Integrated optical frequency division for microwave and mmWave generation.

The generation of ultra-low-noise microwave and mmWave in miniaturized, chip-based platforms can transform communication, radar and sensing systems1-3. Optical frequency division that leverages optical references and optical frequency combs has emerged as a powerful technique to generate microwaves with superior spectral purity than any other approaches4-7. Here we demonstrate a miniaturized optical frequency division system that can potentially transfer the approach to a complementary metal-oxide-semiconductor-compatible integrated photonic platform. Phase stability is provided by a large mode volume, planar-waveguide-based optical reference coil cavity8,9 and is divided down from optical to mmWave frequency by using soliton microcombs generated in a waveguide-coupled microresonator10-12. Besides achieving record-low phase noise for integrated photonic mmWave oscillators, these devices can be heterogeneously integrated with semiconductor lasers, amplifiers and photodiodes, holding the potential of large-volume, low-cost manufacturing for fundamental and mass-market applications13.

A viral biomolecular condensate coordinates assembly of progeny particles.

Biomolecular condensates formed by phase separation can compartmentalize and regulate cellular processes1,2. Emerging evidence has suggested that membraneless subcellular compartments in virus-infected cells form by phase separation3-8. Although linked to several viral processes3-5,9,10, evidence that phase separation contributes functionally to the assembly of progeny particles in infected cells is lacking. Here we show that phase separation of the human adenovirus 52-kDa protein has a critical role in the coordinated assembly of infectious progeny particles. We demonstrate that the 52-kDa protein is essential for the organization of viral structural proteins into biomolecular condensates. This organization regulates viral assembly such that capsid assembly is coordinated with the provision of viral genomes needed to produce complete packaged particles. We show that this function is governed by the molecular grammar of an intrinsically disordered region of the 52-kDa protein, and that failure to form condensates or to recruit viral factors that are critical for assembly results in failed packaging and assembly of only non-infectious particles. Our findings identify essential requirements for coordinated assembly of progeny particles and demonstrate that phase separation of a viral protein is critical for production of infectious progeny during adenovirus infection.

Integrated photonic molecule Brillouin laser with a high-power sub-100-mHz fundamental linewidth.

Photonic integrated lasers with an ultra-low fundamental linewidth and a high output power are important for precision atomic and quantum applications, high-capacity communications, and fiber sensing, yet wafer-scale solutions have remained elusive. Here we report an integrated stimulated Brillouin laser (SBL), based on a photonic molecule coupled resonator design, that achieves a sub-100-mHz fundamental linewidth with greater than 10-mW output power in the C band, fabricated on a 200-mm silicon nitride (Si3N4) CMOS-foundry compatible wafer-scale platform. The photonic molecule design is used to suppress the second-order Stokes (S2) emission, allowing the primary lasing mode to increase with the pump power without phase noise feedback from higher Stokes orders. The nested waveguide resonators have a 184 million intrinsic and 92 million loaded Q, over an order of magnitude improvement over prior photonic molecules, enabling precision resonance splitting of 198 MHz at the S2 frequency. We demonstrate S2-suppressed single-mode SBL with a minimum fundamental linewidth of 71±18 mHz, corresponding to a 23±6-mHz2/Hz white-frequency-noise floor, over an order of magnitude lower than prior integrated SBLs, with an ∼11-mW output power and 2.3-mW threshold power. The frequency noise reaches the resonator-intrinsic thermo-refractive noise from 2-kHz to 1-MHz offset. The laser phase noise reaches -155 dBc/Hz at 10-MHz offset. The performance of this chip-scale SBL shows promise not only to improve the reliability and reduce size and cost but also to enable new precision experiments that require the high-speed manipulation, control, and interrogation of atoms and qubits. Realization in the silicon nitride ultra-low loss platform is adaptable to a wide range of wavelengths from the visible to infrared and enables integration with other components for systems-on-chip solutions for a wide range of precision scientific and engineering applications including quantum sensing, gravitometers, atom interferometers, precision metrology, optical atomic clocks, and ultra-low noise microwave generation.

Osteocyte Sptbn1 Deficiency Alters Cell Survival and Mechanotransduction Following Formation of Plasma Membrane Disruptions (PMD) from Mechanical Loading.

