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1.
Phys Rev Lett ; 130(23): 231001, 2023 Jun 09.
Article in English | MEDLINE | ID: mdl-37354392

ABSTRACT

We report direction detection constraints on the presence of hidden photon dark matter with masses between 20-30 µeV c^{-2}, using a cryogenic emitter-receiver-amplifier spectroscopy setup designed as the first iteration of QUALIPHIDE (quantum limited photons in the dark experiment). A metallic dish sources conversion photons, from hidden photon kinetic mixing, onto a horn antenna which is coupled to a C band kinetic inductance traveling wave parametric amplifier, providing for near quantum-limited noise performance. We demonstrate a first probing of the kinetic mixing parameter χ to the 10^{-12} level for the majority of hidden photon masses in this region. These results not only represent stringent constraints on new dark matter parameter space, but are also the first demonstrated use of wideband quantum-limited amplification for astroparticle applications.


Subject(s)
Photons , Kinetics
2.
HIV Med ; 22(5): 325-333, 2021 05.
Article in English | MEDLINE | ID: mdl-33247876

ABSTRACT

OBJECTIVES: To assess the risk of chronic kidney disease (CKD) associated with tenofovir disoproxil fumarate (TDF) use by baseline D:A:D CKD risk score. METHODS: Adult antiretroviral therapy (ART)-naïve people living with HIV (PLWH) initiating treatment, with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2 , were identified in the OPERA cohort. CKD was defined as two or more consecutive eGFR < 60 mL/min/1.73 m2 , > 90 days apart. Associations between TDF use, baseline D:A:D CKD risk and incident CKD were assessed with incidence rates (IRs; Poisson regression) and adjusted pooled logistic regression. The impact of pharmacoenhancers on the observed association between TDF and CKD was also evaluated. RESULTS: Of 9802 PLWH included, 6222 initiated TDF and 3580 did not (76% and 79% low D:A:D CKD risk, respectively). Overall, 125 CKD events occurred over 24 382 person-years of follow-up. Within strata of D:A:D CKD risk score, IRs were similar across TDF exposure, with high baseline CKD risk associated with highest incidence. Compared with the low-risk group without TDF, there was no statistical difference in odds of incident CKD in the low-risk group with TDF (adjusted odds ratio = 0.55, 95% confidence interval: 0.19-1.54). Odds of incident CKD did not differ statistically significantly by pharmacoenhancer exposure, with or without TDF. CONCLUSIONS: In this large cohort of ART-naïve PLWH, incident CKD following ART initiation was infrequent and strongly associated with baseline CKD risk. TDF-containing regimens did not increase the odds of CKD in those with a low baseline D:A:D CKD risk, the largest group of ART-naïve PLWH, and may remain a viable treatment option in appropriate settings.


Subject(s)
Anti-HIV Agents , HIV Infections , Renal Insufficiency, Chronic , Adult , Anti-HIV Agents/adverse effects , Glomerular Filtration Rate , HIV Infections/complications , HIV Infections/drug therapy , HIV Infections/epidemiology , Humans , Renal Insufficiency, Chronic/chemically induced , Renal Insufficiency, Chronic/epidemiology , Risk Factors , Tenofovir/adverse effects
3.
HIV Med ; 21(5): 299-308, 2020 05.
Article in English | MEDLINE | ID: mdl-31985887

