Comparative Analysis between Side-to-End and End-to-End Lymphaticovenous Anastomosis for Secondary Lower Limb Lymphedema.

BACKGROUND: The purpose of this retrospective study was to describe, evaluate, and compare the outcome between end-to-end and side-to-end lymphaticovenous anastomoses for all stages of lymphedema. METHODS: A total of 123 patients were divided into the end-to-end ( n = 63) or the side-to-end ( n = 60) group. The demographics and intraoperative and postoperative findings were evaluated. In addition, subcategory evaluation was performed for early- and advanced-phase lymphedema. RESULTS: The demographic findings were insignificant. The intraoperative findings showed a significantly higher number of lymphaticovenous anastomoses performed for the end-to-end group (4.1 ± 1.7) over the side-to-end group (3.2 ± 1.2) ( p < 0.001), whereas the number of different lymphatic vessels used per patient was not significant (3.4 ± 1.4 versus 3.2 ± 1.2; p = 0.386). The diameter of the lymphatic vessels was not significant (0.43 ± 0.06 mm versus 0.45 ± 0.09 mm; p = 0.136). Although both groups showed significant postoperative volume reduction, the side-to-end group had a significantly better reduction in all time intervals ( p < 0.03) and longitudinal outcome ( p = 0.004). However, the subcategory evaluation for early-phase patients showed no difference between the two groups, but a significantly better volume reduction ratio was noted for the side-to-end group at all time intervals ( p < 0.025) in addition to overall longitudinal outcome ( p = 0.004) in advanced lymphedema patients. CONCLUSIONS: This is the first study to report the efficacy of end-to-end versus side-to-end lymphaticovenous anastomosis in different phases of lymphedema. Although both end-to-end and side-to-end lymphaticovenous anastomoses are significantly effective in volume reduction, there was a significantly better reduction for the side-to-end group in advanced-phase lymphedema patients with stage II late and stage III disease, whereas no difference was noted for early-phase lymphedema patients. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Retreat of Humboldt Gletscher, North Greenland, Driven by Undercutting From a Warmer Ocean.

Humboldt Gletscher is a 100-km wide, slow-moving glacier in north Greenland which holds a 19-cm global sea level equivalent. Humboldt has been the fourth largest contributor to sea level rise since 1972 but the cause of its mass loss has not been elucidated. Multi-beam echo sounding data collected in 2019 indicate a seabed 200 m deeper than previously known. Conductivity temperature depth data reveal the presence of warm water of Atlantic origin at 0°C at the glacier front and a warming of the ocean waters by 0.9 ± 0.1°C since 1962. Using an ocean model, we reconstruct grounded ice undercutting by the ocean, combine it with calculated retreat caused by ice thinning to floatation, and are able to fully explain the observed retreat. Two thirds of the retreat are caused by undercutting of grounded ice, which is a physical process not included in most ice sheet models.

Automatic delineation of glacier grounding lines in differential interferometric synthetic-aperture radar data using deep learning.

Delineating the grounding line of marine-terminating glaciers-where ice starts to become afloat in ocean waters-is crucial for measuring and understanding ice sheet mass balance, glacier dynamics, and their contributions to sea level rise. This task has been previously done using time-consuming, mostly-manual digitizations of differential interferometric synthetic-aperture radar interferograms by human experts. This approach is no longer viable with a fast-growing set of satellite observations and the need to establish time series over entire continents with quantified uncertainties. We present a fully-convolutional neural network with parallel atrous convolutional layers and asymmetric encoder/decoder components that automatically delineates grounding lines at a large scale, efficiently, and accompanied by uncertainty estimates. Our procedure detects grounding lines within 232 m in 100-m posting interferograms, which is comparable to the performance achieved by human experts. We also find value in the machine learning approach in situations that even challenge human experts. We use this approach to map the tidal-induced variability in grounding line position around Antarctica in 22,935 interferograms from year 2018. Along the Getz Ice Shelf, in West Antarctica, we demonstrate that grounding zones are one order magnitude (13.3 ± 3.9) wider than expected from hydrostatic equilibrium, which justifies the need to map grounding lines repeatedly and comprehensively to inform numerical models.

