personality inventories.

p53 and TAp63 Promote Keratinocyte Proliferation and Differentiation in Breeding Tubercles of the Zebrafish

PubMed Central

Fischer, Boris; Metzger, Manuel; Richardson, Rebecca; Knyphausen, Philipp; Ramezani, Thomas; Franzen, Rainer; Schmelzer, Elmon; Bloch, Wilhelm; Carney, Thomas J.; Hammerschmidt, Matthias

2014-01-01

p63 is a multi-isoform member of the p53 family of transcription factors. There is compelling genetic evidence that ΔNp63 isoforms are needed for keratinocyte proliferation and stemness in the developing vertebrate epidermis. However, the role of TAp63 isoforms is not fully understood, and TAp63 knockout mice display normal epidermal development. Here, we show that zebrafish mutants specifically lacking TAp63 isoforms, or p53, display compromised development of breeding tubercles, epidermal appendages which according to our analyses display more advanced stratification and keratinization than regular epidermis, including continuous desquamation and renewal of superficial cells by derivatives of basal keratinocytes. Defects are further enhanced in TAp63/p53 double mutants, pointing to partially redundant roles of the two related factors. Molecular analyses, treatments with chemical inhibitors and epistasis studies further reveal the existence of a linear TAp63/p53->Notch->caspase 3 pathway required both for enhanced proliferation of keratinocytes at the base of the tubercles and their subsequent differentiation in upper layers. Together, these studies identify the zebrafish breeding tubercles as specific epidermal structures sharing crucial features with the cornified mammalian epidermis. In addition, they unravel essential roles of TAp63 and p53 to promote both keratinocyte proliferation and their terminal differentiation by promoting Notch signalling and caspase 3 activity, ensuring formation and proper homeostasis of this self-renewing stratified epithelium. PMID:24415949

Differences in brain gene expression between sleep and waking as revealed by mRNA differential display and cDNA microarray technology.

PubMed

Cirelli, C; Tononi, G

1999-06-01

The consequences of sleep and sleep deprivation at the molecular level are largely unexplored. Knowledge of such molecular events is essential to understand the restorative processes occurring during sleep as well as the cellular mechanisms of sleep regulation. Here we review the available data about changes in neural gene expression across different behavioural states using candidate gene approaches such as in situ hybridization and immunocytochemistry. We then describe new techniques for systematic screening of gene expression in the brain, such as subtractive hybridization, mRNA differential display, and cDNA microarray technology, outlining advantages and disadvantages of these methods. Finally, we summarize our initial results of a systematic screening of gene expression in the rat brain across behavioural states using mRNA differential display and cDNA microarray technology. The expression pattern of approximately 7000 genes was analysed in the cerebral cortex of rats after 3 h of spontaneous sleep, 3 h of spontaneous waking, or 3 h of sleep deprivation. While the majority of transcripts were expressed at the same level among these three conditions, 14 mRNAs were modulated by sleep and waking. Six transcripts, four more expressed in waking and two more expressed in sleep, corresponded to novel genes. The eight known transcripts were all expressed at higher levels in waking than in sleep and included transcription factors and mitochondrial genes. A possible role for these known transcripts in mediating neural plasticity during waking is discussed.

Understanding the exposure-time effect on speckle contrast measurements for laser displays

NASA Astrophysics Data System (ADS)

Suzuki, Koji; Kubota, Shigeo

2018-02-01

To evaluate the influence of exposure time on speckle noise for laser displays, speckle contrast measurement method was developed observable at a human eye response time using a high-sensitivity camera which has a signal multiplying function. The nonlinearity of camera light sensitivity was calibrated to measure accurate speckle contrasts, and the measuring lower limit noise of speckle contrast was improved by applying spatial-frequency low pass filter to the captured images. Three commercially available laser displays were measured over a wide range of exposure times from tens of milliseconds to several seconds without adjusting the brightness of laser displays. The speckle contrast of raster-scanned mobile projector without any speckle-reduction device was nearly constant over various exposure times. On the contrary to this, in full-frame projection type laser displays equipped with a temporally-averaging speckle-reduction device, some of their speckle contrasts close to the lower limits noise were slightly increased at the shorter exposure time due to the noise. As a result, the exposure-time effect of speckle contrast could not be observed in our measurements, although it is more reasonable to think that the speckle contrasts of laser displays, which are equipped with the temporally-averaging speckle-reduction device, are dependent on the exposure time. This discrepancy may be attributed to the underestimation of temporal averaging factor. We expected that this method is useful for evaluating various laser displays and clarify the relationship between the speckle noise and the exposure time for a further verification of speckle reduction.

Effect of varying displays and room illuminance on caries diagnostic accuracy in digital dental radiographs.

PubMed

Pakkala, T; Kuusela, L; Ekholm, M; Wenzel, A; Haiter-Neto, F; Kortesniemi, M

2012-01-01

In clinical practice, digital radiographs taken for caries diagnostics are viewed on varying types of displays and usually in relatively high ambient lighting (room illuminance) conditions. Our purpose was to assess the effect of room illuminance and varying display types on caries diagnostic accuracy in digital dental radiographs. Previous studies have shown that the diagnostic accuracy of caries detection is significantly better in reduced lighting conditions. Our hypothesis was that higher display luminance could compensate for this in higher ambient lighting conditions. Extracted human teeth with approximal surfaces clinically ranging from sound to demineralized were radiographed and evaluated by 3 observers who detected carious lesions on 3 different types of displays in 3 different room illuminance settings ranging from low illumination, i.e. what is recommended for diagnostic viewing, to higher illumination levels corresponding to those found in an average dental office. Sectioning and microscopy of the teeth validated the presence or absence of a carious lesion. Sensitivity, specificity and accuracy were calculated for each modality and observer. Differences were estimated by analyzing the binary data assuming the added effects of observer and modality in a generalized linear model. The observers obtained higher sensitivities in lower illuminance settings than in higher illuminance settings. However, this was related to a reduction in specificity, which meant that there was no significant difference in overall accuracy. Contrary to our hypothesis, there were no significant differences between the accuracy of different display types. Therefore, different displays and room illuminance levels did not affect the overall accuracy of radiographic caries detection. Copyright © 2012 S. Karger AG, Basel.

Pathogenicity and phenotypic sulfadiazine resistance ofToxoplasma gondii isolates obtained from livestock in northeastern Brazil

PubMed Central

Oliveira, Claudio BS; Meurer, Ywlliane SR; Andrade, Joelma MA; Costa, Maria ESM; Andrade, Milena MC; Silva, Letícia A; Lanza, Daniel CF; Vítor, Ricardo WA; Andrade-Neto, Valter F

2016-01-01

Toxoplasma gondii is the causative protozoan agent of toxoplasmosis, which is a common infection that is widely distributed worldwide. Studies revealed stronger clonal strains in North America and Europe and genetic diversity in South American strains. Our study aimed to differentiate the pathogenicity and sulfadiazine resistance of three T. gondiiisolates obtained from livestock intended for human consumption. The cytopathic effects of the T. gondii isolates were evaluated. The pathogenicity was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) using a CS3 marker and in a rodent model in vivo. Phenotypic sulfadiazine resistance was measured using a kinetic curve of drug activity in Swiss mice. IgM and IgG were measured by ELISA, and the dihydropteroate synthase (DHPS) gene sequence was analysed. The cytopathic effects and the PCR-RFLP profiles from chickens indicated a different infection source. The Ck3 isolate displayed more cytopathic effects in vitro than the Ck2 and ME49 strains. Additionally, the Ck2 isolate induced a differential humoral immune response compared to ME49. The Ck3 and Pg1 isolates, but not the Ck2 isolate, showed sulfadiazine resistance in the sensitivity assay. We did not find any DHPS gene polymorphisms in the mouse samples. These atypical pathogenicity and sulfadiazine resistance profiles were not previously reported and served as a warning to local health authorities. PMID:27276184

Pathogenicity and phenotypic sulfadiazine resistance of Toxoplasma gondii isolates obtained from livestock in northeastern Brazil.

PubMed

Oliveira, Claudio Bs; Meurer, Ywlliane Sr; Andrade, Joelma Ma; Costa, Maria Esm; Andrade, Milena Mc; Silva, Letícia A; Lanza, Daniel Cf; Vítor, Ricardo Wa; Andrade-Neto, Valter F

2016-06-03

Toxoplasma gondii is the causative protozoan agent of toxoplasmosis, which is a common infection that is widely distributed worldwide. Studies revealed stronger clonal strains in North America and Europe and genetic diversity in South American strains. Our study aimed to differentiate the pathogenicity and sulfadiazine resistance of three T. gondii isolates obtained from livestock intended for human consumption. The cytopathic effects of the T. gondii isolates were evaluated. The pathogenicity was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) using a CS3 marker and in a rodent model in vivo. Phenotypic sulfadiazine resistance was measured using a kinetic curve of drug activity in Swiss mice. IgM and IgG were measured by ELISA, and the dihydropteroate synthase (DHPS) gene sequence was analysed. The cytopathic effects and the PCR-RFLP profiles from chickens indicated a different infection source. The Ck3 isolate displayed more cytopathic effects in vitro than the Ck2 and ME49 strains. Additionally, the Ck2 isolate induced a differential humoral immune response compared to ME49. The Ck3 and Pg1 isolates, but not the Ck2 isolate, showed sulfadiazine resistance in the sensitivity assay. We did not find any DHPS gene polymorphisms in the mouse samples. These atypical pathogenicity and sulfadiazine resistance profiles were not previously reported and served as a warning to local health authorities.

Piper and Vismia species from Colombian Amazonia differentially affect cell proliferation of hepatocarcinoma cells.

PubMed

Lizcano, Leandro J; Siles, Maite; Trepiana, Jenifer; Hernández, M Luisa; Navarro, Rosaura; Ruiz-Larrea, M Begoña; Ruiz-Sanz, José Ignacio

2014-12-30

There is an increasing interest to identify plant-derived natural products with antitumor activities. In this work, we have studied the effects of aqueous leaf extracts from Amazonian Vismia and Piper species on human hepatocarcinoma cell toxicity. Results showed that, depending on the cell type, the plants displayed differential effects; thus, Vismia baccifera induced the selective killing of HepG2, while increasing cell growth of PLC-PRF and SK-HEP-1. In contrast, these two last cell lines were sensitive to the toxicity by Piper krukoffii and Piper putumayoense, while the Piperaceae did not affect HepG2 growth. All the extracts induced cytotoxicity to rat hepatoma McA-RH7777, but were innocuous (V. baccifera at concentrations < 75 µg/mL) or even protected cells from basal death (P. putumayoense) in primary cultures of rat hepatocytes. In every case, cytotoxicity was accompanied by an intracellular accumulation of reactive oxygen species (ROS). These results provide evidence for the anticancer activities of the studied plants on specific cell lines and suggest that cell killing could be mediated by ROS, thus involving mechanisms independent of the plants free radical scavenging activities. Results also support the use of these extracts of the Vismia and Piper genera with opposite effects as a model system to study the mechanisms of the antitumoral activity against different types of hepatocarcinoma.

The difficulties of pseudo-Cushing's syndrome (or "non-neoplastic hypercortisolism").

PubMed

Chabre, Olivier

2018-06-01

Pseudo-Cushing's syndrome covers different pathological conditions responsible for mild-to-moderate ACTH-dependent hypercortisolism, related not to an ACTH-secreting tumor but rather to CRH and/or AVP hypothalamic secretion through activation of various neural pathways, in patients generally displaying excess central adiposity. It is better termed "non-neoplastic hypercortisolism" (NNH). The main conditions implicated in NNH comprise: neuropsychiatric disorder, alcohol abuse, insulin-resistant obesity, polycystic ovary syndrome, and end-stage kidney disease. Glucocorticoid resistance is one differential diagnosis, as are some cases of primary adrenal disease with incompletely suppressed ACTH. Differentiating between NNH and mild-to-moderate Cushing's disease can be a real challenge. Clinical analysis, based on thorough history taking and screening for catabolic signs is essential; useful explorations include midnight serum or salivary cortisol and Dex/CRH and ddAVP stimulation response. Pituitary MRI suffers from limitations regarding both sensitivity and specificity, while bilateral inferior petrosal sinus sampling cannot distinguish between pituitary ACTH secretion by a tumor or by normal cells stimulated by endogenous CRH. Definitive diagnosis of functional etiology requires demonstrating that treatment of the underlying condition restores normal secretion of ACTH and cortisol, but this is not always possible. Lingering diagnostic uncertainty has to be accepted in certain patients, who will have to be followed up for some time before diagnosis can be considered more or less definitive. Copyright © 2018. Published by Elsevier Masson SAS.

Therapeutic effects of CSF1R-blocking antibodies in multiple myeloma.

PubMed

Wang, Q; Lu, Y; Li, R; Jiang, Y; Zheng, Y; Qian, J; Bi, E; Zheng, C; Hou, J; Wang, S; Yi, Q

2018-01-01

Our previous studies showed that macrophages (MФs), especially myeloma-associated MФs (MAMs), induce chemoresistance in human myeloma. Here we explored the potential of targeting MФs, by using colony-stimulating factor 1 receptor (CSF1R)-blocking mAbs, to treat myeloma. Our results showed that CSF1R blockade specifically inhibited the differentiation, proliferation and survival of murine M2 MФs and MAMs, and repolarized MAMs towards M1-like MФs in vitro. CSF1R blockade alone inhibited myeloma growth in vivo, by partially depleting MAMs, polarizing MAMs to the M1 phenotype, and inducing a tumor-specific cytotoxic CD4 + T-cell response. Similarly, genetically depleting MФs in myeloma-bearing MM DTR mice retarded myeloma growth in vivo. Furthermore, the combination of CSF1R blockade and chemotherapy such as bortezomib or melphalan displayed an additive therapeutic efficacy against established myeloma. Finally, a fully human CSF1R blocking mAb, similar to its murine counterpart, was able to inhibit the differentiation, proliferation and survival of human MФs. Thus, this study provides the first direct in vivo evidence that MΦs and MAMs are indeed important for myeloma development and progression. Our results also suggest that targeting MAMs by CSF1R blocking mAbs may be promising methods to (re)sensitize myeloma cells to chemotherapy and promote anti-myeloma immune responses in patients.

Differential regulation of insulin-like growth factor-I receptor gene expression by wild type and mutant androgen receptor in prostate cancer cells.

PubMed

Schayek, Hagit; Seti, Hila; Greenberg, Norman M; Sun, Shihua; Werner, Haim; Plymate, Stephen R

2010-07-29

The progression of prostate cancer from an organ-confined, androgen-sensitive disease to a metastatic one is associated with dysregulation of androgen receptor (AR)-regulated target genes and with a decrease in insulin-like growth factor-I receptor (IGF-IR) expression. To investigate the differential effects of wild type (wt) and mutant AR on IGF-IR levels we employed a series of isogenic prostate-derived cell lines and human xenografts. We show that basal and phosphorylated IGF-IR levels progressively decreased as prostate cancer cells became more tumorigenic and metastatic. In addition, we show that wt, but not mutant, AR along with dihydrotestosterone treatment increased IGF-IR promoter activity and endogenous IGF-IR levels. ChIP analysis show enhanced AR binding to the IGF-IR promoter in AR-overexpressing cells. Finally, wt AR-overexpressing cells display an enhanced proliferation rate. In summary, we provide evidence that activated wt AR enhances IGF-IR transcription in prostate cancer cells via a mechanism that involves AR binding to the IGF-IR promoter. AR mutations alter the ability of the mutated protein to regulate IGF-IR expression. Our results suggest that prostate cancer progression is associated with a decrease in IGF-IR expression that could be the result of impaired ability of AR to stimulate IGF-IR gene expression. 2010 Elsevier Ireland Ltd. All rights reserved.

Differential regulation of insulin-like growth factor-I receptor gene expression by wild type and mutant androgen receptor in prostate cancer cells

PubMed Central

Schayek, Hagit; Seti, Hila; Greenberg, Norman M.; Sun, Shihua; Werner, Haim; Plymate, Stephen R.

2010-01-01

The progression of prostate cancer from an organ-confined, androgen-sensitive disease to a metastatic one is associated with dysregulation of androgen receptor (AR)-regulated target genes and with a decrease in insulin-like growth factor-I receptor (IGF-IR) expression. To investigate the differential effects of wild type (wt) and mutant AR on IGF-IR levels we employed a series of isogenic prostate-derived cell lines and human xenografts. We show that basal and phosphorylated IGF-IR levels progressively decreased as prostate cancer cells became more tumorigenic and metastatic. In addition, we show that wt, but not mutant, AR along with dihydrotestosterone treatment increased IGF-IR promoter activity and endogenous IGF-IR levels. ChIP analysis show enhanced AR binding to the IGF-IR promoter in AR-overexpressing cells. Finally, wt AR-overexpressing cells display an enhanced proliferation rate. In summary, we provide evidence that activated wt AR enhances IGF-IR transcription in prostate cancer cells via a mechanism that involves AR binding to the IGF-IR promoter. AR mutations alter the ability of the mutated protein to regulate IGF-IR expression. Our results suggest that prostate cancer progression is associated with a decrease in IGF-IR expression that could be the result of impaired ability of AR to stimulate IGF-IR gene expression. PMID:20417685

Preserving Differential Privacy in Degree-Correlation based Graph Generation

PubMed Central

Wang, Yue; Wu, Xintao

2014-01-01

Enabling accurate analysis of social network data while preserving differential privacy has been challenging since graph features such as cluster coefficient often have high sensitivity, which is different from traditional aggregate functions (e.g., count and sum) on tabular data. In this paper, we study the problem of enforcing edge differential privacy in graph generation. The idea is to enforce differential privacy on graph model parameters learned from the original network and then generate the graphs for releasing using the graph model with the private parameters. In particular, we develop a differential privacy preserving graph generator based on the dK-graph generation model. We first derive from the original graph various parameters (i.e., degree correlations) used in the dK-graph model, then enforce edge differential privacy on the learned parameters, and finally use the dK-graph model with the perturbed parameters to generate graphs. For the 2K-graph model, we enforce the edge differential privacy by calibrating noise based on the smooth sensitivity, rather than the global sensitivity. By doing this, we achieve the strict differential privacy guarantee with smaller magnitude noise. We conduct experiments on four real networks and compare the performance of our private dK-graph models with the stochastic Kronecker graph generation model in terms of utility and privacy tradeoff. Empirical evaluations show the developed private dK-graph generation models significantly outperform the approach based on the stochastic Kronecker generation model. PMID:24723987

Teleoperated robotic sorting system

DOEpatents

Roos, Charles E.; Sommer, Jr., Edward J.; Parrish, Robert H.; Russell, James R.

2008-06-24

A method and apparatus are disclosed for classifying materials utilizing a computerized touch sensitive screen or other computerized pointing device for operator identification and electronic marking of spatial coordinates of materials to be extracted. An operator positioned at a computerized touch sensitive screen views electronic images of the mixture of materials to be sorted as they are conveyed past a sensor array which transmits sequences of images of the mixture either directly or through a computer to the touch sensitive display screen. The operator manually "touches" objects displayed on the screen to be extracted from the mixture thereby registering the spatial coordinates of the objects within the computer. The computer then tracks the registered objects as they are conveyed and directs automated devices including mechanical means such as air jets, robotic arms, or other mechanical diverters to extract the registered objects.

Teleoperated robotic sorting system

DOEpatents

Roos, Charles E.; Sommer, Edward J.; Parrish, Robert H.; Russell, James R.

2000-01-01

A method and apparatus are disclosed for classifying materials utilizing a computerized touch sensitive screen or other computerized pointing device for operator identification and electronic marking of spatial coordinates of materials to be extracted. An operator positioned at a computerized touch sensitive screen views electronic images of the mixture of materials to be sorted as they are conveyed past a sensor array which transmits sequences of images of the mixture either directly or through a computer to the touch sensitive display screen. The operator manually "touches" objects displayed on the screen to be extracted from the mixture thereby registering the spatial coordinates of the objects within the computer. The computer then tracks the registered objects as they are conveyed and directs automated devices including mechanical means such as air jets, robotic arms, or other mechanical diverters to extract the registered objects.

Research Methods

DTIC Science & Technology

1992-01-01

cognitive function. For example. physiological methods allow for visual sensitivity measurements in infants and children with about the same level of...potential (ERP), the event-related magnetic field (ERF), and pupillometry . Where possible, we cite specific experiments that deal with display or stimulus...technical barrier preventing the application of these methods to the analysis of human performance with color displays. Pupillometry . The pupillary

Insulin sensitivity in relation to fat distribution and plasma adipocytokines among abusers of anabolic androgenic steroids.

