Kinodynamic Generation of Wafer Scanners Trajectories Used in Semiconductor Manufacturing

The operation time of an ideal reliable wafer scanner model is defined at the die level where the actual exposure process takes place as the time unit per die, or at the wafer substrate level as the time unit per wafer substrate. Therefore, the machine throughput is given as the reciprocal of the operation time. The involved motion profiles of a machine, namely the step-and-scan trajectories, function as the heartbeats that drive its multidisciplinary elements, which suggests that a multidisciplinary design optimization should be involved when such profiles are selected or designed. This is also true when considering the traverse motion profiles among rows and columns within the wafer substrate. The step-and-scan trajectories affect the machine throughput, performance, and die yield. The effects of tracking such profiles appear as structural vibration, tracking errors, and thermal loading at various machine elements such as the actuators, the reticle, the wafer, and the projection elements specifically when the exposure high-energy duration and frequency are not taken into consideration while designing the reference motion. From the dynamics perspective, having a reference motion with nonzero and bounded higher-order derivatives is recommended since it enhances the tracking performance of the machine, however, its ability to increase the operation time is usually overlooked. In an attempt to understand such effects, we present a case study that outlines the aforementioned aspects using three step-and-scan profiles of mainly $3^{rd}$ -order. Taking the dynamics of the driven stage into consideration through input shaping, both the step-and-scan and traverse motion profiles are analyzed. We provide analytical expressions that can be used to generate both types of motion profiles on the fly without additional optimization. A simulation example of a simplified wafer scanner machine shows the usefulness of the proposed framework. Note to Practitioners - Choosing the most suitable operating conditions of a lithography machine is challenging. These conditions affect machine productivity, profit margin, and maintenance. In this paper, we reveal the relation between the selection of operating conditions based on several decision variables- and the kinodynamic step-and-scan trajectory generation based on specific machine parameters and clients' requirements. Being chart-based, the selection process of an operating point can be less practical at some points. However, using appropriate curve fitting tools, the information provided in the optimal operating charts can be put into suboptimal closed-form expressions that facilitate the selection process. Therefore, the designed trajectories parameters can be easily saved in lookup tables for ease of evaluation and future use. This helps in accommodating changes in the operation plans and flexible manufacturing systems. Also, starting with a given set of machine parameters, it is possible to calculate the optimal machine operating point when the input shaping technique is used, as illustrated in this paper.</p

A multimodal imaging workflow for monitoring CAR T cell therapy against solid tumor from whole-body to single-cell level

CAR T cell research in solid tumors often lacks spatiotemporal information and therefore, there is a need for a molecular tomography to facilitate high-throughput preclinical monitoring of CAR T cells. Furthermore, a gap exists between macro- and microlevel imaging data to better assess intratumor infiltration of therapeutic cells. We addressed this challenge by combining 3D µComputer tomography bioluminescence tomography (µCT/BLT), light-sheet fluorescence microscopy (LSFM) and cyclic immunofluorescence (IF) staining. Methods: NSG mice with subcutaneous AsPC1 xenograft tumors were treated with EGFR CAR T cell (± IL-2) or control BDCA-2 CAR T cell (± IL-2) (n = 7 each). Therapeutic T cells were genetically modified to co-express the CAR of interest and the luciferase CBR2opt. IL-2 was administered s.c. under the xenograft tumor on days 1, 3, 5 and 7 post-therapy-initiation at a dose of 25,000 IU/mouse. CAR T cell distribution was measured in 2D BLI and 3D µCT/BLT every 3-4 days. On day 6, 4 tumors were excised for cyclic IF where tumor sections were stained with a panel of 25 antibodies. On day 6 and 13, 8 tumors were excised from rhodamine lectin-preinjected mice, permeabilized, stained for CD3 and imaged by LSFM. Results: 3D µCT/BLT revealed that CAR T cells pharmacokinetics is affected by antigen recognition, where CAR T cell tumor accumulation based on target-dependent infiltration was significantly increased in comparison to target-independent infiltration, and spleen accumulation was delayed. LSFM supported these findings and revealed higher T cell accumulation in target-positive groups at day 6, which also infiltrated the tumor deeper. Interestingly, LSFM showed that most CAR T cells accumulate at the tumor periphery and around vessels. Surprisingly, LSFM and cyclic IF revealed that local IL-2 application resulted in early-phase increased proliferation, but long-term overstimulation of CAR T cells, which halted the early added therapeutic effect. Conclusion: Overall, we demonstrated that 3D µCT/BLT is a valuable non-isotope-based technology for whole-body cell therapy monitoring and investigating CAR T cell pharmacokinetics. We also presented combining LSFM and MICS for ex vivo 3D- and 2D-microscopy tissue analysis to assess intratumoral therapeutic cell distribution and status

