Photonic candle – focusing light using nano-bore optical fibers

Focusing light represents one of the fundamental optical functionalities that is used in a countless number of situations. Here we introduce the concept of nano-bore optical fiber mediated light focusing that allows to efficiently focus light at micrometer distance from the fiber end face. Since the focusing effect is provided by the fundamental fiber mode, device implementation is extremely straightforward since no post-processing or nano-structuring is necessary. Far-field measurements on implemented fibers, simulations, and a dual-Gaussian beam toy model confirm the validity of the concept. Due to its unique properties such as strong light localization, a close to 100% implementation success rate, extremely high reproducibility, and its compatibility with current fiber circuitry, the concept will find application in numerous areas that demand to focus at remote distances

Ultralong Tracking of Fast‐Diffusing Nano‐Objects inside Nanofluidic Channel−Enhanced Microstructured Optical Fiber

Nanoparticle tracking analysis (NTA) represents one essential technology to characterize diffusing nanoscale objects. Herein, uncovering dynamic processes and high-precision measurements requires tracks with thousands of frames to reach high statistical significance, ideally at high frame rates. Optical fibers with nanochannels are used for NTA, successfully demonstrating acquisition of trajectories of fast diffusion nano-objects with 100 000 frames. Due to the spatial limitation of the central nanofluidic channel, diffusion of objects illuminated by the core mode is confined, enabling the recording of Brownian motion over extraordinarily long time scales at high frame rates. The resulting benefits are discussed on a representative track of a gold nanosphere diffusing in water in over nearly 100 000 frames at 2 kHz frame rate. In addition to the verification of the fiber-based NTA using two data processing methods, a segmented analysis reveals a correlation between precision of determined diameter and continuous time interval (i.e., number of frames per subtrajectory). The presented results demonstrate the capabilities of fiber-based NTA in terms of 1) determining diameters with extraordinary high precision of single species and 2) monitoring dynamic processes of the object or the fluidic environment, both of which are relevant within biology, microrheology, and nano-object characterization

Inactivation of TGFβ receptors in stem cells drives cutaneous squamous cell carcinoma

Melanoma patients treated with oncogenic BRAF inhibitors can develop cutaneous squamous cell carcinoma (cSCC) within weeks of treatment, driven by paradoxical RAS/RAF MAPK pathway activation. Here, we identify frequent TGFBR1 and TGFBR2 mutations in human vemurafenib-induced skin lesions and in sporadic cSCC. Functional analysis reveals these mutations ablate canonical TGFb Smad signaling which is localised to bulge stem cells in both normal human and murine skin. MAPK pathway hyperactivation (through BRafV600E or KRASG12D knockin) and TGFb signaling ablation (through Tgfbr1 deletion) in Lgr5+ve stem cells enables rapid cSCC development in the mouse. Mutation of TP53 (which is commonly mutated in sporadic cSCC) coupled with TGFbR1 deletion in Lgr5+ve cells also results in cSCC development. These findings indicate that Lgr5+ve stem cells can act as a cell of origin for cSCC and that RAS-RAF-MAPK pathway hyperactivation or TP53 mutation, coupled with loss of TGFb signaling, are driving events of skin tumorigenesis

Blockchains for Business Process Management - Challenges and Opportunities

Blockchain technology promises a sizable potential for executing inter-organizational business processes without requiring a central party serving as a single point of trust (and failure). This paper analyzes its impact on business process management (BPM). We structure the discussion using two BPM frameworks, namely the six BPM core capabilities and the BPM lifecycle. This paper provides research directions for investigating the application of blockchain technology to BPM.Comment: Preprint for ACM TMI

Associations Between Lumbar Vertebral Bone Marrow and Paraspinal Muscle Fat Compositions—An Investigation by Chemical Shift Encoding-Based Water-Fat MRI

Purpose: Advanced magnetic resonance imaging (MRI) methods enable non-invasive quantification of body fat situated in different compartments. At the level of the lumbar spine, the paraspinal musculature is the compartment spatially and functionally closely related to the vertebral column, and both vertebral bone marrow fat (BMF) and paraspinal musculature fat contents have independently shown to be altered in various metabolic and degenerative diseases. However, despite their close relationships, potential correlations between fat compositions of these compartments remain largely unclear.Materials and Methods: Thirty-nine female subjects (38.5% premenopausal women, 29.9 ± 7.1 years; 61.5% postmenopausal women, 63.2 ± 6.3 years) underwent MRI at 3T of the lumbar spine using axially- and sagittally-prescribed gradient echo sequences for chemical shift encoding-based water-fat separation. The erector spinae muscles and vertebral bodies of L1–L5 were segmented to determine the proton density fat fraction (PDFF) of the paraspinal and vertebral bone marrow compartments. Correlations were calculated between the PDFF of the paraspinal muscle and bone marrow compartments.Results: The average PDFF of the paraspinal muscle and bone marrow compartments were significantly lower in premenopausal women when compared to postmenopausal women (11.6 ± 2.9% vs. 24.6 ± 7.1% & 28.8 ± 8.3% vs. 47.2 ± 8.5%; p < 0.001 for both comparisons). In premenopausal women, no significant correlation was found between the PDFF of the erector spinae muscles and the PDFF of the bone marrow of lumbar vertebral bodies (p = 0.907). In contrast, a significant correlation was shown in postmenopausal women (r = 0.457, p = 0.025). Significance was preserved after inclusion of age and body mass index (BMI) as control variables (r = 0.472, p = 0.027).Conclusion: This study revealed significant correlations between the PDFF of paraspinal and vertebral bone marrow compartments in postmenopausal women. The PDFF of the paraspinal and vertebral bone marrow compartments and their correlations might potentially serve as biomarkers; however, future studies including more subjects are required to evaluate distinct clinical value and reliability. Future studies should also follow up our findings in patients suffering from metabolic and degenerative diseases to clarify how these correlations change in the course of such diseases

Distinct metabolomic and lipidomic profiles in serum samples of patients with primary sclerosing cholangitis

Intoduction: Identification of specific metabolome and lipidome profile of patients with primary sclerosing cholangitis (PSC) is crucial for diagnosis, targeted personalized therapy, and more accurate risk stratification. Methods: Nuclear magnetic resonance (NMR) spectroscopy revealed an altered metabolome and lipidome of 33 patients with PSC [24 patients with inflammatory bowel disease (IBD) and 9 patients without IBD] compared with 40 age-, sex-, and body mass index (BMI)-matched healthy controls (HC) as well as 64 patients with IBD and other extraintestinal manifestations (EIM) but without PSC. Results: In particular, higher concentrations of pyruvic acid and several lipoprotein subfractions were measured in PSC in comparison to HC. Of clinical relevance, a specific amino acid and lipid profile was determined in PSC compared with IBD and other EIM. Discussion: These results have the potential to improve diagnosis by differentiating PSC patients from HC and those with IBD and EIM