PubMed

Rasmussen, Jon Jarløv; Schou, Morten; Selmer, Christian; Johansen, Marie Louise; Gustafsson, Finn; Frystyk, Jan; Dela, Flemming; Faber, Jens; Kistorp, Caroline

2017-09-01

Abuse of anabolic androgenic steroids (AAS) is prevalent among young men, but information regarding effects on insulin sensitivity and fat distribution is limited. The objective was to investigate insulin sensitivity in relation to fat distribution and adipocytokines among current and former AAS abusers compared with controls. Cross-sectional study among men involved in recreational strength training. Current and former AAS abusers (n=37 and n=33) and controls (n=30) volunteered from the community. We assessed insulin sensitivity by Matsuda index (oral glucose tolerance test). Using overnight fasting blood samples, adiponectin and leptin were measured. Body composition and fat distribution, including visceral adipose tissue (VAT), were assessed by dual energy X-ray absorptiometry. Current and former AAS abusers displayed lower Matsuda index than controls (%-difference (95%CI) from controls, -26% (-45; -1) and -39% (-55; -18)). Testosterone was markedly higher among current AAS abusers and subnormal among former AAS abusers compared with controls. Current AAS abusers displayed higher mean VAT than controls (388 (17) vs 293 (12) cm 3 , P<.001) whereas body fat %, adiponectin and leptin concentrations were lower. In contrast, former AAS abusers showed highest leptin concentrations and body fat %. Multivariate linear regressions identified VAT as independent predictor of lower Matsuda index among current AAS abusers compared with controls; while body fat % independently predicted lower Matsuda index among former AAS abusers. Both current and former AAS abusers displayed lower insulin sensitivity which could be mediated by higher VAT and total body fat %, respectively. © 2017 John Wiley & Sons Ltd.

Children Exposed to Intimate Partner Violence: Identifying Differential Effects of Family Environment on Children’s Trauma and Psychopathology Symptoms through Regression Mixture Models

PubMed Central

McDonald, Shelby Elaine; Shin, Sunny; Corona, Rosalie; Maternick, Anna; Graham-Bermann, Sandra A.; Ascione, Frank R.; Williams, James Herbert

2016-01-01

The majority of analytic approaches aimed at understanding the influence of environmental context on children’s socioemotional adjustment assume comparable effects of contextual risk and protective factors for all children. Using self-reported data from 289 maternal caregiver-child dyads, we examined the degree to which there are differential effects of severity of intimate partner violence (IPV) exposure, yearly household income, and number of children in the family on posttraumatic stress symptoms (PTS) and psychopathology symptoms (i.e., internalizing and externalizing problems) among school-age children between the ages of 7 to 12 years. A regression mixture model identified three latent classes that were primarily distinguished by differential effects of IPV exposure severity on PTS and psychopathology symptoms: (1) asymptomatic with low sensitivity to environmental factors (66% of children), (2) maladjusted with moderate sensitivity (24%), and (3) highly maladjusted with high sensitivity (10%). Children with mothers who had higher levels of education were more likely to be in the maladjusted with moderate sensitivity group than the asymptomatic with low sensitivity group. Latino children were less likely to be in both maladjusted groups compared to the asymptomatic group. Overall, the findings suggest differential effects of family environmental factors on PTS and psychopathology symptoms among children exposed to IPV. Implications for research and practice are discussed. PMID:27337691

On Learning Cluster Coefficient of Private Networks

PubMed Central

Wang, Yue; Wu, Xintao; Zhu, Jun; Xiang, Yang

2013-01-01

Enabling accurate analysis of social network data while preserving differential privacy has been challenging since graph features such as clustering coefficient or modularity often have high sensitivity, which is different from traditional aggregate functions (e.g., count and sum) on tabular data. In this paper, we treat a graph statistics as a function f and develop a divide and conquer approach to enforce differential privacy. The basic procedure of this approach is to first decompose the target computation f into several less complex unit computations f1, …, fm connected by basic mathematical operations (e.g., addition, subtraction, multiplication, division), then perturb the output of each fi with Laplace noise derived from its own sensitivity value and the distributed privacy threshold εi, and finally combine those perturbed fi as the perturbed output of computation f. We examine how various operations affect the accuracy of complex computations. When unit computations have large global sensitivity values, we enforce the differential privacy by calibrating noise based on the smooth sensitivity, rather than the global sensitivity. By doing this, we achieve the strict differential privacy guarantee with smaller magnitude noise. We illustrate our approach by using clustering coefficient, which is a popular statistics used in social network analysis. Empirical evaluations on five real social networks and various synthetic graphs generated from three random graph models show the developed divide and conquer approach outperforms the direct approach. PMID:24429843

Children exposed to intimate partner violence: Identifying differential effects of family environment on children's trauma and psychopathology symptoms through regression mixture models.

PubMed

McDonald, Shelby Elaine; Shin, Sunny; Corona, Rosalie; Maternick, Anna; Graham-Bermann, Sandra A; Ascione, Frank R; Herbert Williams, James

2016-08-01

The majority of analytic approaches aimed at understanding the influence of environmental context on children's socioemotional adjustment assume comparable effects of contextual risk and protective factors for all children. Using self-reported data from 289 maternal caregiver-child dyads, we examined the degree to which there are differential effects of severity of intimate partner violence (IPV) exposure, yearly household income, and number of children in the family on posttraumatic stress symptoms (PTS) and psychopathology symptoms (i.e., internalizing and externalizing problems) among school-age children between the ages of 7-12 years. A regression mixture model identified three latent classes that were primarily distinguished by differential effects of IPV exposure severity on PTS and psychopathology symptoms: (1) asymptomatic with low sensitivity to environmental factors (66% of children), (2) maladjusted with moderate sensitivity (24%), and (3) highly maladjusted with high sensitivity (10%). Children with mothers who had higher levels of education were more likely to be in the maladjusted with moderate sensitivity group than the asymptomatic with low sensitivity group. Latino children were less likely to be in both maladjusted groups compared to the asymptomatic group. Overall, the findings suggest differential effects of family environmental factors on PTS and psychopathology symptoms among children exposed to IPV. Implications for research and practice are discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

Induction of differentiation of human embryonic stem cells into functional hair-cell-like cells in the absence of stromal cells.

PubMed

Ding, Jie; Tang, Zihua; Chen, Jiarong; Shi, Haosong; Chen, Jianling; Wang, Cuicui; Zhang, Cui; Li, Liang; Chen, Ping; Wang, Jinfu

2016-12-01

Sensorineural hearing loss and vestibular dysfunction have become the most common forms of sensory defects. Stem cell-based therapeutic strategies for curing hearing loss are being developed. Several attempts to develop hair cells by using chicken utricle stromal cells as feeder cells have resulted in phenotypic conversion of stem cells into inner ear hair-cell-like cells. Here, we induced the differentiation of human embryonic stem cells (hESCs) into otic epithelial progenitors (OEPs), and further induced the differentiation of OEPs into hair-cell-like cells using different substrates. Our results showed that OEPs cultured on the chicken utricle stromal cells with the induction medium could differentiate into hair-cell-like cells with stereociliary bundles. Co-culture with stromal cells, however, may be problematic for subsequent examination of the induced hair-cell-like cells. In order to avoid the interference from stromal cells, we cultured OEPs on laminin with different induction media and examined the effects of the induction medium on the differentiation potentials of OEPs into hair-cell-like cells. The results revealed that the culture of OEPs on laminin with the conditioned medium from chicken utricle stromal cells supplemented with EGF and all-trans retinoic acid (RA) could promote the organization of cells into epithelial clusters displaying hair-cell-like cells with stereociliary bundles. These cells also displayed the expected electrophysiological properties. Copyright © 2015 Elsevier Ltd. All rights reserved.

Poly(1,3-propylene sebacate) and Poly(sebacoyl diglyceride): A Pair of Potential Polymers for the Proliferation and Differentiation of Retinal Progenitor Cells.

PubMed

Ni, Ni; Ji, Jing; Chen, Shuo; Zhang, Dandan; Wang, Zi; Shen, Bingqiao; Guo, Chunyu; Zhang, Yi; Wang, Shaofei; Fan, Xianqun; You, Zhengwei; Luo, Min; Gu, Ping

2016-09-01

Using suitable polymers as a carrier for growing and delivering retinal progenitor cells (RPCs) is a promising therapeutic strategy in retinal cell-replacement therapy. Herein recently developed polymer, poly(sebacoyl diglyceride) (PSeD), is selected and its nonhydroxylized counterpart poly(1,3-propylene sebacate) (PPS) is designed to evaluate their potentials for RPC growth and future RPC application. The structures and mechanical properties of the polymers are characterized. The cytocompatibility and effects of these polymers on RPC proliferation, differentiation, and migration are systematically investigated in vitro. Our data show that PPS and PSeD display excellent cytocompatibility with low expression of inflammation and apoptosis factors, which benefit RPC growth. In proliferation assays reveal that RPCs expands well on the polymers, but PPS performs the best for RPC expansion, indicating that PPS can remarkably promote RPC proliferation. In differentiation conditions, RPCs grown on PSeD are more likely to differentiate toward retinal neurons, including photoreceptors, the most interesting type of cells for retinal cell-replacement therapy. Additionally, our results demonstrate that RPCs grown on PSeD display an outstanding ability to migrate. In conclusion, PPS can markedly promote RPC proliferation, whereas PSeD can enhance RPC differentiation toward retinal neurons, suggesting that PSeD and PPS have potential applications in future retinal cell-replacement therapies. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Evaluating stereoscopic displays: both efficiency measures and perceived workload sensitive to manipulations in binocular disparity

NASA Astrophysics Data System (ADS)

van Beurden, Maurice H. P. H.; Ijsselsteijn, Wijnand A.; de Kort, Yvonne A. W.

2011-03-01

Stereoscopic displays are known to offer a number of key advantages in visualizing complex 3D structures or datasets. The large majority of studies that focus on evaluating stereoscopic displays for professional applications use completion time and/or the percentage of correct answers to measure potential performance advantages. However, completion time and accuracy may not fully reflect all the benefits of stereoscopic displays. In this paper, we argue that perceived workload is an additional valuable indicator reflecting the extent to which users can benefit from using stereoscopic displays. We performed an experiment in which participants were asked to perform a visual path-tracing task within a convoluted 3D wireframe structure, varying in level of complexity of the visualised structure and level of disparity of the visualisation. The results showed that an optimal performance (completion time, accuracy and workload), depend both on task difficulty and disparity level. Stereoscopic disparity revealed a faster and more accurate task performance, whereas we observed a trend that performance on difficult tasks stands to benefit more from higher levels of disparity than performance on easy tasks. Perceived workload (as measured using the NASA-TLX) showed a similar response pattern, providing evidence that perceived workload is sensitive to variations in disparity as well as task difficulty. This suggests that perceived workload could be a useful concept, in addition to standard performance indicators, in characterising and measuring human performance advantages when using stereoscopic displays.

An Electrochemiluminescence Immunosensor Based on Gold-Magnetic Nanoparticles and Phage Displayed Antibodies

PubMed Central

Mu, Xihui; Tong, Zhaoyang; Huang, Qibin; Liu, Bing; Liu, Zhiwei; Hao, Lanqun; Dong, Hua; Zhang, Jinping; Gao, Chuan

2016-01-01

Using the multiple advantages of the ultra-highly sensitive electrochemiluminescence (ECL) technique, Staphylococcus protein A (SPA) functionalized gold-magnetic nanoparticles and phage displayed antibodies, and using gold-magnetic nanoparticles coated with SPA and coupled with a polyclonal antibody (pcAb) as magnetic capturing probes, and Ru(bpy)32+-labeled phage displayed antibody as a specific luminescence probe, this study reports a new way to detect ricin with a highly sensitive and specific ECL immunosensor and amplify specific detection signals. The linear detection range of the sensor was 0.0001~200 µg/L, and the limit of detection (LOD) was 0.0001 µg/L, which is 2500-fold lower than that of the conventional ELISA technique. The gold-magnetic nanoparticles, SPA and Ru(bpy)32+-labeled phage displayed antibody displayed different amplifying effects in the ECL immunosensor and can decrease LOD 3-fold, 3-fold and 20-fold, respectively, compared with the ECL immunosensors without one of the three effects. The integrated amplifying effect can decrease the LOD 180-fold. The immunosensor integrates the unique advantages of SPA-coated gold-magnetic nanoparticles that improve the activity of the functionalized capturing probe, and the amplifying effect of the Ru(bpy)32+-labeled phage displayed antibodies, so it increases specificity, interference-resistance and decreases LOD. It is proven to be well suited for the analysis of trace amounts of ricin in various environmental samples with high recovery ratios and reproducibility. PMID:26927130

Sensitivity to synchronicity of biological motion in normal and amblyopic vision

PubMed Central

Luu, Jennifer Y.; Levi, Dennis M.

2017-01-01

Amblyopia is a developmental disorder of spatial vision that results from abnormal early visual experience usually due to the presence of strabismus, anisometropia, or both strabismus and anisometropia. Amblyopia results in a range of visual deficits that cannot be corrected by optics because the deficits reflect neural abnormalities. Biological motion refers to the motion patterns of living organisms, and is normally displayed as points of lights positioned at the major joints of the body. In this experiment, our goal was twofold. We wished to examine whether the human visual system in people with amblyopia retained the higher-level processing capabilities to extract visual information from the synchronized actions of others, therefore retaining the ability to detect biological motion. Specifically, we wanted to determine if the synchronized interaction of two agents performing a dancing routine allowed the amblyopic observer to use the actions of one agent to predict the expected actions of a second agent. We also wished to establish whether synchronicity sensitivity (detection of synchronized versus desynchronized interactions) is impaired in amblyopic observers relative to normal observers. The two aims are differentiated in that the first aim looks at whether synchronized actions result in improved expected action predictions while the second aim quantitatively compares synchronicity sensitivity, or the ratio of desynchronized to synchronized detection sensitivities, to determine if there is a difference between normal and amblyopic observers. Our results show that the ability to detect biological motion requires more samples in both eyes of amblyopes than in normal control observers. The increased sample threshold is not the result of low-level losses but may reflect losses in feature integration due to undersampling in the amblyopic visual system. However, like normal observers, amblyopes are more sensitive to synchronized versus desynchronized interactions, indicating that higher-level processing of biological motion remains intact. We also found no impairment in synchronicity sensitivity in the amblyopic visual system relative to the normal visual system. Since there is no impairment in synchronicity sensitivity in either the nonamblyopic or amblyopic eye of amblyopes, our results suggest that the higher order processing of biological motion is intact. PMID:23474301

Fitness Trade-Offs in Competence Differentiation of Bacillus subtilis

PubMed Central

Yüksel, Melih; Power, Jeffrey J.; Ribbe, Jan; Volkmann, Thorsten; Maier, Berenike

2016-01-01

In the stationary phase, Bacillus subtilis differentiates stochastically and transiently into the state of competence for transformation (K-state). The latter is associated with growth arrest, and it is unclear how the ability to develop competence is stably maintained, despite its cost. To quantify the effect differentiation has on the competitive fitness of B. subtilis, we characterized the competition dynamics between strains with different probabilities of entering the K-state. The relative fitness decreased with increasing differentiation probability both during the stationary phase and during outgrowth. When exposed to antibiotics inhibiting cell wall synthesis, transcription, and translation, cells that differentiated into the K-state showed a selective advantage compared to differentiation-deficient bacteria; this benefit did not require transformation. Although beneficial, the K-state was not induced by sub-MIC concentrations of antibiotics. Increasing the differentiation probability beyond the wt level did not significantly affect the competition dynamics with transient antibiotic exposure. We conclude that the competition dynamics are very sensitive to the fraction of competent cells under benign conditions but less sensitive during antibiotic exposure, supporting the picture of stochastic differentiation as a fitness trade-off. PMID:27375604

Fitness Trade-Offs in Competence Differentiation of Bacillus subtilis.

PubMed

Yüksel, Melih; Power, Jeffrey J; Ribbe, Jan; Volkmann, Thorsten; Maier, Berenike

2016-01-01

In the stationary phase, Bacillus subtilis differentiates stochastically and transiently into the state of competence for transformation (K-state). The latter is associated with growth arrest, and it is unclear how the ability to develop competence is stably maintained, despite its cost. To quantify the effect differentiation has on the competitive fitness of B. subtilis, we characterized the competition dynamics between strains with different probabilities of entering the K-state. The relative fitness decreased with increasing differentiation probability both during the stationary phase and during outgrowth. When exposed to antibiotics inhibiting cell wall synthesis, transcription, and translation, cells that differentiated into the K-state showed a selective advantage compared to differentiation-deficient bacteria; this benefit did not require transformation. Although beneficial, the K-state was not induced by sub-MIC concentrations of antibiotics. Increasing the differentiation probability beyond the wt level did not significantly affect the competition dynamics with transient antibiotic exposure. We conclude that the competition dynamics are very sensitive to the fraction of competent cells under benign conditions but less sensitive during antibiotic exposure, supporting the picture of stochastic differentiation as a fitness trade-off.

The Yeast Saccharomyces cerevisiae Contains Two Glutaredoxin Genes That Are Required for Protection against Reactive Oxygen Species

PubMed Central

Luikenhuis, Sandra; Perrone, Gabriel; Dawes, Ian W.; Grant, Chris M.

1998-01-01

Glutaredoxins are small heat-stable proteins that act as glutathione-dependent disulfide oxidoreductases. Two genes, designated GRX1 and GRX2, which share 40–52% identity and 61–76% similarity with glutaredoxins from bacterial and mammalian species, were identified in the yeast Saccharomyces cerevisiae. Strains deleted for both GRX1 and GRX2 were viable but lacked heat-stable oxidoreductase activity using β-hydroxyethylene disulfide as a substrate. Surprisingly, despite the high degree of homology between Grx1 and Grx2 (64% identity), the grx1 mutant was unaffected in oxidoreductase activity, whereas the grx2 mutant displayed only 20% of the wild-type activity, indicating that Grx2 accounted for the majority of this activity in vivo. Expression analysis indicated that this difference in activity did not arise as a result of differential expression of GRX1 and GRX2. In addition, a grx1 mutant was sensitive to oxidative stress induced by the superoxide anion, whereas a strain that lacked GRX2 was sensitive to hydrogen peroxide. Sensitivity to oxidative stress was not attributable to altered glutathione metabolism or cellular redox state, which did not vary between these strains. The expression of both genes was similarly elevated under various stress conditions, including oxidative, osmotic, heat, and stationary phase growth. Thus, Grx1 and Grx2 function differently in the cell, and we suggest that glutaredoxins may act as one of the primary defenses against mixed disulfides formed following oxidative damage to proteins. PMID:9571241

A selective and sensitive D-xylose electrochemical biosensor based on xylose dehydrogenase displayed on the surface of bacteria and multi-walled carbon nanotubes modified electrode.

PubMed

Li, Liang; Liang, Bo; Shi, Jianguo; Li, Feng; Mascini, Marco; Liu, Aihua

2012-03-15

A novel Nafion/bacteria-displaying xylose dehydrogenase (XDH)/multi-walled carbon nanotubes (MWNTs) composite film-modified electrode was fabricated and applied for the sensitive and selective determination of d-xylose (INS 967), where the XDH-displayed bacteria (XDH-bacteria) was prepared using a newly identified ice nucleation protein from Pseudomonas borealis DL7 as an anchoring motif. The XDH-displayed bacteria can be used directly, eliminating further enzyme-extraction and purification, thus greatly improved the stability of the enzyme. The optimal conditions for the construction of biosensor were established: homogeneous Nafion-MWNTs composite dispersion (10 μL) was cast onto the inverted glassy carbon electrode, followed by casting 10-μL of XDH-bacteria aqueous solution to stand overnight to dry, then a 5-μL of Nafion solution (0.05 wt%) is syringed to the electrode surface. The bacteria-displaying XDH could catalyze the oxidization of xylose to xylonolactone with coenzyme NAD(+) in 0.1M PBS buffer (pH7.4), where NAD(+) (nicotinamide adenine dinucleotide) is reduced to NADH (the reduced form of nicotinamide adenine dinucleotide). The resultant NADH is further electrocatalytically oxidized by MWNTs on the electrode, resulting in an obvious oxidation peak around 0.50 V (vs. Ag/AgCl). In contrast, the bacteria-XDH-only modified electrode showed oxidation peak at higher potential of 0.7 V and less sensitivity. Therefore, the electrode/MWNTs/bacteria-XDH/Nafion exhibited good analytical performance such as long-term stability, a wide dynamic range of 0.6-100 μM and a low detection limit of 0.5 μM D-xylose (S/N=3). No interference was observed in the presence of 300-fold excess of other saccharides including D-glucose, D-fructose, D-maltose, D-galactose, D-mannose, D-sucrose, and D-cellbiose as well as 60-fold excess of L-arabinose. The proposed microbial biosensor is stable, specific, sensitive, reproducible, simple, rapid and cost-effective, which holds great potential in real applications. Copyright © 2012 Elsevier B.V. All rights reserved.

Characterization of early and late endocytic compartments of the transferrin cycle. Transferrin receptor antibody blocks erythroid differentiation by trapping the receptor in the early endosome.

