This music score was submitted for the Kaleidoscope 2020 Call for Scores, an open access collaboration with the UCLA Music Library.

Surface melt and mass loss of the Greenland Ice Sheet may play crucial roles in global climate change due to their positive feedbacks and large fresh-water storage. With few other regular meteorological observations available in this extreme environment, measurements from automatic weather stations (AWS) are the primary data source for studying surface energy budgets, and for validating satellite observations and model simulations. Station tilt, due to irregular surface melt, compaction and glacier dynamics, causes considerable biases in the AWS shortwave radiation measurements. In this study, we identify tilt-induced biases in the climatology of surface shortwave radiative flux and albedo, and retrospectively correct these by iterative application of solar geometric principles. We found, over all the AWS from the Greenland Climate Network (GC-Net), the Kangerlussuaq transect (K-transect) and the Programme for Monitoring of the Greenland Ice Sheet (PROMICE) networks, insolation on fewer than 40% of clear days peaks within ±0.5h of solar noon time, with the largest shift exceeding 3h due to tilt. Hourly absolute biases in the magnitude of surface insolation can reach up to 200W m-2, with respect to the well-understood clear-day insolation. We estimate the tilt angles and their directions based on the solar geometric relationship between the simulated insolation at a horizontal surface and the observed insolation by these tilted AWS under clear-sky conditions. Our adjustment reduces the root mean square error (RMSE) against references from both satellite observation and reanalysis by 16W m-2 (24%), and raises the correlation coefficients with them to above 0.95. Averaged over the whole Greenland Ice Sheet in the melt season, the adjustment in insolation to compensate station tilt is ∼ 11W m-2, enough to melt 0.24m of snow water equivalent. The adjusted diurnal cycles of albedo are smoother, with consistent semi-smiling patterns. The seasonal cycles and inter-annual variabilities of albedo agree better with previous studies. This tilt-corrected shortwave radiation data set derived using the Retrospective, Iterative, Geometry-Based (RIGB) method provide more accurate observations and validations for surface energy budgets studies on the Greenland Ice Sheet, including albedo variations, surface melt simulations and cloud radiative forcing estimates.

New opportunities for studying (sub)microcrystalline materials with small unit cells, both organic and inorganic, will open up when the X-ray free electron laser (XFEL) presently being constructed in Switzerland (SwissFEL) comes online in 2017. Our synchrotron-based experiments mimicking the 4%-energy-bandpass mode of the SwissFEL beam show that it will be possible to record a diffraction pattern of up to 10 randomly oriented crystals in a single snapshot, to index the resulting reflections, and to extract their intensities reliably. The crystals are destroyed with each XFEL pulse, but by combining snapshots from several sets of crystals, a complete set of data can be assembled, and crystal structures of materials that are difficult to analyze otherwise will become accessible. Even with a single shot, at least a partial analysis of the crystal structure will be possible, and with 10-50 femtosecond pulses, this offers tantalizing possibilities for time-resolved studies.

The direct observation of amorphous barium carbonate (ABC), which transforms into a previously unknown barium carbonate hydrate (herewith named gortatowskite) within a few hundred milliseconds of formation, is described. In situ X-ray scattering, cryo-, and low-dose electron microscopy were used to capture the transformation of nanoparticulate ABC into gortatowskite crystals, highly anisotropic sheets that are up to 1 μm in width, yet only about 10 nm in thickness. Recrystallization of gortatowskite to witherite starts within 30 seconds. We describe a bulk synthesis and report a first assessment of the composition, vibrational spectra, and structure of gortatowskite. Our findings indicate that transient amorphous and crystalline precursors can play a role in aqueous precipitation pathways that may often be overlooked owing to their extremely short lifetimes and small dimensions. However, such transient precursors may be integral to the formation of more stable phases.