We and others have shown that application of high-level mechanical loading promotes the formation of transient plasma membrane disruptions (PMD) which initiate mechanotransduction. We hypothesized that increasing osteocyte cell membrane fragility, by disrupting the cytoskeleton-associated protein ß2-spectrin (Sptbn1), could alter osteocytic responses and bone adaptation to loading in a PMD-related fashion. In MLO-Y4 cells, treatment with the spectrin-disrupting agent diamide or knockdown of Sptbn1 via siRNA increased the number of PMD formed by fluid shear stress. Primary osteocytes from an osteocyte-targeted DMP1-Cre Sptbn1 conditional knockout (CKO) model mimicked trends seen with diamide and siRNA treatment and suggested the creation of larger PMD, which repaired more slowly, for a given level of stimulus. Post-wounding cell survival was impaired in all three models, and calcium signaling responses from the wounded osteocyte were mildly altered in Sptbn1 CKO cultures. Although Sptbn1 CKO mice did not demonstrate an altered skeletal phenotype as compared to WT littermates under baseline conditions, they showed a blunted increase in cortical thickness when subjected to an osteogenic tibial loading protocol as well as evidence of increased osteocyte death (increased lacunar vacancy) in the loaded limb after 2 weeks of loading. The impaired post-wounding cell viability and impaired bone adaptation seen with Sptbn1 disruption support the existence of an important role for Sptbn1, and PMD formation, in osteocyte mechanotransduction and bone adaptation to mechanical loading.

A Pilot Study to Evaluate the Use of Automated Nicotine Metabolite Ratio Reporting Within Primary Care as an Implementation Strategy to Increase the Use of Tobacco Treatments.

INTRODUCTION: Concerns about safety and effectiveness of tobacco treatments reduce their use. We explored integrating the nicotine metabolite ratio (NMR), and messaging about its potential for improving safety and effectiveness, as a strategy to increase the use of tobacco treatments within primary care. AIMS AND METHODS: Through a prospective cohort design, we explored the effects of integrating NMR testing within primary care on the provision of tobacco treatment; 65 patients completed assessments including NMR before a clinic visit. At the clinic visit, patients' clinicians received an electronic health record (EHR) alert about the patient's NMR and personalized treatment recommendations to improve effectiveness and safety. Being asked about smoking and advised to quit, and a referral for tobacco treatment or medication prescription, were assessed within 30 days of the appointment and were compared to a usual care cohort (N = 85). RESULTS: The NMR and usual care cohorts reported similar rates of being asked about smoking (92.3% vs. 92.9%, p = 1.0), being advised to quit (72.3% vs. 74.1%, p = .85), being referred for tobacco treatment (23.1% vs. 36.5%, p = .11), and receiving tobacco use medications (20% vs. 27.1%, p = .34). In the NMR cohort, fast versus slow metabolizers were more likely to receive medication (26% vs. 0%, p = .003) and all patients who received varenicline (n = 8) were fast metabolizers. CONCLUSIONS: NMR results and treatment recommendations did not increase tobacco treatment rates in primary care, although it may increase treatment rates and the use of varenicline for fast metabolizers. Future studies could test ways to use the NMR to increase tobacco treatment rates in clinical settings. IMPLICATIONS: This study generated a novel implementation strategy, namely an EHR alert about patients' NMR and personalized treatment recommendations, in an effort to increase tobacco treatment rates in primary care. While the strategy did not increase tobacco treatment rates, it may have boosted the rate of varenicline prescription for patients who metabolize nicotine faster, aligning with evidence-based practice.

Integrated programmable strongly coupled three-ring resonator photonic molecule with ultralow-power piezoelectric control.

Photonic molecules can realize complex optical energy modes that simulate states of matter and have application to quantum, linear, and nonlinear optical systems. To achieve their full potential, it is critical to scale the photonic molecule energy state complexity and provide flexible, controllable, stable, high-resolution energy state engineering with low power tuning mechanisms. In this work, we demonstrate a controllable, silicon nitride integrated photonic molecule, with three high-quality factor ring resonators strongly coupled to each other and individually actuated using ultralow-power thin-film lead zirconate titanate (PZT) tuning. The resulting six tunable supermodes can be fully controlled, including their degeneracy, location, and degree of splitting, and the PZT actuator design yields narrow PM energy state linewidths below 58 MHz without degradation as the resonance shifts, with over an order of magnitude improvement in resonance splitting-to-width ratio of 58, and power consumption of 90 nW per actuator, with a 1-dB photonic molecule loss. The strongly coupled PZT-controlled resonator design provides a high-degree of resolution and controllability in accessing the supermodes. Given the low loss of the silicon nitride platform from the visible to infrared and the three individual bus, six-port design, these results open the door to novel device designs and a wide range of applications including tunable lasers, high-order suppression ultranarrow-linewidth lasers, dispersion engineering, optical parametric oscillators, physics simulations, and atomic and quantum photonics.