PubMed

Killisch, I; Steinlein, P; Römisch, K; Hollinshead, R; Beug, H; Griffiths, G

1992-09-01

We describe a detailed morphological characterization of the endocytic pathway in differentiating chicken erythroblasts transformed by a temperature-sensitive mutant of avian erythroblastosis virus (AEV). These cells express high levels of transferrin receptors (TfR) when induced to differentiate at 42 degrees C. Biochemical analysis showed that most (approximately 90%) of the internalized 125I-Tf recycled within approximately 30 min while a smaller fraction of 125I-Tf required up to 2 h for recycling. By immunocytochemistry, the bulk of Tf and TfR was localized at the plasma membrane and in tubuloreticular early endosomes. This structure contained coated buds that labelled with an antibody specific for the clathrin light chain. Decreasing amounts of both Tf and TfR were detected in two distal compartments, spherical endosome vesicles resembling multivesicular bodies and the prelysosomal compartment (PLC) enriched in cation-independent mannose 6-phosphate receptor. As shown by fluorescent (FITC-Tf) labelling of living cells, the movement of Tf/TfR complex into these late structures was accompanied by a significant drop in pH from about 6, the value displayed by early endosomes, to values below pH 5.0. Since no detectable 125I-Tf degradation was observed during a 4 h period we believe that the Tf/TfR detected in these late endocytic structures avoids degradation and recycles back to the cell surface. The addition of an anti-TfR monoclonal antibody to the culture medium of these cells blocks their differentiation. Under this condition the antibody-TfR complex was trapped in an early endosome compartment that enlarged to more than twice its normal size. However, this condition did not affect the transport kinetics of horseradish peroxidase from the medium to the PLC.

Triple-phase helical computed tomography in dogs with solid splenic masses

PubMed Central

KUTARA, Kenji; SEKI, Mamiko; ISHIGAKI, Kumiko; TESHIMA, Kenji; ISHIKAWA, Chieko; KAGAWA, Yumiko; EDAMURA, Kazuya; NAKAYAMA, Tomohiro; ASANO, Kazushi

2017-01-01

We investigated the utility of triple-phase helical computed tomography (CT) in differentiating between benign and malignant splenic masses in dogs. Forty-two dogs with primary splenic masses underwent triple-phase helical CT scanning (before administration of contrast, and in the arterial phase, portal venous phase, and delayed phase) prior to splenectomy. Tissue specimens were sent for pathological diagnosis; these included hematomas (n=14), nodular hyperplasias (n=12), hemangiosarcomas (n=11), and undifferentiated sarcomas (n=5). The CT findings were compared with the histological findings. Nodular hyperplasia significantly displayed a homogeneous normal enhancement pattern in all phases. Hemangiosarcoma displayed 2 significant contrast-enhancement patterns, including a homogeneous pattern of poor enhancement in all phases, and a heterogeneous remarkable enhancement pattern in the arterial and portal venous phases. Hematoma and undifferentiated sarcoma displayed a heterogeneous normal enhancement pattern in all phases. The contrast-enhanced volumetric ratios of hematoma tended to be greater than those of undifferentiated sarcoma. Our study demonstrated that the characteristic findings on triple-phase helical CT could be useful for the preoperative differentiation of hematoma, nodular hyperplasia, hemangiosarcoma, and undifferentiated sarcoma in dogs. Triple-phase helical CT may be a useful diagnostic tool in dogs with splenic masses. PMID:28993600

Auditory Profiles of Classical, Jazz, and Rock Musicians: Genre-Specific Sensitivity to Musical Sound Features.

PubMed

Tervaniemi, Mari; Janhunen, Lauri; Kruck, Stefanie; Putkinen, Vesa; Huotilainen, Minna

2015-01-01

When compared with individuals without explicit training in music, adult musicians have facilitated neural functions in several modalities. They also display structural changes in various brain areas, these changes corresponding to the intensity and duration of their musical training. Previous studies have focused on investigating musicians with training in Western classical music. However, musicians involved in different musical genres may display highly differentiated auditory profiles according to the demands set by their genre, i.e., varying importance of different musical sound features. This hypothesis was tested in a novel melody paradigm including deviants in tuning, timbre, rhythm, melody transpositions, and melody contour. Using this paradigm while the participants were watching a silent video and instructed to ignore the sounds, we compared classical, jazz, and rock musicians' and non-musicians' accuracy of neural encoding of the melody. In all groups of participants, all deviants elicited an MMN response, which is a cortical index of deviance discrimination. The strength of the MMN and the subsequent attentional P3a responses reflected the importance of various sound features in each music genre: these automatic brain responses were selectively enhanced to deviants in tuning (classical musicians), timing (classical and jazz musicians), transposition (jazz musicians), and melody contour (jazz and rock musicians). Taken together, these results indicate that musicians with different training history have highly specialized cortical reactivity to sounds which violate the neural template for melody content.

Auditory Profiles of Classical, Jazz, and Rock Musicians: Genre-Specific Sensitivity to Musical Sound Features

PubMed Central

Tervaniemi, Mari; Janhunen, Lauri; Kruck, Stefanie; Putkinen, Vesa; Huotilainen, Minna

2016-01-01

When compared with individuals without explicit training in music, adult musicians have facilitated neural functions in several modalities. They also display structural changes in various brain areas, these changes corresponding to the intensity and duration of their musical training. Previous studies have focused on investigating musicians with training in Western classical music. However, musicians involved in different musical genres may display highly differentiated auditory profiles according to the demands set by their genre, i.e., varying importance of different musical sound features. This hypothesis was tested in a novel melody paradigm including deviants in tuning, timbre, rhythm, melody transpositions, and melody contour. Using this paradigm while the participants were watching a silent video and instructed to ignore the sounds, we compared classical, jazz, and rock musicians' and non-musicians' accuracy of neural encoding of the melody. In all groups of participants, all deviants elicited an MMN response, which is a cortical index of deviance discrimination. The strength of the MMN and the subsequent attentional P3a responses reflected the importance of various sound features in each music genre: these automatic brain responses were selectively enhanced to deviants in tuning (classical musicians), timing (classical and jazz musicians), transposition (jazz musicians), and melody contour (jazz and rock musicians). Taken together, these results indicate that musicians with different training history have highly specialized cortical reactivity to sounds which violate the neural template for melody content. PMID:26779055

Subcellular distribution of human RDM1 protein isoforms and their nucleolar accumulation in response to heat shock and proteotoxic stress.

PubMed

Messaoudi, Lydia; Yang, Yun-Gui; Kinomura, Aiko; Stavreva, Diana A; Yan, Gonghong; Bortolin-Cavaillé, Marie-Line; Arakawa, Hiroshi; Buerstedde, Jean-Marie; Hainaut, Pierre; Cavaillé, Jérome; Takata, Minoru; Van Dyck, Eric

2007-01-01

The RDM1 gene encodes a RNA recognition motif (RRM)-containing protein involved in the cellular response to the anti-cancer drug cisplatin in vertebrates. We previously reported a cDNA encoding the full-length human RDM1 protein. Here, we describe the identification of 11 human cDNAs encoding RDM1 protein isoforms. This repertoire is generated by alternative pre-mRNA splicing and differential usage of two translational start sites, resulting in proteins with long or short N-terminus and a great diversity in the exonic composition of their C-terminus. By using tagged proteins and fluorescent microscopy, we examined the subcellular distribution of full-length RDM1 (renamed RDM1alpha), and other RDM1 isoforms. We show that RDM1alpha undergoes subcellular redistribution and nucleolar accumulation in response to proteotoxic stress and mild heat shock. In unstressed cells, the long N-terminal isoforms displayed distinct subcellular distribution patterns, ranging from a predominantly cytoplasmic to almost exclusive nuclear localization, suggesting functional differences among the RDM1 proteins. However, all isoforms underwent stress-induced nucleolar accumulation. We identified nuclear and nucleolar localization determinants as well as domains conferring cytoplasmic retention to the RDM1 proteins. Finally, RDM1 null chicken DT40 cells displayed an increased sensitivity to heat shock, compared to wild-type (wt) cells, suggesting a function for RDM1 in the heat-shock response.

From shunting inhibition to dynamic normalization: Attentional selection and decision-making in brief visual displays.

PubMed

Smith, Philip L; Sewell, David K; Lilburn, Simon D

2015-11-01

Normalization models of visual sensitivity assume that the response of a visual mechanism is scaled divisively by the sum of the activity in the excitatory and inhibitory mechanisms in its neighborhood. Normalization models of attention assume that the weighting of excitatory and inhibitory mechanisms is modulated by attention. Such models have provided explanations of the effects of attention in both behavioral and single-cell recording studies. We show how normalization models can be obtained as the asymptotic solutions of shunting differential equations, in which stimulus inputs and the activity in the mechanism control growth rates multiplicatively rather than additively. The value of the shunting equation approach is that it characterizes the entire time course of the response, not just its asymptotic strength. We describe two models of attention based on shunting dynamics, the integrated system model of Smith and Ratcliff (2009) and the competitive interaction theory of Smith and Sewell (2013). These models assume that attention, stimulus salience, and the observer's strategy for the task jointly determine the selection of stimuli into visual short-term memory (VSTM) and the way in which stimulus representations are weighted. The quality of the VSTM representation determines the speed and accuracy of the decision. The models provide a unified account of a variety of attentional phenomena found in psychophysical tasks using single-element and multi-element displays. Our results show the generality and utility of the normalization approach to modeling attention. Copyright © 2014 Elsevier B.V. All rights reserved.

Sleep and vigilance linked to melanism in wild barn owls.

PubMed

Scriba, M F; Rattenborg, N C; Dreiss, A N; Vyssotski, A L; Roulin, A

2014-10-01

Understanding the function of variation in sleep requires studies in the natural ecological conditions in which sleep evolved. Sleep has an impact on individual performance and hence may integrate the costs and benefits of investing in processes that are sensitive to sleep, such as immunity or coping with stress. Because dark and pale melanic animals differentially regulate energy homeostasis, immunity and stress hormone levels, the amount and/or organization of sleep may covary with melanin-based colour. We show here that wild, cross-fostered nestling barn owls (Tyto alba) born from mothers displaying more black spots had shorter non-REM (rapid eye movement) sleep bouts, a shorter latency until the occurrence of REM sleep after a bout of wakefulness and more wakefulness bouts. In male nestlings, the same sleep traits also correlated with their own level of spotting. Because heavily spotted male nestlings and the offspring of heavily spotted biological mothers switched sleep-wakefulness states more frequently, we propose the hypothesis that they could be also behaviourally more vigilant. Accordingly, nestlings from mothers displaying many black spots looked more often towards the nest entrance where their parents bring food and towards their sibling against whom they compete. Owlets from heavily spotted mothers might invest more in vigilance, thereby possibly increasing associated costs due to sleep fragmentation. We conclude that different strategies of the regulation of brain activity have evolved and are correlated with melanin-based coloration. © 2014 The Authors. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

Drosophila Rolling Blackout Displays Lipase Domain-Dependent and Independent Endocytic Functions Downstream of Dynamin

PubMed Central

Vijayakrishnan, Niranjana; Phillips, Scott E.; Broadie, Kendal

2010-01-01

Drosophila temperature-sensitive rolling blackout (rbots) mutants display a total block of endocytosis in non-neuronal cells and a weaker, partial defect at neuronal synapses. RBO is an integral plasma membrane protein and is predicted to be a serine esterase. To determine if lipase activity is required for RBO function, we mutated the catalytic serine 358 to alanine in the G-X-S-X-G active site, and assayed genomic rescue of rbo mutant non-neuronal and neuronal phenotypes. The rboS358A mutant is unable to rescue rbo null 100% embryonic lethality, indicating that the lipase-domain is critical for RBO essential function. Likewise, the rboS358A mutant cannot provide any rescue of endocytic blockade in rbots Garland cells, demonstrating that the lipase-domain is indispensable for non-neuronal endocytosis. In contrast, rbots conditional paralysis, synaptic transmission block and synapse endocytic defects are all fully rescued by the rboS358A mutant, showing that the RBO lipase-domain is dispensable in neuronal contexts. We identified a synthetic lethal interaction between rbots and the well-characterized dynamin GTPase conditional shibire (shits1) mutant. In both non-neuronal cells and neuronal synapses, shits1;rbots phenocopies shits1 endocytic defects, indicating that dynamin and RBO act in the same pathway, with dynamin functioning upstream of RBO. We conclude that RBO possesses both lipase-domain dependent and scaffolding functions with differential requirements in non-neuronal versus neuronal endocytosis mechanisms downstream of dynamin GTPase activity. PMID:21029287

Molecular mechanism: the human dopamine transporter histidine 547 regulates basal and HIV-1 Tat protein-inhibited dopamine transport

PubMed Central

Quizon, Pamela M.; Sun, Wei-Lun; Yuan, Yaxia; Midde, Narasimha M.; Zhan, Chang-Guo; Zhu, Jun

2016-01-01

Abnormal dopaminergic transmission has been implicated as a risk determinant of HIV-1-associated neurocognitive disorders. HIV-1 Tat protein increases synaptic dopamine (DA) levels by directly inhibiting DA transporter (DAT) activity, ultimately leading to dopaminergic neuron damage. Through integrated computational modeling prediction and experimental validation, we identified that histidine547 on human DAT (hDAT) is critical for regulation of basal DA uptake and Tat-induced inhibition of DA transport. Compared to wild type hDAT (WT hDAT), mutation of histidine547 (H547A) displayed a 196% increase in DA uptake. Other substitutions of histidine547 showed that DA uptake was not altered in H547R but decreased by 99% in H547P and 60% in H547D, respectively. These mutants did not alter DAT surface expression or surface DAT binding sites. H547 mutants attenuated Tat-induced inhibition of DA transport observed in WT hDAT. H547A displays a differential sensitivity to PMA- or BIM-induced activation or inhibition of DAT function relative to WT hDAT, indicating a change in basal PKC activity in H547A. These findings demonstrate that histidine547 on hDAT plays a crucial role in stabilizing basal DA transport and Tat-DAT interaction. This study provides mechanistic insights into identifying targets on DAT for Tat binding and improving DAT-mediated dysfunction of DA transmission. PMID:27966610

Established breast cancer stem cell markers do not correlate with in vivo tumorigenicity of tumor-initiating cells

PubMed Central

LEHMANN, CHRISTIAN; JOBS, GABRIELE; THOMAS, MARKUS; BURTSCHER, HELMUT; KUBBIES, MANFRED

2012-01-01

The tumor-initiating capacity of primary human breast cancer cells is maintained in vitro by culturing these cells as spheres/aggregates. Inoculation of small cell numbers derived from these non-adherent cultures leads to rapid xenograft tumor formation in mice. Accordingly, injection of more differentiated monolayer cells derived from spheres results in significantly decelerated tumor growth. For our study, two breast cancer cell lines were generated from primary tumors and cultured as mammospheres or as their adherent counterparts. We examined the in vivo tumorigenicity of these cells by injecting serial dilutions into immunodeficient mice. Inoculation of 106 cells per mouse led to rapid tumor formation, irrespective of cell line or culture conditions. However, after injection of only 103 cells, solely sphere cells were highly tumorigenic. In vitro, we investigated differentiation markers, established breast CSC markers and conducted mRNA profiling. Cytokeratin 5 and 18 were increased in both monolayer cell types, indicating a more differentiated phenotype. All cell lines were CD24−/CD44+ and did not express CD133, CD326 or E-cadherin. ALDH1 activity was not detectable in any cell line. A verapamil-sensitive Hoechst side population was present in sphere cells, but there was no correlation with tumorigenicity in vivo. mRNA profiling did not reveal upregulation of relevant transcription factors. In vitro cell cycle kinetics and in vivo tumor doubling times displayed no difference between sphere and monolayer cultures. Our data indicate that intrinsic genetic and functional markers investigated are not indicative of the in vivo tumori-genicity of putative breast tumor-initiating cells. PMID:23042145

Co-Ultramicronized Palmitoylethanolamide/Luteolin Facilitates the Development of Differentiating and Undifferentiated Rat Oligodendrocyte Progenitor Cells.

PubMed

Skaper, Stephen D; Barbierato, Massimo; Facci, Laura; Borri, Mila; Contarini, Gabriella; Zusso, Morena; Giusti, Pietro

2018-01-01

Oligodendrocytes, the myelin-producing cells of the central nervous system (CNS), have limited capability to bring about repair in chronic CNS neuroinflammatory demyelinating disorders such as multiple sclerosis (MS). MS lesions are characterized by a compromised pool of undifferentiated oligodendrocyte progenitor cells (OPCs) unable to mature into myelin-producing oligodendrocytes. An attractive strategy may be to replace lost OLs and/or promote their maturation. N-palmitoylethanolamine (PEA) is an endogenous fatty acid amide signaling molecule with anti-inflammatory and neuroprotective actions. Recent studies show a co-ultramicronized composite of PEA and the flavonoid luteolin (co-ultraPEALut) to be more efficacious than PEA in improving outcome in CNS injury models. Here, we examined the effects of co-ultraPEALut on development of OPCs from newborn rat cortex cultured under conditions favoring either differentiation (Sato medium) or proliferation (fibroblast growth factor-2 and platelet-derived growth factor (PDGF)-AA-supplemented serum-free medium ("SFM")). OPCs in SFM displayed high expression of PDGF receptor alpha gene and the proliferation marker Ki-67. In Sato medium, in contrast, OPCs showed rapid decreases in PDGF receptor alpha and Ki-67 expression with a concomitant rise in myelin basic protein (MBP) expression. In these conditions, co-ultraPEALut (10 μM) enhanced OPC morphological complexity and expression of MBP and the transcription factor TCF7l2. Surprisingly, co-ultraPEALut also up-regulated MBP mRNA expression in OPCs in SFM. MBP expression in all cases was sensitive to inhibition of mammalian target of rapamycin. Within the context of strategies to promote endogenous remyelination in MS which focus on enhancing long-term survival of OPCs and stimulating their differentiation into remyelinating oligodendrocytes, co-ultraPEALut may represent a novel pharmacological approach.

Psychotic disorder and educational achievement: a family-based analysis.

PubMed

Frissen, Aleida; Lieverse, Ritsaert; Marcelis, Machteld; Drukker, Marjan; Delespaul, Philippe

2015-10-01

Early social and cognitive alterations in psychotic disorder, associated with familial liability and environmental exposures, may contribute to lower than expected educational achievement. The aims of the present study were to investigate (1) how differences in educational level between parents and their children vary across patients, their healthy siblings, and healthy controls (effect familial liability), and across two environmental risk factors for psychotic disorder: childhood trauma and childhood urban exposure (effect environment) and (2) to what degree the association between familial liability and educational differential was moderated by the environmental exposures. Patients with a diagnosis of non-affective psychotic disorder (n = 629), 552 non-psychotic siblings and 326 healthy controls from the Netherlands and Belgium were studied. Participants reported their highest level of education and that of their parents. Childhood trauma was assessed with the Dutch version of the Childhood Trauma Questionnaire-Short Form. Urban exposure, expressed as population density, was rated across five levels. Overall, participants had a higher level of education than their parents. This difference was significantly reduced in the patient group, and the healthy siblings displayed intergenerational differences that were in between those of controls and patients. Higher levels of childhood urban exposure were also associated with a smaller intergenerational educational differential. There was no evidence for differential sensitivity to childhood trauma and childhood urbanicity across the three groups. Intergenerational difference in educational achievements is decreased in patients with psychotic disorder and to a lesser extent in siblings of patients with psychotic disorder, and across higher levels of childhood urban exposure. More research is required to better understand the dynamics between early social and cognitive alterations in those at risk in relation to progress through the educational system and to understand the interaction between urban environment and educational outcomes.

Method and apparatus for non-invasive evaluation of diaphragmatic function

NASA Technical Reports Server (NTRS)

Yost, William T. (Inventor); Wait, Juliette L. (Inventor); Nahormek, Patricia A. (Inventor); Cantrell, John H. (Inventor); Hanna-Hawver, Pamela D. (Inventor)

1995-01-01

A method for non-invasive evaluation of diaphragmatic function in humans measures the thickness of the diaphragm in real time with an ultrasonic device, and displays the variations of diaphragm thickness versus time. Formulae are given for calculating a quantitative value for the reserve fatigue capacity of a patient's diaphragm from data obtained by measuring the time limits for maintaining a constant breathing pattern on the display at two different pressure differentials in series with the patient's airways. An apparatus for displaying the diaphragm thickness in real time is also described. The method can be used both on healthy patients and on patients with so severe breathing dysfunctions that they require breathing support from respirators.

Method and apparatus for non-invasive evaluation of diaphragmatic function

NASA Technical Reports Server (NTRS)

Yost, William T. (Inventor); Wait, Juliette L. (Inventor); Nahormek, Patricia A. (Inventor); Cantrell, John H. (Inventor); Hanna-Hawver, Pamela D. (Inventor)

1994-01-01

A method for non-invasive evaluation of diaphragmatic function in humans measures the thickness of the diaphragm in real time with an ultrasonic device, and displays the variations of diaphragm thickness versus time. Formulae are given for calculating a quantitative value for the reserve fatigue capacity of a patient's diaphragm from data obtained by measuring the time limits for maintaining a constant breathing pattern on the display at two different pressure differentials in series with the patient's airways. An apparatus for displaying the diaphragm thickness in real time is also described. The method can be used both on healthy patients and on patients with so severe breathing dysfunctions that they require breathing support from respirators.

