We compare two optical clocks based on the ^{2}S_{1/2}(F=0)→^{2}D_{3/2}(F=2) electric quadrupole (E2) and the ^{2}S_{1/2}(F=0)→^{2}F_{7/2}(F=3) electric octupole (E3) transition of ^{171}Yb^{+} and ...measure the frequency ratio ν_{E3}/ν_{E2}=0.932829404530965376(32), improving upon previous measurements by an order of magnitude. Using two caesium fountain clocks, we find ν_{E3}=642121496772645.10(8) Hz, the most accurate determination of an optical transition frequency to date. Repeated measurements of both quantities over several years are analyzed for potential violations of local position invariance. We improve by factors of about 20 and 2 the limits for fractional temporal variations of the fine structure constant α to 1.0(1.1)×10^{-18}/yr and of the proton-to-electron mass ratio μ to -8(36)×10^{-18}/yr. Using the annual variation of the Sun's gravitational potential at Earth Φ, we improve limits for a potential coupling of both constants to gravity, (c^{2}/α)(dα/dΦ)=14(11)×10^{-9} and (c^{2}/μ)(dμ/dΦ)=7(45)×10^{-8}.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UL, UM
Trop-2 is a calcium signal transducer that is associated with transformed cell growth in experimental systems. However, its role in human cancer remains essentially unknown. In this study, we ...profiled Trop-2 expression in normal human tissues at the mRNA and protein levels. We then systematically compared Trop-2 mRNA and protein levels in tumours with their tissues of origin. We find that Trop-2 expression is invariably upregulated in tumours, regardless of baseline expression in normal tissues, which suggests a corresponding selective advantage. Thus, we investigated the outcome of Trop-2 upregulation on tumour growth. Overexpression of wild-type Trop-2 was shown to be necessary and sufficient to drive cancer growth in a widely invariant manner across cell type and species. Upregulation of Trop-2 was shown to quantitatively stimulate tumour growth, as proportional to expression levels in vivo, and tumour cell growth was abrogated by somatic knockdown of Trop-2 expression. On the other hand, we found no evidence of tumour-associated TROP2 mutations, nor of TROP2 induction of oncogenic transformation per se. Our data support a model where above-baseline expression of wild-type Trop-2 is a key driver of human cancer growth.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
In cancer metastasis and other physiological processes, cells migrate through the three-dimensional (3D) extracellular matrix of connective tissue and must overcome the steric hindrance posed by ...pores that are smaller than the cells. It is currently assumed that low cell stiffness promotes cell migration through confined spaces, but other factors such as adhesion and traction forces may be equally important. To study 3D migration under confinement in a stiff (1.77 MPa) environment, we use soft lithography to fabricate polydimethylsiloxane (PDMS) devices consisting of linear channel segments with 20 μm length, 3.7 μm height, and a decreasing width from 11.2 to 1.7 μm. To study 3D migration in a soft (550 Pa) environment, we use self-assembled collagen networks with an average pore size of 3 μm. We then measure the ability of four different cancer cell lines to migrate through these 3D matrices, and correlate the results with cell physical properties including contractility, adhesiveness, cell stiffness, and nuclear volume. Furthermore, we alter cell adhesion by coating the channel walls with different amounts of adhesion proteins, and we increase cell stiffness by overexpression of the nuclear envelope protein lamin A. Although all cell lines are able to migrate through the smallest 1.7 μm channels, we find significant differences in the migration velocity. Cell migration is impeded in cell lines with larger nuclei, lower adhesiveness, and to a lesser degree also in cells with lower contractility and higher stiffness. Our data show that the ability to overcome the steric hindrance of the matrix cannot be attributed to a single cell property but instead arises from a combination of adhesiveness, nuclear volume, contractility, and cell stiffness.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We describe a method for quantifying the mechanical properties of cells in suspension with a microfluidic device consisting of a parallel array of micron-sized constrictions. Using a high-speed ...charge-coupled device camera, we measure the flow speed, cell deformation, and entry time into the constrictions of several hundred cells per minute during their passage through the device. From the flow speed and the occupation state of the microconstriction array with cells, the driving pressure across each constriction is continuously computed. Cell entry times into microconstrictions decrease with increased driving pressure and decreased cell size according to a power law. From this power-law relationship, the cell elasticity and fluidity can be estimated. When cells are treated with drugs that depolymerize or stabilize the cytoskeleton or the nucleus, elasticity and fluidity data from all treatments collapse onto a master curve. Power-law rheology and collapse onto a master curve are predicted by the theory of soft glassy materials and have been previously shown to describe the mechanical behavior of cells adhering to a substrate. Our finding that this theory also applies to cells in suspension provides the foundation for a quantitative high-throughput measurement of cell mechanical properties with microfluidic devices.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Sediments in combined sewers may negatively affect the performance of sewer systems and significantly promote the formation of hydrogen sulfide. To prevent this, German sewer systems are cleaned ...regularly but at high costs. In order to optimize the cleaning intervals, this study investigates how deposits build up and change over a defined period under constant conditions. The experiments were performed using real wastewater at a pilot plant consisting of three 10 m long acrylic glass pipes with a diameter of 300 mm, a slope of I = 1‰, a discharge of Q = 2 L/s and a roughness of kS = 0.4 mm. Within the first 30 d, a slow increase of the deposit height (averaged over the pipe length) of 0.75 mm/d was observed. The deposits did not build up continuously, but in between times also decreased due to erosion. The daily changes in deposit amounts occurred partly as a function of the rainfall conditions and could go beyond the average growth many times. Within a day, the deposit height (averaged over pipe length) changed by up to 20 mm, at single measuring points even up to 100 mm. After about 50 d under constant test conditions, the deposit height came to a state of equilibrium between sedimentation and erosion.
