Picojoule-level supercontinuum generation in thin-film lithium niobate on sapphire.

We demonstrate ultraviolet-to-mid-infrared supercontinuum generation (SCG) inside thin-film lithium niobate (TFLN) on sapphire nanowaveguides. This platform combines wavelength-scale confinement and quasi-phasematched nonlinear interactions with a broad transparency window extending from 350 to 4500 nm. Our approach relies on group-velocity-matched second-harmonic generation, which uses an interplay between saturation and a small phase-mismatch to generate a spectrally broadened fundamental and second harmonic using only a few picojoules of in-coupled fundamental pulse energies. As the on-chip pulse energy is increased to tens of picojoules, these nanowaveguides generate harmonics up to the fifth order by a cascade of sum-frequency mixing processes. For in-coupled pulse energies in excess of 25 picojoules, these harmonics merge together to form a supercontinuum spanning 360-2660 nm. We use the overlap between the first two harmonic spectra to detect f-2f beatnotes of the driving laser directly at the waveguide output, which verifies the coherence of the generated harmonics. These results establish TFLN-on-sapphire as a viable platform for generating ultra-broadband coherent light spanning from the ultraviolet to mid-infrared spectral regions.

Single-mode squeezed-light generation and tomography with an integrated optical parametric oscillator.

Quantum optical technologies promise advances in sensing, computing, and communication. A key resource is squeezed light, where quantum noise is redistributed between optical quadratures. We introduce a monolithic, chip-scale platform that exploits the χ(2) nonlinearity of a thin-film lithium niobate (TFLN) resonator device to efficiently generate squeezed states of light. Our system integrates all essential components-except for the laser and two detectors-on a single chip with an area of one square centimeter, reducing the size, operational complexity, and power consumption associated with conventional setups. Using the balanced homodyne measurement subsystem that we implemented on the same chip, we measure a squeezing of 0.55 decibels and an anti-squeezing of 1.55 decibels. We use 20 milliwatts of input power to generate the parametric oscillator pump field by using second harmonic generation on the same chip. Our work represents a step toward compact and efficient quantum optical systems posed to leverage the rapid advances in integrated nonlinear and quantum photonics.

Integrated frequency-modulated optical parametric oscillator.

Optical frequency combs have revolutionized precision measurement, time-keeping and molecular spectroscopy1-7. A substantial effort has developed around 'microcombs': integrating comb-generating technologies into compact photonic platforms5,7-9. Current approaches for generating these microcombs involve either the electro-optic10 or Kerr mechanisms11. Despite rapid progress, maintaining high efficiency and wide bandwidth remains challenging. Here we introduce a previously unknown class of microcomb-an integrated device that combines electro-optics and parametric amplification to yield a frequency-modulated optical parametric oscillator (FM-OPO). In contrast to the other solutions, it does not form pulses but maintains operational simplicity and highly efficient pump power use with an output resembling a frequency-modulated laser12. We outline the working principles of our device and demonstrate it by fabricating the complete optical system in thin-film lithium niobate. We measure pump-to-comb internal conversion efficiency exceeding 93% (34% out-coupled) over a nearly flat-top spectral distribution spanning about 200 modes (over 1 THz). Compared with an electro-optic comb, the cavity dispersion rather than loss determines the FM-OPO bandwidth, enabling broadband combs with a smaller radio-frequency modulation power. The FM-OPO microcomb offers robust operational dynamics, high efficiency and broad bandwidth, promising compact precision tools for metrology, spectroscopy, telecommunications, sensing and computing.

A Novel Perivesical Fat Rotational Flap as an Alternative to Omental Interposition in Challenging Urological Reconstruction.

OBJECTIVE: To introduce the application of the perivesical fat rotational flap as a substitute for omental interposition during several complex urologic reconstruction. We highlight our technique using a case of salvage prostatectomy after initial high-intensity focused ultrasound for recurrent high-risk prostate cancer requiring future adjuvant radiation treatment. We have also successfully used this technique in the management of recurrent vesicovaginal, colovesical, rectourethral fistulas, and postradiation salvage prostatectomy setting. MATERIALS AND METHODS: Our first patient underwent salvage radical prostatectomy after developing high-risk localized prostate cancer after initial high-intensity focused ultrasound. The prostate was radically resected after stepwise posterior and anterior dissections. A flap of perivesical fat with a wide-based pedicle overlying the bladder dome was developed until it was rotated, positioned, and tethered overlying the anterior rectal wall in a tension-free manner. This perivesical fat interposition may have protected a radiated anterior rectal wall from future complications. In the second case, a recurrent vesicovaginal fistula that persisted for 2years postabdominal hysterectomy was repaired using the robotic approach. After fistula excision, layer closure, and perivesical flap interposition, successful repair was achieved. The third patient, who had a history of colon cancer managed with partial colectomy and radiation, developed a recurrent colovesical fistula, which was successfully repaired. Postrepair, a perivesical flap was developed and secured over the site. RESULTS: In the immediate postoperative follow-up period, there were no surgical complications. Long-term follow-up ranges from 1month to 3years without evidence of complication. CONCLUSION: In cases where omentum interposition is not feasible, our novel technique of a perivesical fat flap is a successful alternative for complex reconstruction.

Integrated quantum optical phase sensor in thin film lithium niobate.