Makorin 1 Regulates Developmental Timing in Drosophila.

The central mechanisms coordinating growth and sexual maturation are well conserved across invertebrates and vertebrates. Although mutations in the gene encoding makorin RING finger protein 3 (mkrn3 ) are associated with central precocious puberty in humans, a causal relationship has not been elucidated. Here, we examined the role of mkrn1, a Drosophila ortholog of mammalian makorin genes, in the regulation of developmental timing. Loss of MKRN1 in mkrn1 exS prolonged the 3rd instar stage and delayed the onset of pupariation, resulting in bigger size pupae. MKRN1 was expressed in the prothoracic gland, where the steroid hormone ecdysone is produced. Furthermore, mkrn1 exS larvae exhibited reduced mRNA levels of phantom, which encodes ecdysone-synthesizing enzyme and E74, which is a downstream target of ecdysone. Collectively, these results indicate that MKRN1 fine-tunes developmental timing and sexual maturation by affecting ecdysone synthesis in Drosophila. Moreover, our study supports the notion that malfunction of makorin gene family member, mkrn3 dysregulates the timing of puberty in mammals.

Seasonal to decadal variability in ice discharge from the Greenland Ice Sheet.

Rapid changes in thickness and velocity have been observed at many marine-terminating glaciers in Greenland, impacting the volume of ice they export, or discharge, from the ice sheet. While annual estimates of ice-sheet wide discharge have been previously derived, higher-resolution records are required to fully constrain the temporal response of these glaciers to various climatic and mechanical drivers that vary in sub-annual scales. Here we sample outlet glaciers wider than 1 km (N = 230) to derive the first continuous, ice-sheet wide record of total ice sheet discharge for the 2000-2016 period, resolving a seasonal variability of 6 %. The amplitude of seasonality varies spatially across the ice sheet from 5 % in the southeastern region to 9 % in the northwest region. We analyze seasonal to annual variability in the discharge time series with respect to both modelled meltwater runoff, obtained from RACMO2.3p2, and glacier front position changes over the same period. We find that year-to-year changes in total ice sheet discharge are related to annual front changes (r 2 = 0.59, p = 10-4) and that the annual magnitude of discharge is closely related to cumulative front position changes (r 2 = 0.79), which show a net retreat of > 400 km, or an average retreat of > 2 km at each surveyed glacier. Neither maximum seasonal runoff or annual runoff totals are correlated to annual discharge, which suggests that larger annual quantities of runoff do not relate to increased annual discharge. Discharge and runoff, however, follow similar patterns of seasonal variability with near-coincident periods of acceleration and seasonal maxima. These results suggest that changes in glacier front position drive secular trends in discharge, whereas the impact of runoff is likely limited to the summer months when observed seasonal variations are substantially controlled by the timing of meltwater input.

Vaccinia-related kinase 3 (VRK3) sets the circadian period and amplitude by affecting the subcellular localization of clock proteins in mammalian cells.

In the eukaryotic circadian clock machinery, negative feedback repression of CLOCK (CLK) and BMAL1 transcriptional activity by PERIOD (PER) and CRYPTOCHROME (CRY) underlies the basis for 24 h rhythmic gene expression. Thus, precise regulation of the time-dependent nuclear entry of circadian repressors is crucial to generating normal circadian rhythms. Here, we sought to identify novel kinase(s) that regulate nuclear entry of mammalian CRY1 (mCRY1) with an unbiased screening using red fluorescent protein (RFP)-tagged human kinome expression plasmids in mammalian cells. Transient expression of human vaccinia-related kinase 3 (hVRK3) reduced the nuclear presence of mCRY1. hVRK3 expression also induced alterations in the subcellular localization of other core clock proteins, including mCRY2, mPER2, and BMAL1. In contrast, the subcellular localization of mCLK was not changed. Given that singly expressed mCLK mostly resides in the cytoplasm and that nuclear localization sequence (NLS) mutation of hVRK3 attenuated the effect of hVRK3 co-expression on subcellular localization, ectopically expressed hVRK3 presumably reduces the retention of proteins in the nucleus. Finally, downregulation of hvrk3 using siRNA reduced the amplitude and lengthened the period of the cellular bioluminescence rhythm. Taken together, these data suggest that VRK3 plays a role in setting the amplitude and period length of circadian rhythms in mammalian cells.

Improved Multiple Matching Method for Observing Glacier Motion with Repeat Image Feature Tracking.

Repeat Image Feature Tracking (RIFT) is commonly used to measure glacier surface motion from pairs of images, most often utilizing normalized cross correlation (NCC). The Multiple-Image Multiple-Chip (MIMC) algorithm successfully employed redundant matching (i.e. repeating the matching process over each area using varying combinations of settings) to increase the matching success rate. Due to the large number of repeat calculations, however, the original MIMC algorithm was slow and still prone to failure in areas of high shearing flow. Here we present several major updates to the MIMC algorithm that increase both speed and matching success rate. First, we include additional redundant measurements by swapping the image order and matching direction; a process we term Quadramatching. Second, we utilize a priori ice velocity information to confine the NCC search space through a system we term dynamic linear constraint (DLC), which substantially reduces the computation time and increases the rate of successful matches. Additionally, we develop a novel post-processing algorithm, pseudosmoothing, to determine the most probable displacement. Our tests reveal the complimentary and multiplicative nature of these upgrades in their improvement in overall MIMC performance.

Asymmetric synthesis of aromatic ß-amino acids using ω-transaminase: Optimizing the lipase concentration to obtain thermodynamically unstable ß-keto acids.

Synthesized aromatic ß-amino acids have recently attracted considerable attention for their application as precursors in many pharmacologically relevant compounds. Previous studies on asymmetric synthesis of aromatic ß-amino acids using ω-transaminases could not be done efficiently due to the instability of ß-keto acids. In this study, a strategy to circumvent the instability problem of ß-keto acids was utilized to generate ß-amino acids efficiently via asymmetric synthesis. In this work, thermodynamically stable ß-ketoesters were initially converted to ß-keto acids using lipase, and the ß-keto acids were subsequently aminated using ω-transaminase. By optimizing the lipase concentration, we successfully overcame the instability problem of ß-keto acids and enhanced the production of ß-amino acids. This strategy can be used as a general approach to efficiently generate ß-amino acids from ß-ketoesters.

Performance of Landsat 8 Operational Land Imager for Mapping Ice Sheet Velocity.

Landsat imagery has long been used to measure glacier and ice sheet surface velocity, and this application has increased with increased length and accessibility of the archive. The radiometric characteristics of Landsat sensors, however, have limited these measurements generally to only fast-flowing glaciers with high levels of surface texture and imagery with high sun angles and cloud-free conditions, preventing wide-area velocity mapping at the scale achievable with synthetic aperture radar (SAR). The Operational Land Imager (OLI) aboard the newly launched Landsat 8 features substantially improves radiometric performance compared to preceding sensors: enhancing performance of automated Repeat-Image Feature Tracking (RIFT) for mapping ice flow speed. In order to assess this improvement, we conduct a comparative study of OLI and the Landsat 7 Enhanced Thematic Mapper Plus (ETM+) performance for measuring glacier velocity in a range of surface and atmospheric conditions. To isolate the effects of radiometric quantization and noise level, we construct a model for simulating ETM+ imagery from OLI and compare RIFT results derived from each. We find that a nonlinearity in the relationship between ETM+ and OLI radiances at higher brightness levels results in a particularly large improvement in RIFT performance over the low-textured interior of the ice sheets, as well as improved performance in adverse conditions such as low sun-angles and thin clouds. Additionally, the reduced noise level in OLI imagery results in fewer spurious motion vectors and improved RIFT performance in all conditions and surfaces. We conclude that OLI imagery should enable large-area ice sheet and glacier mapping so that its coverage is comparable to SAR, with a remaining limitation being image geolocation.