5,476 research outputs found
Generation and Characterization of iPS Cells Derived from APECED Patients for Gene Correction
APECED (Autoimmune-Polyendocrinopathy-Candidiasis-Ectodermal-Dystrophy) is a severe and incurable multiorgan autoimmune disease caused by mutations in the AIRE (autoimmune regulator) gene. Without functional AIRE, the development of central and peripheral immune tolerance is severely impaired allowing the accumulation of autoreactive immune cells in the periphery. This leads to multiple endocrine and non-endocrine autoimmune disorders and mucocutaneous candidiasis in APECED patients. Recent studies have suggested that AIRE also has novel functions in stem cells and contributes to the regulatory network of pluripotency. In preparation of therapeutic gene correction, we generated and assessed patient blood cell-derived iPSCs, potentially suitable for cell therapy in APECED. Here, we describe APECED-patient derived iPSCs's properties, expression of AIRE as well as classical stem cell markers by qPCR and immunocytochemistry. We further generated self-aggregated EBs of the iPSCs. We show that APECED patient-derived iPSCs and EBs do not have any major proliferative or apoptotic defects and that they express all the classical pluripotency markers similarly to healthy person iPSCs. The results suggest that the common AIRE R257X truncation mutation does not affect stem cell properties and that APECED iPSCs can be propagated in vitro and used for subsequent gene-correction. This first study on APECED patient-derived iPSCs validates their pluripotency and confirms their ability for differentiation and potential therapeutic use.Peer reviewe
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Rhythm in the speech of a person with right hemisphere damage: Applying the pairwise variability index
Although several aspects of prosody have been studied in speakers with right hemisphere damage (RHD), rhythm remains largely uninvestigated. This study compares the rhythm of an Australian English speaker with right hemisphere damage (due to a stroke, but with no concomitant dysarthria) to that of a neurologically unimpaired individual. The speakers' rhythm is compared using the pairwise variability index (PVI) which allows for an acoustic characterization of rhythm by comparing the duration of successive vocalic and intervocalic intervals. A sample of speech from a structured interview between a speech and language therapist and each participant was analysed. Previous research has shown that speakers with RHD may have difficulties with intonation production, and therefore it was hypothesized that there may also be rhythmic disturbance. Results show that the neurologically normal control uses a similar rhythm to that reported for British English (there are no previous studies available for Australian English), whilst the speaker with RHD produces speech with a less strongly stress-timed rhythm. This finding was statistically significant for the intervocalic intervals measured (t(8) = 4.7, p < .01), and suggests that some aspects of prosody may be right lateralized for this speaker. The findings are discussed in relation to previous findings of dysprosody in RHD populations, and in relation to syllable-timed speech of people with other neurological conditions
Hypertonicity-affected genes are differentially expressed in clear cell renal cell carcinoma and correlate with cancer-specific survival
The heterogeneity of renal cell carcinoma (RCC) subtypes reflects the cell type of origin in the nephron, with consequences for therapy and prognosis. The transcriptional cues that determine segment-specific gene expression patterns are poorly understood. We recently showed that hypertonicity in the renal medulla regulates nephron-specific gene expression. Here, we analyzed a set of 223 genes, which were identified in the present study by RNA-Seq to be differentially expressed by hypertonicity, for the prediction of cancer-specific survival (CSS). Cluster analyses of these genes showed discrimination between tumor and non-tumor samples of clear cell RCC (ccRCC). Refinement of this gene signature to a four-gene score (OSM score) through statistical analyses enabled prediction of CSS in ccRCC patients of The Cancer Genome Atlas (TCGA) (n = 436) in univariate (HR = 4.1; 95% CI: 2.78-6.07; p = 4.39 × 10(-13)), and multivariate analyses including primary tumor (T); regional lymph node (N); distant metastasis (M); grading (G)(p = 2.3 × 10(-5)). The OSM score could be validated in an independent ccRCC study (n = 52) in univariate (HR = 1.29; 95% CI = 1.05-1.59; p = 0.011) and multivariate analyses (p = 0.016). Cell culture experiments using RCC cell lines demonstrated that the expression of the tumor suppressor ELF5 could be restored by hypertonicity. The innovation of our novel gene signature is that these genes are physiologically regulated only by hypertonicity, thereby providing the possibility to be targeted for therapy
OpenVirtualObjects: An open set of standardized and validated 3D household objects for virtual reality-based research, assessment, and therapy
Virtual reality (VR) technology provides clinicians, therapists, and researchers with new opportunities to observe, assess, and train behavior in realistic yet well-controlled environments. However, VR also comes with a number of challenges. For example, compared to more abstract experiments and tests on 2D computer screens, VR-based tasks are more complex to create, which can make it more expensive and time-consuming. One way to overcome these challenges is to create, standardize, and validate VR content and to make it openly available for researchers and clinicians. Here we introduce the OpenVirtualObjects (OVO), a set of 124 realistic 3D household objects that people encounter and use in their everyday lives. The objects were rated by 34 younger and 25 older adults for recognizability, familiarity, details (i.e., visual complexity), contact, and usage (i.e., frequency of usage in daily life). All participants also named and categorized the objects. We provide the data and the experiment- and analysis code online. With OVO, we hope to facilitate VR-based research and clinical applications. Easy and free availability of standardized and validated 3D objects can support systematic VR-based studies and the development of VR-based diagnostics and therapeutic tools
