Investigating the variation of particle distribution and surface texture of top surfaces based on build position in laser powder bed fusion

Quality analysis of additively manufactured (AM) surfaces is complex, yet critical for determining the functionality of parts and technology improvement. To accurately assess the quality of AM parts, it is necessary to consider the industrial application of the technology. This study investigates the variation of accumulated particles on AM top surfaces as a function of build position. It also seeks to study the surface texture variation as a function of build position, focusing on a spatial bandwidth region larger than that of traditional AM surface features, such as weld tracks, to investigate surface tension effects. Ti-6Al-4V cubes were built in a three-by-three array in a single build with fixed processing parameters. Coherence scanning interferometry was used to capture the primary data of the as-built top surfaces of cubes. The ISO 25178-2 methodology was used to extract the S-L surfaces, using the filtration methods defined in ISO 16610-21. The number of particles, coverage, and density were obtained by averaging over five repeated measurements in five different areas on the top surfaces. Particle distribution and surface texture analysis showed a trend from one location to another across the build, which is discussed according to the process variations

Performance Enhancement of Reduced Component Multilevel Inverter with Optimal Placement of Level Shifter

Multi-Level Inverter (MLI) with and without cross-connecting switches is constructed using bi-directional and uni-directional switches and their performances are verified via a real-time experimentation. Here, a cross connecting switch inverter (CCSI) is constructed and then cross connecting switches in CCSI are removed for the modified inverter (MMLI) with reduction of switches. Further, the CCSI and MMLI configuration is studied with the identification of optimal placement of the level shifter circuit in the basic unit and different types of procedures for the design of voltage sources that are used in the inverter to enhance the performance is proposed. The best method of defining the value of voltage sources among the proposed nine different algorithms a 31-level CCSI, a 49 level and 71 level MMLI are designed and tested experimentally. Efficiency, total blocking voltage, harmonic presence, real and reactive powers are obtained for the proposed converters to study their performance. Finally, a comparative analysis is made for the proposed structure against the other MLI in-term of switch count, ON state switches, voltage sources and efficiency

Mechanistic insight into the role of AUXIN RESISTANCE4 in trafficking of AUXIN1 and LIKE AUX1-2

AUXIN RESISTANCE4 (AXR4) regulates the trafficking of auxin influx carrier AUXIN1 (AUX1), a plasma-membrane protein that predominantly localizes to the endoplasmic reticulum (ER) in the absence of AXR4. In Arabidopsis (Arabidopsis thaliana), AUX1 is a member of a small multigene family comprising 4 highly conserved genes—AUX1, LIKE-AUX1 (LAX1), LAX2, and LAX3. We report here that LAX2 also requires AXR4 for correct localization to the plasma membrane. AXR4 is a plant-specific protein and contains a weakly conserved α/β hydrolase fold domain that is found in several classes of lipid hydrolases and transferases. We have previously proposed that AXR4 may either act as (i) a post-translational modifying enzyme through its α/β hydrolase fold domain or (ii) an ER accessory protein, which is a special class of ER protein that regulates targeting of their cognate partner proteins. Here, we show that AXR4 is unlikely to act as a post-translational modifying enzyme as mutations in several highly conserved amino acids in the α/β hydrolase fold domain can be tolerated and active site residues are missing. We also show that AUX1 and AXR4 physically interact with each other and that AXR4 reduces aggregation of AUX1 in a dose-dependent fashion. Our results suggest that AXR4 acts as an ER accessory protein. A better understanding of AXR4-mediated trafficking of auxin transporters in crop plants will be crucial for improving root traits (designer roots) for better acquisition of water and nutrients for sustainable and resilient agriculture

Impact of Vth Instability of Schottky-type p-GaN Gate HEMTs on Switching Behaviors

Schottky-type p-GaN gate Gallium Nitride High Electron Mobility Transistors (GaN-HEMTs) suffer from threshold voltage (Vth) instability phenomenon. Both positive and negative Vth shifts are reported when device undertakes the voltage bias, but the impact of this Vth instability phenomenon on device switching behaviors is less investigated. In this study, the drain-source voltage (Vds) induced bidirectional Vth shift in hard-switching condition is characterized and decoupled by an H-bridge based double-pulse test (DPT). Subsequently, the influence of Vth shift on switching behaviors is theoretically analyzed and demonstrated through SPICE simulation and experiment, showing how a positive shifted Vth can reduce the device turn-on commutation speed and increase the switching losses, and vice versa. The results suggest that the Vth instability phenomenon should be considered in accurate switching modeling

SnoRNAs in cardiovascular development, function, and disease

Small nucleolar RNAs (snoRNAs) are emerging as important regulators of cardiovascular (patho)biology. Several roles of snoRNAs have recently been identified in heart development and congenital heart diseases, as well as their dynamic regulation in hypertrophic and dilated cardiomyopathies, coronary heart disease (CHD), myocardial infarction (MI), cardiac fibrosis, and heart failure. Furthermore, reports of changes in vesicular snoRNA expression and altered levels of circulating snoRNAs in response to cardiac stress suggest that snoRNAs also function in cardiac signaling and intercellular communication. In this review, we summarize and discuss key findings and outline the clinical potential of snoRNAs considering current challenges and gaps in the field of cardiovascular diseases (CVDs)

Performance improvement of the automotive thermoelectric generator by extending the hot side area of the heat exchanger through heat pipes

In pursuit of enhancing the utilization of exhaust heat in the automotive thermoelectric generator (ATEG), this study introduces a novel heat exchanger with integrated heat pipes to extend the effective hot-side surface area. Meanwhile, a numerical model containing multiphysical fields is developed, and the quantity and arrangement of heat pipes are optimized based on this model. Results suggest that (i) The incorporation of heat pipes markedly enhances the recovery of heat energy from the ATEG, leading to a substantial increase in its output power; (ii) With an increasing heat pipe quantity, the ATEG's output power exhibits a continuous upward trend before eventually reaching stability; (iii) The arrangement of heat pipes also influences system performance, and through optimizations, the optimal quantity of heat pipes is determined to be N = 11 and toleration to be d = 1 mm. At an exhaust temperature of 550 K and a mass flow rate of 60 g/s, the ATEG achieves an output power of 213.19 W and a heat absorption of 4318.02 W, which increased by 42.95 % and 55.6 % respectively, compared with the traditional structure without heat pipes. This structural optimization concept for the heat exchanger provides a new approach to performance improvements of ATEGs. This study provides a design basis and guidance for optimizing the design of ATEG systems with integrated heat pipes

Pharmacological inhibition of RAS overcomes FLT3 inhibitor resistance in FLT3-ITD+ AML through AP-1 and RUNX1

AML is characterized by mutations in genes associated with growth regulation such as internal tandem duplications (ITD) in the receptor kinase FLT3. Inhibitors targeting FLT3 (FLT3i) are being used to treat patients with FLT3-ITD+ but most relapse and become resistant. To elucidate the resistance mechanism, we compared the gene regulatory networks (GRNs) of leukemic cells from patients before and after relapse, which revealed that the GRNs of drug-responsive patients were altered by rewiring their AP-1-RUNX1 axis. Moreover, FLT3i induces the upregulation of signaling genes, and we show that multiple cytokines, including interleukin-3 (IL-3), can overcome FLT3 inhibition and send cells back into cycle. FLT3i leads to loss of AP-1 and RUNX1 chromatin binding, which is counteracted by IL-3. However, cytokine-mediated drug resistance can be overcome by a pan-RAS inhibitor. We show that cytokines instruct AML growth via the transcriptional regulators AP-1 and RUNX1 and that pan-RAS drugs bypass this barrier

Strengths and opportunities in research into extracellular matrix ageing: A consultation with the ECMage research community

Ageing causes progressive decline in metabolic, behavioural, and physiological functions, leading to a reduced health span. The extracellular matrix (ECM) is the three‐dimensional network of macromolecules that provides our tissues with structure and biomechanical resilience. Imbalance between damage and repair/regeneration causes the ECM to undergo structural deterioration with age, contributing to age‐associated pathology. The ECM ‘Ageing Across the Life Course’ interdisciplinary research network (ECMage) was established to bring together researchers in the United Kingdom, and internationally, working on the emerging field of ECM ageing. Here we report on a consultation at a joint meeting of ECMage and the Medical Research Council / Versus Arthritis Centre for Integrated Research into Musculoskeletal Ageing, held in January 2023, in which delegates analysed the key questions and research opportunities in the field of ECM ageing. We examine fundamental biological questions, enabling technologies, systems of study and emerging in vitro and in silico models, alongside consideration of the broader challenges facing the field

