Data Work in a Knowledge-Broker Organization: How Cross-Organizational Data Maintenance shapes Human Data Interactions.

The term Human-Data Interaction (HDI) conceptualizes the growing importance of understanding how people need and desire to use and interact with data. Previous HDI cases have mainly focused on the interface between personal health data and the healthcare sector. This paper argues that it is relevant to consider HDI at an organisational level and examines how HDI can look in such a context, where data and data maintenance are core assets and activities. We report on initial findings of a study of a knowledge-broker organisation, where we follow how data are produced, shared, and maintained in a cross-organisational context. We discuss similarities and differences of HDI aroundpersonal health data and cross-organisational data maintenance. We propose to extend the notion of HDI to include the complexity of cross-organisational data work

A Multilaboratory Comparison of Calibration Accuracy and the Performance of External References in Analytical Ultracentrifugation

Analytical ultracentrifugation (AUC) is a first principles based method to determine absolute sedimentation coefficients and buoyant molar masses of macromolecules and their complexes, reporting on their size and shape in free solution. The purpose of this multi-laboratory study was to establish the precision and accuracy of basic data dimensions in AUC and validate previously proposed calibration techniques. Three kits of AUC cell assemblies containing radial and temperature calibration tools and a bovine serum albumin (BSA) reference sample were shared among 67 laboratories, generating 129 comprehensive data sets. These allowed for an assessment of many parameters of instrument performance, including accuracy of the reported scan time after the start of centrifugation, the accuracy of the temperature calibration, and the accuracy of the radial magnification. The range of sedimentation coefficients obtained for BSA monomer in different instruments and using different optical systems was from 3.655 S to 4.949 S, with a mean and standard deviation of (4.304 ± 0.188) S (4.4%). After the combined application of correction factors derived from the external calibration references for elapsed time, scan velocity, temperature, and radial magnification, the range of s-values was reduced 7-fold with a mean of 4.325 S and a 6-fold reduced standard deviation of ± 0.030 S (0.7%). In addition, the large data set provided an opportunity to determine the instrument-to-instrument variation of the absolute radial positions reported in the scan files, the precision of photometric or refractometric signal magnitudes, and the precision of the calculated apparent molar mass of BSA monomer and the fraction of BSA dimers. These results highlight the necessity and effectiveness of independent calibration of basic AUC data dimensions for reliable quantitative studies

Intra-fractional per-beam adaptive workflow to mitigate the need for a rotating gantry during MRI-guided proton therapy

The integration of real-time magnetic resonance imaging (MRI) guidance and proton therapy would potentially improve the proton dose steering capability by reducing daily uncertainties due to anatomical variations. The use of a fixed beamline coupled with an axial patient couch rotation would greatly simplify the proton delivery with MRI guidance. Nonetheless, it is mandatory to assure that the plan quality is not deteriorated by the anatomical deformations due to patient rotation. In this work, an in-house tool allowing for intra-fractional per-beam adaptation of intensity-modulated proton plans (BeamAdapt) was implemented through features available in RayStation. A set of three MRIs was acquired for two healthy volunteers (V1, V2): (1) no rotation/static, (2) rotation to the right and (3) left. V1 was rotated by 15°, to simulate a clinical pediatric abdominal case and V2 by 45°, to simulate an extreme patient rotation case. For each volunteer, a total of four intensity-modulated pencil beam scanning plans were optimized on the static MRI using virtual abdominal targets and two-three posterior-oblique beams. Beam angles were defined according to the angulations on the rotated MRIs. With BeamAdapt, each original plan was initially converted into separate plans with one beam per plan. In an iterative order, individual beam doses were non-rigidly deformed to the rotated anatomies and re-optimized accounting for the consequent deformations and the beam doses delivered so far. For evaluation, the final accumulated dose distribution was propagated back to the static MRI. Planned and adapted dose distributions were compared by computing relative differences between dose-volume histogram metrics. Absolute target dose differences were on average below 1% and organs-at-risk mean dose differences were below 3%. With BeamAdapt, not only intra-fractional per-beam proton plan adaptation coupled with axial patient rotation is possible but also the need for a rotating gantry during MRI guidance might be mitigated

Deep learning prediction of proton and photon dose distributions for paediatric abdominal tumours