Seeing Through the Blind: Belief about Treatment Randomization and Smoking Cessation Outcome among People with Current or Past Major Depressive Disorder who Smoke in a Placebo-Controlled Trial of Varenicline.

INTRODUCTION: Blinding participants to randomization is a cornerstone of science. However, participant beliefs about their allocation can influence outcomes. We examined blind integrity, the association between trial arm belief and cessation, and potential mechanisms linking treatment arm and treatment arm belief among people with major depressive disorder (MDD) who smoke receiving varenicline in a placebo-controlled trial. METHODS: 175 participants were asked at the end of treatment (EOT) if they thought they received placebo, varenicline, or were not sure. We assessed the relationship between treatment arm belief and actual treatment allocation, examined the association between treatment arm belief and EOT cessation, and evaluated changes in craving, withdrawal, side effects, depression symptoms, and smoking reward as mediators through which treatment arm was believed. RESULTS: Treatment arm belief was significantly associated with actual arm assignment (χ2(2)=13.0, p=0.002). Participants in the varenicline arm were >3 times as likely to believe they were taking varenicline, vs. "not sure" (RR=3.05 [1.41-6.60], p=0.005). Participants in the placebo arm were just as likely to believe they were taking placebo vs. "not sure" (χ2[2]=0.75, p=0.69). Controlling for treatment arm, belief that one received varenicline was significantly associated with an increase in cessation rate (OR=5.91 [2.06-16.92], p=0.001). Change in the rewarding experience of smoking may mediate participant ability to discern getting varenicline B=0.077 [0.002-0.192], p <0.05). CONCLUSIONS: Participants receiving varenicline can discern that they received varenicline and this belief is associated with higher cessation rates. Research is needed to continue to examine how participants correctly identify their allocation to varenicline.

An interdomain helix in IRE1α mediates the conformational change required for the sensor's activation.

The unfolded protein response plays an evolutionarily conserved role in homeostasis, and its dysregulation often leads to human disease, including diabetes and cancer. IRE1α is a major transducer that conveys endoplasmic reticulum stress via biochemical signals, yet major gaps persist in our understanding of how the detection of stress is converted to one of several molecular outcomes. It is known that, upon sensing unfolded proteins via its endoplasmic reticulum luminal domain, IRE1α dimerizes and then oligomerizes (often visualized as clustering). Once assembled, the kinase domain trans-autophosphorylates a neighboring IRE1α, inducing a conformational change that activates the RNase effector domain. However, the full details of how the signal is transmitted are not known. Here, we describe a previously unrecognized role for helix αK, located between the kinase and RNase domains of IRE1α, in conveying this critical conformational change. Using constructs containing mutations within this interdomain helix, we show that distinct substitutions affect oligomerization, kinase activity, and the RNase activity of IRE1α differentially. Furthermore, using both biochemical and computational methods, we found that different residues at position 827 specify distinct conformations at distal sites of the protein, such as in the RNase domain. Of importance, an RNase-inactive mutant, L827P, can still dimerize with wildtype monomers, but this mutation inactivates the wildtype molecule and renders leukemic cells more susceptible to stress. We surmise that helix αK is a conduit for the activation of IRE1α in response to stress.

LFA-1 signals to promote actin polymerization and upstream migration in T cells.