OpenVirtualObjects (OVO): An open set of standardized and validated 3D household objects for virtual reality-based research, assessment, and therapy
Virtual reality (VR) technology provides clinicians, therapists, and researchers with new opportunities to observe, assess, and train behaviour in realistic yet well-controlled environments. However, VR also comes with a number of challenges. For example, compared to more abstract experiments and tests on 2D computer screens, VR-based tasks are more complex to create, which can make it more expensive and time-consuming. One way to overcome these challenges is to create, standardize, and validate VR content and to make it openly available for researchers and clinicians. Here we introduce the OpenVirtualObjects (OVO), a set of 124 realistic 3D household objects that people encounter and use in their everyday lives. The objects were rated by 34 younger and 25 older adults for recognizability, familiarity, details (i.e., visual complexity), contact, and usage (i.e., frequency of usage in daily life). All participants also named and categorized the objects. We provide the data and the experiment- and analysis code online. With OVO, we hope to facilitate VR-based research and clinical applications. Easy and free availability of standardized and validated 3D objects can support systematic VR-based studies and the development of VR-based diagnostics and therapeutic tools
Feasibility study for a numerical aerodynamic simulation facility. Volume 1
A Numerical Aerodynamic Simulation Facility (NASF) was designed for the simulation of fluid flow around three-dimensional bodies, both in wind tunnel environments and in free space. The application of numerical simulation to this field of endeavor promised to yield economies in aerodynamic and aircraft body designs. A model for a NASF/FMP (Flow Model Processor) ensemble using a possible approach to meeting NASF goals is presented. The computer hardware and software are presented, along with the entire design and performance analysis and evaluation
Constraints on new interactions from neutron scattering experiments
Constraints for the constants of hypothetical Yukawa-type corrections to the
Newtonian gravitational potential are obtained from analysis of neutron
scattering experiments. Restrictions are obtained for the interaction range
between 10^{-12} and 10^{-7} cm, where Casimir force experiments and atomic
force microscopy are not sensitive. Experimental limits are obtained also for
non-electromagnetic inverse power law neutron-nucleus potential. Some
possibilities are discussed to strengthen these constraints.Comment: 18 pages, 3 figure
Gentle Perturbations of the Free Bose Gas I
It is demonstrated that the thermal structure of the noncritical free Bose
Gas is completely described by certain periodic generalized Gaussian stochastic
process or equivalently by certain periodic generalized Gaussian random field.
Elementary properties of this Gaussian stochastic thermal structure have been
established. Gentle perturbations of several types of the free thermal
stochastic structure are studied. In particular new models of non-Gaussian
thermal structures have been constructed and a new functional integral
representation of the corresponding euclidean-time Green functions have been
obtained rigorously.Comment: 51 pages, LaTeX fil
Mass wasting triggered by seasonal CO<sub>2</sub> sublimation under Martian atmospheric conditions: Laboratory experiments
Sublimation is a recognized process by which planetary landscapes can be modified. However, interpretation of whether sublimation is involved in downslope movements on Mars and other bodies is restricted by a lack of empirical data to constrain this mechanism of sediment transport and its influence on landform morphology. Here we present the first set of laboratory experiments under Martian atmospheric conditions which demonstrate that the sublimation of CO2 ice from within the sediment body can trigger failure of unconsolidated, regolith slopes and can measurably alter the landscape. Previous theoretical studies required CO2 slab ice for movements, but we find that only frost is required. Hence, sediment transport by CO2 sublimation could be more widely applicable (in space and time) on Mars than previously thought. This supports recent work suggesting CO2 sublimation could be responsible for recent modification in Martian gullies
Testbeam and Laboratory Characterization of CMS 3D Pixel Sensors
The pixel detector is the innermost tracking device in CMS, reconstructing
interaction vertices and charged particle trajectories. The sensors located in
the innermost layers of the pixel detector must be upgraded for the ten-fold
increase in luminosity expected with the High- Luminosity LHC (HL-LHC) phase.
As a possible replacement for planar sensors, 3D silicon technology is under
consideration due to its good performance after high radiation fluence. In this
paper, we report on pre- and post- irradiation measurements for CMS 3D pixel
sensors with different electrode configurations. The effects of irradiation on
electrical properties, charge collection efficiency, and position resolution of
3D sensors are discussed. Measurements of various test structures for
monitoring the fabrication process and studying the bulk and surface
properties, such as MOS capacitors, planar and gate-controlled diodes are also
presented.Comment: 14 page
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