ABSTRACT

OBJECTIVES: The aim of the study was to assess the validity of an easy-to-calculate chronic kidney disease (CKD) risk score developed by the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) group in a longitudinal observational study of people living with HIV (PLWH) in the USA. METHODS: PLWH (2002-2016) without prior exposure to potentially nephrotoxic antiretroviral agents and with at least three estimated glomerular filtration rate (eGFR) test results were identified in the Observational Pharmaco-Epidemiology Research and Analysis (OPERA® ) cohort. Three samples were drawn independently using the same eligibility criteria but each using a different eGFR equation, specifically the Cockcroft-Gault (C-G), Modification of Diet in Renal Disease (MDRD) or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFR estimation method. Full and short D:A:D risk scores were applied. CKD was defined as a confirmed decrease in eGFR to < 60 mL/min/1.73 m2 (stages 3-5). Poisson models estimated the association between CKD incidence and a one-point increase in the continuous risk score. The incidence rate ratio (IRR), adjusted IRR (aIRR), and Harrell's discrimination statistic were used to assess validity. RESULTS: There were 19 444, 22 727 and 22 748 PLWH in the OPERA C-G, CKD-EPI and MDRD samples, respectively. The median (minimum-maximum) follow-up duration was 6.1 (0.3-9.1) years in the D:A:D cohort and ranged from 3.2 to 3.5 (0.2-15.5) years in the OPERA validation samples. The observation time for the majority of PLWH in the D:A:D cohort began prior to 2006, in stark contrast to the OPERA validation samples, where the majority of PLWH were observed after 2011. The CKD incidence ranged from 7.3 per 1000 person-years [95% confidence interval (CI) 6.8, 7.9 per 1000 person-years] in OPERA C-G to 11.0 (95% CI 10.4, 11.6 per 1000 person-years) in OPERA MDRD. In OPERA samples, IRRs by risk group and adjusted IRRs (full risk score) were similar to those in the D:A:D derivation cohort (adjusted IRR 1.3; 95% CI 1.3, 1.3). Harrell's c-statistic ranged from 0.87 to 0.92 in the OPERA samples, comparable to that in the derivation cohort (0.92). Results for short scores were similar. CONCLUSIONS: The findings support the validity of the D:A:D risk scoring method for assessing CKD (stages 3-5) probability in an exclusively USA-based sample regardless of eGFR method.


Subject(s)
Anti-HIV Agents/adverse effects , HIV Infections/drug therapy , Renal Insufficiency, Chronic/epidemiology , Adult , Aged , Aged, 80 and over , Anti-HIV Agents/therapeutic use , Female , Glomerular Filtration Rate/drug effects , Humans , Incidence , Longitudinal Studies , Male , Middle Aged , Renal Insufficiency, Chronic/chemically induced , Renal Insufficiency, Chronic/physiopathology , United States/epidemiology
4.
Genesis ; 55(1-2)2017 01.
Article in English | MEDLINE | ID: mdl-28095644

ABSTRACT

Collective cell migration is essential in many fundamental aspects of normal development, like morphogenesis, organ formation, wound healing, and immune responses, as well as in the etiology of severe pathologies, like cancer metastasis. In spite of the huge amount of data accumulated on cell migration, such a complex process involves many molecular actors, some of which still remain to be functionally characterized. One of these signals is the heterotrimeric G-protein pathway that has been studied mainly in gastrulation movements. Recently we have reported that Ric-8A, a GEF for Gα proteins, plays an important role in neural crest migration in Xenopus development. Xenopus neural crest cells, a highly migratory embryonic cell population induced at the border of the neural plate that migrates extensively in order to differentiate in other tissues during development, have become a good model to understand the dynamics that regulate cell migration. In this review, we aim to provide sufficient evidence supporting how useful Xenopus model with its different tools, such as explants and transplants, paired with improved in vivo imaging techniques, will allow us to tackle the multiple signaling mechanisms involved in neural crest cell migration.


Subject(s)
Cell Movement/genetics , Heterotrimeric GTP-Binding Proteins/genetics , Morphogenesis/genetics , Xenopus laevis/genetics , Animals , Gene Expression Regulation, Developmental , Heterotrimeric GTP-Binding Proteins/metabolism , Neural Crest/growth & development , Neural Crest/metabolism , Neural Plate/growth & development , Neural Plate/metabolism , Signal Transduction/genetics , Xenopus laevis/growth & development
5.
Opt Express ; 25(22): 26792-26801, 2017 Oct 30.
Article in English | MEDLINE | ID: mdl-29092164

ABSTRACT

For photon-counting applications at ultraviolet wavelengths, there are currently no detectors that combine high efficiency (> 50%), sub-nanosecond timing resolution, and sub-Hz dark count rates. Superconducting nanowire single-photon detectors (SNSPDs) have seen success over the past decade for photon-counting applications in the near-infrared, but little work has been done to optimize SNSPDs for wavelengths below 400 nm. Here, we describe the design, fabrication, and characterization of UV SNSPDs operating at wavelengths between 250 and 370 nm. The detectors have active areas up to 56 µm in diameter, 70 - 80% efficiency at temperatures up to 4.2 K, timing resolution down to 60 ps FWHM, blindness to visible and infrared photons, and dark count rates of ∼ 0.25 counts/hr for a 56 µm diameter pixel. These performance metrics make UV SNSPDs ideal for applications in trapped-ion quantum information processing, lidar studies of the upper atmosphere, UV fluorescent-lifetime imaging microscopy, and photon-starved UV astronomy.

