Search

Despite being the object of intense study, embryonic development has been difficult to model due to a number of reasons. First, complex tissues can be comprised of many cell types, of which we probably only know a subset. Therefore, we first focused on the discovery of cell types by single-cell RNA-sequencing (scRNA-seq). Cell types are routinely identified by clustering scRNA-seq data, however, there was no principled way to determine the right number of clusters. To improve cell type classification, we developed phiclust, a clusterability measure for scRNA-seq. Another challenge in a developing tissue is that many signaling processes and morphogenic events occur simultaneously, which makes it hard to isolate the individual contributions. For this purpose, I looked at stem cell derived in vitro systems, in which a small number of specific cell types can be combined deliberately and studied in isolation. My analysis of different model systems shows that cellular communication causes structural and transcriptional changes in the developing cells. Finally, while tissue organization has been characterized extensively, we lack generative models that can relate specific patterns to the underlying gene regulatory mechanisms. Therefore, I later focused on deep learning-based approaches to infer gene regulatory networks from observed spatial patterns.

To evaluate the efficacy and safety of microwave (MW) ablation as first-line locoregional therapy (LRT) for bridging patients with hepatocellular carcinoma (HCC) to liver transplant.This retrospective study evaluated 88 patients who received percutaneous MW ablation for 141 tumors as first-line LRT for HCC and who were listed for liver transplantation at a single medical center between 2011 and 2019. The overall survival (OS) rate statuses after liver transplant, waitlist retention, and disease progression were evaluated using the Kaplan-Meier techniques.Among the 88 patients (72 men and 16 women; mean age, 60 years; Model for End-Stage Liver Disease score, 11.2) who were listed for transplant, the median waitlist time was 9.4 months (interquartile range, 5.5-18.9). Seventy-one (80.7%) patients received transplant after a median waitlist time of 8.5 months. Seventeen (19.3%) patients were removed from the waitlist; of these, 4 (4.5%) were removed because of tumors outside of the Milan criteria (HCC-specific dropout). No difference in tumor size or alpha-fetoprotein was observed in the transplanted versus nontransplanted patients at the time of ablation (2.1 vs 2.1 cm and 34.4 vs 34.7 ng/mL for transplanted vs nontransplanted, respectively; P.05). Five (5.1%) of the 88 patients experienced adverse events after ablation; however, they all recovered. There were no cases of tract seeding. The local tumor progression (LTP) rate was 7.2%. The OS status after liver transplant at 5 years was 76.7%, and the disease-specific survival after LTP was 89.6%, with a median follow-up of 61 months for all patients.MW ablation appears to be safe and effective for bridging patients with HCC to liver transplant without waitlist removal from seeding, adverse events, or LTP.

The objective of this study is to introduce cooled radiofrequency ablation technical feasibility as an alternative percutaneous image-guided treatment of chronic pain and stiffness in the setting of uncomplicated total knee arthroplasty.This retrospective pilot study includes a total of 19 consecutive patients experiencing persistent chronic pain after total knee arthroplasty, without underlying hardware complications who had failed conservative care. Patients initially underwent anesthetic blocks of the genicular nerve branches to determine C-RFA candidacy. After adequate response to the anesthetic blocks ( 50% immediate pain relief), patients were subjected to cooled radiofrequency ablations 2-3 weeks later. Treatment response was evaluated utilizing clinically validated questionnaires (KOOS, the Knee Injury and Osteoarthritis Outcome Score) and visual analog scale (VAS) to assess pain severity, stiffness, functional activities of daily living, and use of pain medication. Follow-up outcome scores were collected up to 1 year after C-RFA procedure.A total of 21 knees were treated consecutively between 4/2019 and 1/2020 (mean age 70.5 years; 5 M:14F). The mean total KOOS score improved significantly from baseline at 35.0 ± 14.0 to 64.2 ± 14.7 at a mean of 10.2 months after treatment (p 0.0001), with significant improvement in mean stiffness score from 44.8 ± 16.7 to 68.8 ± 20 (p 0.0001). The mean VAS score improved significantly from baseline at 8.30 ± 1.1 to 2.45 ± 1.8 (p 0.0001). No major complications were encountered. No patients went on to receive re-treatment, surgical revision, or other intervention.Image-guided genicular nerve cooled radiofrequency ablation offers a promising alternative in treating chronic pain/stiffness in the setting of uncomplicated TKA.

This paper presents the design optimization and prototyping of a three-phase double-sided axial-flux ferrite-magnet micro-wind generator with inner coreless stator and two twin spoke-type ferrite-magnet outer rotors. Sensitivity analysis of the initial basic design is first conducted with respect to changes in stator and rotor geometries by using comprehensive magnetic-field finite-element analyses (FEAs). Then, genetic algorithm-based design bi-objective optimization is carried out, and FEA-computed results for initial and optimized are comparatively assessed. The optimally-designed micro-wind generator prototype fabrication technology is further described. Lastly, experiments on the built prototype under active rectifier –resistor load operating conditions are performed by using laboratory test bench with implemented maximum wind-power extracting control technique.

Future networks are expected to deliver low-latency,\ud user-specific services in a flexible and efficient manner. Operators\ud have to ensure infrastructure resilience in the face of such\ud challenges, while maintaining service guarantees for subscribed\ud users. One approach to support emerging use cases is through the\ud introduction and user of virtualised network functions (VNFs)\ud at the edge of the network. While placement of VNFs at the\ud network edge has been previously studied, it has not taken into\ud account services comprised of multiple VNFs and considerations\ud for network security.\ud In this paper we propose a mathematical model for latencyoptimal on-path allocation of VNF chains on physical servers\ud within an edge network infrastructure, with special considerations for network security applications and operator’s best\ud practices. We acknowledge the challenges of employing optimal\ud solutions in real networks and provide the Minimal Path Deviation\ud Allocation algorithm for placement of security-focused network\ud services in a distributed edge environment, minimising end-to-end latency for users.\ud We then evaluate our placement results over a simulated\ud nation-wide network using real-world latency characteristics.\ud We show that our placement algorithm provides near-optimal\ud placement, with minimal latency violations with respect an\ud optimal solution, whilst offering robust tolerance to temporal\ud latency variations.