T cell entry into inflamed tissue requires firm adhesion, cell spreading, and migration along and through the endothelial wall. These events require the T cell integrins LFA-1 and VLA-4 and their endothelial ligands ICAM-1 and VCAM-1, respectively. T cells migrate against the direction of shear flow on ICAM-1 and with the direction of shear flow on VCAM-1, suggesting that these two ligands trigger distinct cellular responses. However, the contribution of specific signaling events downstream of LFA-1 and VLA-4 has not been explored. Using primary mouse T cells, we found that engagement of LFA-1, but not VLA-4, induces cell shape changes associated with rapid 2D migration. Moreover, LFA-1 ligation results in activation of the phosphoinositide 3-kinase (PI3K) and ERK pathways, and phosphorylation of multiple kinases and adaptor proteins, whereas VLA-4 ligation triggers only a subset of these signaling events. Importantly, T cells lacking Crk adaptor proteins, key LFA-1 signaling intermediates, or the ubiquitin ligase cCbl (also known as CBL), failed to migrate against the direction of shear flow on ICAM-1. These studies identify novel signaling differences downstream of LFA-1 and VLA-4 that drive T cell migratory behavior.This article has an associated First Person interview with the first author of the paper.

Silicon nitride stress-optic microresonator modulator for optical control applications.

Modulation-based control and locking of lasers, filters and other photonic components is a ubiquitous function across many applications that span the visible to infrared (IR), including atomic, molecular and optical (AMO), quantum sciences, fiber communications, metrology, and microwave photonics. Today, modulators used to realize these control functions consist of high-power bulk-optic components for tuning, sideband modulation, and phase and frequency shifting, while providing low optical insertion loss and operation from DC to 10s of MHz. In order to reduce the size, weight and cost of these applications and improve their scalability and reliability, modulation control functions need to be implemented in a low loss, wafer-scale CMOS-compatible photonic integration platform. The silicon nitride integration platform has been successful at realizing extremely low waveguide losses across the visible to infrared and components including high performance lasers, filters, resonators, stabilization cavities, and optical frequency combs. Yet, progress towards implementing low loss, low power modulators in the silicon nitride platform, while maintaining wafer-scale process compatibility has been limited. Here we report a significant advance in integration of a piezo-electric (PZT, lead zirconate titanate) actuated micro-ring modulation in a fully-planar, wafer-scale silicon nitride platform, that maintains low optical loss (0.03 dB/cm in a 625 µm resonator) at 1550 nm, with an order of magnitude increase in bandwidth (DC - 15 MHz 3-dB and DC - 25 MHz 6-dB) and order of magnitude lower power consumption of 20 nW improvement over prior PZT modulators. The modulator provides a >14 dB extinction ratio (ER) and 7.1 million quality-factor (Q) over the entire 4 GHz tuning range, a tuning efficiency of 162 MHz/V, and delivers the linearity required for control applications with 65.1 dB·Hz2/3 and 73.8 dB·Hz2/3 third-order intermodulation distortion (IMD3) spurious free dynamic range (SFDR) at 1 MHz and 10 MHz respectively. We demonstrate two control applications, laser stabilization in a Pound-Drever Hall (PDH) lock loop, reducing laser frequency noise by 40 dB, and as a laser carrier tracking filter. This PZT modulator design can be extended to the visible in the ultra-low loss silicon nitride platform with minor waveguide design changes. This integration of PZT modulation in the ultra-low loss silicon nitride waveguide platform enables modulator control functions in a wide range of visible to IR applications such as atomic and molecular transition locking for cooling, trapping and probing, controllable optical frequency combs, low-power external cavity tunable lasers, quantum computers, sensors and communications, atomic clocks, and tunable ultra-low linewidth lasers and ultra-low phase noise microwave synthesizers.

Ultra-low loss visible light waveguides for integrated atomic, molecular, and quantum photonics.

Atomic, molecular and optical (AMO) visible light systems are the heart of precision applications including quantum, atomic clocks and precision metrology. As these systems scale in terms of number of lasers, wavelengths, and optical components, their reliability, space occupied, and power consumption will push the limits of using traditional laboratory-scale lasers and optics. Visible light photonic integration is critical to advancing AMO based sciences and applications, yet key performance aspects remain to be addressed, most notably waveguide losses and laser phase noise and stability. Additionally, a visible light integrated solution needs to be wafer-scale CMOS compatible and capable of supporting a wide array of photonic components. While the regime of ultra-low loss has been achieved at telecommunication wavelengths, progress at visible wavelengths has been limited. Here, we report the lowest waveguide losses and highest resonator Qs to date in the visible range, to the best of our knowledge. We report waveguide losses at wavelengths associated with strontium transitions in the 461 nm to 802 nm wavelength range, of 0.01 dB/cm to 0.09 dB/cm and associated intrinsic resonator Q of 60 Million to 9.5 Million, a decrease in loss by factors of 6x to 2x and increase in Q by factors of 10x to 1.5x over this visible wavelength range. Additionally, we measure an absorption limited loss and Q of 0.17 dB/m and 340 million at 674 nm. This level of performance is achieved in a wafer-scale foundry compatible Si3N4 platform with a 20 nm thick core and TEOS-PECVD deposited upper cladding oxide, and enables waveguides for different wavelengths to be fabricated on the same wafer with mask-only changes per wavelength. These results represent a significant step forward in waveguide platforms that operate in the visible, opening up a wide range of integrated applications that utilize atoms, ions and molecules including sensing, navigation, metrology and clocks.