Experience, Context, and the Visual Perception of Human Movement

ERIC Educational Resources Information Center

Jacobs, Alissa; Pinto, Jeannine; Shiffrar, Maggie

2004-01-01

Why are human observers particularly sensitive to human movement? Seven experiments examined the roles of visual experience and motor processes in human movement perception by comparing visual sensitivities to point-light displays of familiar, unusual, and impossible gaits across gait-speed and identity discrimination tasks. In both tasks, visual…

Differentiation of ileostomy from colostomy procedures: assessing the accuracy of current procedural terminology codes and the utility of natural language processing.

PubMed

Vo, Elaine; Davila, Jessica A; Hou, Jason; Hodge, Krystle; Li, Linda T; Suliburk, James W; Kao, Lillian S; Berger, David H; Liang, Mike K

2013-08-01

Large databases provide a wealth of information for researchers, but identifying patient cohorts often relies on the use of current procedural terminology (CPT) codes. In particular, studies of stoma surgery have been limited by the accuracy of CPT codes in identifying and differentiating ileostomy procedures from colostomy procedures. It is important to make this distinction because the prevalence of complications associated with stoma formation and reversal differ dramatically between types of stoma. Natural language processing (NLP) is a process that allows text-based searching. The Automated Retrieval Console is an NLP-based software that allows investigators to design and perform NLP-assisted document classification. In this study, we evaluated the role of CPT codes and NLP in differentiating ileostomy from colostomy procedures. Using CPT codes, we conducted a retrospective study that identified all patients undergoing a stoma-related procedure at a single institution between January 2005 and December 2011. All operative reports during this time were reviewed manually to abstract the following variables: formation or reversal and ileostomy or colostomy. Sensitivity and specificity for validation of the CPT codes against the mastery surgery schedule were calculated. Operative reports were evaluated by use of NLP to differentiate ileostomy- from colostomy-related procedures. Sensitivity and specificity for identifying patients with ileostomy or colostomy procedures were calculated for CPT codes and NLP for the entire cohort. CPT codes performed well in identifying stoma procedures (sensitivity 87.4%, specificity 97.5%). A total of 664 stoma procedures were identified by CPT codes between 2005 and 2011. The CPT codes were adequate in identifying stoma formation (sensitivity 97.7%, specificity 72.4%) and stoma reversal (sensitivity 74.1%, specificity 98.7%), but they were inadequate in identifying ileostomy (sensitivity 35.0%, specificity 88.1%) and colostomy (75.2% and 80.9%). NLP performed with greater sensitivity, specificity, and accuracy than CPT codes in identifying stoma procedures and stoma types. Major differences where NLP outperformed CPT included identifying ileostomy (specificity 95.8%, sensitivity 88.3%, and accuracy 91.5%) and colostomy (97.6%, 90.5%, and 92.8%, respectively). CPT codes can identify effectively patients who have had stoma procedures and are adequate in distinguishing between formation and reversal; however, CPT codes cannot differentiate ileostomy from colostomy. NLP can be used to differentiate between ileostomy- and colostomy-related procedures. The role of NLP in conjunction with electronic medical records in data retrieval warrants further investigation. Published by Mosby, Inc.

NR2B Expression in Rat DRG Is Differentially Regulated Following Peripheral Nerve Injuries That Lead to Transient or Sustained Stimuli-Evoked Hypersensitivity

PubMed Central

Norcini, Monica; Sideris, Alexandra; Adler, Samantha M.; Hernandez, Lourdes A. M.; Zhang, Jin; Blanck, Thomas J. J.; Recio-Pinto, Esperanza

2016-01-01

Following injury, primary sensory neurons undergo changes that drive central sensitization and contribute to the maintenance of persistent hypersensitivity. NR2B expression in the dorsal root ganglia (DRG) has not been previously examined in neuropathic pain models. Here, we investigated if changes in NR2B expression within the DRG are associated with hypersensitivities that result from peripheral nerve injuries. This was done by comparing the NR2B expression in the DRG derived from two modalities of the spared nerve injury (SNI) model, since each variant produces different neuropathic pain phenotypes. Using the electronic von Frey to stimulate the spared and non-spared regions of the hindpaws, we demonstrated that sural-SNI animals develop sustained neuropathic pain in both regions while the tibial-SNI animals recover. NR2B expression was measured at Day 23 and Day 86 post-injury. At Day 23 and 86 post-injury, sural-SNI animals display strong hypersensitivity, whereas tibial-SNI animals display 50 and 100% recovery from post-injury-induced hypersensitivity, respectively. In tibial-SNI at Day 86, but not at Day 23 the perinuclear region of the neuronal somata displayed an increase in NR2B protein. This retention of NR2B protein within the perinuclear region, which will render them non-functional, correlates with the recovery observed in tibial-SNI. In sural-SNI at Day 86, DRG displayed an increase in NR2B mRNA which correlates with the development of sustained hypersensitivity in this model. The increase in NR2B mRNA was not associated with an increase in NR2B protein within the neuronal somata. The latter may result from a decrease in kinesin Kif17, since Kif17 mediates NR2B transport to the soma’s plasma membrane. In both SNIs, microglia/macrophages showed a transient increase in NR2B protein detected at Day 23 but not at Day 86, which correlates with the initial post-injury induced hypersensitivity in both SNIs. In tibial-SNI at Day 86, but not at Day 23, satellite glia cells (SGCs) displayed an increase in NR2B protein. This study is the first to characterize of cell-specific changes in NR2B expression within the DRG following peripheral nerve injury. We discuss how the observed NR2B changes in DRG can contribute to the different neuropathic pain phenotypes displayed by each SNI variant. PMID:27803647

NR2B Expression in Rat DRG Is Differentially Regulated Following Peripheral Nerve Injuries That Lead to Transient or Sustained Stimuli-Evoked Hypersensitivity.

PubMed

Norcini, Monica; Sideris, Alexandra; Adler, Samantha M; Hernandez, Lourdes A M; Zhang, Jin; Blanck, Thomas J J; Recio-Pinto, Esperanza

2016-01-01

Following injury, primary sensory neurons undergo changes that drive central sensitization and contribute to the maintenance of persistent hypersensitivity. NR2B expression in the dorsal root ganglia (DRG) has not been previously examined in neuropathic pain models. Here, we investigated if changes in NR2B expression within the DRG are associated with hypersensitivities that result from peripheral nerve injuries. This was done by comparing the NR2B expression in the DRG derived from two modalities of the spared nerve injury (SNI) model, since each variant produces different neuropathic pain phenotypes. Using the electronic von Frey to stimulate the spared and non-spared regions of the hindpaws, we demonstrated that sural-SNI animals develop sustained neuropathic pain in both regions while the tibial-SNI animals recover. NR2B expression was measured at Day 23 and Day 86 post-injury. At Day 23 and 86 post-injury, sural-SNI animals display strong hypersensitivity, whereas tibial-SNI animals display 50 and 100% recovery from post-injury-induced hypersensitivity, respectively. In tibial-SNI at Day 86, but not at Day 23 the perinuclear region of the neuronal somata displayed an increase in NR2B protein. This retention of NR2B protein within the perinuclear region, which will render them non-functional, correlates with the recovery observed in tibial-SNI. In sural-SNI at Day 86, DRG displayed an increase in NR2B mRNA which correlates with the development of sustained hypersensitivity in this model. The increase in NR2B mRNA was not associated with an increase in NR2B protein within the neuronal somata. The latter may result from a decrease in kinesin Kif17, since Kif17 mediates NR2B transport to the soma's plasma membrane. In both SNIs, microglia/macrophages showed a transient increase in NR2B protein detected at Day 23 but not at Day 86, which correlates with the initial post-injury induced hypersensitivity in both SNIs. In tibial-SNI at Day 86, but not at Day 23, satellite glia cells (SGCs) displayed an increase in NR2B protein. This study is the first to characterize of cell-specific changes in NR2B expression within the DRG following peripheral nerve injury. We discuss how the observed NR2B changes in DRG can contribute to the different neuropathic pain phenotypes displayed by each SNI variant.

Electrophoresis Gel Quantification with a Flatbed Scanner and Versatile Lighting from a Screen Scavenged from a Liquid Crystal Display (LCD) Monitor

ERIC Educational Resources Information Center

Yeung, Brendan; Ng, Tuck Wah; Tan, Han Yen; Liew, Oi Wah

2012-01-01

The use of different types of stains in the quantification of proteins separated on gels using electrophoresis offers the capability of deriving good outcomes in terms of linear dynamic range, sensitivity, and compatibility with specific proteins. An inexpensive, simple, and versatile lighting system based on liquid crystal display backlighting is…

A receptor tyrosine kinase, UFO/Axl, and other genes isolated by a modified differential display PCR are overexpressed in metastatic prostatic carcinoma cell line DU145.

PubMed

Jacob, A N; Kalapurakal, J; Davidson, W R; Kandpal, G; Dunson, N; Prashar, Y; Kandpal, R P

1999-01-01

We have used a modified differential display PCR protocol for isolating 3' restriction fragments of cDNAs specifically expressed or overexpressed in metastatic prostate carcinoma cell line DU145. Several cDNA fragments were identified that matched to milk fat globule protein, UFO/Axl, a receptor tyrosine kinase, human homologue of a Xenopus maternal transcript, laminin and laminin receptor, human carcinoma-associated antigen, and some expressed sequence tags. The transcript for milk fat globule protein, a marker protein shown to be overexpressed in breast tumors, was elevated in DU145 cells. The expression of UFO/Axl, a receptor tyrosine kinase, was considerably higher in DU145 cells as compared to normal prostate cells and prostatic carcinoma cell line PC-3. The overexpression of UFO oncogene in DU145 cells is discussed in the context of prostate cancer metastasis.

[Isolation of ABA-regulated genes in Oryza sativa through fluorescent differential display PCR (FDD-PCR)].

PubMed

Xu, Shou Ling; Shen, Si Shi; Xu, Zhi Hong; Xue, Hong Wei

2002-12-01

Abscisic acid (ABA) was critical in plant seed development and response to environmental factors such as stress situations. To study the possible ABA related signaling transduction pathways, we tried to isolate the ABA-regulated genes through fluorescent differential display PCR (FDD-PCR) technology using rice seedling as materials (treated with ABA for 2, 4, 8 and 12h). In the 17 fragments isolated, 14 and 3 clones were up-and down-regulated respectively. Sequence analyses revealed that the encoded proteins were involved in photosynthesis (7 fragments), signal transduction (1 fragments), transcription (2 fragments), metabolism and resistance (6 fragments), and unknown protein (1 fragments). 3 clones, encoding putative alpha/beta hydrolase fold, putative vacuolar H+ -ATPase B subunit, putative tyrosine phosphatase, were confirmed to be regulated under ABA treatment by RT-PCR and northern blot analysis. FDD-PCR and possible functional mechanisms of ABA were discussed.

Human Immune Disorder Arising from Mutation of the α Chain of the Interleukin-2 Receptor

NASA Astrophysics Data System (ADS)

Sharfe, Nigel; Dadi, Harjit K.; Shahar, Michal; Roifman, Chaim M.

1997-04-01

Profound cellular immunodeficiency occurs as the result of mutations in proteins involved in both the differentiation and function of mature lymphoid cells. We describe here a novel human immune aberration arising from a truncation mutation of the interleukin-2 receptor α chain (CD25), a subunit of the tripartite high-affinity receptor for interleukin 2. This immunodeficiency is characterized by decreased numbers of peripheral T cells displaying abnormal proliferation but normal B cell development. Extensive lymphocytic infiltration of tissues, including lung, liver, gut, and bone, is observed, accompanied by tissue atrophy and inflammation. Although mature T cells are present, the absence of CD25 does affect the differentiation of thymocytes. While displaying normal development of CD2, CD3, CD4, and CD8 expression, CD25-deficient cortical thymocytes do not express CD1, and furthermore they fail to normally down-regulate levels of the anti-apoptotic protein bcl-2.

Psychophysical Calibration of Mobile Touch-Screens for Vision Testing in the Field

NASA Technical Reports Server (NTRS)

Mulligan, Jeffrey B.

2015-01-01

The now ubiquitous nature of touch-screen displays in cell phones and tablet computers makes them an attractive option for vision testing outside of the laboratory or clinic. Accurate measurement of parameters such as contrast sensitivity, however, requires precise control of absolute and relative screen luminances. The nonlinearity of the display response (gamma) can be measured or checked using a minimum motion technique similar to that developed by Anstis and Cavanagh (1983) for the determination of isoluminance. While the relative luminances of the color primaries vary between subjects (due to factors such as individual differences in pre-retinal pigment densities), the gamma nonlinearity can be checked in the lab using a photometer. Here we compare results obtained using the psychophysical method with physical measurements for a number of different devices. In addition, we present a novel physical method using the device's built-in front-facing camera in conjunction with a mirror to jointly calibrate the camera and display. A high degree of consistency between devices is found, but some departures from ideal performance are observed. In spite of this, the effects of calibration errors and display artifacts on estimates of contrast sensitivity are found to be small.

Sociability modifies dogs' sensitivity to biological motion of different social relevance.

PubMed

Ishikawa, Yuko; Mills, Daniel; Willmott, Alexander; Mullineaux, David; Guo, Kun

2018-03-01

Preferential attention to living creatures is believed to be an intrinsic capacity of the visual system of several species, with perception of biological motion often studied and, in humans, it correlates with social cognitive performance. Although domestic dogs are exceptionally attentive to human social cues, it is unknown whether their sociability is associated with sensitivity to conspecific and heterospecific biological motion cues of different social relevance. We recorded video clips of point-light displays depicting a human or dog walking in either frontal or lateral view. In a preferential looking paradigm, dogs spontaneously viewed 16 paired point-light displays showing combinations of normal/inverted (control condition), human/dog and frontal/lateral views. Overall, dogs looked significantly longer at frontal human point-light display versus the inverted control, probably due to its clearer social/biological relevance. Dogs' sociability, assessed through owner-completed questionnaires, further revealed that low-sociability dogs preferred the lateral point-light display view, whereas high-sociability dogs preferred the frontal view. Clearly, dogs can recognize biological motion, but their preference is influenced by their sociability and the stimulus salience, implying biological motion perception may reflect aspects of dogs' social cognition.

Detecting free-mass common-mode motion induced by incident gravitational waves

NASA Astrophysics Data System (ADS)

Tobar, Michael Edmund; Suzuki, Toshikazu; Kuroda, Kazuaki

1999-05-01

In this paper we show that information on both the differential and common mode free-mass response to a gravitational wave can provide important information on discriminating the direction of the gravitational wave source and between different theories of gravitation. The conventional Michelson interferometer scheme only measures the differential free-mass response. By changing the orientation of the beam splitter, it is possible to configure the detector so it is sensitive to the common-mode of the free-mass motion. The proposed interferometer is an adaptation of the Fox-Smith interferometer. A major limitation to the new scheme is its enhanced sensitivity to laser frequency fluctuations over the conventional, and we propose a method of cancelling these fluctuations. The configuration could be used in parallel to the conventional differential detection scheme with a significant sensitivity and bandwidth.

Ethylene Responses in Rice Roots and Coleoptiles Are Differentially Regulated by a Carotenoid Isomerase-Mediated Abscisic Acid Pathway[OPEN

PubMed Central

Yin, Cui-Cui; Ma, Biao; Collinge, Derek Phillip; Pogson, Barry James; He, Si-Jie; Xiong, Qing; Duan, Kai-Xuan; Chen, Hui; Yang, Chao; Lu, Xiang; Wang, Yi-Qin; Zhang, Wan-Ke; Chu, Cheng-Cai; Sun, Xiao-Hong; Fang, Shuang; Chu, Jin-Fang; Lu, Tie-Gang; Chen, Shou-Yi; Zhang, Jin-Song

2015-01-01

Ethylene and abscisic acid (ABA) act synergistically or antagonistically to regulate plant growth and development. ABA is derived from the carotenoid biosynthesis pathway. Here, we analyzed the interplay among ethylene, carotenoid biogenesis, and ABA in rice (Oryza sativa) using the rice ethylene response mutant mhz5, which displays a reduced ethylene response in roots but an enhanced ethylene response in coleoptiles. We found that MHZ5 encodes a carotenoid isomerase and that the mutation in mhz5 blocks carotenoid biosynthesis, reduces ABA accumulation, and promotes ethylene production in etiolated seedlings. ABA can largely rescue the ethylene response of the mhz5 mutant. Ethylene induces MHZ5 expression, the production of neoxanthin, an ABA biosynthesis precursor, and ABA accumulation in roots. MHZ5 overexpression results in enhanced ethylene sensitivity in roots and reduced ethylene sensitivity in coleoptiles. Mutation or overexpression of MHZ5 also alters the expression of ethylene-responsive genes. Genetic studies revealed that the MHZ5-mediated ABA pathway acts downstream of ethylene signaling to inhibit root growth. The MHZ5-mediated ABA pathway likely acts upstream but negatively regulates ethylene signaling to control coleoptile growth. Our study reveals novel interactions among ethylene, carotenogenesis, and ABA and provides insight into improvements in agronomic traits and adaptive growth through the manipulation of these pathways in rice. PMID:25841037

Distinct and Cooperative Roles of amh and dmrt1 in Self-Renewal and Differentiation of Male Germ Cells in Zebrafish.

PubMed

Lin, Qiaohong; Mei, Jie; Li, Zhi; Zhang, Xuemei; Zhou, Li; Gui, Jian-Fang

2017-11-01

Spermatogenesis is a fundamental process in male reproductive biology and depends on precise balance between self-renewal and differentiation of male germ cells. However, the regulative factors for controlling the balance are poorly understood. In this study, we examined the roles of amh and dmrt1 in male germ cell development by generating their mutants with Crispr/Cas9 technology in zebrafish. Amh mutant zebrafish displayed a female-biased sex ratio, and both male and female amh mutants developed hypertrophic gonads due to uncontrolled proliferation and impaired differentiation of germ cells. A large number of proliferating spermatogonium-like cells were observed within testicular lobules of the amh -mutated testes, and they were demonstrated to be both Vasa- and PH3-positive. Moreover, the average number of Sycp3- and Vasa-positive cells in the amh mutants was significantly lower than in wild-type testes, suggesting a severely impaired differentiation of male germ cells. Conversely, all the dmrt1 -mutated testes displayed severe testicular developmental defects and gradual loss of all Vasa-positive germ cells by inhibiting their self-renewal and inducing apoptosis. In addition, several germ cell and Sertoli cell marker genes were significantly downregulated, whereas a prominent increase of Insl3-positive Leydig cells was revealed by immunohistochemical analysis in the disorganized dmrt1 -mutated testes. Our data suggest that amh might act as a guardian to control the balance between proliferation and differentiation of male germ cells, whereas dmrt1 might be required for the maintenance, self-renewal, and differentiation of male germ cells. Significantly, this study unravels novel functions of amh gene in fish. Copyright © 2017 by the Genetics Society of America.

Adipogenesis in thyroid eye disease.

PubMed

Crisp, M; Starkey, K J; Lane, C; Ham, J; Ludgate, M

2000-10-01

Adipogenesis contributes to the pathogenesis of thyroid eye disease (TED). Thyrotropin receptor (TSHR) transcripts are present in orbital fat. This study was conducted to determine whether they are expressed as functional protein, and if so, whether this is restricted to TED orbits or to a particular stage in adipocyte differentiation. Samples of fat were obtained from 18 TED-affected orbits and 4 normal orbits, and 9 were obtained from nonorbital locations. Frozen sections were examined by immunocytochemistry using monoclonal antibodies specific for the human TSHR. Samples were disaggregated and the preadipocytes separated from the mature by differential centrifugation and cultured in serum-free or DM and examined for morphologic changes, oil red O and TSHR staining, and TSH-induced cyclic adenosine monophosphate (cAMP) production. Marked immunoreactivity was observed in frozen sections from all three TED samples and faint staining in both normal orbital fat samples. In vitro, 1% to 5% of preadipocytes displayed TSHR immunoreactivity in five of six TED and two of three normal orbital samples and in three of five nonorbital samples. Differentiation, was induced in all 14 orbital samples. Three of four nonorbital samples contained occasional differentiated cells. Fifty percent to 70% of differentiating cells demonstrated receptor immunoreactivity. Two of three TED and four of four nonorbital preadipocytes in DM and/or mature adipocytes displayed a TSH-mediated increase in cAMP. The results indicate that orbital fat TSHR transcripts are expressed as protein, which can be functional. This is not aberrant in TED orbits, although expression may be upregulated. The majority of preadipocytes undergoing differentiation express the receptor, indicating a key role for this population in one mechanism for increasing orbital volume.

Lanthanide complexes as luminogenic probes to measure sulfide levels in industrial samples.

PubMed

Thorson, Megan K; Ung, Phuc; Leaver, Franklin M; Corbin, Teresa S; Tuck, Kellie L; Graham, Bim; Barrios, Amy M

2015-10-08

A series of lanthanide-based, azide-appended complexes were investigated as hydrogen sulfide-sensitive probes. Europium complex 1 and Tb complex 3 both displayed a sulfide-dependent increase in luminescence, while Tb complex 2 displayed a decrease in luminescence upon exposure to NaHS. The utility of the complexes for monitoring sulfide levels in industrial oil and water samples was investigated. Complex 3 provided a sensitive measure of sulfide levels in petrochemical water samples (detection limit ∼ 250 nM), while complex 1 was capable of monitoring μM levels of sulfide in partially refined crude oil. Copyright © 2015 Elsevier B.V. All rights reserved.

