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We report on the 1,000-element transition-edge sensor (TES) x-ray spectrometer implementation of the TOMographic Circuit Analysis Tool (TOMCAT). TOMCAT combines a high spatial resolution scanning electron microscope (SEM) with a highly efficient and pixelated TES spectrometer to reconstruct three-dimensional maps of nanoscale integrated circuits (ICs). A 240-pixel prototype spectrometer was recently used to reconstruct ICs at the 130 nm technology node, but to increase imaging speed to more practical levels, the detector efficiency needs to be improved. For this reason, we are building a spectrometer that will eventually contain 3,000 TES microcalorimeters read out with microwave superconducting quantum interference device (SQUID) multiplexing, and we currently have commissioned a 1,000 TES subarray. This still represents a significant improvement from the 240-pixel system and allows us to begin characterizing the full spectrometer performance. Of the 992 maximimum available readout channels, we have yielded 818 devices, representing the largest number of TES x-ray microcalorimeters simultaneously read out to date. These microcalorimeters have been optimized for pulse speed rather than purely energy resolution, and we measure a FWHM energy resolution of 14 eV at the 8.0 keV Cu K$\alpha$ line., Comment: 5 pages, 4 figures, submitted to IEEE Transactions on Applied Superconductivity

The mechanisms behind Alzheimer's disease are not yet fully described, and changes in the electrophysiology of patients across the continuum of the disease could help to understand them. In this work, we study the power spectral distribution of a set of 129 individuals from the Connectomics of Brian Aging and Dementia project. From this sample, we acquired task-free data, with eyes closed, and estimated the power spectral distribution in source space. We compared the spectral profiles of three groups of individuals: 70 healthy controls, 27 patients with amnestic MCI, and 32 individuals showing cognitive impairment without subjective complaints (IWOC). The results showed a slowing of the brain activity in the aMCI patients, when compared to both the healthy controls and the IWOC individuals. These differences appeared both as a decrease in power for high frequency oscillations and an increase in power in alpha oscillations. The slowing of the spectrum was significant mainly in parietal and medial frontal areas. We were able to validate the slowing of the brain activity in individuals with aMCI, appearing in our sample in areas related to the default mode network. However, this pattern did not appear in the IWOC individuals, suggesting that their condition is not part of the AD continuum. This work raises interesting questions about this group of individuals, and the underlying brain mechanisms behind their cognitive impairment.

The multivariate normative comparison (MNC) method has been used for identifying cognitive impairment. When participants' cognitive brain domains are evaluated regularly, the longitudinal MNC (LMNC) has been introduced to correct for the intercorrelation among repeated assessments of multiple cognitive domains in the same participant. However, it may not be practical to wait until the end of study for diagnosis. For example, in participants of the Multicenter AIDS Cohort Study (MACS), cognitive functioning has been evaluated repeatedly for more than 35 years. Therefore, it is optimal to identify cognitive impairment at each assessment, while the family-wise error rate (FWER) is controlled with unknown number of assessments in future. In this work, we propose to use the difference of consecutive LMNC test statistics to construct independent tests. Frequency modeling can help predict how many assessments each participant will have, so Bonferroni-type correction can be easily adapted. A chi-squared test is used under the assumption of multivariate normality, and permutation test is proposed where this assumption is violated. We showed through simulation and the MACS data that our method controlled FWER below a predetermined level.