The incidence of melanoma has increased over the past several decades. Despite improved case mortality, overall deaths from melanoma have increased because of the large increase in incidence. ...Although we have a better understanding of the pathogenesis of melanoma and improved early diagnostic capabilities, the burden of disease and societal costs remain high. This article provides an update on the epidemiology of cutaneous melanoma worldwide and the common risk factors including heritable and modifiable risks, emphasizing the importance of education, early detection, and prevention in reducing the disease burden.
We amplified Ehrlichia and Anaplasma DNA from Amblyomma dubitatum tick-infested capybaras (Hydrochoerus hydrochaeris) in southern Brazil. Sequencing of 16S rRNA, sodB, and groEL indicated a novel ...Ehrlichia species, and sequencing of 16S rRNA from 2 capybaras indicated a novel Anaplasma species. The tick vectors remain unknown.
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DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Aortic stenosis is a frequent valvular disease especially in elderly patients. Catheter-based valve implantation has emerged as a valuable treatment approach for these patients being either at very ...high risk for conventional surgery or even deemed inoperable. The German Aortic Valve Registry (GARY) provides data on conventional and catheter-based aortic procedures on an all-comers basis.
A total of 13 860 consecutive patients undergoing repair for aortic valve disease conventional surgery and transvascular (TV) or transapical (TA) catheter-based techniques have been enrolled in this registry during 2011 and baseline, procedural, and outcome data have been acquired. The registry summarizes the results of 6523 conventional aortic valve replacements without (AVR) and 3464 with concomitant coronary bypass surgery (AVR + CABG) as well as 2695 TV AVI and 1181 TA interventions (TA AVI). Patients undergoing catheter-based techniques were significantly older and had higher risk profiles. The stroke rate was low in all groups with 1.3% (AVR), 1.9% (AVR + CABG), 1.7% (TV AVI), and 2.3% (TA AVI). The in-hospital mortality was 2.1% (AVR) and 4.5% (AVR + CABG) for patients undergoing conventional surgery, and 5.1% (TV AVI) and AVI 7.7% (TA AVI).
The in-hospital outcome results of this registry show that conventional surgery yields excellent results in all risk groups and that catheter-based aortic valve replacements is an alternative to conventional surgery in high risk and elderly patients.
We present improved constraints on the coupling of ultralight bosonic dark matter to photons based on long-term measurements of two optical frequency ratios. In these optical clock comparisons, we ...relate the frequency of the ^{2}S_{1/2}(F=0)↔^{2}F_{7/2}(F=3) electric-octupole (E3) transition in ^{171}Yb^{+} to that of the ^{2}S_{1/2}(F=0)↔^{2}D_{3/2}(F=2) electric-quadrupole (E2) transition of the same ion, and to that of the ^{1}S_{0}↔^{3}P_{0} transition in ^{87}Sr. Measurements of the first frequency ratio ν_{E3}/ν_{E2} are performed via interleaved interrogation of both transitions in a single ion. The comparison of the single-ion clock based on the E3 transition with a strontium optical lattice clock yields the second frequency ratio ν_{E3}/ν_{Sr}. By constraining oscillations of the fine-structure constant α with these measurement results, we improve existing bounds on the scalar coupling d_{e} of ultralight dark matter to photons for dark matter masses in the range of about (10^{-24}-10^{-17}) eV/c^{2}. These results constitute an improvement by more than an order of magnitude over previous investigations for most of this range. We also use the repeated measurements of ν_{E3}/ν_{E2} to improve existing limits on a linear temporal drift of α and its coupling to gravity.
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We search for transient variations of the fine structure constant using data from a European network of fiber-linked optical atomic clocks. By searching for coherent variations in the recorded clock ...frequency comparisons across the network, we significantly improve the constraints on transient variations of the fine structure constant. For example, we constrain the variation to |δα/α| < 5 × 10−17 for transients of duration 103 s. This analysis also presents a possibility to search for dark matter, the mysterious substance hypothesised to explain galaxy dynamics and other astrophysical phenomena that is thought to dominate the matter density of the universe. At the current sensitivity level, we find no evidence for dark matter in the form of topological defects (or, more generally, any macroscopic objects), and we thus place constraints on certain potential couplings between the dark matter and standard model particles, substantially improving upon the existing constraints, particularly for large (≳104 km) objects.
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