The relationship between ambient illumination and psychological factors in viewing of display Images

NASA Astrophysics Data System (ADS)

Iwanami, Takuya; Kikuchi, Ayano; Kaneko, Takashi; Hirai, Keita; Yano, Natsumi; Nakaguchi, Toshiya; Tsumura, Norimichi; Yoshida, Yasuhiro; Miyake, Yoichi

2009-01-01

In this paper, we have clarified the relationship between ambient illumination and psychological factors in viewing of display images. Psychological factors were obtained by the factor analysis with the results of the semantic differential (SD) method. In the psychological experiments, subjects evaluated the impressions of displayed images with changing ambient illuminating conditions. The illumination conditions were controlled by a fluorescent ceiling light and a color LED illumination which was located behind the display. We experimented under two kinds of conditions. One was the experiment with changing brightness of the ambient illumination. The other was the experiment with changing the colors of the background illumination. In the results of the experiment, two factors "realistic sensation, dynamism" and "comfortable," were extracted under different brightness of the ambient illumination of the display surroundings. It was shown that the "comfortable" was improved by the brightness of display surroundings. On the other hand, when the illumination color of surroundings was changed, three factors "comfortable," "realistic sensation, dynamism" and "activity" were extracted. It was also shown that the value of "comfortable" and "realistic sensation, dynamism" increased when the display surroundings were illuminated by the average color of the image contents.

Statis omnidirectional stereoscopic display system

NASA Astrophysics Data System (ADS)

Barton, George G.; Feldman, Sidney; Beckstead, Jeffrey A.

1999-11-01

A unique three camera stereoscopic omnidirectional viewing system based on the periscopic panoramic camera described in the 11/98 SPIE proceedings (AM13). The 3 panoramic cameras are equilaterally combined so each leg of the triangle approximates the human inter-ocular spacing allowing each panoramic camera to view 240 degree(s) of the panoramic scene, the most counter clockwise 120 degree(s) being the left eye field and the other 120 degree(s) segment being the right eye field. Field definition may be by green/red filtration or time discrimination of the video signal. In the first instance a 2 color spectacle is used in viewing the display or in the 2nd instance LCD goggles are used to differentiate the R/L fields. Radially scanned vidicons or re-mapped CCDs may be used. The display consists of three vertically stacked 120 degree(s) segments of the panoramic field of view with 2 fields/frame. Field A being the left eye display and Field B the right eye display.

Seafloor Pressure Array Studies at Ultra-Low Frequencies

DTIC Science & Technology

1991-01-01

broadband instrument design and deployment. In order to measure broadband noise routinely, a low frequency pressure gauge designed for deep ocean...below the microseism band (Moore et al, 1981). A differential pressure gauge , developed for low frequency recordings by Cox et al (1984) and sensitive to...design differential pressure gauge (Cox et al, 1984) with a sensitivity -3- ULF Seafloor Pressure Array Studies range of 0.01-5 Hz. The high

Human-scale interaction for virtual model displays: a clear case for real tools

NASA Astrophysics Data System (ADS)

Williams, George C.; McDowall, Ian E.; Bolas, Mark T.

1998-04-01

We describe a hand-held user interface for interacting with virtual environments displayed on a Virtual Model Display. The tool, constructed entirely of transparent materials, is see-through. We render a graphical counterpart of the tool on the display and map it one-to-one with the real tool. This feature, combined with a capability for touch- sensitive, discrete input, results in a useful spatial input device that is visually versatile. We discuss the tool's design and interaction techniques it supports. Briefly, we look at the human factors issues and engineering challenges presented by this tool and, in general, by the class of hand-held user interfaces that are see-through.

Spin-dependent limits from the DRIFT-IId directional dark matter detector

NASA Astrophysics Data System (ADS)

Daw, E.; Fox, J. R.; Gauvreau, J.-L.; Ghag, C.; Harmon, L. J.; Gold, M.; Lee, E. R.; Loomba, D.; Miller, E. H.; Murphy, A. Stj.; Paling, S. M.; Landers, J. M.; Pipe, M.; Pushkin, K.; Robinson, M.; Snowden-Ifft, D. P.; Spooner, N. J. C.; Walker, D.

2012-02-01

Data are presented from the DRIFT-IId detector operated in the Boulby Underground Science Facility in England. A 0.8 m3 fiducial volume, containing partial pressures of 30 Torr CS2 and 10 Torr CF4, was exposed for a duration of 47.4 live-time days with sufficient passive shielding to provide a neutron free environment within the detector. The nuclear recoil events seen are consistent with a remaining low-level background from the decay of radon daughters attached to the central cathode of the detector. However, charge from such events must drift across the entire width of the detector, and thus display large diffusion upon reaching the readout planes of the device. Exploiting this feature, it is shown to be possible to reject energy depositions from these Radon Progeny Recoil events while still retaining sensitivity to fiducial-volume nuclear recoil events. The response of the detector is then interpreted, using the F nuclei content of the gas, in terms of sensitivity to proton spin-dependent WIMP-nucleon interactions, displaying a minimum in sensitivity cross section at 1.8 pb for a WIMP mass of 100 GeV/c2. This sensitivity was achieved without compromising the direction sensitivity of DRIFT.

Infants’ sensitivity to emotion in music and emotion-action understanding

PubMed Central

Siu, Tik-Sze Carrey; Cheung, Him

2017-01-01

Emerging evidence has indicated infants’ early sensitivity to acoustic cues in music. Do they interpret these cues in emotional terms to represent others’ affective states? The present study examined infants’ development of emotional understanding of music with a violation-of-expectation paradigm. Twelve- and 20-month-olds were presented with emotionally concordant and discordant music-face displays on alternate trials. The 20-month-olds, but not the 12-month-olds, were surprised by emotional incongruence between musical and facial expressions, suggesting their sensitivity to musical emotion. In a separate non-music task, only the 20-month-olds were able to use an actress’s affective facial displays to predict her subsequent action. Interestingly, for the 20-month-olds, such emotion-action understanding correlated with sensitivity to musical expressions measured in the first task. These two abilities however did not correlate with family income, parental estimation of language and communicative skills, and quality of parent-child interaction. The findings suggest that sensitivity to musical emotion and emotion-action understanding may be supported by a generalised common capacity to represent emotion from social cues, which lays a foundation for later social-communicative development. PMID:28152081

Behavioral profiles of feline breeds in Japan.

PubMed

Takeuchi, Yukari; Mori, Yuji

2009-08-01

To clarify the behavioral profiles of 9 feline purebreds, 2 Persian subbreeds and the Japanese domestic cat, a questionnaire survey was distributed to 67 small-animal veterinarians. We found significant differences among breeds in all behavioral traits examined except for "inappropriate elimination". In addition, sexual differences were observed in certain behaviors, including "aggression toward cats", "general activity", "novelty-seeking", and "excitability". These behaviors were more common in males than females, whereas "nervousness" and "inappropriate elimination" were rated higher in females. When all breeds were categorized into four groups on the basis of a cluster analysis using the scores of two behavioral trait factors called "aggressiveness/sensitivity" and "vivaciousness", the group including Abyssinian, Russian Blue, Somali, Siamese, and Chinchilla breeds showed high aggressiveness/sensitivity and low vivaciousness. In contrast, the group including the American Shorthair and Japanese domestic cat displayed low aggressiveness/sensitivity and high vivaciousness, and the Himalayan and Persian group showed mild aggressiveness/sensitivity and very low vivaciousness. Finally, the group containing Maine Coon, Ragdoll, and Scottish Fold breeds displayed very low aggressiveness/sensitivity and low vivaciousness. The present results demonstrate that some feline behavioral traits vary by breed and/or sex.

Methodology for sensitivity analysis, approximate analysis, and design optimization in CFD for multidisciplinary applications

NASA Technical Reports Server (NTRS)

Taylor, Arthur C., III; Hou, Gene W.

1994-01-01

The straightforward automatic-differentiation and the hand-differentiated incremental iterative methods are interwoven to produce a hybrid scheme that captures some of the strengths of each strategy. With this compromise, discrete aerodynamic sensitivity derivatives are calculated with the efficient incremental iterative solution algorithm of the original flow code. Moreover, the principal advantage of automatic differentiation is retained (i.e., all complicated source code for the derivative calculations is constructed quickly with accuracy). The basic equations for second-order sensitivity derivatives are presented; four methods are compared. Each scheme requires that large systems are solved first for the first-order derivatives and, in all but one method, for the first-order adjoint variables. Of these latter three schemes, two require no solutions of large systems thereafter. For the other two for which additional systems are solved, the equations and solution procedures are analogous to those for the first order derivatives. From a practical viewpoint, implementation of the second-order methods is feasible only with software tools such as automatic differentiation, because of the extreme complexity and large number of terms. First- and second-order sensitivities are calculated accurately for two airfoil problems, including a turbulent flow example; both geometric-shape and flow-condition design variables are considered. Several methods are tested; results are compared on the basis of accuracy, computational time, and computer memory. For first-order derivatives, the hybrid incremental iterative scheme obtained with automatic differentiation is competitive with the best hand-differentiated method; for six independent variables, it is at least two to four times faster than central finite differences and requires only 60 percent more memory than the original code; the performance is expected to improve further in the future.

Defective erythroid differentiation in miR-451 mutant mice mediated by 14-3-3ζ

PubMed Central

Patrick, David M.; Zhang, Cheng C.; Tao, Ye; Yao, Huiyu; Qi, Xiaoxia; Schwartz, Robert J.; Jun-Shen Huang, Lily; Olson, Eric N.

2010-01-01

Erythrocyte formation occurs throughout life in response to cytokine signaling. We show that microRNA-451 (miR-451) regulates erythropoiesis in vivo. Mice lacking miR-451 display a reduction in hematrocrit, an erythroid differentiation defect, and ineffective erythropoiesis in response to oxidative stress. 14-3-3ζ, an intracellular regulator of cytokine signaling that is repressed by miR-451, is up-regulated in miR-451−/− erythroblasts, and inhibition of 14-3-3ζ rescues their differentiation defect. These findings reveal an essential role of 14-3-3ζ as a mediator of the proerythroid differentiation actions of miR-451, and highlight the therapeutic potential of miR-451 inhibitors. PMID:20679397

Characterizing the Performance of Nonlinear Differential Operators

DTIC Science & Technology

2012-09-01

differential Riccati equations. Submitted to SIAM J . Control & Optimization, 29 pages, 2012. [B8] P.M. Dower, C.M. Kellett, and H. Zhang. A weak L2-gain...to a penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. 1. REPORT DATE 07...Parkville,Victoria 3010,Australia,NA,NA 8. PERFORMING ORGANIZATION REPORT NUMBER N/ A 9. SPONSORING/MONITORING AGENCY NAME(S) AND ADDRESS(ES) AOARD, UNIT

Differentiation of Mesenchymal Stem Cells from Human Umbilical Cord Tissue into Odontoblast-Like Cells Using the Conditioned Medium of Tooth Germ Cells In Vitro

PubMed Central

Li, Tian Xia; Yuan, Jie; Chen, Yan; Pan, Li Jie; Song, Chun; Bi, Liang Jia; Jiao, Xiao Hui

2013-01-01

The easily accessible mesenchymal stem cells in the Wharton's jelly of human umbilical cord tissue (hUCMSCs) have excellent proliferation and differentiation potential, but it remains unclear whether hUCMSCs can differentiate into odontoblasts. In this study, mesenchymal stem cells were isolated from the Wharton's jelly of human umbilical cord tissue using the simple method of tissue blocks culture attachment. UCMSC surface marker expression was then evaluated for the isolated cells using flow cytometry. The third-passage hUCMSCs induced by conditioned medium from developing tooth germ cells (TGC-CM) displayed high alkaline phosphatase (ALP) levels (P < 0.001), an enhanced ability to proliferate (P < 0.05), and the presence of mineralized nodules. These effects were not observed in cells treated with regular medium. After induction of hUCMSCs, the results of reverse transcriptional polymerase chain reaction (PCR) indicated that the dentin sialophosphoprotein (DSPP) and dentin matrix protein 1 (DMP1) genes were significantly tested. Additionally, dentin sialoprotein (DSP) and DMP1 demonstrated significant levels of staining in an immunofluorescence analysis. In contrast, the control cells failed to display the characteristics of odontoblasts. Taken together, these results suggest that hUCMSCs can be induced to differentiate into odontoblast-like cells with TGC-CM and provide a novel strategy for tooth regeneration research. PMID:23762828

Seven diverse human embryonic stem cell-derived chondrogenic clonal embryonic progenitor cell lines display site-specific cell fates.

PubMed

Sternberg, Hal; Kidd, Jennifer; Murai, James T; Jiang, Jianjie; Rinon, Ariel; Erickson, Isaac E; Funk, Walter D; Wang, Qian; Chapman, Karen B; Vangsness, C Thomas; West, Michael D

2013-03-01

The transcriptomes of seven diverse clonal human embryonic progenitor cell lines with chondrogenic potential were compared with that of bone marrow-derived mesenchymal stem cells (MSCs). The cell lines 4D20.8, 7PEND24, 7SMOO32, E15, MEL2, SK11 and SM30 were compared with MSCs using immunohistochemical methods, gene expression microarrays and quantitative real-time PCR. In the undifferentiated progenitor state, each line displayed unique combinations of site-specific markers, including AJAP1, ALDH1A2, BMP5, BARX1, HAND2, HOXB2, LHX1, LHX8, PITX1, TBX15 and ZIC2, but none of the lines expressed the MSC marker CD74. The lines showed diverse responses when differentiated in the presence of combinations of TGF-β3, BMP2, 4, 6 and 7 and GDF5, with the lines 4D20.8, SK11, SM30 and MEL2 showing osteogenic markers in some differentiation conditions. The line 7PEND24 showed evidence of regenerating articular cartilage and, in some conditions, markers of tendon differentiation. The scalability of site-specific clonal human embryonic stem cell-derived embryonic progenitor cell lines may provide novel models for the study of differentiation and methods for preparing purified and identified cells types for use in therapy.

PLETHORA gradient formation mechanism separates auxin responses.

PubMed

Mähönen, Ari Pekka; Ten Tusscher, Kirsten; Siligato, Riccardo; Smetana, Ondřej; Díaz-Triviño, Sara; Salojärvi, Jarkko; Wachsman, Guy; Prasad, Kalika; Heidstra, Renze; Scheres, Ben

2014-11-06

During plant growth, dividing cells in meristems must coordinate transitions from division to expansion and differentiation, thus generating three distinct developmental zones: the meristem, elongation zone and differentiation zone. Simultaneously, plants display tropisms, rapid adjustments of their direction of growth to adapt to environmental conditions. It is unclear how stable zonation is maintained during transient adjustments in growth direction. In Arabidopsis roots, many aspects of zonation are controlled by the phytohormone auxin and auxin-induced PLETHORA (PLT) transcription factors, both of which display a graded distribution with a maximum near the root tip. In addition, auxin is also pivotal for tropic responses. Here, using an iterative experimental and computational approach, we show how an interplay between auxin and PLTs controls zonation and gravitropism. We find that the PLT gradient is not a direct, proportionate readout of the auxin gradient. Rather, prolonged high auxin levels generate a narrow PLT transcription domain from which a gradient of PLT protein is subsequently generated through slow growth dilution and cell-to-cell movement. The resulting PLT levels define the location of developmental zones. In addition to slowly promoting PLT transcription, auxin also rapidly influences division, expansion and differentiation rates. We demonstrate how this specific regulatory design in which auxin cooperates with PLTs through different mechanisms and on different timescales enables both the fast tropic environmental responses and stable zonation dynamics necessary for coordinated cell differentiation.

INSM1 is a Sensitive and Specific Marker of Neuroendocrine Differentiation in Head and Neck Tumors.

PubMed

Rooper, Lisa M; Bishop, Justin A; Westra, William H

2018-05-01

The head and neck is the site of a wide and sometimes bewildering array of neuroendocrine (NE) tumors. Although recognition of NE differentiation may be necessary for appropriate tumor classification and treatment, traditional NE markers such as synaptophysin, chromogranin, and CD56 are not always sufficiently sensitive or specific to make this distinction. Insulinoma-associated protein 1 (INSM1) is a novel transcription factor that has recently demonstrated excellent sensitivity and specificity for NE differentiation in various anatomic sites, but has not yet been extensively evaluated in tumors of the head and neck. We performed INSM1 immunohistochemistry on NE tumors (n=97) and non-NE tumors (n=626) across all histologic grades and anatomic subsites of the head and neck. INSM1 was positive in all types of head and neck NE tumors evaluated here (99.0% sensitivity), including middle ear adenoma, pituitary adenoma, paraganglioma, medullary thyroid carcinoma, olfactory neuroblastoma, small cell carcinoma, large cell NE carcinoma, and sinonasal teratocarcinosarcoma. Notably, it was positive in the vast majority of high-grade NE malignancies (95.8% sensitivity). INSM1 also was negative in almost all non-NE tumors (97.6% specificity) with the highest rates of reactivity in alveolar rhabdomyosarcoma and SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily B, member 1 (SMARCB1)-deficient sinonasal carcinoma. These findings confirm that INSM1 may be used as a standalone first-line marker of NE differentiation for tumors of the head and neck.

Cocaine counteracts LPS-induced hypolocomotion and triggers locomotor sensitization expression.

PubMed

Tortorelli, Lucas Silva; Engelke, Douglas Senna; Lunardi, Paula; Mello E Souza, Tadeu; Santos-Junior, Jair Guilherme; Gonçalves, Carlos-Alberto

2015-01-01

Neuroimmune signalling underlies addiction and comorbid depression. Clinical observations indicate that infections and chronic lesions are more frequent in drug users and elevated inflammatory states are evident in cocaine dependents. Therefore, lipopolysaccharide (LPS) and inflammatory cytokines represent an important tool for the investigation of sickness, depressive illness and addiction behaviour. A major component of addiction is the progressive and persistent increase in locomotor activity after repeated drug administration and even prolonged periods of abstinence. The aim of this study was to investigate the response of locomotor sensitization when a non-sensitizing dose of cocaine is paired with a systemic inflammatory stimulus. LPS and cocaine were administered intraperitonealy in young-adult male C57bl/6 mice during a 5-day acquisition phase. After a 48-h withdrawal period all groups were challenged with cocaine to evaluate locomotor expression. During the acquisition phase, the LPS-treated groups displayed characteristic hypolocomotion related to sickness behaviour. The low dose of cocaine did not increase the distance travelled, characterizing a non-sensitization dose. Groups that received both LPS and cocaine did not display hypolocomotion, indicating that cocaine might counteract hypolocomotion sickness behaviour. Moreover, during challenge, only these animals expressed locomotor sensitization. Our results indicate that LPS could facilitate the expression of locomotor sensitization in mice and that the immune system may modulate cocaine-induced sensitization. Copyright © 2015 Elsevier B.V. All rights reserved.

Differential Processing of Isolated Object and Multi-item Pop-Out Displays in LIP and PFC.

PubMed

Meyers, Ethan M; Liang, Andy; Katsuki, Fumi; Constantinidis, Christos

2017-10-11

Objects that are highly distinct from their surroundings appear to visually "pop-out." This effect is present for displays in which: (1) a single cue object is shown on a blank background, and (2) a single cue object is highly distinct from surrounding objects; it is generally assumed that these 2 display types are processed in the same way. To directly examine this, we applied a decoding analysis to neural activity recorded from the lateral intraparietal (LIP) area and the dorsolateral prefrontal cortex (dlPFC). Our analyses showed that for the single-object displays, cue location information appeared earlier in LIP than in dlPFC. However, for the display with distractors, location information was substantially delayed in both brain regions, and information first appeared in dlPFC. Additionally, we see that pattern of neural activity is similar for both types of displays and across different color transformations of the stimuli, indicating that location information is being coded in the same way regardless of display type. These results lead us to hypothesize that 2 different pathways are involved processing these 2 types of pop-out displays. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

A 14-gene region of rat chromosome 8 in SHR-derived polydactylous congenic substrain affects muscle-specific insulin resistance, dyslipidaemia and visceral adiposity.

PubMed

Seda, O; Liska, F; Sedová, L; Kazdová, L; Krenová, D; Kren, V

2005-01-01

The SHR and the PD/Cub are two established rodent models of human metabolic syndrome. Introgression of a ca 30 cM region of rat chromosome 8 from PD/Cub onto the genetic background of SHR was previously shown to influence several of the metabolic syndrome-related traits along with causing the PLS in the SHR-Lx congenic strain. In the process of identification of the causative alleles, we have produced several congenic sublines. The differential segment of SHR-Lx PD5 congenic substrain [SHR.PD(D8Rat42-D8Arb23)/Cub] spans approximately 1.4 Mb encompassing only 14 genes. When comparing the metabolic, morphometric and gene expression profiles of the SHR-Lx PD5 vs. SHR, the polydactyly and several distinct metabolic features observed in the original SHR-Lx congenic were still manifested, suggesting that the responsible genes were "trapped" within the relatively short differential segment of PD/Cub origin in SHR-Lx PD5. Particularly, the SHR-Lx PD5 displayed substantial reduction of insulin sensitivity confined to skeletal muscle. Among the candidate genes, the promyelocytic leukaemia zinc-finger Plzf (Zbtb16) transcription repressor is most likely responsible for the Lx mutation resulting in PLS and could also be involved in the alteration of metabolic pathways. The sequence analysis of the Plzf gene revealed a SNP leading to a threonine to serine substitution in SHR at aminoacid position 208 (T208S). In summary, we have isolated a 1.4 Mb genomic region syntenic to human chromosome 11q23, which, apart from causing polydactyly-luxate syndrome (PLS), affects total body weight, adiposity, lipid profile, insulin sensitivity of skeletal muscle and related gene expression as shown in the SHR-Lx PD5 congenic substrain.