Ultralow 0.034†dB/m loss wafer-scale integrated photonics realizing 720 million Q and 380 µW threshold Brillouin lasing.

We demonstrate 0.034 dB/m loss waveguides in a 200-mm wafer-scale, silicon nitride (Si3N4) CMOS-foundry-compatible integration platform. We fabricate resonators that measure up to a 720 million intrinsic Q resonator at 1615 nm wavelength with a 258 kHz intrinsic linewidth. This resonator is used to realize a Brillouin laser with an energy-efficient 380 µW threshold power. The performance is achieved by reducing scattering losses through a combination of single-mode TM waveguide design and an etched blanket-layer low-pressure chemical vapor deposition (LPCVD) 80 nm Si3N4 waveguide core combined with thermal oxide lower and tetraethoxysilane plasma-enhanced chemical vapor deposition (TEOS-PECVD) upper oxide cladding. This level of performance will enable photon preservation and energy-efficient generation of the spectrally pure light needed for photonic integration of a wide range of future precision scientific applications, including quantum, precision metrology, and optical atomic clocks.

Associations Between Industry Payments to Physicians for Antiplatelet Drugs and Utilization of Cardiac Procedures and Stents.

BACKGROUND: A study has shown that industry payments to physicians for drugs are associated not only with higher drug prescriptions but also with higher non-drug costs due to additional utilization of healthcare services. However, the association between industry payments to cardiologists for antiplatelet drugs and the costs and number of percutaneous coronary interventions they perform has not been investigated. OBJECTIVE: To examine the association between industry payments to cardiologists for antiplatelet drugs and the costs and number of percutaneous coronary interventions they perform. DESIGN: Using the 2016 Open Payments Database linked to the 2017 Medicare Provider Utilization and Payment Data, we examined the association between the value of industry payments related to the antiplatelet drugs prasugrel and ticagrelor and healthcare spending and volume for cardiovascular procedures, adjusted for potential cofounders. SUBJECTS: A total of 7456 cardiologists who performed diagnostic cardiac catheterizations on Medicare beneficiaries in 2017. MAIN MEASURES: Primary outcomes included (1) healthcare spending on cardiac procedures, (2) diagnostic cardiac catheterization volumes, and (3) rates of coronary stenting. Secondary outcomes were total expenditures for all drugs and for antiplatelet drugs. KEY RESULTS: Industry payments for antiplatelet drugs were associated with higher healthcare spending on cardiac procedures (adjusted difference, +$50.9 for additional $100 industry payments; 95% CI, +$25.5 to +$76.2; P < 0.001), diagnostic cardiac catheterizations (+0.1 procedures per cardiologist; 95% CI, +0.03 to +0.1; P=0.001), and stent use (+0.5 per 1000 diagnostic cardiac catheterizations per cardiologist; 95% CI, +0.2 to +0.9; P=0.002). Industry payments for antiplatelet drugs were associated with higher total costs for all drugs and antiplatelet drugs. CONCLUSIONS: Industry payments to cardiologists for antiplatelet drugs were associated with both prescribing of antiplatelet drugs and the use of cardiac procedures and stents. Further research is warranted to understand whether the observed associations are causal or reflect a greater propensity for higher volume proceduralists to have relationships with industry.

A core viral protein binds host nucleosomes to sequester immune danger signals.

