Selective laser melting using holographic beam manipulation: influence of polypropylene molecular weight

Purpose – There is a requirement to match selective laser melting (SLM) technologies to a wider range of polymeric materials, since the existing market for SLM powders is dominated by polyamide PA12. Drivers include the tailoring of physical properties to individual applications, or cost reduction. Polypropylene (PP) currently has limited use in SLM, so the potential use of PP materials of varying molecular weight (Mw) is explored here. Design / methodology / approach – PP polymers of differing molecular weight were characterised using a range of analytical techniques, including DSC, thermogravimetric analysis (TGA), rotational rheometry and real-time hot-stage (optical) microscopy. Findings – The techniques are sufficiently sensitive to distinguish molecular weight effects, notably in terms of material viscosity. The stable sintering region for SLM has been defined clearly. Some success was achieved in melting parts using some grades of PP, including higher molecular weight grades, which potentially offer improved mechanical performance. Research limitations / implications – The range of techniques (DSC, OIT and TGA) form an effective analytical package with which to consider new polymeric materials for SLM. Practical implications – High-MW PP polymers, in tape or powder form, have potential use in SLM processes, providing scope to enhance part properties in future. Originality / value - This is believed to be the first in-depth study noting the influence of PP molecular weight on important physical performance in a proprietary SLM process, using holographic beam manipulation (HBM)

Additional file 1 of Accelerated parallel algorithm for gene network reverse engineering

Source code. The source code developed are available in the Bitbucket repository: https://github.com/califano-lab/GPU-ARACNE . (ZIP 25 kb

Total Synthesis of (±)-Bisabosqual A

The synthesis of the novel squalene synthase inhibitor, bisabosqual A, was completed in 14 steps (longest linear sequence) from commercially available starting materials. The doubly convergent route employs a tandem 5-exo, 6-exo radical cyclization as the key step. This reaction assembles the fully functionalized tetracyclic core and introduces three stereogenic centers. Other effective transformations are the regioselective deoxygenation of an advanced enone intermediate and the chemo- and diastereoselective addition of trimethylaluminum to a ketone in the presence of esters

Total Synthesis of (±)-Bisabosqual A

The synthesis of the novel squalene synthase inhibitor, bisabosqual A, was completed in 14 steps (longest linear sequence) from commercially available starting materials. The doubly convergent route employs a tandem 5-exo, 6-exo radical cyclization as the key step. This reaction assembles the fully functionalized tetracyclic core and introduces three stereogenic centers. Other effective transformations are the regioselective deoxygenation of an advanced enone intermediate and the chemo- and diastereoselective addition of trimethylaluminum to a ketone in the presence of esters

Total Synthesis of (±)-Bisabosqual A

The synthesis of the novel squalene synthase inhibitor, bisabosqual A, was completed in 14 steps (longest linear sequence) from commercially available starting materials. The doubly convergent route employs a tandem 5-exo, 6-exo radical cyclization as the key step. This reaction assembles the fully functionalized tetracyclic core and introduces three stereogenic centers. Other effective transformations are the regioselective deoxygenation of an advanced enone intermediate and the chemo- and diastereoselective addition of trimethylaluminum to a ketone in the presence of esters

Dual Stimuli-Responsive Hybrid Polymeric Nanoparticles Self-Assembled from POSS-Based Starlike Copolymer-Drug Conjugates for Efficient Intracellular Delivery of Hydrophobic Drugs

To further fine tune drug release and enhance therapeutic effects of polyhedral oligomericsilsesquioxane (POSS)-based nanomedicine, a starlike organic–inorganic conjugate was synthesized by grafting semitelechelic <i>N</i>-(2-hydroxypropyl) methacrylamide (HPMA) copolymers to a POSS rigid core through reductively degradable disulfide bonds. The hydrophobic docetaxel (DTX) was attached to the grafts by pH-sensitive hydrazone bonds and also encapsulated into the POSS core (SP-DTX). Thus, the final amphiphilic star-shaped conjugates could self-assemble into nanoparticles and exhibited conspicuous drug-loading capacity (20.1 wt %) based on the covalently conjugated accompanied by physically encapsulated DTX. The stimuli-responsive DTX release under acidic lysosomal and reducing cytoplasmic environments was verified, leading to enhanced cytotoxicity against PC-3 human prostate carcinoma cells. To evaluate the in vivo therapeutic effects of the DTX-loaded nanovehicles objectively, a stroma-rich, prostate xenograft tumor model was generated. SP-DTX displayed uniform tumor distribution and suppressed tumor growth to a more pronounced level (tumor inhibition of 78.9%) than nonredox-sensitive SP-DTX-A (67.4%), SP-DTX-C contained DTX only in the core (65.5%) or linear P-DTX (60.7%) through enhanced depletion of cancer-associated fibroblasts and induction of apoptosis. The hybrid POSS-based polymeric nanoparticles offer an efficient approach to transport hydrophobic drugs for cancer therapy