Use of fish parasite species richness indices in analyzing anthropogenically impacted coastal marine ecosystems

NASA Astrophysics Data System (ADS)

Dzikowski, R.; Paperna, I.; Diamant, A.

2003-10-01

The diversity of fish parasite life history strategies makes these species sensitive bioindicators of aquatic ecosystem health. While monoxenous (single-host) species may persist in highly perturbed, extreme environments, this is not necessarily true for heteroxenous (multiple-host) species. As many parasites possess complex life cycles and are transmitted through a chain of host species, their dependency on the latter to complete their life cycles renders them sensitive to perturbed environments. In the present study, parasite communities of grey mullet Liza aurata and Liza ramada (Mugilidae) were investigated at two Mediterranean coastal sites in northern Israel: the highly polluted Kishon Harbor (KH) and the relatively unspoiled reference site, Ma'agan Michael (MM). Both are estuarine sites in which grey mullet are one of the most common fish species. The results indicate that fish at the polluted site had significantly less trematode metacercariae than fish at the reference site. Heteroxenous gut helminths were completely absent at the polluted sampling site. Consequently, KH fish displayed lower mean parasite species richness. At the same time, KH fish mean monoxenous parasite richness was higher, although the prevalence of different monoxenous taxa was variable. Copepods had an increased prevalence while monogenean prevalence was significantly reduced at the polluted site. This variability may be attributed to the differential susceptibility of the parasites to the toxicity of different pollutants, their concentration, the exposure time and possible synergistic effects. In this study, we used the cumulative species curve model that extrapolates "true" species richness of a given habitat as a function of increasing sample size. We considered the heteroxenous and monoxenous species separately for each site, and comparison of curves yielded significant results. It is proposed to employ this approach, originally developed for estimating the "true" parasite species richness for a given habitat, in the characterization of communities of differentially impacted coastal marine ecosystems.

Is contextual cueing more than the guidance of visual-spatial attention?

PubMed

Schankin, Andrea; Hagemann, Dirk; Schubö, Anna

2011-04-01

When search displays are repeatedly presented, participants become faster in finding the target (contextual cueing, CC). It has been debated whether a more liberal response criterion might contribute to CC. In the current experiment, participants had to search through target-absent and target-present trials to compute d-prime as the measurement of sensitivity and beta as the measurement of response bias. Results showed that participants' sensitivity was not affected by the repetition of search displays. Although repeated displays led to both faster RTs and a more liberal response criterion, these effects were uncorrelated. In the event-related potential, RT effects were reflected by a late positive activity, which reflects response-related processes, but not by differences in the N2pc as electrophysiological correlate of focused attention. These results indicate that a more liberal response criterion is not the cause for CC effects in RTs but that other response-related processes might still contribute to the effect. Copyright © 2011 Elsevier B.V. All rights reserved.

Detection and quantification of microcystins (cyanobacterial hepatotoxins) with recombinant antibody fragments isolated from a naïve human phage display library.

PubMed

McElhiney, J; Lawton, L A; Porter, A J

2000-12-01

Single-chain antibody fragments against the cyanobacterial hepatotoxin microcystin-LR were isolated from a naive human phage display library and expressed in Escherichia coli. In competition enzyme-linked immunosorbent assay (ELISA), the most sensitive antibody clone selected from the library detected free microcystin-LR with an IC(50) value of 4 microM. It was found to cross react with three other microcystin variants - microcystin-RR, microcystin-LW and microcystin-LF - and detected microcystins in extracts of the cyanobacterium Microcystis aeruginosa, found to contain the toxins by high-performance liquid chromatography (HPLC). The quantification of microcystins in these extracts by ELISA and HPLC showed good correlation. Although the antibody isolated in this study was considerably less sensitive than the polyclonal and monoclonal antibodies already available for microcystin detection, phage display technology represents a cheaper, more rapid alternative for the production of anti-microcystin antibodies than the methods currently in use.

A fat option for the pig: Hepatocytic differentiated mesenchymal stem cells for translational research

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

Brückner, Sandra, E-mail: sandra.brueckner@medizin.uni-leipzig.de; Tautenhahn, Hans-Michael, E-mail: hans-michael.tautenhahn@medizin.uni-leipzig.de; TRM, Translational Centre for Regenerative Medicine, Philipp-Rosenthal-Str. 55, Leipzig D-04103

Study background: Extended liver resection is the only curative treatment option of liver cancer. Yet, the residual liver may not accomplish the high metabolic and regenerative capacity needed, which frequently leads to acute liver failure. Because of their anti-inflammatory and -apoptotic as well as pro-proliferative features, mesenchymal stem cells differentiated into hepatocyte-like cells might provide functional and regenerative compensation. Clinical translation of basic research requires pre-clinical approval in large animals. Therefore, we characterized porcine mesenchymal stem cells (MSC) from adipose tissue and bone marrow and their hepatocyte differentiation potential for future assessment of functional liver support after surgical intervention inmore » the pig model. Methods: Mesenchymal surface antigens and multi-lineage differentiation potential of porcine MSC isolated by collagenase digestion either from bone marrow or adipose tissue (subcutaneous/visceral) were assessed by flow cytometry. Morphology and functional properties (urea-, glycogen synthesis and cytochrome P450 activity) were determined during culture under differentiation conditions and compared with primary porcine hepatocytes. Results: MSC from porcine adipose tissue and from bone marrow express the typical mesenchymal markers CD44, CD29, CD90 and CD105 but not haematopoietic markers. MSC from both sources displayed differentiation into the osteogenic as well as adipogenic lineage. After hepatocyte differentiation, expression of CD105 decreased significantly and cells adopted the typical polygonal morphology of hepatocytes. Glycogen storage was comparable in adipose tissue- and bone marrow-derived cells. Urea synthesis was about 35% lower in visceral than in subcutaneous adipose tissue-derived MSC. Cytochrome P450 activity increased significantly during differentiation and was twice as high in hepatocyte-like cells generated from bone marrow as from adipose tissue. Conclusion: The hepatocyte differentiation of porcine adipose tissue-derived MSC was shown for the first time yielding hepatocyte-like cells with specific functions similar in bone marrow and subcutaneous adipose tissue-derived MSC. That makes them good pre-clinical candidates for supportive approaches after liver resection in the pig. - Highlights: • First time to show hepatocytic differentiation of porcine adipose tissue-derived MSC. • Hepatocytic-differentiated MSC display metabolic qualities of primary hepatocytes. • Metabolic potency varies between differentiated MSC from different tissues. • MSC are good candidates for pre-clinical evaluation of stem cell-based therapies.« less

The Permeability Transition Pore Controls Cardiac Mitochondrial Maturation and Myocyte Differentiation

PubMed Central

Hom, Jennifer R.; Quintanilla, Rodrigo A.; Hoffman, David L.; Karen L., de Mesy Bentley; Molkentin, Jeffery D.; Sheu, Shey-Shing; Porter, George A.

2011-01-01

SUMMARY Although mature myocytes rely on mitochondria as the primary source of energy, the role of mitochondria in the developing heart is not well known. Here, we find closure of the mitochondrial permeability transition pore (mPTP) drives maturation of mitochondrial structure and function and myocyte differentiation. Cardiomyocytes at embryonic day (E) 9.5, when compared to E13.5, displayed fragmented mitochondria with few cristae, a less polarized mitochondrial membrane potential, higher reactive oxygen species (ROS) levels, and an open mPTP. Pharmacologic and genetic closing of the mPTP yielded maturation of mitochondrial structure and function, lowered ROS, and increased myocyte differentiation (measured by counting Z-bands). Furthermore, myocyte differentiation was inhibited and enhanced with oxidant and antioxidant treatment, respectively, suggesting that redox signaling pathways lie downstream of mitochondria to regulate cardiac myocyte differentiation. PMID:21920313

The Habitat Project

ERIC Educational Resources Information Center

Hein, Annamae J.

2011-01-01

The Habitat Project is a multiday, differentiated, interdisciplinary environmental science lesson that incorporates skill-building and motivational strategies to internalize ecosystem vocabulary. Middle school students research an animal, display its physical characteristics on a poster, build a three-dimensional habitat and present their work…

Microarray and differential display identify genes involved in jasmonate-dependent anther development.

PubMed

Mandaokar, Ajin; Kumar, V Dinesh; Amway, Matt; Browse, John

2003-07-01

Jasmonate (JA) is a signaling compound essential for anther development and pollen fertility in Arabidopsis. Mutations that block the pathway of JA synthesis result into male sterility. To understand the processes of anther and pollen maturation, we used microarray and differential display approaches to compare gene expression pattern in anthers of wild-type Arabidopsis and the male-sterile mutant, opr3. Microarray experiment revealed 25 genes that were up-regulated more than 1.8-fold in wild-type anthers as compared to mutant anthers. Experiments based on differential display identified 13 additional genes up-regulated in wild-type anthers compared to opr3 for a total of 38 differentially expressed genes. Searches of the Arabidopsis and non-redundant databases disclosed known or likely functions for 28 of the 38 genes identified, while 10 genes encode proteins of unknown function. Northern blot analysis of eight representative clones as probes confirmed low expression in opr3 anthers compared with wild-type anthers. JA responsiveness of these same genes was also investigated by northern blot analysis of anther RNA isolated from wild-type and opr3 plants, In these experiments, four genes were induced in opr3 anthers within 0.5-1 h of JA treatment while the remaining genes were up-regulated only 1-8 h after JA application. None of these genes was induced by JA in anthers of the coil mutant that is deficient in JA responsiveness. The four early-induced genes in opr3 encode lipoxygenase, a putative bHLH transcription factor, epithiospecifier protein and an unknown protein. We propose that these and other early components may be involved in JA signaling and in the initiation of developmental processes. The four late genes encode an extensin-like protein, a peptide transporter and two unknown proteins, which may represent components required later in anther and pollen maturation. Transcript profiling has provided a successful approach to identify genes involved in anther and pollen maturation in Arabidopsis.

Evaluation of genetic diversity and population structure of West-Central Indian cattle breeds.

PubMed

Shah, Tejas M; Patel, Jaina S; Bhong, Chandrakant D; Doiphode, Aakash; Umrikar, Uday D; Parmar, Shivnandan S; Rank, Dharamshibhai N; Solanki, Jitendra V; Joshi, Chaitanya G

2013-08-01

Evaluations of genetic diversity in domestic livestock populations are necessary to implement region-specific conservation measures. We determined the genetic diversity and evolutionary relationships among eight geographically and phenotypically diverse cattle breeds indigenous to west-central India by genotyping these animals for 22 microsatellite loci. A total of 326 alleles were detected, and the expected heterozygosity ranged from 0.614 (Kenkatha) to 0.701 (Dangi). The mean number of alleles among the cattle breeds ranged from 7.182 (Khillar) to 9.409 (Gaolao). There were abundant genetic variations displayed within breeds, and the genetic differentiation was also high between the Indian cattle breeds, which displayed 15.9% of the total genetic differentiation among the different breeds. The genetic differentiation (pairwise FST ) among the eight Indian breeds varied from 0.0126 for the Kankrej-Malvi pair to 0.2667 for Khillar-Kenkatha pair. The phylogeny, principal components analysis, and structure analysis further supported close grouping of Kankrej, Malvi, Nimari and Gir; Gaolao and Kenkatha, whereas Dangi and Khillar remained at distance from other breeds. © 2012 The Authors, Animal Genetics © 2012 Stichting International Foundation for Animal Genetics.

Alternative dominance of the parental genomes in hybrid cells generated through the fusion of mouse embryonic stem cells with fibroblasts.

PubMed

Matveeva, Natalia M; Fishman, Veniamin S; Zakharova, Irina S; Shevchenko, Alexander I; Pristyazhnyuk, Inna E; Menzorov, Aleksei G; Serov, Oleg L

2017-12-22

For the first time, two types of hybrid cells with embryonic stem (ES) cell-like and fibroblast-like phenotypes were produced through the fusion of mouse ES cells with fibroblasts. Transcriptome analysis of 2,848 genes differentially expressed in the parental cells demonstrated that 34-43% of these genes are expressed in hybrid cells, consistent with their phenotypes; 25-29% of these genes display intermediate levels of expression, and 12-16% of these genes maintained expression at the parental cell level, inconsistent with the phenotype of the hybrid cell. Approximately 20% of the analyzed genes displayed unexpected expression patterns that differ from both parents. An unusual phenomenon was observed, namely, the illegitimate activation of Xist expression and the inactivation of one of two X-chromosomes in the near-tetraploid fibroblast-like hybrid cells, whereas both Xs were active before and after in vitro differentiation of the ES cell-like hybrid cells. These results and previous data obtained on heterokaryons suggest that the appearance of hybrid cells with a fibroblast-like phenotype reflects the reprogramming, rather than the induced differentiation, of the ES cell genome under the influence of a somatic partner.

Essential role of citron kinase in cytokinesis of spermatogenic precursors.

PubMed

Cunto, Ferdinando Di; Imarisio, Sara; Camera, Paola; Boitani, Carla; Altruda, Fiorella; Silengo, Lorenzo

2002-12-15

During spermatogenesis, the first morphological indication of spermatogonia differentiation is incomplete cytokinesis, followed by the assembly of stable intercellular cytoplasmic communications. This distinctive feature of differentiating male germ cells has been highly conserved during evolution, suggesting that regulation of the cytokinesis endgame is a crucial aspect of spermatogenesis. However, the molecular mechanisms underlying testis-specific regulation of cytokinesis are still largely unknown. Citron kinase is a myotonin-related protein acting downstream of the GTPase Rho in cytokinesis control. We previously reported that Citron kinase knockout mice are affected by a complex neurological syndrome caused by cytokinesis block and apoptosis of specific neuronal precursors. In this report we show that, in addition, these mice display a dramatic testicular impairment, with embryonic and postnatal loss of undifferentiated germ cells and complete absence of mature spermatocytes. By contrast, the ovaries of mutant females appear essentially normal. Developmental analysis revealed that the cellular depletion observed in mutant testes is caused by increased apoptosis of undifferentiated and differentiating precursors. The same cells display a severe cytokinesis defect, resulting in the production of multinucleated cells and apoptosis. Our data indicate that Citron kinase is specifically required for cytokinesis of the male germ line.

Maltodextrin and sucrose preferences in sweet-sensitive (C57BL/6J) and subsensitive (129P3/J) mice revisited.

PubMed

Ackroff, Karen; Sclafani, Anthony

2016-10-15

Mice are attracted to the tastes of sugar and maltodextrin solutions. Sugar taste is mediated by the T1R2/T1R3 sweet taste receptor, while maltodextrin taste is dependent upon a different as yet unidentified receptor. In a prior study sweet-sensitive C57BL/6J (B6) mice displayed similar preferences for sucrose and maltodextrin solutions in 24-h saccharide vs. water choice tests that exceeded those of sweet-subsensitive 129P3/J (129) mice. In a subsequent experiment reported here, sucrose and maltodextrin (Polycose) preference and acceptance were compared in the two strains in saccharide vs. saccharide choice tests with isocaloric concentrations (0.5-32%). The 129 mice displayed significantly greater maltodextrin preferences than B6 mice at mid-range concentrations (2-8%), while the mice displayed an opposite preference profile at the highest concentration (32%). As in prior studies, 129 mice consumed less total saccharide than B6 mice at lower concentrations. These findings show that the conclusions reached from tastant vs. water tests may differ from those pitting one tastant against another. The increased sucrose preference and intake of B6 mice, relative to 129 mice, is consistent with their sweet-sensitive phenotype. Copyright © 2016 Elsevier Inc. All rights reserved.

Sex dimorphisms of crossbridge cycling kinetics in transgenic hypertrophic cardiomyopathy mice.

PubMed

Birch, Camille L; Behunin, Samantha M; Lopez-Pier, Marissa A; Danilo, Christiane; Lipovka, Yulia; Saripalli, Chandra; Granzier, Henk; Konhilas, John P

2016-07-01

Familial hypertrophic cardiomyopathy (HCM) is a disease of the sarcomere and may lead to hypertrophic, dilated, restrictive, and/or arrhythmogenic cardiomyopathy, congestive heart failure, or sudden cardiac death. We hypothesized that hearts from transgenic HCM mice harboring a mutant myosin heavy chain increase the energetic cost of contraction in a sex-specific manner. To do this, we assessed Ca(2+) sensitivity of tension and crossbridge kinetics in demembranated cardiac trabeculas from male and female wild-type (WT) and HCM hearts at an early time point (2 mo of age). We found a significant effect of sex on Ca(2+) sensitivity such that male, but not female, HCM mice displayed a decrease in Ca(2+) sensitivity compared with WT counterparts. The HCM transgene and sex significantly impacted the rate of force redevelopment by a rapid release-restretch protocol and tension cost by the ATPase-tension relationship. In each of these measures, HCM male trabeculas displayed a gain-of-function when compared with WT counterparts. In addition, cardiac remodeling measured by echocardiography, histology, morphometry, and posttranslational modifications demonstrated sex- and HCM-specific effects. In conclusion, female and male HCM mice display sex dimorphic crossbridge kinetics accompanied by sex- and HCM-dependent cardiac remodeling at the morphometric, histological, and cellular level. Copyright © 2016 the American Physiological Society.

The effects of display time and eccentricity on the detection of amplitude and phase degradations in textured stimuli.

PubMed

Clarke, Alasdair D F; Green, Patrick R; Chantler, Mike J

2012-03-08

The amplitude and phase spectra of an image contain important information for perception, and a large body of work has investigated the effects of manipulating these spectra on the recognition or classification of image content. Here, we use a novel means of investigating sensitivity to amplitude and phase spectra properties, testing the ability of observers to detect degradations of the spectral content of synthetic images of textured surfaces that are broadband in the frequency domain. The effects of display time and retinal eccentricity on sensitivity to these two manipulations are compared using stimuli matched for difficulty of detection. We find no difference between the time courses for the detection of degradation in the two spectra; in both cases, accuracy rises above chance when display times are greater than 80 ms. Increasing retinal eccentricity to 8.7°, however, has a significantly stronger effect on the accuracy of detecting degradations of the amplitude spectrum than of the phase spectrum. Further, sensitivity to phase randomization that is restricted to low spatial frequencies is greater in the periphery (at 8.7° eccentricity) than in the fovea. These last two results imply that the fovea and periphery are specialized for the processing of phase spectrum information in distinct spatial frequency bands.

Writing next-generation display photomasks

NASA Astrophysics Data System (ADS)

Sandstrom, Tor; Wahlsten, Mikael; Park, Youngjin

2016-10-01

Recent years have seen a fast technical development within the display area. Displays get ever higher pixel density and the pixels get smaller. Current displays have over 800 PPI and market forces will eventually drive for densities of 2000 PPI or higher. The transistor backplanes also get more complex. OLED displays require 4-7 transistors per pixel instead of the typical 1-2 transistors used for LCDs, and they are significantly more sensitive to errors. New large-area maskwriters have been developed for masks used in high volume production of screens for state-of-theart smartphones. Redesigned laser optics with higher NA and lower aberrations improve resolution and CD uniformity and reduce mura effects. The number of beams has been increased to maintain the throughput despite the higher writing resolution. OLED displays are highly sensitive to placement errors and registration in the writers has been improved. To verify the registration of produced masks a separate metrology system has been developed. The metrology system is self-calibrated to high accuracy. The calibration is repeatable across machines and sites using Z-correction. The repeatability of the coordinate system makes it possible to standardize the coordinate system across an entire supply chain or indeed across the entire industry. In-house metrology is a commercial necessity for high-end mask shop, but also the users of the masks, the panel makers, would benefit from having in-house metrology. It would act as the reference for their mask suppliers, give better predictive and post mortem diagnostic power for the panel process, and the metrology could be used to characterize and improve the entire production loop from data to panel.

Long Noncoding RNAs: New Players in the Osteogenic Differentiation of Bone Marrow- and Adipose-Derived Mesenchymal Stem Cells.