Viral proteins mimic host protein structure and function to redirect cellular processes and subvert innate defenses. Small basic proteins compact and regulate both viral and cellular DNA genomes. Nucleosomes are the repeating units of cellular chromatin and play an important part in innate immune responses. Viral-encoded core basic proteins compact viral genomes, but their impact on host chromatin structure and function remains unexplored. Adenoviruses encode a highly basic protein called protein VII that resembles cellular histones. Although protein VII binds viral DNA and is incorporated with viral genomes into virus particles, it is unknown whether protein VII affects cellular chromatin. Here we show that protein VII alters cellular chromatin, leading us to hypothesize that this has an impact on antiviral responses during adenovirus infection in human cells. We find that protein VII forms complexes with nucleosomes and limits DNA accessibility. We identified post-translational modifications on protein VII that are responsible for chromatin localization. Furthermore, proteomic analysis demonstrated that protein VII is sufficient to alter the protein composition of host chromatin. We found that protein VII is necessary and sufficient for retention in the chromatin of members of the high-mobility-group protein B family (HMGB1, HMGB2 and HMGB3). HMGB1 is actively released in response to inflammatory stimuli and functions as a danger signal to activate immune responses. We showed that protein VII can directly bind HMGB1 in vitro and further demonstrated that protein VII expression in mouse lungs is sufficient to decrease inflammation-induced HMGB1 content and neutrophil recruitment in the bronchoalveolar lavage fluid. Together, our in vitro and in vivo results show that protein VII sequesters HMGB1 and can prevent its release. This study uncovers a viral strategy in which nucleosome binding is exploited to control extracellular immune signaling.

Comparison of Patient Outcomes of Surgeons Who Are US Versus International Medical Graduates.

OBJECTIVE: The aim of this study was to compare patient outcomes between International Medical Graduate (IMG) versus US medical graduate (USMG) surgeons. SUMMARY BACKGROUND DATA: One in 7 surgeons practicing in the US graduated from a foreign medical school. However, it remains unknown whether patient outcomes differ between IMG versus USMG surgeons. METHODS: Using 20% random sample of Medicare fee-for-service beneficiaries aged 65 to 99 years who underwent 1 of 13 common nonelective surgical procedures (as a "natural experiment" as surgeons are less likely to select patients in this context) in 2011 to 2014 (638,973 patients treated by 37,221 surgeons for the mortality analysis), we compared operative mortality, complications, and length of stay (LOS) between IMG and USMG surgeons, adjusting for patient and surgeon characteristics and hospital-specific fixed effects (effectively comparing IMG and USMG surgeons within the same hospital). We also conducted stratified analyses by patients' severity of illness and procedure type. RESULTS: We found no evidence that patient outcomes differ between IMG and USMG surgeons for operative mortality [adjusted mortality, 7.3% for IMGs vs 7.3% for USMGs; adjusted odds ratio (aOR), 1.01; 95% confidence interval (CI), 0.96-1.05; P = 0.79], complication rate (adjusted complication rate, 0.6% vs 0.6%; aOR, 0.95; 95% CI, 0.85-1.06; P = 0.43), and LOS (adjusted LOS, 6.6 days vs 6.6 days; adjusted difference, +0.02 days; 95% CI, -0.05 to +0.08; P = 0.54). We also found no difference when we stratified by severity of illness and procedures. CONCLUSION: Using national data of Medicare beneficiaries who underwent common surgical procedures, we found no evidence that outcomes differ between IMG and USMG surgeons.

Sex Differences in Achievement and Faculty Rank in Academic Infectious Diseases.

BACKGROUND: This study assesses differences in faculty rank between female and male infectious diseases (ID) faculty with academic appointments at US medical schools. METHODS: We analyzed a complete database of US physicians with medical school faculty appointments in 2014. This database consists of a linkage between the American Association of Medical Colleges faculty roster and a physician database from Doximity, and includes physician age, sex, years since residency completion, publications, National Institutes of Health grants, and registered clinical trials for all academic physicians by specialty. We used multivariable logistic regression models with medical school-specific fixed effects to assess sex differences in full professorship by specialty and the relationship between these factors and achieving the rank of full professor within ID. We compared this adjusted difference in ID to that of peer subspecialties. RESULTS: Among a total of 2016 academic ID physicians, there were 742 (37%) women who together accounted for 48.1% of assistant professors, 39.7% of associate professors, and 19.2% of full professors. Women faculty had fewer total (16.3 vs 28.3, P < .001) and first/last author publications (9.8 vs 20.4, P < .001). In adjusted models, the rate of full professorship (vs assistant or associate) among female compared to male ID physicians was large and significant (absolute adjusted difference, -8.0% [95% confidence interval, -11.9% to -4.1%]). This difference was greater in ID than in cardiology. CONCLUSIONS: Significant sex differences in achieving the rank of full professor exist in academic ID, after adjustment for multiple factors known to influence these outcomes. Greater efforts should be made to address equity in academic ID.

