293 research outputs found
Measurement of optical to electrical and electrical to optical delays with ps-level uncertainty
We present a new measurement principle to determine the absolute time delay
of a waveform from an optical reference plane to an electrical reference plane
and vice versa. We demonstrate a method based on this principle with 2 ps
uncertainty. This method can be used to perform accurate time delay
determinations of optical transceivers used in fibre-optic time-dissemination
equipment. As a result the time scales in optical and electrical domain can be
related to each other with the same uncertainty. We expect this method to break
new grounds in high-accuracy time transfer and absolute calibration of
time-transfer equipment
XUV frequency comb metrology on the ground state of helium
The operation of a frequency comb at extreme ultraviolet (XUV) wavelengths
based on pair-wise amplification and nonlinear upconversion to the 15th
harmonic of pulses from a frequency comb laser in the near-infrared range is
reported. Following a first account of the experiment [Kandula et al., Phys.
Rev. Lett. 105, 063001 (2010)], an extensive review is given of the
demonstration that the resulting spectrum at 51 nm is fully phase coherent and
can be applied to precision metrology. The pulses are used in a scheme of
direct-frequency-comb excitation of helium atoms from the ground state to the
1s4p and 1s5p 1P_1 states. Laser ionization by auxiliary 1064 nm pulses is used
to detect the excited state population, resulting in a cosine-like signal as a
function of the repetition rate of the frequency comb with a modulation
contrast of up to 55%. Analysis of the visibility of this comb structure yields
an estimated timing jitter between the two upconverted comb laser pulses of 50
attoseconds, whch indicates that extension to even shorter wavelengths should
be feasible. The helium metrology investigation results in transition
frequencies of 5740806993(10) MHz and 5814248672(6) MHz for excitation of the
1s4p and 1s5p 1P_1 states, respectively. This constitutes the first absolute
frequency measurement in the XUV, attaining unprecedented accuracy in this
windowless part of the electromagnetic spectrum. From the measured transition
frequencies an eight-fold improved 4He ionization energy of 5945204212(6) MHz
is derived. Also a new value for the 4He ground state Lamb shift is found of
41247(6) MHz. This experimental value is in agreement with recent theoretical
calculations up to order m\alpha^6 and m^2/(M\alpha^5), but with a six times
higher precision, therewith providing a stringent test of quantum
electrodynamics in bound two-electron systems.Comment: 18 pages, 13 figure
The murine male reproductive organ at a glance: Three-dimensional insights and virtual histology using label-free light sheet microcopy
Background:The unique anatomy of the male reproductive organ reflects its complex function from sperm maturation to their storage for months until emission. Since light microscopy in two dimensions (2d) cannot sufficiently demonstrate its complex morphology, a comprehensive visualization is required to identify pathologic alterations in its entire anatomical context.Objectives:Aim of this study was to use three-dimensional (3d) light sheet fluorescence microscopy (LSFM) to visualize entire murine testes in 3d, label-free and at subcellular resolution, and to assign local autofluorescence to testicular and deferent structures.Materials and methods:Murine testes were fixed with four different fixatives and subsequently cleared with benzoic acid/benzyl benzoate. Hereafter, complete murine testes were scanned with LSFM with different fluorescence filter sets and subsequently embedded in paraffin for further conventional planar histology.Results:Autofluorescence signals of the murine reproductive organ allowed the unambiguous identification of the testicular anatomy from the seminiferous tubules to the vas deferens with their specific stratification independent of the used fixative. Blood vessels were visualized from the pampiniform plexus to the small capillaries of single tubules. Moreover, due to the specific intrinsic fluorescence properties of the efferent ducts and the epididymis, luminal caliber, the epithelial stratification and retronuclear cytoplasmic inclusions gave a unique insight into the interface of both morphological structures. Subsequent 2d histology confirmed the identified morphological structures.Discussion:LSFM analysis of the murine reproductive organ allows due to its intrinsic fluorescence a simple, label-free 3d assessment of its entire duct morphology, the epithelial composition, and the associated blood supply in its anatomical relation.Conclusion:LSFM provides the technical basis for comprehensive analyses of pathologically altered murine testes in its entirety by depicting specific autofluorescence. Thereby it facilitates mouse studies of testicular disease or their drug-related alterations in more detail potentially for clinical translation assessing human testicular biopsies.<br
3D virtual histology of murine kidneys-high resolution visualization of pathological alterations by micro computed tomography