OBJECTIVE: Dose prediction using deep-learning networks prior to radiotherapy might lead to more efficient modality selections. The study goal was to predict proton and photon dose distributions based on the patient-specific anatomy and to assess their clinical usage for paediatric abdominal tumours. MATERIAL &METHODS: Data from 80 patients with neuroblastoma or Wilms' tumour was included. Pencil beam scanning (PBS) (5mm/3%) and volumetric-modulated arc therapy (VMAT) plans (5mm) were robustly optimized on the internal target volume (ITV). Separate 3-dimensional patch-based U-net networks were trained to predict PBS and VMAT dose distributions. Doses, planning-computed tomography images and relevant optimization masks (ITV, vertebra and organs-at-risk) of 60 patients were used for training with a 5-fold cross validation. The networks' performance was evaluated by computing the relative error between planned and predicted dose-volume histogram (DVH) parameters for 20 inference patients. In addition, the organs-at-risk mean dose difference between modalities was calculated using planned and predicted dose distributions (ΔDmean= DVMAT-DPBS). Two radiation oncologists performed a blind PBS/VMAT modality selection based on either planned or predicted ΔDmean. RESULTS: Average DVH differences between planned and predicted dose distributions were ≤|6%|for both modalities. The networks classified the organs-at-risk difference as a gain (ΔDmean>0) with 98% precision. An identical modality selection based on planned compared to predicted ΔDmean was made for 18/20 patients. CONCLUSION: Deep-learning networks for accurate prediction of proton and photon dose distributions for abdominal paediatric tumours were established. These networks allowing fast dose visualization might aid in identifying the optimal radiotherapy technique when experience and/or resources are unavailable

Loss of exogenous androgen dependence by prostate tumor cells is associated with elevated glucuronidation potential

Prostate epithelial cells control the potency and availability of androgen hormones in part by inactivation and elimination. UDP-glucose dehydrogenase (UGDH) catalyzes the NAD+-dependent oxidation of UDP-glucose to UDP-glucuronate, an essential precursor for androgen inactivation by the prostate glucuronidation enzymes UGT2B15 and UGT2B17. UGDH expression is androgen stimulated, which increases the production of UDP-glucuronate, and fuels UGT-catalyzed glucuronidation. In this study, we compared the glucuronidation potential and its impact on androgen-mediated gene expression in an isogenic LNCaP model for androgen dependent versus castration resistant prostate cancer. Despite significantly lower androgen-glucuronide output, LNCaP 81 castration resistant tumor cells expressed higher levels of UGDH, UGT2B15, and UGT2B17. However, the magnitude of androgen-activated UGDH and PSA expression, as well as the AR-dependent repression of UGT2B15 and UGT2B17, was blunted several-fold in these cells. Consistent with these results, the ligand-activated binding of AR to the PSA promoter and subsequent transcriptional activation were also significantly reduced in castration resistant cells. Analysis of the UDP-sugar pools and flux through pathways downstream of UDP-glucuronate production revealed that these glucuronidation precursor metabolites were channeled through proteoglycan and glycosaminoglycan biosynthetic pathways, leading to increased surface expression of Notch 1. Knockdown of UGDH diminished Notch1 and increased glucuronide output. Overall, these results support a model in which the aberrant partitioning of UDP-glucuronate and other UDP-sugars into alternative pathways during androgen deprivation contributes to the loss of prostate tumor cell androgen sensitivity by promoting altered cell surface proteoglycan expression

Loss of exogenous androgen dependence by prostate tumor cells is associated with elevated glucuronidation potential

Prostate epithelial cells control the potency and availability of androgen hormones in part by inactivation and elimination. UDP-glucose dehydrogenase (UGDH) catalyzes the NAD+-dependent oxidation of UDP-glucose to UDP-glucuronate, an essential precursor for androgen inactivation by the prostate glucuronidation enzymes UGT2B15 and UGT2B17. UGDH expression is androgen stimulated, which increases the production of UDP-glucuronate, and fuels UGT-catalyzed glucuronidation. In this study, we compared the glucuronidation potential and its impact on androgen-mediated gene expression in an isogenic LNCaP model for androgen dependent versus castration resistant prostate cancer. Despite significantly lower androgen-glucuronide output, LNCaP 81 castration resistant tumor cells expressed higher levels of UGDH, UGT2B15, and UGT2B17. However, the magnitude of androgen-activated UGDH and PSA expression, as well as the AR-dependent repression of UGT2B15 and UGT2B17, was blunted several-fold in these cells. Consistent with these results, the ligand-activated binding of AR to the PSA promoter and subsequent transcriptional activation were also significantly reduced in castration resistant cells. Analysis of the UDP-sugar pools and flux through pathways downstream of UDP-glucuronate production revealed that these glucuronidation precursor metabolites were channeled through proteoglycan and glycosaminoglycan biosynthetic pathways, leading to increased surface expression of Notch 1. Knockdown of UGDH diminished Notch1 and increased glucuronide output. Overall, these results support a model in which the aberrant partitioning of UDP-glucuronate and other UDP-sugars into alternative pathways during androgen deprivation contributes to the loss of prostate tumor cell androgen sensitivity by promoting altered cell surface proteoglycan expression

Overexpression of \u3ci\u3eSbMyb60\u3c/i\u3e in \u3ci\u3eSorghum bicolor\u3c/i\u3e impacts both primary and secondary metabolism