PubMed

Yang, Qiaolin; Jia, Lingfei; Li, Xiaobei; Guo, Runzhi; Huang, Yiping; Zheng, Yunfei; Li, Weiran

2018-06-01

Mesenchymal stem cells (MSCs) are an important population of multipotent stem cells that differentiate into multiple lineages and display great potential in bone regeneration and repair. Although the role of protein-coding genes in the osteogenic differentiation of MSCs has been extensively studied, the functions of noncoding RNAs in the osteogenic differentiation of MSCs are unclear. The recent application of next-generation sequencing to MSC transcriptomes has revealed that long noncoding RNAs (lncRNAs) are associated with the osteogenic differentiation of MSCs. LncRNAs are a class of non-coding transcripts of more than 200 nucleotides in length. Noncoding RNAs are thought to play a key role in osteoblast differentiation through various regulatory mechanisms including chromatin modification, transcription factor binding, competent endogenous mechanism, and other post-transcriptional mechanisms. Here, we review the roles of lncRNAs in the osteogenic differentiation of bone marrow- and adipose-derived stem cells and provide a theoretical foundation for future research.

Dual-sensing porphyrin-containing copolymer nanosensor as full-spectrum colorimeter and ultra-sensitive thermometer.

PubMed

Yan, Qiang; Yuan, Jinying; Kang, Yan; Cai, Zhinan; Zhou, Lilin; Yin, Yingwu

2010-04-28

A porphyrin-containing copolymer has dual-sensing in response to metal ions and temperature as a novel nanosensor. Triggered by ions, the sensor exhibits full-color tunable behavior as a cationic detector and colorimeter. Responding to temperature, the sensor displays an "isothermal" thermochromic point as an ultra-sensitive thermometer.

Perceiving Group Behavior: Sensitive Ensemble Coding Mechanisms for Biological Motion of Human Crowds

ERIC Educational Resources Information Center

Sweeny, Timothy D.; Haroz, Steve; Whitney, David

2013-01-01

Many species, including humans, display group behavior. Thus, perceiving crowds may be important for social interaction and survival. Here, we provide the first evidence that humans use ensemble-coding mechanisms to perceive the behavior of a crowd of people with surprisingly high sensitivity. Observers estimated the headings of briefly presented…

Dynamic and differential expression of the gonadal aromatase during the process of sexual differentiation in a novel transgenic cyp19a1a-eGFP zebrafish line.

PubMed

Hinfray, Nathalie; Sohm, Frédéric; Caulier, Morgane; Chadili, Edith; Piccini, Benjamin; Torchy, Camille; Porcher, Jean-Marc; Guiguen, Yann; Brion, François

2018-05-15

In zebrafish, there exists a clear need for new tools to study sex differentiation dynamic and its perturbation by endocrine disrupting chemicals. In this context, we developed and characterized a novel transgenic zebrafish line expressing green fluorescent protein (GFP) under the control of the zebrafish cyp19a1a (gonadal aromatase) promoter. In most gonochoristic fish species including zebrafish, cyp19a1a, the enzyme responsible for the synthesis of estrogens, has been shown to play a critical role in the processes of reproduction and sexual differentiation. This novel cyp19a1a-eGFP transgenic line allowed a deeper characterization of expression and localization of cyp19a1a gene in zebrafish gonads both at the adult stage and during development. At the adult stage, GFP expression was higher in ovaries than in testis. We showed a perfect co-expression of GFP and endogenous Cyp19a1a protein in gonads that was mainly localized in the cytoplasm of peri-follicular cells in the ovary and of Leydig and germ cells in the testis. During development, GFP was expressed in all immature gonads of 20 dpf-old zebrafish. Then, GFP expression increased in early differentiated female at 30 and 35dpf to reach a high GFP intensity in well-differentiated ovaries at 40dpf. On the contrary, males consistently displayed low GFP expression as compared to female whatever their stage of development, resulting in a clear dimorphic expression between both sexes. Interestingly, fish that undergoes ovary-to-testis transition (35 and 40dpf) presented GFP levels similar to males or intermediate between females and males. In this transgenic line our results confirm that cyp19a1a is expressed early during development, before the histological differentiation of the gonads, and that the down-regulation of cyp19a1a expression is likely responsible for the testicular differentiation. Moreover, we show that although cyp19a1a expression exhibits a clear dimorphic expression pattern in gonads during sexual differentiation, its expression persists whatever the sex suggesting that estradiol synthesis is important for gonadal development of both sexes. Monitoring the expression of GFP in control and exposed-fish will help determine the sensitivity of this transgenic line to EDCs and to refine mechanistic based-assays for the study of EDCs. In fine, this transgenic zebrafish line will be a useful tool to study physiological processes such as reproduction and sexual differentiation, and their perturbations by EDCs. Copyright © 2017 Elsevier Inc. All rights reserved.

Specific serine-proline phosphorylation and glycogen synthase kinase 3β-directed subcellular targeting of stathmin 3/Sclip in neurons.

PubMed

Devaux, Sara; Poulain, Fabienne E; Devignot, Véronique; Lachkar, Sylvie; Irinopoulou, Theano; Sobel, André

2012-06-22

During nervous system development, neuronal growth, migration, and functional morphogenesis rely on the appropriate control of the subcellular cytoskeleton including microtubule dynamics. Stathmin family proteins play major roles during the various stages of neuronal differentiation, including axonal growth and branching, or dendritic development. We have shown previously that stathmins 2 (SCG10) and 3 (SCLIP) fulfill distinct, independent and complementary regulatory roles in axonal morphogenesis. Although the two proteins have been proposed to display the four conserved phosphorylation sites originally identified in stathmin 1, we show here that they possess distinct phosphorylation sites within their specific proline-rich domains (PRDs) that are differentially regulated by phosphorylation by proline-directed kinases involved in the control of neuronal differentiation. ERK2 or CDK5 phosphorylate the two proteins but with different site specificities. We also show for the first time that, unlike stathmin 2, stathmin 3 is a substrate for glycogen synthase kinase (GSK) 3β both in vitro and in vivo. Interestingly, stathmin 3 phosphorylated at its GSK-3β target site displays a specific subcellular localization at neuritic tips and within the actin-rich peripheral zone of the growth cone of differentiating hippocampal neurons in culture. Finally, pharmacological inhibition of GSK-3β induces a redistribution of stathmin 3, but not stathmin 2, from the periphery toward the Golgi region of neurons. Stathmin proteins can thus be either regulated locally or locally targeted by specific phosphorylation, each phosphoprotein of the stathmin family fulfilling distinct and specific roles in the control of neuronal differentiation.

Slave boson theory of orbital differentiation with crystal field effects: Application to UO 2

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

Lanatà, Nicola; Yao, Yongxin; Deng, Xiaoyu

We derive an exact operatorial reformulation of the rotational invariant slave boson method, and we apply it to describe the orbital differentiation in strongly correlated electron systems starting from first principles. The approach enables us to treat strong electron correlations, spin-orbit coupling, and crystal field splittings on the same footing by exploiting the gauge invariance of the mean-field equations. Furthermore, we apply our theory to the archetypical nuclear fuel UO 2 and show that the ground state of this system displays a pronounced orbital differentiation within the 5f manifold, with Mott-localized Γ 8 and extended Γ 7 electrons.

[DIFFERENTIAL DIAGNOSIS OF TUMOROID-LIKE ABSCESS AND LUNG CANCER].

PubMed

Churylin, R

2015-01-01

The purpose of work is development and clarification of roentgenology displays of tumoroidea variant of abscess of lungs for differential diagnostics him with the cancer of lungs. Practically in most cases abscess of lungs there is a necessity of leadthrough of differential diagnostics with in a number of nosology forms, including with the cavernous form of peripheral cancer of lungs. The features of flow of roentgenologic picture of tumoroidea variant are resulted, alike symptoms, differ ences and signs which allow to set a correct diagnosis, are resulted, the value of follow-up of roent genologic research and use of computed tomography is underlined.

Slave boson theory of orbital differentiation with crystal field effects: Application to UO 2

DOE PAGES

Lanatà, Nicola; Yao, Yongxin; Deng, Xiaoyu; ...

2017-03-23

We derive an exact operatorial reformulation of the rotational invariant slave boson method, and we apply it to describe the orbital differentiation in strongly correlated electron systems starting from first principles. The approach enables us to treat strong electron correlations, spin-orbit coupling, and crystal field splittings on the same footing by exploiting the gauge invariance of the mean-field equations. Furthermore, we apply our theory to the archetypical nuclear fuel UO 2 and show that the ground state of this system displays a pronounced orbital differentiation within the 5f manifold, with Mott-localized Γ 8 and extended Γ 7 electrons.

Slave Boson Theory of Orbital Differentiation with Crystal Field Effects: Application to UO_{2}.

PubMed

Lanatà, Nicola; Yao, Yongxin; Deng, Xiaoyu; Dobrosavljević, Vladimir; Kotliar, Gabriel

2017-03-24

We derive an exact operatorial reformulation of the rotational invariant slave boson method, and we apply it to describe the orbital differentiation in strongly correlated electron systems starting from first principles. The approach enables us to treat strong electron correlations, spin-orbit coupling, and crystal field splittings on the same footing by exploiting the gauge invariance of the mean-field equations. We apply our theory to the archetypical nuclear fuel UO_{2} and show that the ground state of this system displays a pronounced orbital differentiation within the 5f manifold, with Mott-localized Γ_{8} and extended Γ_{7} electrons.

Use of the stereoscopic virtual reality display system for the detection and characterization of intracranial aneurysms: A Icomparison with conventional computed tomography workstation and 3D rotational angiography.

PubMed

Liu, Xiujuan; Tao, Haiquan; Xiao, Xigang; Guo, Binbin; Xu, Shangcai; Sun, Na; Li, Maotong; Xie, Li; Wu, Changjun

2018-07-01

This study aimed to compare the diagnostic performance of the stereoscopic virtual reality display system with the conventional computed tomography (CT) workstation and three-dimensional rotational angiography (3DRA) for intracranial aneurysm detection and characterization, with a focus on small aneurysms and those near the bone. First, 42 patients with suspected intracranial aneurysms underwent both 256-row CT angiography (CTA) and 3DRA. Volume rendering (VR) images were captured using the conventional CT workstation. Next, VR images were transferred to the stereoscopic virtual reality display system. Two radiologists independently assessed the results that were obtained using the conventional CT workstation and stereoscopic virtual reality display system. The 3DRA results were considered as the ultimate reference standard. Based on 3DRA images, 38 aneurysms were confirmed in 42 patients. Two cases were misdiagnosed and 1 was missed when the traditional CT workstation was used. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of the conventional CT workstation were 94.7%, 85.7%, 97.3%, 75%, and99.3%, respectively, on a per-aneurysm basis. The stereoscopic virtual reality display system missed a case. The sensitivity, specificity, PPV, NPV, and accuracy of the stereoscopic virtual reality display system were 100%, 85.7%, 97.4%, 100%, and 97.8%, respectively. No difference was observed in the accuracy of the traditional CT workstation, stereoscopic virtual reality display system, and 3DRA in detecting aneurysms. The stereoscopic virtual reality display system has some advantages in detecting small aneurysms and those near the bone. The virtual reality stereoscopic vision obtained through the system was found as a useful tool in intracranial aneurysm diagnosis and pre-operative 3D imaging. Copyright © 2018 Elsevier B.V. All rights reserved.

Optimal cure cycle design for autoclave processing of thick composites laminates: A feasibility study

NASA Technical Reports Server (NTRS)

Hou, Jean W.

1985-01-01

The thermal analysis and the calculation of thermal sensitivity of a cure cycle in autoclave processing of thick composite laminates were studied. A finite element program for the thermal analysis and design derivatives calculation for temperature distribution and the degree of cure was developed and verified. It was found that the direct differentiation was the best approach for the thermal design sensitivity analysis. In addition, the approach of the direct differentiation provided time histories of design derivatives which are of great value to the cure cycle designers. The approach of direct differentiation is to be used for further study, i.e., the optimal cycle design.

Nano-Filament Field Emission Cathode Development Final Report CRADA No. TSB-0731-93

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

Bernhardt, Tony; Fahlen, Ted

At the time the CRADA was established, Silicon Video Corporation, of Cupertino, CA was a one-year-old rapidly growing start-up company. SVC was developing flat panel displays (FPDs) to replace Cathode Ray Terminals (CRTs) for personal computers, work stations and televisions. They planned to base their products on low cost and energy efficient field emission technology. It was universally recognized that the display was both the dominant cost item and differentiating feature of many products such as laptop computers and hand-held electronics and that control of the display technology through U.S. sources was essential to success in these markets. The purposemore » of this CRADA project was to determine if electrochemical planarization would be a viable, inexpensive alternative to current optical polishing techniques for planarizing the surface of a ceramic backplate of a thin film display.« less

Differential behavioral sensitivity to carbon dioxide (CO2) inhalation in rats

PubMed Central

Winter, Andrew; Ahlbrand, Rebecca; Naik, Devanshi; Sah, Renu

2017-01-01

Inhalation of carbon dioxide (CO2) is frequently employed as a biological challenge to evoke intense fear and anxiety. In individuals with panic disorder, CO2 reliably evokes panic attacks. Sensitivity to CO2 is highly heterogeneous among individuals, and although a genetic component is implicated, underlying mechanisms are not clear. Preclinical models that can simulate differential responsivity to CO2 are therefore relevant. In the current study we investigated CO2-evoked behavioral responses in four different rat strains: Sprague-Dawley (SD), Wistar (W), Long Evans (LE) and Wistar-Kyoto, (WK) rats. We also assessed tryptophan hydroxylase 2 (TPH-2)-positive serotonergic neurons in anxiety/panic regulatory subdivisions of the dorsal raphe nucleus (DR), as well as dopamine β hydroxylase (DβH)-positive noradrenergic neurons in the locus coeruleus, implicated in central CO2-chemosensitivity. Behavioral responsivity to CO2 inhalation varied between strains. CO2-evoked immobility was significantly higher in LE and WK rats as compared with W and SD cohorts. Differences were also observed in CO2-evoked rearing and grooming behaviors. Exposure to CO2 did not produce conditioned behavioral responses upon re-exposure to CO2 context in any strain. Reduced TPH-2 positive cell counts were observed specifically in the panic-regulatory dorsal raphe ventrolateral (DRVL)-ventrolateral periaqueductal grey (VLPAG) subdivision in CO2-sensitive strains. Conversely, DβH positive cell counts within the LC were significantly higher in CO2-sensitive strains. Collectively, our data provide evidence for strain dependent, differential CO2-sensitivity and potential differences in monoaminergic systems regulating panic and anxiety. Comparative studies between CO2-vulnerable and resistant strains may facilitate the mechanistic understanding of differential CO2-sensitivity in the development of panic and anxiety disorders. PMID:28087339

A Lateral Differential Resonant Pressure Microsensor Based on SOI-Glass Wafer-Level Vacuum Packaging.

PubMed

Xie, Bo; Xing, Yonghao; Wang, Yanshuang; Chen, Jian; Chen, Deyong; Wang, Junbo

2015-09-21

This paper presents the fabrication and characterization of a resonant pressure microsensor based on SOI-glass wafer-level vacuum packaging. The SOI-based pressure microsensor consists of a pressure-sensitive diaphragm at the handle layer and two lateral resonators (electrostatic excitation and capacitive detection) on the device layer as a differential setup. The resonators were vacuum packaged with a glass cap using anodic bonding and the wire interconnection was realized using a mask-free electrochemical etching approach by selectively patterning an Au film on highly topographic surfaces. The fabricated resonant pressure microsensor with dual resonators was characterized in a systematic manner, producing a quality factor higher than 10,000 (~6 months), a sensitivity of about 166 Hz/kPa and a reduced nonlinear error of 0.033% F.S. Based on the differential output, the sensitivity was increased to two times and the temperature-caused frequency drift was decreased to 25%.

A Lateral Differential Resonant Pressure Microsensor Based on SOI-Glass Wafer-Level Vacuum Packaging

PubMed Central

Xie, Bo; Xing, Yonghao; Wang, Yanshuang; Chen, Jian; Chen, Deyong; Wang, Junbo

2015-01-01

This paper presents the fabrication and characterization of a resonant pressure microsensor based on SOI-glass wafer-level vacuum packaging. The SOI-based pressure microsensor consists of a pressure-sensitive diaphragm at the handle layer and two lateral resonators (electrostatic excitation and capacitive detection) on the device layer as a differential setup. The resonators were vacuum packaged with a glass cap using anodic bonding and the wire interconnection was realized using a mask-free electrochemical etching approach by selectively patterning an Au film on highly topographic surfaces. The fabricated resonant pressure microsensor with dual resonators was characterized in a systematic manner, producing a quality factor higher than 10,000 (~6 months), a sensitivity of about 166 Hz/kPa and a reduced nonlinear error of 0.033% F.S. Based on the differential output, the sensitivity was increased to two times and the temperature-caused frequency drift was decreased to 25%. PMID:26402679

Sensitivity derivatives for advanced CFD algorithm and viscous modelling parameters via automatic differentiation

NASA Technical Reports Server (NTRS)

Green, Lawrence L.; Newman, Perry A.; Haigler, Kara J.

1993-01-01

The computational technique of automatic differentiation (AD) is applied to a three-dimensional thin-layer Navier-Stokes multigrid flow solver to assess the feasibility and computational impact of obtaining exact sensitivity derivatives typical of those needed for sensitivity analyses. Calculations are performed for an ONERA M6 wing in transonic flow with both the Baldwin-Lomax and Johnson-King turbulence models. The wing lift, drag, and pitching moment coefficients are differentiated with respect to two different groups of input parameters. The first group consists of the second- and fourth-order damping coefficients of the computational algorithm, whereas the second group consists of two parameters in the viscous turbulent flow physics modelling. Results obtained via AD are compared, for both accuracy and computational efficiency with the results obtained with divided differences (DD). The AD results are accurate, extremely simple to obtain, and show significant computational advantage over those obtained by DD for some cases.

Sampling-Based Stochastic Sensitivity Analysis Using Score Functions for RBDO Problems with Correlated Random Variables

DTIC Science & Technology

2010-08-01

a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. a ...SECURITY CLASSIFICATION OF: This study presents a methodology for computing stochastic sensitivities with respect to the design variables, which are the...Random Variables Report Title ABSTRACT This study presents a methodology for computing stochastic sensitivities with respect to the design variables

Differential Susceptibility to the Environment: Are Developmental Models Compatible with the Evidence from Twin Studies?

ERIC Educational Resources Information Center

Del Giudice, Marco

2016-01-01

According to models of differential susceptibility, the same neurobiological and temperamental traits that determine increased sensitivity to stress and adversity also confer enhanced responsivity to the positive aspects of the environment. Differential susceptibility models have expanded to include complex developmental processes in which genetic…

Characterization of three human cell line models for high-throughput neuronal cytotoxicity screening.

PubMed

Tong, Zhi-Bin; Hogberg, Helena; Kuo, David; Sakamuru, Srilatha; Xia, Menghang; Smirnova, Lena; Hartung, Thomas; Gerhold, David

2017-02-01

More than 75 000 man-made chemicals contaminate the environment; many of these have not been tested for toxicities. These chemicals demand quantitative high-throughput screening assays to assess them for causative roles in neurotoxicities, including Parkinson's disease and other neurodegenerative disorders. To facilitate high throughput screening for cytotoxicity to neurons, three human neuronal cellular models were compared: SH-SY5Y neuroblastoma cells, LUHMES conditionally-immortalized dopaminergic neurons, and Neural Stem Cells (NSC) derived from human fetal brain. These three cell lines were evaluated for rapidity and degree of differentiation, and sensitivity to 32 known or candidate neurotoxicants. First, expression of neural differentiation genes was assayed during a 7-day differentiation period. Of the three cell lines, LUHMES showed the highest gene expression of neuronal markers after differentiation. Both in the undifferentiated state and after 7 days of neuronal differentiation, LUHMES cells exhibited greater cytotoxic sensitivity to most of 32 suspected or known neurotoxicants than SH-SY5Y or NSCs. LUHMES cells were also unique in being more susceptible to several compounds in the differentiating state than in the undifferentiated state; including known neurotoxicants colchicine, methyl-mercury (II), and vincristine. Gene expression results suggest that differentiating LUHMES cells may be susceptible to apoptosis because they express low levels of anti-apoptotic genes BCL2 and BIRC5/survivin, whereas SH-SY5Y cells may be resistant to apoptosis because they express high levels of BCL2, BIRC5/survivin, and BIRC3 genes. Thus, LUHMES cells exhibited favorable characteristics for neuro-cytotoxicity screening: rapid differentiation into neurons that exhibit high level expression neuronal marker genes, and marked sensitivity of LUHMES cells to known neurotoxicants. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

METAL BIOSENSORS: DEVELOPMENT AND ENVIRONMENTAL TESTING

EPA Science Inventory

Proteomic and Transcriptional Findings

P. putida cells responded differentially to Cd and Cu exposures at the proteomic and transcriptome levels. The cells displayed different stress responses that correlated with a more intense oxidative stress imposed...

