These approaches can be easily combined with lignin micro-/nanoparticles (LMNP) production. The processes should also be cost-efficient compared to traditional lignin modifications. Biorefinery processes allow much greater flexibility in optimizing the lignin characteristics desirable for specific applications than traditional pulping processes. Such lignin engineering, at the same time, requires an efficient strategy capable of handling large datasets to find correlations between process variables, lignin structures and properties and finally their performance in different applications.Ion exchange chromatography is a powerful and ubiquitous unit operation in the purification of therapeutic proteins. However, the performance of an ion-exchange process depends on a complex interrelationship between several parameters, such as protein properties, mobile phase conditions, and chromatographic resin characteristics. Consequently, batch variations of ion exchange resins play a significant role in the robustness of these downstream processing steps. Ligand density is known to be one of the main lot-to-lot variations, affecting protein adsorption and separation performance. The use of a model-based approach can be an effective tool for comprehending the impact of parameter variations (e.g., ligand density) and their influence on the process. The objective of this work was to apply mechanistic modeling to gain a deeper understanding of the influence of ligand density variations in anion exchange chromatography. To achieve this, 13 prototype resins having the same support as the strong anion exchange resin Fractogel® EMD TMAE (M), but differing in ligand density, were analyzed. Linear salt gradient elution experiments were performed to observe the elution behavior of a monoclonal antibody and bovine serum albumin. A proposed isotherm model for ion exchange chromatography, describing the dependence of ligand density variations on protein retention, was successfully applied.
  The novel morpholino antisense oligonucleotide viltolarsen targets exon 53 of the dystrophin gene, and could be an effective treatment for patients with Duchenne muscular dystrophy (DMD). We investigated viltolarsen's ability to induce dystrophin expression and examined its safety in DMD patients.
 
  In this open-label, multicenter, parallel-group, phase 1/2, exploratory study, 16 ambulant and nonambulant males aged 5-12years with DMD received viltolarsen 40 or 80mg/kg/week via intravenous infusion for 24weeks. Primary endpoints were dystrophin expression and exon 53 skipping levels.
 
  In western blot analysis, mean changes in dystrophin expression (% normal) from baseline to Weeks 12 and 24 were-1.21 (P=0.5136) and 1.46 (P=0.1636), respectively, in the 40mg/kg group, and 0.76 (P=0.2367) and 4.81 (P=0.0536), respectively, in the 80mg/kg group.  https://www.selleckchem.com/products/act001-dmamcl.html  The increase in mean dystrophin level at Weeks 12 and 24 was significant in the 80mg/kg group (2.78%; P=0.0364). Patients receiving 80mg/kg showed a higher mean exon 53 skipping level (42.4%) than those receiving 40mg/kg (21.8%). All adverse events were judged to be mild or moderate in intensity and none led to study discontinuation.
 
  Treatment with viltolarsen 40 or 80mg/kg elicited an increasing trend in dystrophin expression and exon 53 skipping levels, and was safe and well tolerated. The decline in motor function appeared less marked in patients with higher dystrophin levels; this may warrant further investigation. This study supports the potential clinical benefit of viltolarsen.
 Treatment with viltolarsen 40 or 80 mg/kg elicited an increasing trend in dystrophin expression and exon 53 skipping levels, and was safe and well tolerated. The decline in motor function appeared less marked in patients with higher dystrophin levels; this may warrant further investigation. This study supports the potential clinical benefit of viltolarsen.
  To investigate a planning technique that can possibly reduce low-to-intermediate dose spillage (measured by R50%, D2cm values) in lung SBRT plans.
 
  Dose falloff outside the target was studied retrospectively in 102 SBRT VMAT plans of lung tumor. Plans having R50% and/or D2cm higher than recommended tolerances in RTOG protocols 0813 and 0915 were replanned with new optimization constraints using novel shell structures and novel constraints. Violations in the RTOG R50% value can be rectified with a dose constraint to a novel shell structure ("OptiForR50"). The construction of structure OptiForR50% and the novel optimization criteria translate the RTOG goals for R50% into direct inputs for the optimizer. Violations in the D2cm can be rectified using constraints on a 0.5cm thick shell structure with inner surface 2cm from the PTV surface. Wilcoxon signed-rank test was used to compare differences in dose conformity, volume of hot spots, R50%, D2cm of the target in addition to the OAR doses. A two-sided P-value SBRT plans. All plans were successfully brought into the zone of no RTOG violations.
  The hallmark of myelodysplastic syndrome (MDS) remains dysplasia in the bone marrow (BM). However, diagnosing MDS may be challenging and subject to inter-observer variability. Thus, there is an unmet need for novel objective, standardized and reproducible methods for evaluating dysplasia. Imaging flow cytometry (IFC) offers combined analyses of phenotypic and image-based morphometric parameters, for example, cell size and nuclearity. Hence, we hypothesized IFC to be a useful tool in MDS diagnostics.
 
  Using a different-from-normal approach, we investigated dyserythropoiesis by quantifying morphometric features in a median of 5953 erythroblasts (range 489-68,503) from 14 MDS patients, 11 healthy donors, 6 non-MDS controls with increased erythropoiesis, and 6 patients with cytopenia.
 
  First, we morphometrically confirmed normal erythroid maturation, as immunophenotypically defined erythroid precursors could be sequenced by significantly decreasing cell-, nuclear- and cytoplasm area. In MDS samples, we demons We propose that IFC holds great promise as a powerful and objective tool in the complex setting of MDS diagnostics with the potential for minimizing inter-observer variability.