Few transcription factors have been identified in C4 grasses that either positively or negatively regulate monolignol biosynthesis. Previously, the overexpression of SbMyb60 in sorghum (Sorghum bicolor) has been shown to induce monolignol biosynthesis, which leads to elevated lignin deposition and altered cell wall composition. To determine how SbMyb60 overexpression impacts other metabolic pathways, RNA-Seq and metabolite profiling were performed on stalks and leaves. 35S::SbMyb60 was associated with the transcriptional activation of genes involved in aromatic amino acid, S-adenosyl methionine (SAM) and folate biosynthetic pathways. The high coexpression values between SbMyb60 and genes assigned to these pathways indicate that SbMyb60 may directly induce their expression. In addition, 35S::SbMyb60 altered the expression of genes involved in nitrogen (N) assimilation and carbon (C) metabolism, which may redirect C and N towards monolignol biosynthesis. Genes linked to UDP-sugar biosynthesis and cellulose synthesis were also induced, which is consistent with the observed increase in cellulose deposition in the internodes of 35S::SbMyb60 plants. However, SbMyb60 showed low coexpression values with these genes and is not likely to be a direct regulator of cell wall polysaccharide biosynthesis. These findings indicate that SbMyb60 can activate pathways beyond monolignol biosynthesis, including those that synthesize the substrates and cofactors required for lignin biosynthesis

Understanding the Effets of Dopants and Substrates on the Photoemission of Monolayer MoS2 Flakes

Bidimensional transition metal dichalcogenides are a class of semiconducting nanomaterials presenting very interesting electronic and optical properties.[1] Monolayer molybdenum disulphide (1L-MoS2) is particularly interesting for its high charge-carrier mobility and its strong light-absorption capabilities. Such properties, originating from the bidimensional structure of the material, are allowed by directtransitions occurring through its bandgap.[2] Visible-light photoexcitation allows 1LMoS2 to generate an intense emission which has been shown to be caused by excitonic recombination and which, moreover, is strongly coupled to the strain and doping of the semiconductor’s crystalline flakes.[3] As such, it is possible to modify the bandgap's properties of 1L-MoS2 by acting on its electronic and structural characteristics and, especially, to tune and control the shape and intensity of its peculiar emission in order to tailor it towards the development of optoelectronic nanodevices. Here we show how thermal treatments carried out on 1L-MoS2 under a controlled gaseous atmosphere are able to alter the optical properties of such bidimensional material. We have compared the effects of different atmospheres and the influence of the substrate’s conductivity and roughness in order to try and shed light on the causes of such modifications, finally aiming to enhance the overall optical properties of 1L-MoS2. Through the usage of a micro-photoluminescence setup developed inhouse and coupled to a tunable pulsed laser we are able to study single monolayer flakes under a wide variety of excitation conditions and its photoemission in both steady-state and time-resolved regimes. Our results are aimed at further understanding the optical properties of 1L-MoS2 and the factors influencing them. By being able to control the light-emitting capabilities of such material we aim to tailor it for its usage in the field of optoelectronics and towards the development of devices in which the electronic and optical properties of 1L-MoS2 are carefully coupled. [1] C. Ferrari, A. et al. Nanoscale 7, 4598–4810 (2015). [2] Splendiani, A. et al. Nano Lett. 10, 1271–1275 (2010). [3] Panasci, S. E. et al. ACS Appl. Mater. Interfaces 13, 31248–31259 (2021)

Cautionary Tale of Using Tris(alkyl)phosphine Reducing Agents with NAD+-Dependent Enzymes

Protein biochemistry protocols typically include disulfide bond reducing agents to guard against unwanted thiol oxidation and protein aggregation. Commonly used disulfide bond reducing agents include dithiothreitol, β-mercaptoethanol, glutathione, and the tris(alkyl)phosphine compounds tris(2-carboxyethyl)phosphine (TCEP) and tris(3-hydroxypropyl)phosphine (THPP). While studying the catalytic activity of the NAD(P)H-dependent enzyme Δ1-pyrroline-5-carboxylate reductase, we unexpectedly observed a rapid non-enzymatic chemical reaction between NAD+ and the reducing agents TCEP and THPP. The product of the reaction exhibits a maximum ultraviolet absorbance peak at 334 nm and forms with an apparent association rate constant of 231–491 M−1 s−1. The reaction is reversible, and nuclear magnetic resonance characterization (1H, 13C, and 31P) of the product revealed a covalent adduct between the phosphorus of the tris(alkyl)phosphine reducing agent and the C4 atom of the nicotinamide ring of NAD+. We also report a 1.45 Å resolution crystal structure of short-chain dehydrogenase/reductase with the NADP+–TCEP reaction product bound in the cofactor binding site, which shows that the adduct can potentially inhibit enzymes. These findings serve to caution researchers when using TCEP or THPP in experimental protocols with NAD(P)+. Because NAD(P)+-dependent oxidoreductases are widespread in nature, our results may be broadly relevant