The increasing number of patients with end stage chronic kidney disease not only calls for novel therapeutics but also for pioneering research using convincing preclinical disease models and innovative analytical techniques. The aim of this study was to introduce a virtual histology approach using micro computed tomography (mu CT) for the entire murine kidney in order to close the gap between single slice planar histology and a 3D high resolution dataset. An ex vivo staining protocol based on phosphotungstic acid diffusion was adapted to enhance renal soft tissue x-ray attenuation. Subsequent CT scans allowed (i) the detection of the renal cortex, medulla and pelvis in greater detail, (ii) the analysis of morphological alterations, (iii) the quantification of the volume as well as the radio-opacity of these portions and (iv) the quantification of renal fibrotic remodeling based on altered radio-opacity using the unilateral ureteral obstruction model. Thus, virtual histology based on PTA contrast enhanced CT will in future help to refine the outcome of preclinical research on kidney associated murine disease models
Klotho pathways, myelination disorders, neurodegenerative diseases, and epigenetic drugs
In this review we outline a rationale for identifying neuroprotectants aimed at inducing endogenous Klotho activity and expression, which is epigenetic action, by definition. Such an approach should promote remyelination and/or stimulate myelin repair by acting on mitochondrial function, thereby heralding a life-saving path forward for patients suffering from neuroinflammatory diseases. Disorders of myelin in the nervous system damage the transmission of signals, resulting in loss of vision, motion, sensation, and other functions depending on the affected nerves, currently with no effective treatment. Klotho genes and their single-pass transmembrane Klotho proteins are powerful governors of the threads of life and death, true to the origin of their name, Fates, in Greek mythology. Among its many important functions, Klotho is an obligatory co-receptor that binds, activates, and/or potentiates critical fibroblast growth factor activity. Since the discovery of Klotho a little over two decades ago, it has become ever more apparent that when Klotho pathways go awry, oxidative stress and mitochondrial dysfunction take over, and age-related chronic disorders are likely to follow. The physiological consequences can be wide ranging, potentially wreaking havoc on the brain, eye, kidney, muscle, and more. Central nervous system disorders, neurodegenerative in nature, and especially those affecting the myelin sheath, represent worthy targets for advancing therapies that act upon Klotho pathways. Current drugs for these diseases, even therapeutics that are disease modifying rather than treating only the symptoms, leave much room for improvement. It is thus no wonder that this topic has caught the attention of biomedical researchers around the world.https://www.liebertpub.com/doi/10.1089/biores.2020.0004Published versio
Antimicrobial Footprints, Fairness, and Collective Harm
This chapter explores the question of whether or not individual agents
are under a moral obligation to reduce their ‘antimicrobial footprint’. An agent’s
antimicrobial footprint measures the extent to which her actions are causally linked
to the use of antibiotics. As such, it is not necessarily a measure of her contribution
to antimicrobial resistance. Talking about people’s antimicrobial footprint in a way
we talk about our carbon footprint may be helpful for drawing attention to the global
effects of individual behaviour and for highlighting that our choices can collectively
make a real difference. But can we be morally obligated to make a contribution to
resolving a collective action problem when our individual contributions by themselves
make no discernible difference? I will focus on two lines of argument in
favour of such obligations: whether a failure to reduce one’s antimicrobial footprint
is unfair and whether it constitutes wrongdoing because it is harmful. I conclude by
suggesting that the argument from collective harm is ultimately more successful
Identification of Colletotrichum species associated with anthracnose disease of coffee in Vietnam
Colletotrichum gloeosporioides, C. acutatum, C. capsici and C. boninense associated with anthracnose disease on coffee (Coffea spp.) in Vietnam were identified based on morphology and DNA analysis. Phylogenetic analysis of DNA sequences from the internal transcribed spacer region of nuclear rDNA and a portion of mitochondrial small subunit rRNA were concordant and allowed good separation of the taxa. We found several Colletotrichum isolates of unknown species and their taxonomic position remains unresolved. The majority of Vietnamese isolates belonged to C. gloeosporioides and they grouped together with the coffee berry disease (CBD) fungus, C. kahawae. However, C. kahawae could be distinguished from the Vietnamese C. gloeosporioides isolates based on ammonium tartrate utilization, growth rate and pathogenictity. C. gloeosporioides isolates were more pathogenic on detached green berries than isolates of the other species, i.e. C. acutatum, C capsici and C. boninense. Some of the C. gloeosporioides isolates produced slightly sunken lesion on green berries resembling CBD symptoms but it did not destroy the bean. We did not find any evidence of the presence of C. kahawae in Vietnam
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