6.
J Microsc ; 268(3): 259-268, 2017 12.
Article in English | MEDLINE | ID: mdl-28960298

ABSTRACT

The atomic structure of (GaIn)As/Ga(AsSb)/(GaIn)As-'W'-type quantum well heterostructures ('W'-QWHs) is investigated by scanning transmission electron microscopy (STEM). These structures were grown by metal organic vapour phase epitaxy and are built for type-II laser systems in the infrared wavelength regime. For two samples grown at 525°C and 550°C, intensity profiles are extracted from the STEM images for each sublattice separately. These intensity profiles are compared to the one obtained from an image simulation of an ideal 'W'-QWH that is modelled in close agreement with the experiment. From the intensity profiles, the width of the different quantum wells (QWs) can be determined. Additionally, characteristics connected to the growth of the structures, such as segregation coefficients and material homogeneity, are calculated. Finally, composition profiles are derived from the STEM intensity profiles to a first approximation. For these composition profiles, the expected photoluminescence (PL) is computed based using the semiconductor luminescence equations. The PL spectra are then compared to experimental measurements for both samples.

7.
Opt Express ; 24(15): 17470-85, 2016 Jul 25.
Article in English | MEDLINE | ID: mdl-27464193

ABSTRACT

We present an active fiber-based retroreflector providing high quality phase-retracing anti-parallel Gaussian laser beams for precision spectroscopy of Doppler sensitive transitions. Our design is well-suited for a number of applications where implementing optical cavities is technically challenging and corner cubes fail to match the demanded requirements, most importantly retracing wavefronts and preservation of the laser polarization. To illustrate the performance of the system, we use it for spectroscopy of the 2S-4P transition in atomic hydrogen and demonstrate an average suppression of the first order Doppler shift to 4 parts in 106 of the full collinear shift. This high degree of cancellation combined with our cryogenic source of hydrogen atoms in the metastable 2S state is sufficient to enable determinations of the Rydberg constant and the proton charge radius with competitive uncertainties. Advantages over the usual Doppler cancellation based on corner cube type retroreflectors are discussed as well as an alternative method using a high finesse cavity.

8.
J Microsc ; 262(2): 171-7, 2016 May.
Article in English | MEDLINE | ID: mdl-26224521

ABSTRACT

The usable aperture sizes in (scanning) transmission electron microscopy ((S)TEM) have significantly increased in the past decade due to the introduction of aberration correction. In parallel with the consequent increase of convergence angle the depth of focus has decreased severely and optical sectioning in the STEM became feasible. Here we apply STEM defocus series to derive the local sample thickness of a TEM sample. To this end experimental as well as simulated defocus series of thin Si foils were acquired. The systematic blurring of high resolution high angle annular dark field images is quantified by evaluating the standard deviation of the image intensity for each image of a defocus series. The derived dependencies exhibit a pronounced maximum at the optimum defocus and drop to a background value for higher or lower values. The full width half maximum (FWHM) of the curve is equal to the sample thickness above a minimum thickness given by the size of the used aperture and the chromatic aberration of the microscope. The thicknesses obtained from experimental defocus series applying the proposed method are in good agreement with the values derived from other established methods. The key advantages of this method compared to others are its high spatial resolution and that it does not involve any time consuming simulations.

9.
Langmuir ; 30(40): 11945-54, 2014 Oct 14.
Article in English | MEDLINE | ID: mdl-25225717

ABSTRACT

Copper(II) oxalate was grown on carboxy-terminated self-assembled monolayers using a step-by-step approach by dipping the surfaces alternately in ethanolic solutions of copper(II) acetate and oxalic acid with intermediate thorough rinsing steps. The deposition was monitored by reflection absorption infrared spectroscopy (RAIRS), a quartz microbalance with dissipation measurement (QCM-D), scanning electron microscopy (SEM), and helium ion microscopy (HIM). Amounts of material corresponding to a coverage of 75% of a monolayer are deposited in each dipping step in copper(II) acetate solution while deposition of oxalic acid produces a viscoelastic layer that is partially removed by rinsing. This points toward initial aggregation but acid not bound to Cu(2+) ions as oxalate ions is removed by the rinsing steps. RAIRS further indicates that the material grows as copper(II) oxalate ribbons similar to the crystal structure but with ribbons oriented roughly parallel to the surface. SEM and HIM give evidence of the formation of needle-shaped structures which are a possible explanation for the viscoelastic behavior of the layer.

10.
Nanotechnology ; 25(46): 465306, 2014 Nov 21.
Article in English | MEDLINE | ID: mdl-25360747

ABSTRACT

We present a method to fabricate nanometer scale gaps within InAs nanowires by selectively etching InAs/InP heterostructure nanowires. We used vapor-liquid-solid grown InAs nanowires with embedded InP segments of 10-60 nm length and developed an etching recipe to selectively remove the InP segment. A photo-assisted wet etching process in a mixture of acetic acid and hydrobromic acid gave high selectivity, with accurate removal of InP segments down to 20 nm, leaving the InAs wire largely unattacked, as verified using scanning electron and transmission electron microscopy. The obtained nanogaps in InAs wires have potential as semiconducting electrodes to investigate electronic transport in nanoscale objects. We demonstrate this functionality by dielectrophoretically trapping 30 nm diameter gold nanoparticles into the gap.

11.
Nanotechnology ; 24(34): 345301, 2013 Aug 30.
Article in English | MEDLINE | ID: mdl-23899908

ABSTRACT

The current understanding in the study of focused electron beam induced processing (FEBIP) is that the growth of a deposit is mainly the result of secondary electrons (SEs). This suggests that the growth rate for FEBIP is affected by the SE emission from the support. Our experiments, with membranes thinner than the SE escape depth, confirm this hypothesis. We used membranes of 1.4 and 4.3 nm amorphous carbon as supports. At the very early stage, the growth is support-dominated and the growth rate on a 4.3 nm thick membrane is three times higher than on a 1.4 nm thick membrane. This is consistent with Monte Carlo simulations for SE emission. The results suggest that SEs are dominant in the dissociation of W(CO)6 on thin membranes. The best agreement between simulations and experiment is obtained for SEs with energies between 3 and 6 eV.With this work we revisit earlier experiments, working at a precursor pressure 20 times lower than previously. Then, despite using membranes thinner than the SE escape depth, we did not see an effect on the experimental growth rate. We explain our current results by the fact that very early in the process, the growth becomes dominated by the growing deposit itself.

12.
Gesundheitswesen ; 75(2): 77-81, 2013 Feb.
Article in German | MEDLINE | ID: mdl-23073981

ABSTRACT

AIM: There is limited research about the acceptance of population-based prevention activities, offered systematically and directly at home. Screening data about smoking behaviour in families with children younger than 3 years were used. We examined associations between family variables (education, employment, number of children in the household), the "proportion of persons on social welfare" (PPSW) in the population aged 15-65 years and the following dependent variables: participation rate in a systematic screening, proportion of smokers within the sample of screened families and participation rate in counselling. METHODS: For postal and personal contacts reporting data of children aged < 3 years, resident in Stralsund (due date 01.06.2008, N=1 298) were used. A total number of 827 families participated in the screening. The counselling was offered if at least 1 adult had smoked at least 1 cigarette per day in the last 4 weeks. Associations between family variables, PPSW and dependent variables were analysed using multilevel statistics. RESULTS: The higher the PPSP the lower is the probability for participation in the screening (odds ratio=0.982; 95% confidence interval=0.970-0.996). There was at least one adult smoker in 425 (51.4%) of these 827 families participating in the screening. The counselling was offered in 425 families, whereby 65.9% (280) participated. There was no association between family variables, PPSW and participation in the counselling. CONCLUSION: Differences in participation in the screening procedure are low: a high proportion of families in districts with a high PPSW took part. Even in districts with a PPSW rate of more than 30%, 71.3% of the families were successfully contacted. There is the recommendation to offer prevention measures in social< deprived city areas in a more proactive way considering the association between the prevalence of smoking in families and the proportion of PPSW.