Introduction: The human brain shows modest traits of sexual dimorphism, with the female brain, on average, 10% smaller than the male brain. These differences do not imply a lowered cognitive performance, but suggest a more optimal brain organization in women. Here we evaluate the patterns of functional connectivity (FC) in women and men from the Connectomics of Brain Aging and Dementia sample. Methods: We used phase locking values to calculate FC from the magnetoencephalography time series in a sample of 138 old adults (87 females and 51 males). We compared the FC patterns between sexes, with the intention of detecting regions with different levels of connectivity. Results: We found a frontal cluster, involving anterior cingulate and the medial frontal lobe, where women showed higher FC values than men. Involved connections included the following: (1) medial parietal areas, such as posterior cingulate cortices and precunei; (2) right insula; and (3) medium cingulate and paracingulate cortices. Moreover, these differences persisted when considering only cognitively intact individuals, but not when considering only cognitively impaired individuals. Discussion: Increased anteroposterior FC has been identified as a biomarker for increased risk of developing cognitive impairment or dementia. In our study, cognitively intact women showed higher levels of FC than their male counterparts. This result suggests that neurodegenerative processes could be taking place in these women, but the changes are undetected by current diagnosis tools. FC, as measured here, might be valuable for early identification of this neurodegeneration.

Contemporary law enforcement methods are largely defined by crime control and militarization in the “warrior” policing model. In 2013, the Washington State Criminal Justice Training Commission (WSCJTC) adopted an alternative “guardian” training model for the Basic Law Enforcement Academy (BLEA) focused on procedural justice, community partnerships, de-escalation, and crisis intervention. The current study investigates BLEA graduates’ perceptions of guardian policing and training elements. Researchers interviewed new officers who completed BLEA training with the guardian curriculum ( n = 17) and officers trained in a warrior-based curriculum ( n = 11). Themes are analyzed from interview data, including officer perceptions of BLEA guardian training and related programs. The paper concludes with discussion of limitations, themes, and policy implications of the research.

Carbonaceous asteroids, such as (101955) Bennu, preserve material from the early Solar System, including volatile compounds and organic molecules. We report spacecraft imaging and spectral data collected during and after retrieval of a sample from Bennu’s surface. The sampling event mobilized rocks and dust into a debris plume, excavating a 9-meter-long elliptical crater. This exposed material is darker, spectrally redder, and more abundant in fine particulates than the original surface. The bulk density of the displaced subsurface material was 500 to 700 kilograms per cubic meter, which is about half that of the whole asteroid. Particulates that landed on instrument optics spectrally resemble aqueously altered carbonaceous meteorites. The spacecraft stored 250 ± 101 grams of material, which will be delivered to Earth in 2023.

Reconfigurable modular robots, which can actively assemble and disassemble on command, offer the possibility of mesoscale (milliscale and microscale) manufacturing with robustness and controllability. In this study, we present a design of a scalable modular subunit with embedded permanent magnets in a 3-D printed cubic body. The subunit can be wirelessly controlled by an external uniform magnetic field. We also present controlled assembly–disassembly techniques for these subunits. Our modular robotic platform is highly reconfigurable and can create programmable, predetermined patterns based on open-loop control. The 2-D motion planner computes all reachable polyomino shapes from an arbitrary initial configuration and provides the shortest movement sequences to form each shape. Experimental results match computational modeling, demonstrating robust and reproducible behavior of the modular robotic platform that is promising for mesoscale manufacturing applications. Two cube sizes were tested: 10-mm edge lengths and 2.8-mm edge lengths.

We demonstrate ferroelectric and bipolar impedance switching behavior in 18-nm-thick epitaxial BaTiO3 (BTO) films in an electrolyte–ferroelectric–semiconductor (EFS) configuration. The system is explored for its potential as a ferroelectric microelectrode in bioelectronics. Cyclic voltammetry measurements in EFS configuration, with a phosphate-buffered saline solution acting as the liquid electrolyte top contact, indicate characteristic ferroelectric switching peaks in the bipolar current–voltage loop. Moreover, small-signal electrochemical impedance spectroscopy measurements (applied root mean square voltage VRMS = 10 mV) on pre-poled EFS devices indicate bipolar impedance switching behavior. Also, a maximum ratio of the two different impedance magnitudes of ∼1.5 was observed at frequency f = 100 Hz. The observed impedance switching corresponds to a resistive switching effect, which could be explained by the modulation of the space charge region at the BTO/electrolyte interface via fixed ferroelectric polarization charges. Our approach represents a key step toward neural recordings with ferroelectric microelectrodes.