Binary feedback, providing information solely about task success or failure, can be sufficient to drive motor learning. While binary feedback can induce explicit adjustments in movement strategy, it remains unclear if this type of feedback also induces implicit learning. We examined this question in a center-out reaching task by gradually moving an invisible reward zone away from a visual target to a final rotation of 7.5° or 25° in a between-group design. Participants received binary feedback, indicating if the movement intersected the reward zone. By the end of the training, both groups modified their reach angle by about 95% of the rotation. We quantified implicit learning by measuring performance in a subsequent no-feedback aftereffect phase, in which participants were told to forgo any adopted movement strategies and reach directly to the visual target. The results showed a small, but robust (2-3°) aftereffect in both groups, highlighting that binary feedback elicits implicit learning. Notably, for both groups, reaches to two flanking generalization targets were biased in the same direction as the aftereffect. This pattern is at odds with the hypothesis that implicit learning is a form of use-dependent learning. Rather, the results suggest that binary feedback can be sufficient to recalibrate a sensorimotor map.

Basal sliding is a main control on glacier flow primarily driven by water pressure at the glacier base. The ongoing increase in surface melting of the Greenland Ice Sheet warrants an examination of its impact on basal water pressure and in turn on basal sliding. Here we examine the case of Russell Glacier, in West Greenland, where an extensive set of observations has been collected. These observations suggest that the recent increase in melt has had an equivocal impact on the annual velocity, with stable flow on the lower part of the drainage basin but accelerated flow above the Equilibrium Line Altitude (ELA). These distinct behaviors have been attributed to different evolutions of the subglacial draining system during and after the melt season. Here we use a high-resolution subglacial hydrological model forced by reconstructed surface runoff for the period 2008 to 2012 to investigate the cause of these distinct behaviors. We find that the increase in meltwater production at low elevation yields a more efficient drainage system compatible with the observed stagnation of the mean annual flow below the ELA. At higher elevation, the model indicates that the drainage system is mostly inefficient and is therefore strongly sensitive to an increase in meltwater availability, which is consistent with the observed increase in ice velocity.

The solution chemistry of a chelator developed for ²²⁷Th targeted alpha therapy was probed. The compound of interest is an octadentate ligand comprising four N-methyl-3-hydroxy-pyridine-2-one metal-binding units, two tertiary amine groups, and one carboxylate arm appended for bioconjugation. The seven p K_a values of the ligand and the stability constants of complexes formed with Th(IV), Hf(IV), Zr(IV), Gd(III), Eu(III), Al(III), and Fe(III) were determined. The ligand exhibits extreme thermodynamic selectivity toward tetravalent metal ions with a ca. 20 orders of magnitude difference between the formation constant of the Th(IV) species formed at physiological pH, namely [ThL]^-, and that of its Eu(III) analogue. Likewise, log β₁₁₀ values of 41.7 ± 0.3 and 26.9 ± 0.3 (T = 25 °C) were measured for [ThL]^- and [Fe^IIIL]^2-, respectively, highlighting the high affinity and selectivity of the ligand for Th ions over potentially competing endogenous metals. Single crystal X-ray analysis of the Fe(III) complex revealed a dinuclear 2:2 metal:chelator complex crystallizing in the space group P1̅. The formation of this dimeric species is likely favored by several intramolecular hydrogen bonds and the protonation state of the chelator in acidic media. L_III edge EXAFS data on the Th(IV) complexes of both the ligand and a monoclonal antibody conjugate revealed the expected mononuclear 1:1 metal:chelator coordination environment. This was also confirmed by high resolution mass spectrometry. Finally, kinetic experiments demonstrated that labeling the bioconjugated ligand with Th(IV) could be achieved and completed after 1 h at room temperature, reinforcing the high suitability of this chelator for ²²⁷Th targeted alpha therapy.