Subject(s)
Employment/statistics & numerical data , Health Promotion , Residential Facilities/statistics & numerical data , Smoking Prevention , Smoking/epidemiology , Social Welfare/statistics & numerical data , Adolescent , Adult , Age Distribution , Aged , Educational Status , Family Characteristics , Germany/epidemiology , Humans , Male , Middle Aged , Prevalence , Risk Assessment , Sex Distribution , Socioeconomic Factors , Young Adult
13.
Nat Genet ; 17(4): 449-52, 1997 Dec.
Article in English | MEDLINE | ID: mdl-9398848

ABSTRACT

Human peroxisome biogenesis disorders (PBDs) are a group of genetically heterogeneous autosomal-recessive disease caused by mutations in PEX genes that encode peroxins, proteins required for peroxisome biogenesis. These lethal diseases include Zellweger syndrome (ZS), neonatal adrenoleukodystrophy (NALD) and infantile Refsum's disease (IRD), three phenotypes now thought to represent a continuum of clinical features that are most severe in ZS, milder in NALD and least severe in IRD2. At least eleven PBD complementation groups have been identified by somatic-cell hybridization analysis compared to the eighteen PEX complementation groups that have been found in yeast. We have cloned the human PEX1 gene encoding a 147-kD member of the AAA protein family (ATPases associated with diverse cellular activities), which is the putative orthologue of Saccharomyces cerevisiae Pex1p (ScPex1p). Human PEX1 has been identified by computer-based 'homology probing' using the ScPex1p sequence to screen databases of expressed sequence tags (dbEST) for human cDNA clones. Expression of PEX1 rescued the cells from the biogenesis defect in human fibroblasts of complementation group 1 (CG1), the largest PBD complementation group. We show that PEX1 is mutated in CG1 patients.


Subject(s)
Adenosine Triphosphatases/genetics , Genetic Complementation Test , Mutation , Peroxisomal Disorders/genetics , Proteins/genetics , Amino Acid Sequence , Animals , Cell Line , Fibroblasts , Humans , Molecular Sequence Data , PHEX Phosphate Regulating Neutral Endopeptidase , Pichia/genetics , Rats , Saccharomyces cerevisiae/genetics , Sequence Alignment , Sequence Homology, Amino Acid , Swine
14.
Neuroscience ; 523: 31-46, 2023 07 15.
Article in English | MEDLINE | ID: mdl-37225049

ABSTRACT

Spinal sympathetic preganglionic neurons (SPNs) are among the many neuronal populations in the mammalian central nervous system (CNS) where there is evidence for electrical coupling between cell pairs linked by gap junctions composed of connexin36 (Cx36). Understanding the organization of this coupling in relation to autonomic functions of spinal sympathetic systems requires knowledge of how these junctions are deployed among SPNs. Here, we document the distribution of immunofluorescence detection of Cx36 among SPNs identified by immunolabelling of their various markers, including choline acetyltransferase, nitric oxide and peripherin in adult and developing mouse and rat. In adult animals, labelling of Cx36 was exclusively punctate and dense concentrations of Cx36-puncta were distributed along the entire length of the spinal thoracic intermediolateral cell column (IML). These puncta were also seen in association with SPN dendritic processes in the lateral funiculus, the intercalated and central autonomic areas and those within and extending medially from the IML. All labelling for Cx36 was absent in spinal cords of Cx36 knockout mice. High densities of Cx36-puncta were already evident among clusters of SPNs in the IML of mouse and rat at postnatal days 10-12. In Cx36BAC::eGFP mice, eGFP reporter was absent in SPNs, thus representing false negative detection, but was localized to some glutamatergic and GABAergic synaptic terminals. Some eGFP+ terminals were found contacting SPN dendrites. These results indicate widespread Cx36 expression in SPNs, further supporting evidence of electrical coupling between these cells, and suggest that SPNs are innervated by neurons that themselves may be electrically coupled.


Subject(s)
Electrical Synapses , Gap Junctions , Mice , Rats , Animals , Electrical Synapses/metabolism , Rats, Sprague-Dawley , Gap Junctions/metabolism , Connexins/metabolism , Neurons/metabolism , Spinal Cord/metabolism , Mice, Knockout , Mammals/metabolism , Gap Junction delta-2 Protein
15.
Ultramicroscopy ; 240: 113550, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35724620

ABSTRACT

High-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM) is a valuable method for composition determination of nanomaterials. However, light elements do not scatter efficiently into the scattering angles employed for HAADF-STEM which hinders the composition determination of material systems containing light elements by HAADF-STEM. This makes the usage of lower scattering angles favourable. Moreover, static atomic displacements (SADs) caused by the small covalent radius of the substituting light elements in semiconductor alloys increase the scattering intensity at low angles. Nevertheless, at low angles, a quantitative match between complementary image simulations and experiments is not straight forward, since e.g. inelastic scattering and correlated phonon movement is often neglected in simulations. In this study, we establish a method to quantify material systems containing light elements at low angles by resolving the remaining sources of discrepancy. An outstanding agreement between simulations and experiments is achieved by using a combination of an in-column energy filter and a fast pixelated detector. By applying this method to GaNxAs1-x quantum wells, a good agreement of the TEM results with results from high-resolution x-ray diffraction is obtained. The method developed enables the nanoscale analysis of functional materials containing light elements, especially in the presence of SADs.