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PDF file - 729KB, Supplementary Table 1: Adverse events. Supplementary Figure 1: Patient allocation. Supplementary Figure 2: DNA immunization elicits PAP-specific cellular immune responses. Supplementary Figure 3: Immune responses to PSA and tetanus evaluated by intracellular cytokine staining. Supplementary Figure 4: Immune responses to PAP, PSA and tetanus evaluated by cytokine secretion.

Purpose: We have previously reported that a DNA vaccine encoding prostatic acid phosphatase (PAP) could elicit PAP-specific T cells in patients with early recurrent prostate cancer. In the current pilot trial, we sought to evaluate whether prolonged immunization with regular booster immunizations, or “personalized” schedules of immunization determined using real-time immune monitoring, could elicit persistent, antigen-specific T cells, and whether treatment was associated with changes in PSA doubling time (PSA DT).Experimental Design: Sixteen patients with castration-resistant, nonmetastatic prostate cancer received six immunizations at 2-week intervals and then either quarterly (arm 1) or as determined by multiparameter immune monitoring (arm 2).Results: Patients were on study a median of 16 months; four received 24 vaccinations. Only one event associated with treatment >grade 2 was observed. Six of 16 (38%) remained metastasis-free at 2 years. PAP-specific T cells were elicited in 12 of 16 (75%), predominantly of a Th1 phenotype, which persisted in frequency and phenotype for at least 1 year. IFNγ-secreting T-cell responses measured by ELISPOT were detectable in 5 of 13 individuals at 1 year, and this was not statistically different between study arms. The overall median fold change in PSA DT from pretreatment to posttreatment was 1.6 (range, 0.6–7.0; P = 0.036).Conclusions: Repetitive immunization with a plasmid DNA vaccine was safe and elicited Th1-biased antigen-specific T cells that persisted over time. Modifications in the immunization schedule based on real-time immune monitoring did not increase the frequency of patients developing effector and memory T-cell responses with this DNA vaccine. Clin Cancer Res; 20(14); 3692–704. ©2014 AACR.

Background A variety of human computer interfaces are used by robotic surgical systems to control and actuate camera scopes during minimally invasive surgery. The purpose of this review is to examine the different user interfaces used in both commercial systems and research prototypes. Methods A comprehensive scoping review of scientific literature was conducted using PubMed and IEEE Xplore databases to identify user interfaces used in commercial products and research prototypes of robotic surgical systems and robotic scope holders. Papers related to actuated scopes with human–computer interfaces were included. Several aspects of user interfaces for scope manipulation in commercial and research systems were reviewed. Results Scope assistance was classified into robotic surgical systems (for multiple port, single port, and natural orifice) and robotic scope holders (for rigid, articulated, and flexible endoscopes). Benefits and drawbacks of control by different user interfaces such as foot, hand, voice, head, eye, and tool tracking were outlined. In the review, it was observed that hand control, with its familiarity and intuitiveness, is the most used interface in commercially available systems. Control by foot, head tracking, and tool tracking are increasingly used to address limitations, such as interruptions to surgical workflow, caused by using a hand interface. Conclusion Integrating a combination of different user interfaces for scope manipulation may provide maximum benefit for the surgeons. However, smooth transition between interfaces might pose a challenge while combining controls.

Opportunities continue to be lost with a high rate of kidneys recovered for transplant but not utilized, particularly those considered less than ideal quality. The Organ Procurement and Transplantation Network (OPTN) Organ Center is tasked with allocating arguably the most difficult-to-place kidneys, and we hypothesized an accelerated placement pathway would increase utilization of kidneys placed by the Organ Center. The Kidney Accelerated Placement (KAP) project, implemented by the Organ Center from July 18, 2019 to July 15, 2020, aimed to offer kidneys with a high kidney donor profile index to programs that had a history of accepting such organs. We compared OPTN kidney match run, donor, and transplant recipient data during the project period and 1 year prior. There was no statistically significant change in the percentage of KAP-eligible donors accepted during the project period (16.4%) compared to the prior year (17.5%). Conversion from acceptance to transplant was higher under KAP (72.7% vs. 71.2%), though not significant. Waiting to accelerate placement after kidneys have been declined by multiple transplant programs locally and regionally is an intervention that may come too late to effectively increase utilization. Transplant rates of nationally shared and marginal kidneys remain a challenge, and future iterations of this project should be investigated.

Double-stranded RNA produced during viral replication and transcription activates both protein kinase R (PKR) and ribonuclease L (RNase L), which limits viral gene expression and replication through host shutoff of translation. In this study, we find that APOBEC3B forms a complex with PABPC1 to stimulate PKR and counterbalances the PKR-suppressing activity of ADAR1 in response to infection by many types of viruses. This leads to translational blockage and the formation of stress granules. Furthermore, we show that APOBEC3B localizes to stress granules through the interaction with PABPC1. APOBEC3B facilitates the formation of protein-RNA condensates with stress granule assembly factor (G3BP1) by protecting mRNA associated with stress granules from RNAse L-induced RNA cleavage during viral infection. These results not only reveal that APOBEC3B is a key regulator of different steps of the innate immune response throughout viral infection but also highlight an alternative mechanism by which APOBEC3B can impact virus replication without editing viral genomes.

Background: Prognosis of overall survival is instrumental for patient management and can improve conduct of clinical trials and real-world data analysis. With the shift towards cancer immunotherapy, modeling of overall host fitness becomes increasingly important. Here, we compare the performance of contemporary prognostic scores constructed from routinely measured biomarkers. Patients and methods: We used patient data from the Flatiron Health electronic-health record de-identified oncology database and from 16 clinical studies sponsored by Roche. A total of 64,233 patients were analyzed, covering the most prevailing solid tumor and hematology cancer types. We compared the Royal Marsden Hospital score (solid tumors), international prognostic index (IPI) (blood tumors), the Eastern Cooperative Oncology Group (ECOG) performance status, and the ‘Real wOrld PROgnostic score (ROPRO)’. OS was modeled from the start of treatment using Kaplan-Meier analysis and Cox regression. Results: All investigated scores proved to be prognostic, both in RWD and clinical trial data, and in all indications from the respectively intended range of application. The ROPRO uniformly outperformed other prognostic scores. Concordance indices / hazard ratios in the range of [0.64;0.73]/[2.80;4.50] were found for ROPRO, and in the range of [0.53;0.65]/[1.55; 3.10] for the remaining scores. In hematology trials, the IPI came close to the performance of ROPRO. Conclusions: Strong and easy-to-apply prognostic scores for overall survival exist. The usage of all investigated scores can be recommended. With moderate extra effort, the implementation of ROPRO can create considerable improvement.

Spondweni virus (SPONV) is the closest known relative of Zika virus (ZIKV). SPONV pathogenesis resembles that of ZIKV in pregnant mice, and both viruses are transmitted byAedes aegyptimosquitoes. We aimed to develop a translational model to further understand SPONV transmission and pathogenesis. We found that cynomolgus macaques (Macaca fascicularis) inoculated with ZIKV or SPONV were susceptible to ZIKV, but resistant to SPONV infection. In contrast, rhesus macaques (Macaca mulatta) supported productive infection with both ZIKV and SPONV and developed robust neutralizing antibody responses. Crossover serial challenge in rhesus macaques revealed that SPONV immunity did not protect against ZIKV infection, whereas ZIKV immunity was fully protective against SPONV infection. These findings establish a viable model for future investigation into SPONV pathogenesis, and suggest the risk of SPONV emergence is low in areas with high ZIKV seroprevalence due to one-way cross-protection between ZIKV and SPONV.TeaserIdentification of asymmetric immune interactions between Zika and Spondweni viruses in macaque monkeys.

APOBEC3B is an innate immune effector enzyme capable of introducing mutations in viral genomes through DNA cytosine-to-uracil editing. Recent studies have shown that gamma-herpesviruses, such as Epstein-Barr virus (EBV), have evolved a potent APOBEC3B neutralization mechanism to protect lytic viral DNA replication intermediates in the nuclear compartment. APOBEC3B is additionally unique as the only human DNA deaminase family member that is constitutively nuclear. Nuclear localization has therefore been inferred to be essential for innate antiviral function. Here, we combine evolutionary, molecular, and cell biology approaches to address whether nuclear localization is a conserved feature of APOBEC3B in primates. Despite the relatively recent emergence of

Aims Evidence suggests that suicide stigma (i.e. negative attitudes towards persons affected by suicide/suicidality) and suicide normalisation (i.e. liberal attitudes towards suicide) are both associated with increased suicide risk. Despite conceptual similarities and potential interaction, suicide stigma and suicide normalisation have usually been investigated separately. We used cross-sectional data from a community sample to test the association between suicide stigma and suicide normalisation as well as to identify their respective determinants and consequences. Methods Participants were N = 3.269 adults recruited from an established online-panel using quotas to reflect the composition of the German general population with regard to age, gender, education and region. We collected information about suicide stigma, suicide normalisation, intentions to seek help for suicidality, current suicidality, suicide literacy, negative mood and socio-demographic variables. We used regression modelling to determine the association between suicide stigma and suicide normalisation as well as to identify their determinants and consequences. Results Suicide stigma and suicide normalisation were inversely associated so that higher suicide stigma scores were linked to lower suicide normalisation. More suicide stigma was associated with reduced intentions to seeking professional help, increased willingness to seek help from family and friends and lower odds to experience current suicidality, however the association between suicide stigma and intentions to seek professional help diminished after controlling for confounding variables. Increased suicide normalisation was linked to reduced intentions to seek help from professionals or family and friends, as well as higher odds to experience current suicidality, even after controlling for confounding variables. Conclusions Our findings suggest that interventions to reduce public suicide stigma are at risk to unintentionally increase suicide normalisation, which appears to be a key barrier to seeking help for suicidality. Future research should therefore identify strategies to improve attitudes towards persons affected by suicidality that avoid normalisation, i.e. do not convey the message of suicide as an acceptable solution for difficult life situations. One strategy with great potential to safely reduce public suicide sigma could be interventions that stimulate interpersonal contact with affected persons sharing their recovery story.

This study examines patterns and trends in 911 calls from Boston public school addresses related to mental health and physical assaults/fights generated from 2014 to 2018. We analyzed 12,113 Boston Police Department (BPD) 911 call records from 102 Boston Public School addresses during the 2014-2018 school years. In addition, we separately analyzed calls coded by BPD as Emotionally Disturbed Person ("EDP"), indicating a psychiatric crisis was the primary reason for the call, as well as calls coded as "Fight," "Assault," or "Assault and battery." Call frequency ranged from 0 to 277 per school each year. Although the annual average number of calls increased each school year over the 4-year period, this was primarily due to an increase in hang-ups and abandoned calls. Overall, 7.4% calls were coded as EDP and 6.5% were coded as assault/fight. Call volume was highest in the middle of the school day, with a median time of 12 pm. EDP calls were significantly earlier in the day than non-EDP calls, and the percentage of calls labeled as EDP decreased in frequency each day over the course of the week. There were more overall 911 calls, on average, per day in late spring than in other seasons. The frequency with which schools call upon police as emergency service providers for psychiatric crises indicates a need for additional school-based resources. Such resources may be most effective if they are allocated mid-day, responsive to changing student needs over the course of the week, and increased in spring.

In island systems, nitrogen-rich seabird guano is a marine subsidy that can shape terrestrial plant communities. In zones of nutrient upwelling such as the Gulf of California, copious seabird guano is commonplace on bird islands. Several bird islands host regionally unique cactus forests, especially of the large columnar cactus, cardón (Pachycereus pringlei). We show that a chain of interactions across the land-sea interface yields an allochthonous input of nitrogen in the form of seabird guano, fueling the production of some of the densest cactus populations in the world. Fish, seabird, guano, soil, and cactus samples were taken from the representative seabird island of San Pedro Mártir for nitrogen stable isotope ratio measurements, which were compared to soil and cactus samples from other seabird and non-seabird Gulf islands and terrestrial ecosystems throughout the range of the cardón. Isla San Pedro Mártir δ15N values are distinctively high, ranging from fish + 17.7, seabird + 19.7, guano + 14.8, soil + 34.3 and cactus + 30.3 compared to average values across non-bird sites of + 13.0 (N = 213, S.D. = 3.7) for soil and + 9.8 (N = 212, S.D. = 3.4) for cactus. These δ15N values are among the highest ever reported for plants. Seabird island soil and cactus δ15N values were consistently significantly enriched relative to mainland and non-bird islands, a relationship expected due to the progressive volatilization of 14N rich ammonia from decomposing guano deposits. Our findings demonstrate that seabird-mediated marine nutrient deposits provide the source for solubilized nitrogen on desert islands, which stimulate terrestrial plant production in the cardón cactus beyond that seen in either mainland ecosystems or non-seabird islands.

BackgroundThe gold standard to evaluate treatment efficacy in oncology clinical trials is Overall Survival (OS). Its utility, however, is limited by the need for long trial duration and large sample sizes. Thus methods such as Progression-Free Survival (PFS) are applied to obtain early OS estimates across clinical trial phases, particularly to decide on further development of new molecular entities. Especially for cancer-immunotherapy, these established methods may be less suitable. Therefore, alternative approaches to obtain early OS estimates are required. In this work, we present a first evaluation of a new method, ΔRisk. ΔRisk uses the ROPRO, a state-of-the-art pan-cancer OS prognostic score, or DeepROPRO to predict OS benefit by measuring the patient’s improvement since baseline.Patients and methodsWe modeled the ΔRisk using Joint Models and tested whether a significant ΔRisk decrease correlated with OS improvement. We studied this hypothesis by comparing classical OS analysis against ΔRisk in a retrospective analysis of 12 real-world data emulated clinical trials, and 3 additional recent phase III immunotherapy clinical trials.ResultsOur new ΔRisk method correlated with the final OS readout in 14 out of 15 clinical trials. The ΔRisk, however, identified the treatment benefit up to seven months earlier than the OS log-rank test. Additionally, in two immunotherapy trials where PFS would have failed as an early OS estimate, the ΔRisk correctly predicted the treatment benefit.ConclusionsWe introduced a new method, ΔRisk, and demonstrated its correlation with OS. In retrospective analysis, ΔRisk is able to identify OS benefit earlier than standard methodology, and we show examples of lung cancer trials, where it maintains its predictive relevance whereas PFS does not correlate with OS. ΔRisk may prove useful for early decision support resulting in reduced need of resources. We also show the potential of ΔRisk as a candidate to define surrogate endpoints. To this purpose, more methodological work and further investigation of treatment-specific performance will be done in the future.

Viruses have evolved diverse mechanisms to antagonize host immunity such as direct inhibition and relocalization of cellular APOBEC3B (A3B) by the ribonucleotide reductase (RNR) of Epstein-Barr virus. Here, we investigate the mechanistic conservation and evolutionary origin of this innate immune counteraction strategy. First, we find that human gamma-herpesvirus RNRs engage A3B via largely distinct surfaces. Second, we show that RNR-mediated enzymatic inhibition and relocalization of A3B depend upon binding to different regions of the catalytic domain. Third, we show that the capability of viral RNRs to antagonize A3B is conserved among gamma-herpesviruses that infect humans and Old World monkeys that encode this enzyme but absent in homologous viruses that infect New World monkeys that naturally lack the A3B gene. Finally, we reconstruct the ancestral primate A3B protein and demonstrate that it is active and similarly engaged by the RNRs from viruses that infect humans and Old World monkeys but not by the RNRs from viruses that infect New World monkeys. These results combine to indicate that the birth of A3B at a critical branchpoint in primate evolution may have been a driving force in selecting for an ancestral gamma-herpesvirus with an expanded RNR functionality through counteraction of this antiviral enzyme.

Recent years have seen growing public interest in how college and university administrators respond to sexual misconduct. Despite policy changes in this area, minimal research exists on how institutions of higher education (IHEs) are sharing and processing information about students found responsible for sexual misconduct. Aiming to establish some of the key questions and parameters in this line of research, this practitioner–researcher collaboration offers a first look at how IHEs share information about students who have been found responsible both within their campus and between campuses, as well as how IHEs respond when that information is shared (e.g., admitting a student applicant who has been previously sanctioned for a sexual misconduct violation). Practitioners designed and disseminated a questionnaire to campus administrators, including Title IX coordinators and student conduct administrators, via higher education association listservs. Exploratory results from 176 participants showed that 80% reported having some form of policy regarding sharing information within their institution, while approximately half have policies regarding sharing information to other IHEs regarding students found responsible of sexual misconduct. Nearly one-third of participants reported that their IHEs are engaging in campus information sharing through the use of transcript notation. In terms of IHEs receiving information about student applicants having been previously sanctioned for a sexual misconduct violation, approximately one-fourth of participants indicated their IHE has chosen not to accept a student for this reason within the past 5 years, and a quarter of IHEs have accepted such students. For those IHEs that have accepted a student previously found responsible, the majority of IHEs are not following the outcomes of these students, indicating an unknown in terms of whether information sharing policies were effective. As a result, preliminary findings suggest that more evaluation research is needed before any further policies are mandated.

The Hyperspectral X-ray Imaging (HXI) project will enable non-destructive chemical-state determination of nano-scale samples in the electron microscope for nuclear safeguards applications. To efficiently measure chemical state through electron-excited X-ray emission requires a combination of wide spectral bandwidth, high resolution, and high count rate capability. We are building a next-generation X-ray detector based on an array of transition edge sensors (TESs) to make these measurements possible and routine in the scanning electron microscope (SEM). Leveraging the large pixel densities afforded by microwave multiplexing readout and continuous, uninterrupted operation of a cryogen-free dilution refrigerator, this instrument will have efficiency to allow chemical species identification of nano-scale samples in hours instead of days to weeks. We describe prototype pixel designs for this HXI instrument, comprising three pixel types that will make up the hybrid TES array. Engineering design of the integrated HXI cryostat and SEM system is in progress, with full detector commissioning expected in Spring 2021 followed closely by full-scale integration with the SEM. We also report on the commissioning of a complementary TES-based X-ray emission spectroscopy platform for bulk samples to build a spectral library for HXI sample identification.

Robotic scope assistant systems are used to visualise and navigate the operative field during a laparoscopic surgery. The objective of this work is to design a surgical scope adapter that enables control of different scope types (zero-degree, angulated, and articulated), and can be connected to any six degree-of-freedom robotic manipulator for usage as a robotic scope assistant system.A surgical scope adapter compatible with different camera heads and scope types was designed and prototyped. The technical performance of the scope adapter was evaluated and a user study was conducted to assess the human-in-the-loop control.All the subjects were able to navigate the simulated operative field. The scope adapter permits continuous motion to explore the operative field as well as intermittent motion to accurately focus on the targeted anatomical landmarks.The modular and generic nature of the surgical scope adapter may enable its usage across different minimally invasive surgeries.

The main protease, M pro , of SARS-CoV-2 is an essential viral protein required for the earliest steps of infection. It is therefore an attractive target for antiviral drug development.