Transoral robotic surgery (TORS): a new tool for high risk tracheostomy decannulation

La decannulazione è sempre stata considerata una procedura con un certo grado di rischio, specie nei pazienti con ridotti diametri delle via aeree, come nel caso della sindrome delle apnee ostruttive (OSA). Presentiamo 4 casi nei quali la chirurgia robotica transorale (TORS) ha permesso un appropriato management di pazienti tracheotomizzati da divers mesi. Gli obiettivi del nostro lavoro sono: 1. Dimostrare come il team otorinolaringoiatrico possa favorire il riconoscimento di pazienti ad alto rischio di decannulazione inefficace e 2. Evidenziare il ruolo nella TORS nel trattamento dellipertrofia della base della lingua, responsabile dellostruzione delle vie aeree superiori. Dalla nostra esperienza la TORS appare una tecnica efficace nella decannulazione di pazienti affetti da ipertrofia della base della lingua e da epiglottide flottante

A Second-Generation Device for Automated Training and Quantitative Behavior Analyses of Molecularly-Tractable Model Organisms

A deep understanding of cognitive processes requires functional, quantitative analyses of the steps leading from genetics and the development of nervous system structure to behavior. Molecularly-tractable model systems such as Xenopus laevis and planaria offer an unprecedented opportunity to dissect the mechanisms determining the complex structure of the brain and CNS. A standardized platform that facilitated quantitative analysis of behavior would make a significant impact on evolutionary ethology, neuropharmacology, and cognitive science. While some animal tracking systems exist, the available systems do not allow automated training (feedback to individual subjects in real time, which is necessary for operant conditioning assays). The lack of standardization in the field, and the numerous technical challenges that face the development of a versatile system with the necessary capabilities, comprise a significant barrier keeping molecular developmental biology labs from integrating behavior analysis endpoints into their pharmacological and genetic perturbations. Here we report the development of a second-generation system that is a highly flexible, powerful machine vision and environmental control platform. In order to enable multidisciplinary studies aimed at understanding the roles of genes in brain function and behavior, and aid other laboratories that do not have the facilities to undergo complex engineering development, we describe the device and the problems that it overcomes. We also present sample data using frog tadpoles and flatworms to illustrate its use. Having solved significant engineering challenges in its construction, the resulting design is a relatively inexpensive instrument of wide relevance for several fields, and will accelerate interdisciplinary discovery in pharmacology, neurobiology, regenerative medicine, and cognitive science

Activation and clinical significance of the unfolded protein response in breast cancer

introduction: The tumour microenvironment is hypoglycaemic, hypoxic and acidotic. This activates a stress signalling pathway: the unfolded protein response (UPR). The UPR is cytoprotective if the stressor is mild, but may initiate apoptosis if severe.Activation of the UPR in breast carcinoma is induced by microenvironmental stress such as glucose and oxygen deprivation, but may also be linked to oestrogen stimulation. It may be clinically significant as it may alter chemosensitivity to doxorubicin. methods: 395 human breast adenocarcinomas were immunohistochemically stained for UPR activation markers (glucose-regulated protein (GRP-78 and XBP-1). A model of UPR activation in vitro by glucose deprivation of T47D breast cancer cells was developed to determine how the UPR affects cellular sensitivity to doxorubicin and 5-fluorouracil. Cytotoxicity was assessed using a colorimetric cytotoxicity assay (MTT). The effect of oestrogen stimulation and tamoxifen exposure on UPR activation by T47D cells was determined by western blotting measurement of the key UPR protein, GRP-78. results: Expression of GRP78 and XBP-1 was demonstrated in 76% and 90% of the breast cancers, respectively, and correlated with oestrogen receptor positivity (P=0.045 and 0.017, respectively). In vitro UPR activation induced resistance to both doxorubicin and 5-flurouracil, (P<0.05). Oestrogen stimulation induced GRP78 and XBP1 over-expression on western blotting. Tamoxifen did not block this response and may induce UPR activation in its own right. conclusions: The UPR is activated in the majority of breast cancers and confers resistance to chemotherapy. In vitro oestrogen stimulates UPR induction. UPR activation may contribute to breast cancer chemoresistance and interact with oestrogen response elements

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely