Nanoscale Three-Dimensional Imaging of Integrated Circuits Using a Scanning Electron Microscope and Transition-Edge Sensor Spectrometer.

X-ray nanotomography is a powerful tool for the characterization of nanoscale materials and structures, but it is difficult to implement due to the competing requirements of X-ray flux and spot size. Due to this constraint, state-of-the-art nanotomography is predominantly performed at large synchrotron facilities. We present a laboratory-scale nanotomography instrument that achieves nanoscale spatial resolution while addressing the limitations of conventional tomography tools. The instrument combines the electron beam of a scanning electron microscope (SEM) with the precise, broadband X-ray detection of a superconducting transition-edge sensor (TES) microcalorimeter. The electron beam generates a highly focused X-ray spot on a metal target held micrometers away from the sample of interest, while the TES spectrometer isolates target photons with a high signal-to-noise ratio. This combination of a focused X-ray spot, energy-resolved X-ray detection, and unique system geometry enables nanoscale, element-specific X-ray imaging in a compact footprint. The proof of concept for this approach to X-ray nanotomography is demonstrated by imaging 160 nm features in three dimensions in six layers of a Cu-SiO2 integrated circuit, and a path toward finer resolution and enhanced imaging capabilities is discussed.

Potential Impact of Race and Ethnicity on Pharmacy Residency Match Rate and Match Participation.

OBJECTIVE: The purpose of this study was to investigate if a correlation exists between a student's self-identified race or ethnicity and their rates of participating in the match or matching with a pharmacy residency. METHODS: This retrospective cohort study included pharmacy graduates from 2016 through 2021 at two schools/colleges of pharmacy, a Historically Black College or University and a non-Historically Black College or University. The primary outcome was to compare the percentage of underrepresented minority (URM) students and non-URM students who successfully matched with a postgraduate year 1 pharmacy residency. The secondary outcomes compared rates of participation in the match and the effects of student-related factors that influenced match success and participation rates between URM students and non-URM students. RESULTS: Of the 900 included students, 273 participated in the match. The match rate among students participating in the match was 53.5% (146 of 273) with 50.3% (84 of 167) in the URM group compared to 58.5% (62 of 106) in the non-URM group (P = .186) successfully matching. Rates of match participation were lower for students identified as URM (26% vs 39.3%, P < .001). When adjusting for previously published predictors of match success, URM status did not significantly affect match rates or match participation. CONCLUSION: At two schools of pharmacy, URM students were less likely to participate in the match but just as likely to match to an American Society of Health-System Pharmacists residency in the univariable analysis. However, when adjusting for other characteristics, there was no difference in match participation or match success in students who self-identified as URM.

Efficient optimization of time-varying inputs in a fed-batch cell culture process using design of dynamic experiments.

In cell culture process development, we rely largely on an iterative, one-factor-at-a-time procedure based on experiments that explore a limited process space. Design of experiments (DoE) addresses this issue by allowing us to analyze the effects of process inputs on process responses systematically and efficiently. However, DoE cannot be applied directly to study time-varying process inputs unless an impractically large number of bioreactors is used. Here, we adopt the methodology of design of dynamic experiments (DoDE) and incorporate dynamic feeding profiles efficiently in late-stage process development of the manufacture of therapeutic monoclonal antibodies. We found that, for the specific cell line used in this article, (1) not only can we estimate the effect of nutrient feed amount on various product attributes, but we can also estimate the effect, develop a statistical model, and use the model to optimize the slope of time-trended feed rates; (2) in addition to the slope, higher-order dynamic characteristics of time-trended feed rates can be incorporated in the design but do not have any significant effect on the responses we measured. Based on the DoDE data, we developed a statistical model and used the model to optimize several process conditions. Our effort resulted in a tangible improvement in productivity-compared with the baseline process without dynamic feeding, this optimized process in a 200-L batch achieved a 27% increase in titer and > 92% viability. We anticipate our application of DoDE to be a starting point for more efficient workflows to optimize dynamic process conditions in process development.

Atogepant for the prevention of episodic migraine in adults.