Human renal membrane transporters play key roles in the disposition of renally cleared drugs and endogenous substrates, but their ontogeny is largely unknown. Using 184 human postmortem frozen renal cortical tissues (preterm newborns to adults) and a subset of 62 tissue samples, we measured the mRNA levels of 11 renal transporters and the transcription factor pregnane X receptor (PXR) with quantitative real-time polymerase chain reaction, and protein abundance of nine transporters using liquid chromatography tandem mass spectrometry selective reaction monitoring, respectively. Expression levels of p-glycoprotein, urate transporter 1, organic anion transporter 1, organic anion transporter 3, and organic cation transporter 2 increased with age. Protein levels of multidrug and toxin extrusion transporter 2-K and breast cancer resistance protein showed no difference from newborns to adults, despite age-related changes in mRNA expression. Multidrug and toxin extrusion transporter 1, glucose transporter 2, multidrug resistance-associated protein 2, multidrug resistance-associated protein 4 (MRP4), and PXR expression levels were stable. Using immunohistochemistry, we found that MRP4 localization in pediatric samples was similar to that in adult samples. Collectively, our study revealed that renal drug transporters exhibited different rates and patterns of maturation, suggesting that renal handling of substrates may change with age.

Human renal membrane transporters play key roles in the disposition of renally cleared drugs and endogenous substrates, but their ontogeny is largely unknown. Using 184 human postmortem frozen renal cortical tissues (preterm newborns to adults) and a subset of 62 tissue samples, we measured the mRNA levels of 11 renal transporters and the transcription factor pregnane X receptor (PXR) with quantitative real-time polymerase chain reaction, and protein abundance of nine transporters using liquid chromatography tandem mass spectrometry selective reaction monitoring, respectively. Expression levels of p-glycoprotein, urate transporter 1, organic anion transporter 1, organic anion transporter 3, and organic cation transporter 2 increased with age. Protein levels of multidrug and toxin extrusion transporter 2-K and breast cancer resistance protein showed no difference from newborns to adults, despite age-related changes in mRNA expression. Multidrug and toxin extrusion transporter 1, glucose transporter 2, multidrug resistance-associated protein 2, multidrug resistance-associated protein 4 (MRP4), and PXR expression levels were stable. Using immunohistochemistry, we found that MRP4 localization in pediatric samples was similar to that in adult samples. Collectively, our study revealed that renal drug transporters exhibited different rates and patterns of maturation, suggesting that renal handling of substrates may change with age.

Background

Deep brain stimulation (DBS) can be an effective therapy for tics and comorbidities in select cases of severe, treatment-refractory Tourette syndrome (TS). Clinical responses remain variable across patients, which may be attributed to differences in the location of the neuroanatomical regions being stimulated. We evaluated active contact locations and regions of stimulation across a large cohort of patients with TS in an effort to guide future targeting.

Methods

We collected retrospective clinical data and imaging from 13 international sites on 123 patients. We assessed the effects of DBS over time in 110 patients who were implanted in the centromedial (CM) thalamus (n=51), globus pallidus internus (GPi) (n=47), nucleus accumbens/anterior limb of the internal capsule (n=4) or a combination of targets (n=8). Contact locations (n=70 patients) and volumes of tissue activated (n=63 patients) were coregistered to create probabilistic stimulation atlases.

Results

Tics and obsessive-compulsive behaviour (OCB) significantly improved over time (p<0.01), and there were no significant differences across brain targets (p>0.05). The median time was 13 months to reach a 40% improvement in tics, and there were no significant differences across targets (p=0.84), presence of OCB (p=0.09) or age at implantation (p=0.08). Active contacts were generally clustered near the target nuclei, with some variability that may reflect differences in targeting protocols, lead models and contact configurations. There were regions within and surrounding GPi and CM thalamus that improved tics for some patients but were ineffective for others. Regions within, superior or medial to GPi were associated with a greater improvement in OCB than regions inferior to GPi.

Conclusion

The results collectively indicate that DBS may improve tics and OCB, the effects may develop over several months, and stimulation locations relative to structural anatomy alone may not predict response. This study was the first to visualise and evaluate the regions of stimulation across a large cohort of patients with TS to generate new hypotheses about potential targets for improving tics and comorbidities.