Medication use in adults with attention deficit/hyperactivity disorder in a commercially-insured population in the United States

<p><b>Objective:</b> To examine real-world prescription medication usage among commercially-insured adults with attention deficit/hyperactivity disorder (ADHD) in the US.</p> <p><b>Methods:</b> Adults with ADHD who received ≥1 ADHD medication during 2013 were identified from a large US claims database. Combination therapy was defined as an overlap of ≥30 days between the index (first treatment ≥30 days in 2013) and another medication(s). Patients were classified into six groups: long-acting (LA) monotherapy, short-acting (SA) monotherapy, LA + LA, SA + SA, LA + SA, and >2 therapies. Analyses compared baseline characteristics by regimen, ranked combination regimens, and estimated daily average consumption (DACON) for monotherapy users.</p> <p><b>Results:</b> Of 206,443 adults with ADHD (mean age = 32.9 years; 51.6% female), 56.9% used LA monotherapy, 30.7% SA monotherapy, and 12.5% used combination therapies (LA + SA: 10.3%; LA + LA: 1.3%; SA + SA: 0.4%; >2 therapies: 0.5%). Extended-release mixed amphetamine salts (MAS-XR, 39.2%) and lisdexamfetamine (LDX, 31.5%) were the most common LA monotherapies. Nearly all SA monotherapy patients received immediate-release mixed amphetamine salts (MAS-IR; 81.7%). The top three therapies among combination categories were: (a) LA + LA: branded MAS-XR + generic MAS-XR (13.7%), LDX + generic MAS-XR (10.8%), LDX + guanfacine ER (10.7%); (b) SA + SA: generic MAS-IR + clonidine IR (33.5%), generic MAS-IR + generic MPH SA (17.9%), branded MAS-IR + generic MAS-IR (11.1%); (c) LA + SA: generic MAS-XR+/-IR (39.2%), LDX + generic MAS-IR (16.7%), LA + SA generic MPH (12.6%). Among monotherapy users, DACON was 1.2 ± 0.6 (LA) and 2.1 ± 0.9 (SA) tablets.</p> <p><b>Conclusions:</b> There is significant treatment heterogeneity among US adults with ADHD. A sizable proportion of patients received monotherapies at above the recommended dosages or combination therapies, suggesting existing single-tablet regimens may not meet patients’ needs.</p

Upregulated IL-1 Receptor-associated Kinase 1 (IRAK1) in Systemic Lupus Erythematosus: IRAK1 Inhibition Represses Th17 Differentiation with Therapeutic Potential

<p>Systemic lupus erythematosus (SLE) is a typical autoimmune disease. Genome-wide analyses have revealed that interleukin-1 receptor-associated kinase 1 (IRAK1) is associated with susceptibility to SLE. Our previous study investigated the role of IRAK1 in nuclear factor-κB (NF-κB)-related pathways in a mouse model of lupus. In this study, we aimed to further explore the etiological role of IRAK1. The gene expression and phosphorylation of IRAK1 in CD4⁺ T cells from lupus patients and healthy controls were examined by quantitative reverse transcription-polymerase chain reaction and western blotting, respectively. The percentage of circulating Th17 cells and plasma IL-17A levels were evaluated by flow cytometry and enzyme-linked immunosorbent assay, respectively. The influence of IRAK1 suppression on Th17 development was assessed using an IRAK1 inhibitor and small interfering RNA. We found that IRAK1 transcript levels in CD4⁺ T cells were significantly upregulated in SLE patients in comparison to controls and were positively correlated with disease activity. <i>In vitro</i> experiments showed that lupus CD4⁺ T cells had more pronounced IRAK1 phosphorylation at threonine-209 upon IL-1β stimulation than did control cells. Moreover, IRAK1 expression was positively associated with Th17/IL-17A in patients. When naïve CD4⁺ T cells were polarized toward the Th17 subset, IRAK1 inhibition significantly repressed IL-17A production and the gene expression of Th17 markers, namely, retinoic acid receptor-related orphan receptor c, IL-23 receptor and IL-17A. In summary, IRAK1 is overexpressed and hyperactivated in CD4⁺ T cells from SLE patients. IRAK1 inhibition attenuates Th17 differentiation in the context of human SLE, suggesting a therapeutic opportunity.</p

Copper-Catalyzed <i>N</i>‑Cyanation of Sulfoximines by AIBN

The direct copper-catalyzed <i>N</i>-cyanation of sulfoximines was achieved by using AIBN as a safe cyanide source. It represents a simple and environmentally benign procedure for the construction of the N–CN bond. Furthermore, some <i>sec</i>-amines can also be tolerated well under this procedure

BDNF increased tau protein expression in RA-differentiated SH-SY5Y cells.

<p>RA treatment induced neurite formation/elongation in SH-SY5Y cells and increased tau expression. Subsequent BDNF treatment further increased neurite number/length and tau protein expression (Bar = 50 μm).</p