16.
Neuroscience ; 485: 91-115, 2022 03 01.
Article in English | MEDLINE | ID: mdl-35090881

ABSTRACT

Large cholinergic neurons (V0c neurons; aka, partition cells) in the spinal cord project profusely to motoneurons on which they form C-terminal contacts distinguished by their specialized postsynaptic subsurface cisterns (SSCs). The V0c neurons are known to be rhythmically active during locomotion and release of acetylcholine (ACh) from their terminals is known to modulate the excitability of motoneurons in what appears to be a task-dependent manner. Here, we present evidence that a subpopulation of V0c neurons express the gap junction forming protein connexin36 (Cx36), indicating that they are coupled by electrical synapses. Based on immunofluorescence imaging and the use of Cx36BAC-enhanced green fluorescent protein (eGFP) mice in which C-terminals immunolabelled for their marker vesicular acetylcholine transporter (vAChT) are also labelled for eGFP, we found a heterogeneous distribution of eGFP+ C-terminals on motoneurons at cervical, thoracic and lumber spinal levels. The density of C-terminals on motoneurons varied as did the proportion of those that were eGFP+ vs. eGFP-. We present evidence that fast vs. slow motoneurons have a greater abundance of these terminals and fast motoneurons also have the highest density that were eGFP+. Thus, our results indicate that a subpopulation of V0c neurons projects preferentially to fast motoneurons, suggesting that the capacity for synchronous activity conferred by electrical synapses among networks of coupled V0c neurons enhances their dynamic capabilities for synchronous regulation of motoneuron excitability during high muscle force generation. The eGFP+ vs. eGFP- V0c neurons were more richly innervated by serotonergic terminals, suggesting their greater propensity for regulation by descending serotonergic systems.


Subject(s)
Motor Neurons , Spinal Cord , Animals , Cholinergic Agents , Cholinergic Neurons , Connexins , Mice , Motor Neurons/physiology , Rats , Rats, Sprague-Dawley , Spinal Cord/metabolism , Gap Junction delta-2 Protein
17.
Function (Oxf) ; 3(5): zqac043, 2022.
Article in English | MEDLINE | ID: mdl-36168588

ABSTRACT

Telomerase reverse transcriptase (TERT) (catalytic subunit of telomerase) is linked to the development of coronary artery disease (CAD); however, whether the role of nuclear vs. mitchondrial actions of TERT is involved is not determined. Dominant-negative TERT splice variants contribute to decreased mitochondrial integrity and promote elevated reactive oxygen species production. We hypothesize that a decrease in mitochondrial TERT would increase mtDNA damage, promoting a pro-oxidative redox environment. The goal of this study is to define whether mitochondrial TERT is sufficient to maintain nitric oxide as the underlying mechanism of flow-mediated dilation by preserving mtDNA integrity.Immunoblots and quantitative polymerase chain reaction were used to show elevated levels of splice variants α- and ß-deletion TERT tissue from subjects with and without CAD. Genetic, pharmacological, and molecular tools were used to manipulate TERT localization. Isolated vessel preparations and fluorescence-based quantification of mtH2O2 and NO showed that reduction of TERT in the nucleus increased flow induced NO and decreased mtH2O2 levels, while prevention of mitochondrial import of TERT augmented pathological effects. Further elevated mtDNA damage was observed in tissue from subjects with CAD and initiation of mtDNA repair mechanisms was sufficient to restore NO-mediated dilation in vessels from patients with CAD. The work presented is the first evidence that catalytically active mitochondrial TERT, independent of its nuclear functions, plays a critical physiological role in preserving NO-mediated vasodilation and the balance of mitochondrial to nuclear TERT is fundamentally altered in states of human disease that are driven by increased expression of dominant negative splice variants.