The Effect of Tranexamic Acid on Neurosurgical Intervention in Spontaneous Intracerebral Hematoma: Data From 121 Surgically Treated Participants From the Tranexamic Acid in IntraCerebral Hemorrhage-2 Randomized Controlled Trial

BACKGROUND AND OBJECTIVES: An important proportion of patients with spontaneous intracerebral hemorrhage (ICH) undergo neurosurgical intervention to reduce mass effect from large hematomas and control the complications of bleeding, including hematoma expansion and hydrocephalus. The Tranexamic acid (TXA) for hyperacute primary IntraCerebral Hemorrhage (TICH-2) trial demonstrated that tranexamic acid (TXA) reduces the risk of hematoma expansion. We hypothesized that TXA would reduce the frequency of surgery (primary outcome) and improve functional outcome at 90 days in surgically treated patients in the TICH-2 data set.METHODS: Participants enrolled in TICH-2 were randomized to placebo or TXA. Participants randomized to either TXA or placebo were analyzed for whether they received neurosurgery within 7 days and their characteristics, outcomes, hematoma volumes (HVs) were compared. Characteristics and outcomes of participants who received surgery were also compared with those who did not.RESULTS: Neurosurgery was performed in 5.2% of participants (121/2325), including craniotomy (57%), hematoma drainage (33%), and external ventricular drainage (21%). The number of patients receiving surgery who received TXA vs placebo were similar at 4.9% (57/1153) and 5.5% (64/1163), respectively (odds ratio [OR] 0.893; 95% CI 0.619-1.289; P-value = .545). TXA did not improve outcome compared with placebo in either surgically treated participants (OR 0.79; 95% CI 0.30-2.09; P = .64) or those undergoing hematoma evacuation by drainage or craniotomy (OR 1.19 95% 0.51-2.78; P-value = .69). Postoperative HV was not reduced by TXA (mean difference −8.97 95% CI −23.77, 5.82; P-value = .45).CONCLUSION: TXA was not associated with less neurosurgical intervention, reduced HV, or improved outcomes after surgery

Needle fasciotomy versus limited fasciectomy for the treatment of Dupuytren’s contractures of the fingers (Hand-2): study protocol for a randomised controlled trial

Background: Dupuytren’s contractures (DC) are fibrous cords under the skin of the hand that cause one or more fingers to curl gradually and irreversibly towards the palm. These contractures are usually painless but can cause a loss of hand function. Two treatments for Dupuytren’s contractures are widely used within the National Health Service (NHS) in the UK: removal of the contractures via surgery (limited fasciectomy) and division of the contractures via a needle inserted through the skin (needle fasciotomy). This study aims to establish the clinical and cost-effectiveness of needle fasciotomy (NF) versus limited fasciectomy (LF) for the treatment of DC in the NHS, in terms of patient-reported hand function and resource utilisation. Methods/design: Hand-2 is a national multi-centre, two-arm, parallel-group randomised, non-inferiority trial. Patients will be eligible to join the trial if they are aged 18 years or older, have at least one previously untreated finger with a well-defined Dupuytren’s contracture of 30° or greater that causes functional problems and is suitable for treatment with either LF or NF. Patients with a contracture of the distal interphalangeal joint only are ineligible. Eligible consenting patients will be randomised 1:1 to receive either NF or LF and will be followed up for 24 months post-treatment. A QuinteT Recruitment Intervention will be used to optimise recruitment. The primary outcome measure is the participant-reported assessment of hand function, assessed by the Hand Health Profile of the Patient Evaluation Measure (PEM) questionnaire at 12 months post-treatment. Secondary outcomes include other patient-reported measures, loss of finger movement, and cost-effectiveness, reported over the 24-month post-treatment. Embedded qualitative research will explore patient experiences and acceptability of treatment at 2 years post-surgery. Discussion: This study will determine whether treatment with needle fasciotomy is non-inferior to limited fasciectomy in terms of patient-reported hand function at 12 months post-treatment. Trial registration: International Standard Registered Clinical/soCial sTudy ISRCTN12525655. Registered on 18th September 2020