Development and evaluation of a method of calibrating medical displays based on fixed adaptation

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

Sund, Patrik, E-mail: patrik.sund@vgregion.se; Månsson, Lars Gunnar; Båth, Magnus

2015-04-15

Purpose: The purpose of this work was to develop and evaluate a new method for calibration of medical displays that includes the effect of fixed adaptation and by using equipment and luminance levels typical for a modern radiology department. Methods: Low contrast sinusoidal test patterns were derived at nine luminance levels from 2 to 600 cd/m{sup 2} and used in a two alternative forced choice observer study, where the adaptation level was fixed at the logarithmic average of 35 cd/m{sup 2}. The contrast sensitivity at each luminance level was derived by establishing a linear relationship between the ten pattern contrastmore » levels used at every luminance level and a detectability index (d′) calculated from the fraction of correct responses. A Gaussian function was fitted to the data and normalized to the adaptation level. The corresponding equation was used in a display calibration method that included the grayscale standard display function (GSDF) but compensated for fixed adaptation. In the evaluation study, the contrast of circular objects with a fixed pixel contrast was displayed using both calibration methods and was rated on a five-grade scale. Results were calculated using a visual grading characteristics method. Error estimations in both observer studies were derived using a bootstrap method. Results: The contrast sensitivities for the darkest and brightest patterns compared to the contrast sensitivity at the adaptation luminance were 37% and 56%, respectively. The obtained Gaussian fit corresponded well with similar studies. The evaluation study showed a higher degree of equally distributed contrast throughout the luminance range with the calibration method compensated for fixed adaptation than for the GSDF. The two lowest scores for the GSDF were obtained for the darkest and brightest patterns. These scores were significantly lower than the lowest score obtained for the compensated GSDF. For the GSDF, the scores for all luminance levels were statistically separated from the average value; three were lower and two were higher. For the compensated GSDF, three of the scores could not be separated from the average value. Conclusions: An observer study using clinically relevant displays and luminance settings has demonstrated that the calibration of displays according to the GSDF causes the perceived contrast to be unevenly distributed when using displays with a high luminance range. As the luminance range increases, the perceived contrast in the dark and bright regions will be significantly lower than the perceived contrast in the middle of the luminance range. A new calibration method that includes the effect of fixed adaptation was developed and evaluated in an observer study and was found to distribute the contrast of the display more evenly throughout the grayscale than the GSDF.« less

Quantitative Analysis of Color Differences within High Contrast, Low Power Reversible Electrophoretic Displays

DOE PAGES

Giera, Brian; Bukosky, Scott; Lee, Elaine; ...

2018-01-23

Here, quantitative color analysis is performed on videos of high contrast, low power reversible electrophoretic deposition (EPD)-based displays operated under different applied voltages. This analysis is coded in an open-source software, relies on a color differentiation metric, ΔE * 00, derived from digital video, and provides an intuitive relationship between the operating conditions of the devices and their performance. Time-dependent ΔE * 00 color analysis reveals color relaxation behavior, recoverability for different voltage sequences, and operating conditions that can lead to optimal performance.

Quantitative Analysis of Color Differences within High Contrast, Low Power Reversible Electrophoretic Displays

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

Giera, Brian; Bukosky, Scott; Lee, Elaine

Here, quantitative color analysis is performed on videos of high contrast, low power reversible electrophoretic deposition (EPD)-based displays operated under different applied voltages. This analysis is coded in an open-source software, relies on a color differentiation metric, ΔE * 00, derived from digital video, and provides an intuitive relationship between the operating conditions of the devices and their performance. Time-dependent ΔE * 00 color analysis reveals color relaxation behavior, recoverability for different voltage sequences, and operating conditions that can lead to optimal performance.

Applicability of the two-angle differential method to response measurement of neutron-sensitive devices at the RCNP high-energy neutron facility

NASA Astrophysics Data System (ADS)

Masuda, Akihiko; Matsumoto, Tetsuro; Iwamoto, Yosuke; Hagiwara, Masayuki; Satoh, Daiki; Sato, Tatsuhiko; Iwase, Hiroshi; Yashima, Hiroshi; Nakane, Yoshihiro; Nishiyama, Jun; Shima, Tatsushi; Tamii, Atsushi; Hatanaka, Kichiji; Harano, Hideki; Nakamura, Takashi

2017-03-01

Quasi-monoenergetic high-energy neutron fields induced by 7Li(p,n) reactions are used for the response evaluation of neutron-sensitive devices. The quasi-monoenergetic high-energy field consists of high-energy monoenergetic peak neutrons and unwanted continuum neutrons down to the low-energy region. A two-angle differential method has been developed to compensate for the effect of the continuum neutrons in the response measurements. In this study, the two-angle differential method was demonstrated for Bonner sphere detectors, which are typical examples of moderator-based neutron-sensitive detectors, to investigate the method's applicability and its dependence on detector characteristics. Experiments were performed under 96-387 MeV quasi-monoenergetic high-energy neutron fields at the Research Center for Nuclear Physics (RCNP), Osaka University. The measurement results for large high-density polyethylene (HDPE) sphere detectors agreed well with Monte Carlo calculations, which verified the adequacy of the two-angle differential method. By contrast, discrepancies were observed in the results for small HDPE sphere detectors and metal-induced sphere detectors. The former indicated that detectors that are particularly sensitive to low-energy neutrons may be affected by penetrating neutrons owing to the geometrical features of the RCNP facility. The latter discrepancy could be consistently explained by a problem in the evaluated cross-section data for the metals used in the calculation. Through those discussions, the adequacy of the two-angle differential method was experimentally verified, and practical suggestions were made pertaining to this method.

Differentiating of cross-reactions in patients with latex allergy with the use of ISAC test.

PubMed

Chełmińska, Marta; Specjalski, Krzysztof; Różyło, Anna; Kołakowska, Agata; Jassem, Ewa

2016-04-01

Differentiating between cross-reactivity and double sensitization is still a challenging issue in allergology. To differentiate cross-reactions accompanying latex allergy with the use of the ISAC test. Thirty-nine patients reporting immediate allergic reactions to latex were enrolled into the study (group A). The control group was comprised of 41 patients with allergic diseases not associated with latex (group B) and 20 healthy individuals (group C). Their history was recorded and skin prick tests were performed with latex, airborne and food allergens. Specific IgE against food allergens, latex (k82) and recombined latex allergens were determined. ImmunoCAP ISAC test was performed with 103 molecules. Sensitization to latex was found by means of skin tests in 16 cases and sIgE against latex was revealed in 12 cases (including 10 positive in both SPT and sIgE). In the ISAC test antibodies against recombined latex allergens were found in 8 patients with rHev b 6 as the most common. All the patients positive for rHev b 1, 5, 6, 8 had allergy or asymptomatic sensitization to food allergens cross-reacting with latex. Some reactions could not have been differentiated due to the lack of allergens in the ISAC test. Others, not related to latex-fruits syndrome were explained by cross-reactivity with other profilins or PR-10 proteins. ImmunoCAP ISAC test could be useful in differentiating between cross-reactions and double sensitizations. However, in the case of latex its advantages are limited due to a small panel of allergens.

Pupil measures of alertness and mental load

NASA Technical Reports Server (NTRS)

Backs, Richard W.; Walrath, Larry C.

1988-01-01

A study of eight adults given active and passive search tasks showed that evoked pupillary response was sensitive to information processing demands. In particular, large pupillary diameter was observed in the active search condition where subjects were actively processing information relevant to task performance, as opposed to the passive search (control) condition where subjects passively viewed the displays. However, subjects may have simply been more aroused in the active search task. Of greater importance was that larger pupillary diameter, corresponding to longer search time, was observed for noncoded than for color-coded displays in active search. In the control condition, pupil diameter was larger with the color displays. The data indicate potential usefulness of pupillary responses in evaluating the information processing requirements of visual displays.

Island Concept Electrically Variable Transmission (EVT)

DTIC Science & Technology

2006-10-01

ice. There are also known sophisticated differential types (such as Torsen , speed-sensitive, self locking, magnetoreological, etc) which are able in...complex torsen differential can be replaced by a simple planetary gear set). Apparently more complex, the configuration can lead to a superior vehicle...with the EM2 through a differential mechanism, whereas typically one may find using a planetary gear set for this application. The differential

The effect of a new lifetime-cardiovascular-risk display on patients' motivation to participate in shared decision-making.

PubMed

Jegan, Nikita Roman A; Kürwitz, Sarah Anna; Kramer, Lena Kathrin; Heinzel-Gutenbrunner, Monika; Adarkwah, Charles Christian; Popert, Uwe; Donner-Banzhoff, Norbert

2018-06-09

This study investigated the effects of three different risk displays used in a cardiovascular risk calculator on patients' motivation for shared decision-making (SDM). We compared a newly developed time-to-event (TTE) display with two established absolute risk displays (i.e. emoticons and bar charts). The accessibility, that is, how understandable, helpful, and trustworthy patients found each display, was also investigated. We analysed a sample of 353 patients recruited in general practices. After giving consent, patients were introduced to one of three fictional vignettes with low, medium or high cardiovascular risk. All three risk displays were shown in a randomized order. Patients were asked to rate each display with regard to motivation for SDM and accessibility. Two-factorial repeated measures analyses of variance were conducted to compare the displays and investigate possible interactions with age. Regarding motivation for SDM, the TTE elicited the highest motivation, followed by the emoticons and bar chart (p < .001). The displays had no differential influence on the age groups (p = .445). While the TTE was generally rated more accessible than the emoticons and bar chart (p < .001), the emoticons were only superior to the bar chart in the younger subsample. However, this was only to a small effect (interaction between display and age, p < .01, η 2  = 0.018). Using fictional case vignettes, the novel TTE display was superior regarding motivation for SDM and accessibility when compared to established displays using emoticons and a bar chart. If future research can replicate these results in real-life consultations, the TTE display will be a valuable addition to current risk calculators and decision aids by improving patients' participation.

Negative affect is related to reduced differential neural responses to social and non-social stimuli in 5-to-8-month-old infants: A functional near-infrared spectroscopy-study.

PubMed

van der Kant, Anne; Biro, Szilvia; Levelt, Claartje; Huijbregts, Stephan

2018-04-01

Both social perception and temperament in young infants have been related to social functioning later in life. Previous functional Near-Infrared Spectroscopy (fNIRS) data (Lloyd-Fox et al., 2009) showed larger blood-oxygenation changes for social compared to non-social stimuli in the posterior temporal cortex of five-month-old infants. We sought to replicate and extend these findings by using fNIRS to study the neural basis of social perception in relation to infant temperament (Negative Affect) in 37 five-to-eight-month-old infants. Infants watched short videos displaying either hand and facial movements of female actors (social dynamic condition) or moving toys and machinery (non-social dynamic condition), while fNIRS data were collected over temporal brain regions. Negative Affect was measured using the Infant Behavior Questionnaire. Results showed significantly larger blood-oxygenation changes in the right posterior-temporal region in the social compared to the non-social condition. Furthermore, this differential activation was smaller in infants showing higher Negative Affect. Our results replicate those of Lloyd-Fox et al. and confirmed that five-to-eight-month-old infants show cortical specialization for social perception. Furthermore, the decreased cortical sensitivity to social stimuli in infants showing high Negative Affect may be an early biomarker for later difficulties in social interaction. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Ultrasonic model and system for measurement of corneal biomechanical properties and validation on phantoms.

PubMed

Liu, Jun; He, Xiaoyin; Pan, Xueliang; Roberts, Cynthia J

2007-01-01

Non-invasive measurement of biomechanical properties of corneas may provide important information for ocular disease management and therapeutic procedures. An ultrasonic non-destructive evaluation method with a wave propagation model was developed to determine corneal biomechanical properties in vivo. In this study, we tested the feasibility of the approach in differentiating the mechanical properties of soft contact lenses as corneal phantoms. Three material types of soft contact lenses (six samples in each group) were measured using a broadband ultrasound transducer. The ultrasonic reflections from the contact lenses were recorded by a 500MHz/8-bit digitizer, and displayed and processed by a PC. A reference signal was recorded to compute the normalized power spectra using Fast Fourier Transformation. An inverse algorithm based on least-squares minimization was used to reconstruct three parameters of the contact lenses: density, thickness, and elastic constants lambda+2micro. The thickness of each sample was verified using an electronic thickness gauge, and the averaged density for each type of lenses was verified using Archimedes' principle and manufacturer's report. Our results demonstrated that the ultrasonic system was able to differentiate the elastic properties of the three types of the soft contact lenses with statistical significance (P-value<0.001). The reconstructed thicknesses and densities agreed well with the independent measurements. Our studies on corneal phantoms indicated that the ultrasonic system was sensitive and accurate in measuring the material properties of cornea-like structures. It is important to optimize the system for in vivo measurements.

Microfluidic device capable of medium recirculation for non-adherent cell culture

PubMed Central

Dixon, Angela R.; Rajan, Shrinidhi; Kuo, Chuan-Hsien; Bersano, Tom; Wold, Rachel; Futai, Nobuyuki; Takayama, Shuichi; Mehta, Geeta

2014-01-01

We present a microfluidic device designed for maintenance and culture of non-adherent mammalian cells, which enables both recirculation and refreshing of medium, as well as easy harvesting of cells from the device. We demonstrate fabrication of a novel microfluidic device utilizing Braille perfusion for peristaltic fluid flow to enable switching between recirculation and refresh flow modes. Utilizing fluid flow simulations and the human promyelocytic leukemia cell line, HL-60, non-adherent cells, we demonstrate the utility of this RECIR-REFRESH device. With computer simulations, we profiled fluid flow and concentration gradients of autocrine factors and found that the geometry of the cell culture well plays a key role in cell entrapping and retaining autocrine and soluble factors. We subjected HL-60 cells, in the device, to a treatment regimen of 1.25% dimethylsulfoxide, every other day, to provoke differentiation and measured subsequent expression of CD11b on day 2 and day 4 and tumor necrosis factor-alpha (TNF-α) on day 4. Our findings display perfusion sensitive CD11b expression, but not TNF-α build-up, by day 4 of culture, with a 1:1 ratio of recirculation to refresh flow yielding the greatest increase in CD11b levels. RECIR-REFRESH facilitates programmable levels of cell differentiation in a HL-60 non-adherent cell population and can be expanded to other types of non-adherent cells such as hematopoietic stem cells. PMID:24753733

Networking Senescence-Regulating Pathways by Using Arabidopsis Enhancer Trap Lines1

PubMed Central

He, Yuehui; Tang, Weining; Swain, Johnnie D.; Green, Anthony L.; Jack, Thomas P.; Gan, Susheng

2001-01-01

The last phase of leaf development, generally referred to as leaf senescence, is an integral part of plant development that involves massive programmed cell death. Due to a sharp decline of photosynthetic capacity in a leaf, senescence limits crop yield and forest plant biomass production. However, the biochemical components and regulatory mechanisms underlying leaf senescence are poorly characterized. Although several approaches such as differential cDNA screening, differential display, and cDNA subtraction have been employed to isolate senescence-associated genes (SAGs), only a limited number of SAGs have been identified, and information regarding the regulation of these genes is fragmentary. Here we report on the utilization of enhancer trap approach toward the identification and analysis of SAGs. We have developed a sensitive large-scale screening method and have screened 1,300 Arabidopsis enhancer trap lines and have identified 147 lines in which the reporter gene GUS (β-glucuronidase) is expressed in senescing leaves but not in non-senescing ones. We have systematically analyzed the regulation of β-glucuronidase expression in 125 lines (genetically, each contains single T-DNA insertion) by six senescence-promoting factors, namely abscisic acid, ethylene, jasmonic acid, brassinosteroid, darkness, and dehydration. This analysis not only reveals the complexity of the regulatory circuitry but also allows us to postulate the existence of a network of senescence-promoting pathways. We have also cloned three SAGs from randomly selected enhancer trap lines, demonstrating that reporter expression pattern reflects the expression pattern of the endogenous gene. PMID:11402199

Improved Sensitivity Relations in State Constrained Optimal Control

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

Bettiol, Piernicola, E-mail: piernicola.bettiol@univ-brest.fr; Frankowska, Hélène, E-mail: frankowska@math.jussieu.fr; Vinter, Richard B., E-mail: r.vinter@imperial.ac.uk

2015-04-15

Sensitivity relations in optimal control provide an interpretation of the costate trajectory and the Hamiltonian, evaluated along an optimal trajectory, in terms of gradients of the value function. While sensitivity relations are a straightforward consequence of standard transversality conditions for state constraint free optimal control problems formulated in terms of control-dependent differential equations with smooth data, their verification for problems with either pathwise state constraints, nonsmooth data, or for problems where the dynamic constraint takes the form of a differential inclusion, requires careful analysis. In this paper we establish validity of both ‘full’ and ‘partial’ sensitivity relations for an adjointmore » state of the maximum principle, for optimal control problems with pathwise state constraints, where the underlying control system is described by a differential inclusion. The partial sensitivity relation interprets the costate in terms of partial Clarke subgradients of the value function with respect to the state variable, while the full sensitivity relation interprets the couple, comprising the costate and Hamiltonian, as the Clarke subgradient of the value function with respect to both time and state variables. These relations are distinct because, for nonsmooth data, the partial Clarke subdifferential does not coincide with the projection of the (full) Clarke subdifferential on the relevant coordinate space. We show for the first time (even for problems without state constraints) that a costate trajectory can be chosen to satisfy the partial and full sensitivity relations simultaneously. The partial sensitivity relation in this paper is new for state constraint problems, while the full sensitivity relation improves on earlier results in the literature (for optimal control problems formulated in terms of Lipschitz continuous multifunctions), because a less restrictive inward pointing hypothesis is invoked in the proof, and because it is validated for a stronger set of necessary conditions.« less

Screening of eye-position related genes with DD-RT-PCR and RDA in the hybrids between Japanese flounder Paralichthys olivaceus and stone flounder Kareius bicoloratus

NASA Astrophysics Data System (ADS)

Chen, Yanjie; Zhang, Quanqi; Qi, Jie; Sun, Yeying; Zhong, Qiwang; Wang, Xubo; Wang, Zhigang; Li, Shuo; Li, Chunmei

2009-02-01

Flatfish or flounder moves one eye to change body proportion into vertebral asymmetry during metamorphosis, during which some become sinistral while others dextral. However, the mechanism behinds the eye-position has not been well understood. In this research, hybrids between Japanese flounder(♀) and stone flounder (♂) show mixed eye-location in both dextral type and sinistral type, and thus become good samples for studying the eye-migration. mRNAs from pro-metamorphosis sinistral and dextral hybrids larvae were screened with classical differential display RT-PCR (DD-RT-PCR) and representational difference analysis of cDNA (cDNA-RDA); 30 and 47 putative fragments were isolated, respectively. The cDNA fragments of creatine kinase and trypsinogen 2 precursor genes isolated by cDNA-RDA exhibited eye-position expression patterns during metamorphosis. However, none of the fragments was proved to be related to flatfishes’ eye-position specifically. Therefore, further studies and more sensitive gene isolated methods are needed to solve the problems.

Effects of novel triple-stage antimalarial ionic liquids on lipid membrane models.

PubMed

Ferraz, Ricardo; Pinheiro, Marina; Gomes, Ana; Teixeira, Cátia; Prudêncio, Cristina; Reis, Salette; Gomes, Paula

2017-09-01

Primaquine-based ionic liquids, obtained by acid-base reaction between parent primaquine and cinnamic acids, were recently found as triple-stage antimalarial hits. These ionic compounds displayed significant activity against both liver- and blood-stage Plasmodium parasites, as well as against stage V P. falciparum parasites. Remarkably, blood-stage activity of the ionic liquids against both chloroquine-sensitive (3D7) and resistant (Dd2) P. falciparum strains was clearly superior to those of the respective covalent (amide) analogues and of parent primaquine. Having hypothesized that such behaviour might be ascribed to an enhanced ability of the ionic compounds to permeate into Plasmodium-infected erythrocytes, we have carried out a differential scanning calorimetry-based study of the interactions between the ionic liquids and membrane models. Results provide evidence, at the molecular level, that the primaquine-derived ionic liquids may contribute to an increased permeation of the parent drug into malaria-infected erythrocytes, which has relevant implications towards novel antimalarial approaches based on ionic liquids. Copyright © 2017 Elsevier Ltd. All rights reserved.

Simultaneous electrochemical determination of dopamine and paracetamol on multiwalled carbon nanotubes/graphene oxide nanocomposite-modified glassy carbon electrode.

PubMed

Cheemalapati, Srikanth; Palanisamy, Selvakumar; Mani, Veerappan; Chen, Shen-Ming

2013-12-15

In the present study, multiwalled carbon nanotubes (MWCNT)/graphene oxide (GO) nanocomposite was prepared by homogenous dispersion of MWCNT and GO and used for the simultaneous voltammetric determination of dopamine (DA) and paracetamol (PA). The TEM results confirmed that MWCNT walls were wrapped well with GO sheets. The MWCNT/GO nanocomposite showed superior electrocatalytic activity towards the oxidation of DA and PA, when compared with either pristine MWCNT or GO. The major reason for the efficient simultaneous detection of DA and PA at nanocomposite was the synergistic effect between MWCNT and GO. The electrochemical oxidation of DA and PA was investigated by cyclic voltammetry, differential pulse voltammetry and amperometry. The nanocomposite modified electrode showed electrocatalytic oxidation of DA and PA in the linear response range from 0.2 to 400 µmol L(-1) and 0.5 to 400 µmol L(-1) with the detection limit of 22 nmol L(-1) and 47 nmol L(-1) respectively. The proposed sensor displayed good selectivity, sensitivity, stability with appreciable consistency and precision. © 2013 Elsevier B.V. All rights reserved.