Subject(s)
Coronary Artery Disease , Telomerase , Humans , Telomerase/genetics , Hydrogen Peroxide/metabolism , Coronary Artery Disease/genetics , Vasodilation , Oxidation-Reduction
18.
Opt Express ; 19(12): 11059-70, 2011 Jun 06.
Article in English | MEDLINE | ID: mdl-21716334

ABSTRACT

The imaging of hydrated biological samples - especially in the energy window of 284-540 eV, where water does not obscure the signal of soft organic matter and biologically relevant elements - is of tremendous interest for life sciences. Free-electron lasers can provide highly intense and coherent pulses, which allow single pulse imaging to overcome resolution limits set by radiation damage. One current challenge is to match both the desired energy and the intensity of the light source. We present the first images of dehydrated biological material acquired with 3rd harmonic radiation from FLASH by digital in-line zone plate holography as one step towards the vision of imaging hydrated biological material with photons in the water window. We also demonstrate the first application of ultrathin molecular sheets as suitable substrates for future free-electron laser experiments with biological samples in the form of a rat fibroblast cell and marine biofouling bacteria Cobetia marina.


Subject(s)
Bacteria/cytology , Electrons , Fibroblasts/cytology , Holography/methods , Lasers , Microscopy/methods , Water/chemistry , Animals , Nanostructures , Rats , Seawater/microbiology , X-Rays
19.
Eur Cell Mater ; 22: 403-19, 2011 Dec 17.
Article in English | MEDLINE | ID: mdl-22179938

ABSTRACT

Due to their broad differentiation potential and their persistence into adulthood, human neural crest-derived stem cells (NCSCs) harbour great potential for autologous cellular therapies, which include the treatment of neurodegenerative diseases and replacement of complex tissues containing various cell types, as in the case of musculoskeletal injuries. The use of serum-free approaches often results in insufficient proliferation of stem cells and foetal calf serum implicates the use of xenogenic medium components. Thus, there is much need for alternative cultivation strategies. In this study we describe for the first time a novel, human blood plasma based semi-solid medium for cultivation of human NCSCs. We cultivated human neural crest-derived inferior turbinate stem cells (ITSCs) within a blood plasma matrix, where they revealed higher proliferation rates compared to a standard serum-free approach. Three-dimensionality of the matrix was investigated using helium ion microscopy. ITSCs grew within the matrix as revealed by laser scanning microscopy. Genetic stability and maintenance of stemness characteristics were assured in 3D cultivated ITSCs, as demonstrated by unchanged expression profile and the capability for self-renewal. ITSCs pre-cultivated in the 3D matrix differentiated efficiently into ectodermal and mesodermal cell types, particularly including osteogenic cell types. Furthermore, ITSCs cultivated as described here could be easily infected with lentiviruses directly in substrate for potential tracing or gene therapeutic approaches. Taken together, the use of human blood plasma as an additive for a completely defined medium points towards a personalisable and autologous cultivation of human neural crest-derived stem cells under clinical grade conditions.


Subject(s)
Cell Culture Techniques , Neural Crest/cytology , Neural Stem Cells/cytology , Antigens, Differentiation/metabolism , Biomimetic Materials , Cell Differentiation , Cell Proliferation , Culture Media, Serum-Free , Fibrin/ultrastructure , Gene Expression Profiling , Humans , Nanofibers/ultrastructure , Nerve Regeneration , Neural Stem Cells/metabolism , Neural Stem Cells/physiology , Plasma , Porosity , Spheroids, Cellular/cytology
20.
Nanotechnology ; 22(11): 115303, 2011 Mar 18.
Article in English | MEDLINE | ID: mdl-21301081

ABSTRACT

It is often suggested that the growth in focused electron beam induced processing (FEBIP) is caused not only by primary electrons, but also (and even predominantly) by secondary electrons (SEs). If that is true, the growth rate for FEBIP can be changed by modifying the SE yield. Results from our Monte Carlo simulations show that the SE yield changes strongly with substrate thickness for thicknesses below the SE escape depth. However, our experimental results show that the growth rate is independent of the substrate thickness. Deposits with an average size of about 3 nm were written on 1 and 9 nm thick carbon substrates. The apparent contradiction between simulation and experiment is explained by simulating the SE emission from a carbon substrate with platinum deposits on the surface. It appears that the SE emission is dominated by the deposits rather than the carbon substrate, even for deposits as small as 0.32 nm(3).

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