Objective: Atogepant is a newly approved medication for the prevention of migraine. This review aims to discuss the efficacy, safety, cost, and place in therapy of atogepant. Methods: The authors performed a systematic search for sources, including articles, abstracts, and poster presentations. Queried databases were the National Institute of Health, US National Library of Medicine Clinical Trials, PubMed, European PMC, and the Cochrane Library. Search terms included atogepant, QULIPTA™, AGN-241689, MK-803, and N02CD07. Full-text, English language, randomized-controlled trials from 1 February 2012 to 1 February 2022 were included in the review. Additional relevant prescribing information, abstracts, and articles identified through the search were considered for inclusion in this review. A total of 193 database entries were evaluated for inclusion in this narrative review. Three articles representing two randomized controlled trials were reviewed. Results and conclusions: Atogepant, a small-molecule calcitonin gene-related peptide (CGRP) receptor antagonist, is a daily oral treatment for migraine prevention. In placebo-controlled clinical trials, atogepant decreased mean monthly migraine days (MMD) over 12 weeks in patients with episodic migraine. Major treatment-related adverse effects include nausea and constipation. Long-term placebo-controlled efficacy and safety studies, chronic migraine studies, and studies in patients that failed more than two classes of preventive therapies are still pending. Atogepant represents one of many novel therapies for the prevention of migraine. To date, no head-to-head comparisons of atogepant versus other agents indicated for migraine prevention have been published. Atogepant offers patients an alternative therapy to injectable or infusion monoclonal antibody treatments and offers an alternative to non-specific migraine medications that are associated with poor tolerability. Due to its high cost and narrower therapeutic indications, atogepant may be reserved for a small subset of migraineurs who prefer oral therapy.

Eptinezumab: A calcitonin gene-related peptide monoclonal antibody infusion for migraine prevention.

This article seeks to analyze the clinical trials concerning the newly approved eptinezumab to assess its efficacy, safety, and application to current clinical practice. The Institute of Health US National Library of Medicine Clinical Trials, PubMed, and Cochrane Library databases were searched for relevant abstracts, journal articles, and other published sources. Search terms included eptinezumab, Vyepti®, and ALD403. Relevant English-language articles were evaluated and included in the narrative. Two randomized controlled trials compared quarterly infusions of eptinezumab 100 mg, eptinezumab 300 mg, and placebo in chronic and episodic migraine sufferers. In episodic migraine, eptinezumab resulted in a reduction of approximately 4 monthly migraine days, which was significant compared to placebo. In chronic migraine, eptinezumab reduced monthly migraine days by approximately 8 days, also significant compared to placebo. More patients who received eptinezumab experienced at least 75% reduction in monthly migraine days compared to placebo, resulting in a number needed to treat as low as 6, depending on the study population and the dose. The preventive impact was noticed day one post-infusion. The most common treatment-emergent adverse events were nausea and fatigue, and there was a low incidence of hypersensitivity or study withdrawal. Eptinezumab is the fourth Calcitonin Gene-related Peptide monoclonal antibody to receive Federal Drug Administration approval. Its delivery as a quarterly infusion sets it apart from the other agents in this class. As an infusion, eptinezumab has a quick onset of action that may prove especially beneficial to those with severe or refractory episodic or chronic migraines, despite the perceived increased direct and indirect cost of an infusion.

Broadband high-energy resolution hard x-ray spectroscopy using transition edge sensors at SPring-8.

We have succeeded in operating a transition-edge sensor (TES) spectrometer and evaluating its performance at the SPring-8 synchrotron x-ray light source. The TES spectrometer consists of a 240 pixel National Institute of Standards and Technology (NIST) TES system, and 220 pixels are operated simultaneously with an energy resolution of 4 eV at 6 keV at a rate of ∼1 c/s pixel-1. The tolerance for high count rates is evaluated in terms of energy resolution and live time fraction, leading to an empirical compromise of ∼2 × 103 c/s (all pixels) with an energy resolution of 5 eV at 6 keV. By utilizing the TES's wideband spectroscopic capability, simultaneous multi-element analysis is demonstrated for a standard sample. We conducted x-ray absorption near-edge structure (XANES) analysis in fluorescence mode using the TES spectrometer. The excellent energy resolution of the TES enabled us to detect weak fluorescence lines from dilute samples and trace elements that have previously been difficult to resolve due to the nearly overlapping emission lines of other dominant elements. The neighboring lines of As Kα and Pb Lα2 of the standard sample were clearly resolved, and the XANES of Pb Lα2 was obtained. Moreover, the x-ray spectrum from the small amount of Fe in aerosols was distinguished from the spectrum of a blank target, which helps us to understand the targets and the environment. These results are the first important step for the application of high resolution TES-based spectroscopy at hard x-ray synchrotron facilities.

Design of a 3000-Pixel Transition-Edge Sensor X-Ray Spectrometer for Microcircuit Tomography.

Feature sizes in integrated circuits have decreased substantially over time, and it has become increasingly difficult to three-dimensionally image these complex circuits after fabrication. This can be important for process development, defect analysis, and detection of unexpected structures in externally sourced chips, among other applications. Here, we report on a non-destructive, tabletop approach that addresses this imaging problem through x-ray tomography, which we uniquely realize with an instrument that combines a scanning electron microscope (SEM) with a transition-edge sensor (TES) x-ray spectrometer. Our approach uses the highly focused SEM electron beam to generate a small x-ray generation region in a carefully designed target layer that is placed over the sample being tested. With the high collection efficiency and resolving power of a TES spectrometer, we can isolate x-rays generated in the target from background and trace their paths through regions of interest in the sample layers, providing information about the various materials along the x-ray paths through their attenuation functions. We have recently demonstrated our approach using a 240 Mo/Cu bilayer TES prototype instrument on a simplified test sample containing features with sizes of ∼ 1 µm. Currently, we are designing and building a 3000 Mo/Au bilayer TES spectrometer upgrade, which is expected to improve the imaging speed by factor of up to 60 through a combination of increased detector number and detector speed.

A model for excess Johnson noise in superconducting transition-edge sensors.

Transition-edge sensors (TESs) are two-dimensional superconducting films utilized as highly sensitive detectors of energy or power. These detectors are voltage biased in the superconducting-normal transition where the film resistance is both finite and a strong function of temperature. Unfortunately, the amount of electrical noise observed in TESs exceeds the predictions of existing noise theories. We describe a possible mechanism for the unexplained excess noise, which we term "mixed-down noise." The source is Johnson noise, which is mixed down to low frequencies by Josephson oscillations in devices with a nonlinear current-voltage relationship. We derive an expression for the power spectral density of this noise and show that its predictions agree with measured data.

Novel Therapies in Acute Migraine Management: Small-Molecule Calcitonin Gene-Receptor Antagonists and Serotonin 1F Receptor Agonist.

OBJECTIVE: To review the efficacy, safety, and cost of 3 newly approved agents-ubrogepant, lasmiditan, and rimegepant-representing 2 therapeutic classes, calcitonin gene-related peptide (CGRP) receptor antagonist and serotonin 1F (5-HT1F) agonists, for the acute treatment of migraine with or without aura. DATA SOURCES: The Institute of Health US National Library of Medicine Clinical Trials, PubMed, and Cochrane databases were queried. Abstracts, journal articles, and other relevant sources published or present were reviewed. Search terms included the following: ubrogepant, MK-1602, Ubrelvy®, rimegepant, Nurtec®, BHV-3000, BMS-927711, lasmiditan, Reyvow®, LY573144. STUDY SELECTION AND DATA EXTRACTION: Relevant English-language articles from June 30, 2010, to August 31, 2020, were evaluated and included in the narrative. DATA SYNTHESIS: CGRP receptor antagonists, ubrogepant and rimegepant, achieved 2-hour pain freedom and freedom from the most bothersome migraine symptom (MBS) at 2 hours. Both agents were well tolerated, with adverse effects similar to placebo. Lasmiditan, a 5-HT1F receptor antagonist, also improved 2-hour pain freedom and freedom from the MBS at 2 hours. Lasmiditan is associated with dizziness, paresthesia, somnolence, nausea, fatigue, and lethargy. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Ubrogepant, rimegepant, and lasmiditan represent a new and exciting chapter in acute migraine therapy. To date, no head-to-head studies have compared these agents with the triptans. Ubrogepant and lasmiditan are effective in triptan nonresponders. None of the 3 agents is contraindicated in cardiovascular disease, unlike the triptans. CONCLUSIONS: Based on available data, ubrogepant, rimegepant, and lasmiditan should be reserved as second-line therapy and may be safe in patients with cardiovascular risk. Lasmiditan's adverse effect profile may limit its use.

Discovery of Six Ramoplanin Family Gene Clusters and the Lipoglycodepsipeptide Chersinamycin*.

Ramoplanins and enduracidins are peptidoglycan lipid intermediate II-binding lipodepsipeptides with broad-spectrum activity against methicillin- and vancomycin-resistant Gram-positive pathogens. Targeted genome mining using probes from conserved sequences within the ramoplanin/enduracidin biosynthetic gene clusters (BGCs) was used to identify six microorganisms with BGCs predicted to produce unique lipodepsipeptide congeners of ramoplanin and enduracidin. Fermentation of Micromonospora chersina yielded a novel lipoglycodepsipeptide, called chersinamycin, which exhibited good antibiotic activity against Gram-positive bacteria (1-2 µg/mL) similar to the ramoplanins and enduracidins. The covalent structure of chersinamycin was determined by NMR spectroscopy and tandem mass spectrometry in conjunction with chemical degradation studies. These six new BGCs and isolation of a new antimicrobial peptide provide much-needed tools to investigate the fundamental aspects of lipodepsipeptide biosynthesis and to facilitate efforts to produce novel antibiotics capable of combating antibiotic-resistant infections.

Toward a New Primary Standardization of Radionuclide Massic Activity Using Microcalorimetry and Quantitative Milligram-Scale Samples.

We present a new paradigm for the primary standardization of radionuclide activity per mass of solution (Bq/g). Two key enabling capabilities are 4π decay-energy spectrometry using chip-scale sub-Kelvin microcalorimeters and direct realization of mass by gravimetric inkjet dispensing using an electrostatic force balance. In contrast to traditional traceability, which typically relies on chemical separation of single-radionuclide samples, 4π integral counting, and additional spectrometry methods to verify purity, the system described here has both 4π counting efficiency and spectroscopic resolution sufficient to identify multiple radionuclides in the same sample at once. This enables primary standardization of activity concentrations of mixed-radionuclide samples. A major benefit of this capability, beyond metrology, is in assay of environmental and forensics samples, for which the quantification of multiplenuclide samples can be achieved where presently inhibited by interferences. This can be achieved without the need for chemical separations or efficiency tracers, thereby vastly reducing time, radioactive waste, and resulting measurement uncertainty.

Soft X-ray spectroscopy with transition-edge sensors at Stanford Synchrotron Radiation Lightsource beamline 10-1.

We present results obtained with a new soft X-ray spectrometer based on transition-edge sensors (TESs) composed of Mo/Cu bilayers coupled to bismuth absorbers. This spectrometer simultaneously provides excellent energy resolution, high detection efficiency, and broadband spectral coverage. The new spectrometer is optimized for incident X-ray energies below 2 keV. Each pixel serves as both a highly sensitive calorimeter and an X-ray absorber with near unity quantum efficiency. We have commissioned this 240-pixel TES spectrometer at the Stanford Synchrotron Radiation Lightsource beamline 10-1 (BL 10-1) and used it to probe the local electronic structure of sample materials with unprecedented sensitivity in the soft X-ray regime. As mounted, the TES spectrometer has a maximum detection solid angle of 2 × 10-3 sr. The energy resolution of all pixels combined is 1.5 eV full width at half maximum at 500 eV. We describe the performance of the TES spectrometer in terms of its energy resolution and count-rate capability and demonstrate its utility as a high throughput detector for synchrotron-based X-ray spectroscopy. Results from initial X-ray emission spectroscopy and resonant inelastic X-ray scattering experiments obtained with the spectrometer are presented.

Use of Transition Models to Design High Performance TESs for the LCLS-II Soft X-Ray Spectrometer.

We are designing an array of transition-edge sensor (TES) microcalorimeters for a soft X-ray spectrometer at the Linac Coherent Light Source at SLAC National Accelerator Laboratory to coincide with upgrades to the free electron laser facility. The complete spectrometer will have 1000 TES pixels with energy resolution of 0.5 eV full-width at half-maximum (FWHM) for incident energies below 1 keV while maintaining pulse decay-time constants shorter than 100 µs. Historically, TES pixels have often been designed for a particular scientific application via a combination of simple scaling relations and trial-and-error experimentation with device geometry. We have improved upon this process by using our understanding of transition physics to guide TES design. Using the two-fluid approximation of the phase-slip line model for TES resistance, we determine how the geometry and critical temperature of a TES will affect the shape of the transition. We have used these techniques to design sensors with a critical temperature of 55 mK. The best sensors achieve an energy resolution of 0.75 eV FWHM at 1.25 keV. Building upon this result, we show how the next generation of sensors can be designed to reach our goal of 0.5 eV resolution.

Configurable error correction of code-division multiplexed TES detectors with a cryotron switch.

The development of a superconducting analog to the transistor with extremely low power dissipation will accelerate the proliferation of low-temperature circuitry operating in the milliKelvin regime. The thin-film, magnetically actuated cryotron switch is a candidate building block for more complicated and flexible milliKelvin circuitry. We demonstrate its utility for implementing reconfigurable circuitry by integrating a cryotron switch into flux-summed code-division SQUID multiplexed readout for large arrays of transition-edge-sensor (TES) microcalorimeters. Code-division multiplexing eliminates the noise penalty of time-division multiplexing while being drop-in compatible with the latter's control electronics. However, code-division multiplexing is susceptible to single-point failure mechanisms which can result in an unconstrained demodulation matrix and the loss of information from many sensing elements. In the event of a failure, the integrated cryotron switch provides a zero-signal output from a single TES, enabling the demodulation matrix used to compute TES signals from SQUID signals to be constrained and data recovered from the remaining sensors. This demonstration of configurable error correction provides both a realworld application of the cryotron switch and a foundation for more complex circuitry at milliKelvin temperatures.

L-edge spectroscopy of dilute, radiation-sensitive systems using a transition-edge-sensor array.

We present X-ray absorption spectroscopy and resonant inelastic X-ray scattering (RIXS) measurements on the iron L-edge of 0.5 mM aqueous ferricyanide. These measurements demonstrate the ability of high-throughput transition-edge-sensor (TES) spectrometers to access the rich soft X-ray (100-2000 eV) spectroscopy regime for dilute and radiation-sensitive samples. Our low-concentration data are in agreement with high-concentration measurements recorded by grating spectrometers. These results show that soft-X-ray RIXS spectroscopy acquired by high-throughput TES spectrometers can be used to study the local electronic structure of dilute metal-centered complexes relevant to biology, chemistry, and catalysis. In particular, TES spectrometers have a unique ability to characterize frozen solutions of radiation- and temperature-sensitive samples.

Level of FACT defines the transcriptional landscape and aggressive phenotype of breast cancer cells.

Although breast cancer (BrCa) may be detected at an early stage, there is a shortage of markers that predict tumor aggressiveness and a lack of targeted therapies. Histone chaperone FACT, expressed in a limited number of normal cells, is overexpressed in different types of cancer, including BrCa. Recently, we found that FACT expression in BrCa correlates with markers of aggressive BrCa, which prompted us to explore the consequences of FACT inhibition in BrCa cells with varying levels of FACT.FACT inhibition using a small molecule or shRNA caused reduced growth and viability of all BrCa cells tested. Phenotypic changes were more severe in "high- FACT" cells (death or growth arrest) than in "low-FACT" cells (decreased proliferation). Though inhibition had no effect on the rate of general transcription, expression of individual genes was changed in a cell-specific manner. Initially distinct transcriptional profiles of BrCa cells became similar upon equalizing FACT expression. In "high-FACT" cells, FACT supports expression of genes involved in the regulation of cell cycle, DNA replication, maintenance of an undifferentiated cell state and regulated by the activity of several proto-oncogenes. In "low-FACT" cells, the presence of FACT reduces expression of genes encoding enzymes of steroid metabolism that are characteristic of differentiated mammary epithelia.Thus, we propose that FACT is both a marker and a target of aggressive BrCa cells, whose inhibition results in the death of BrCa or convertion of them to a less aggressive subtype.

A low-spin Fe(iii) complex with 100-ps ligand-to-metal charge transfer photoluminescence.