Clustering of IRE1α depends on sensing ER stress but not on its RNase activity.

The sensors of the unfolded protein response react to endoplasmic reticulum (ER) stress by transient activation of their enzymatic activities, which initiate various signaling cascades. In addition, the sensor IRE1α exhibits stress-induced clustering in a transient time frame similar to activation of its endoRNase activity. Previous work had suggested that the clustering response and RNase activity of IRE1α are functionally linked, but here we show that they are independent of each other and have different behaviors and modes of activation. Although both clustering and the RNase activity are responsive to luminal stress conditions and to depletion of the ER chaperone binding protein, RNase-inactive IRE1α still clusters and, conversely, full RNase activity can be accomplished without clustering. The clusters formed by RNase-inactive IRE1α are much larger and persist longer than those induced by ER stress. Clustering requires autophosphorylation, and an IRE1α mutant whose RNase domain is responsive to ligands that bind the kinase domain forms yet a third type of stress-independent cluster, with distinct physical properties and half-lives. These data suggest that IRE1α clustering can follow distinct pathways upon activation of the sensor.-Ricci, D., Marrocco, I., Blumenthal, D., Dibos, M., Eletto, D., Vargas, J., Boyle, S., Iwamoto, Y., Chomistek, S., Paton, J. C., Paton, A. W., Argon, Y. Clustering of IRE1α depends on sensing ER stress but not on its RNase activity.

Sex differences in academic rank in allergy/immunology.

BACKGROUND: Female physicians are significantly less likely than male physicians to be full professors, even after accounting for age, experience, specialty, and measures of research and clinical productivity. OBJECTIVE: We sought to evaluate sex differences in academic rank in the allergy and immunology workforce. METHODS: We used a cross-sectional physician data set containing the allergist's sex, age, years since residency, faculty appointment, authored publications, National Institutes of Health (NIH) funding, clinical trial investigation, and Medicare reimbursement to investigate sex differences in the academic allergy and immunology workforce using multilevel logistic regression models. RESULTS: Among 507 academic allergists (9.3% of practicing US allergists in 2014), 323 (63.7%) were men, and 184 (36.3%) were women. Female allergists were younger (47.9 vs 56.9 years, P < .001), had fewer total (12.5 vs 28.7, P < .001) and first/last author (8.0 vs 21.5, P < .001) average publications, were less likely to have NIH funding (13.0% vs 23.5%, P = .004), were less frequently a clinical trial investigator (10.3% vs 16.1%, P = .07), and generated less average annual Medicare revenue ($44,000 vs $23,000, P = .10). Of 152 (30.0%) full professors, 126 (82.9%) were male, and 26 (17.0%) were female. After multivariable adjustment, rates of full professorship among female and male allergists were not significantly different (absolute adjusted difference for female vs male allergists, 6.0%; 95% CI, -8.3% to 20.2%). CONCLUSIONS: Among allergists with US medical school faculty appointments, men and women were similarly likely to be full professors after accounting for factors influencing promotion. Underlying differences in research productivity and NIH funding not explained by age differences alone warrant additional investigation.

High index contrast photonic platforms for on-chip Raman spectroscopy.

Nanophotonic waveguide enhanced Raman spectroscopy (NWERS) is a sensing technique that uses a highly confined waveguide mode to excite and collect the Raman scattered signal from molecules in close vicinity of the waveguide. The most important parameters defining the figure of merit of an NWERS sensor include its ability to collect the Raman signal from an analyte, i.e. "the Raman conversion efficiency" and the amount of "Raman background" generated from the guiding material. Here, we compare different photonic integrated circuit (PIC) platforms capable of on-chip Raman sensing in terms of the aforementioned parameters. Among the four photonic platforms under study, tantalum oxide and silicon nitride waveguides exhibit high signal collection efficiency and low Raman background. In contrast, the performance of titania and alumina waveguides suffers from a strong Raman background and a weak signal collection efficiency, respectively.