Transition-metal complexes are used as photosensitizers, in light-emitting diodes, for biosensing and in photocatalysis. A key feature in these applications is excitation from the ground state to a charge-transfer state; the long charge-transfer-state lifetimes typical for complexes of ruthenium and other precious metals are often essential to ensure high performance. There is much interest in replacing these scarce elements with Earth-abundant metals, with iron and copper being particularly attractive owing to their low cost and non-toxicity. But despite the exploration of innovative molecular designs, it remains a formidable scientific challenge to access Earth-abundant transition-metal complexes with long-lived charge-transfer excited states. No known iron complexes are considered photoluminescent at room temperature, and their rapid excited-state deactivation precludes their use as photosensitizers. Here we present the iron complex [Fe(btz)3]3+ (where btz is 3,3'-dimethyl-1,1'-bis(p-tolyl)-4,4'-bis(1,2,3-triazol-5-ylidene)), and show that the superior σ-donor and π-acceptor electron properties of the ligand stabilize the excited state sufficiently to realize a long charge-transfer lifetime of 100 picoseconds (ps) and room-temperature photoluminescence. This species is a low-spin Fe(iii) d5 complex, and emission occurs from a long-lived doublet ligand-to-metal charge-transfer (2LMCT) state that is rarely seen for transition-metal complexes. The absence of intersystem crossing, which often gives rise to large excited-state energy losses in transition-metal complexes, enables the observation of spin-allowed emission directly to the ground state and could be exploited as an increased driving force in photochemical reactions on surfaces. These findings suggest that appropriate design strategies can deliver new iron-based materials for use as light emitters and photosensitizers.

Mapping of the resistance of a superconducting transition edge sensor as a function of temperature, current, and applied magnetic field.

We have measured the resistance R(T, I, B ext) of a superconducting transition edge sensor over the entire transition region on a fine scale, producing a 4-dimensional map of the resistance surface. The dimensionless temperature and current sensitivities ( α ≡ ∂ log R / ∂ log T | I and ß ≡ ∂ log R / ∂ log I | T ) of the TES resistance have been determined at each point. α and ß are closely related to the sensor performance, but show a great deal of complex, large amplitude fine structure over large portions of the surface that is sensitive to the applied magnetic field. We discuss the relation of this structure to the presence of Josephson "weak link" fringes.

ARTIK-52 induces replication-dependent DNA damage and p53 activation exclusively in cells of prostate and breast cancer origin.

The realization, that the androgen receptor (AR) is essential for prostate cancer (PC) even after relapse following androgen deprivation therapy motivated the search for novel types of AR inhibitors. We proposed that targeting AR expression versus its function would work in cells having either wild type or mutant AR as well as be independent of androgen synthesis pathways. Previously, using a phenotypic screen in androgen-independent PC cells we identified a small molecule inhibitor of AR, ARTIK-52. Treatment with ARTIK-52 caused the loss of AR protein and death of AR-positive, but not AR-negative, PC cells. Here we present data that ARTIK-52 induces degradation of AR mRNA through a mechanism that we were unable to establish. However, we found that ARTIK-52 is toxic to breast cancer (BC) cells expressing AR, although they were not sensitive to AR knockdown, suggesting an AR-independent mechanism of toxicity. Using different approaches we detected that ARTIK-52 induces replication-dependent double strand DNA breaks exclusively in cancer cells of prostate and breast origin, while not causing DNA damage, or any toxicity, in normal cells, as well as in non-PC and non-BC tumor cells, independent of their proliferation status. This amazing specificity, combined with such a basic mechanism of toxicity, makes ARTIK-52 a potentially useful tool to discover novel attractive targets for the treatment of BC and PC. Thus, phenotypic screening allowed us to identify a compound, whose properties cannot be predicted based on existing knowledge and moreover, uncover a barely known link between AR and DNA damage response in PC and BC epithelial cells.

Fabrication of superconducting Mo/Cu bilayers using ion-beam-assisted e-beam evaporation.

Superconducting/normal metal bilayers with tunable transition temperature are a critical ingredient to the fabrication of high performance transition edge-sensors (TES). Popular material choices include Mo/Au and Mo/Cu, which exhibit good environmental stability and provide low resistivity films to achieve adequate thermal conductivity. The deposition of high quality Mo films requires sufficient adatom mobility, which can be provided by energetic ions in sputter deposition, or by heating the substrate in an e-beam evaporation process. The bilayer T c depends sensitively on the exact deposition conditions of the Mo layer and the superconducting/normal metal interface. Because the individual contributions (strain, crystalline structure, contamination) are difficult to disentangle and control, reproducibility remains a challenge. Recently, we have demonstrated that low energy ion beam assist during e-beam evaporation offers an alternative route to reliably produce high quality Mo films without the use of substrate heating. The energy and momentum delivered by the ion beam provides an additional control knob to tune film properties such as resistivity and stress. In this report we describe modifications made to the commercial end-Hall ion-source to avoid iron contamination allowing us to produce superconducting Mo films. We show that the ion beam is effective at enhancing the bilayer interface transparency and that bilayers can be further tuned to reduced T c and higher conductivity by vacuum annealing.