The quantum noise of light, attributed to the random arrival time of photons from a coherent light source, fundamentally limits optical phase sensors. An engineered source of squeezed states suppresses this noise and allows phase detection sensitivity beyond the quantum noise limit (QNL). We need ways to use quantum light within deployable quantum sensors. Here we present a photonic integrated circuit in thin-film lithium niobate that meets these requirements. We use the second-order nonlinearity to produce a squeezed state at the same frequency as the pump light and realize circuit control and sensing with electro-optics. Using 26.2 milliwatts of optical power, we measure (2.7 ± 0.2)% squeezing and apply it to increase the signal-to-noise ratio of phase measurement. We anticipate that photonic systems like this, which operate with low power and integrate all of the needed functionality on a single die, will open new opportunities for quantum optical sensing.

Tracking water dimers in ambient nanocapsules by vibrational spectroscopy.

Nanoconfined few-molecule water clusters are invaluable systems to study fundamental aspects of hydrogen bonding. Unfortunately, most experiments on water clusters must be performed at cryogenic temperatures. Probing water clusters in noncryogenic systems is however crucial to understand the behavior of confined water in atmospheric or biological settings, but such systems usually require either complex synthesis and/or introduce many confounding external bonds to the clusters. Here, we show that combining Raman spectroscopy with the molecular nanocapsule cucurbituril is a powerful technique to sequester and analyze water clusters in ambient conditions. We observe sharp peaks in vibrational spectra arising from a single rigid confined water dimer. The high resolution and rich information in these vibrational spectra allow us to track specific isotopic exchanges inside the water dimer, verified with density-functional theory and kinetic population modeling. We showcase the versatility of such molecular nanocapsules by tracking water cluster vibrations through systematic changes in confinement size, in temperatures up to 120° C, and in their chemical environment.

Racial Disparities in Opioid Analgesia Administration Among Adult Emergency Department Patients with Abdominal Pain.

INTRODUCTION: Racial disparities in pain management have been reported among emergency department (ED) patients. In this study we evaluated the association between patients' self-identified race/ethnicity and the administration of opioid analgesia among ED patients with abdominal pain, the most common chief complaint for ED presentations in the United States. METHODS: This was a retrospective cohort study of adult (age ≥18 years) patients who presented to the ED of a single center with abdominal pain from January 1, 2019-December 31, 2020. We collected demographic and clinical information, including patients' race and ethnicity, from the electronic health record. The primary outcome was the ED administration of any opioid analgesic (binary). Secondary outcomes included the administration of non-opioid analgesia (binary) and administration of any analgesia (binary). We used logistic regression models to estimate odds ratios (OR) of the association between a patient's race/ethnicity and analgesia administration. Covariates included age, sex, initial pain score, Emergency Severity Index, and ED visits in the prior 30 days. Subgroup analyses were performed in non-pregnant patients, those who underwent any imaging study, were admitted to the hospital, and who underwent surgery within 24 hours of ED arrival. RESULTS: We studied 7,367 patients: 45% (3,314) were non-Hispanic (NH) White; 28% (2,092) were Hispanic/Latinx; 19% (1,384) were NH Black, and 8% (577) were Asian. Overall, 44% (3,207) of patients received opioid analgesia. In multivariable regression models, non-White patients were less likely to receive opioid analgesia compared with White patients (OR 0.73, 95% CI 0.65-0.83 for Hispanic/Latinx patients; OR 0.62, 95% CI 0.54-0.72 for Black patients; and OR 0.64, 95% CI 0.52-0.78 for Asian patients). Black patients were also less likely to receive non-opioid analgesia, and Black and Hispanic/Latinx patients were less likely than White patients to receive any analgesia. The associations were similar across subgroups; however, the association was attenuated among patients who underwent surgery within 24 hours of ED arrival. CONCLUSION: Hispanic/Latinx, Black, and Asian patients were significantly less likely to receive opioid analgesia than White patients when presenting to the ED with abdominal pain. Black patients were also less likely than White patients to receive non-opioid analgesia.

Ultra-broadband mid-infrared generation in dispersion-engineered thin-film lithium niobate.

Thin-film lithium niobate (TFLN) is an emerging platform for compact, low-power nonlinear-optical devices, and has been used extensively for near-infrared frequency conversion. Recent work has extended these devices to mid-infrared wavelengths, where broadly tunable sources may be used for chemical sensing. To this end, we demonstrate efficient and broadband difference frequency generation between a fixed 1-µm pump and a tunable telecom source in uniformly-poled TFLN-on-sapphire by harnessing the dispersion-engineering available in tightly-confining waveguides. We show a simultaneous 1-2 order-of-magnitude improvement in conversion efficiency and ∼5-fold enhancement of operating bandwidth for mid-infrared generation when compared to equal-length conventional lithium niobate waveguides. We also examine the effects of mid-infrared loss from surface-adsorbed water on the performance of these devices.

High-efficiency second harmonic generation of blue light on thin-film lithium niobate.

The strength of interactions between photons in a χ(2) nonlinear optical waveguide increases at shorter wavelengths. These larger interactions enable coherent spectral translation and light generation at a lower power, over a broader bandwidth, and in a smaller device: all of which open the door to new technologies spanning fields from classical to quantum optics. Stronger interactions may also grant access to new regimes of quantum optics to be explored at the few-photon level. One promising platform that could enable these advances is thin-film lithium niobate (TFLN), due to its broad optical transparency window and possibility for quasi-phase matching and dispersion engineering. In this Letter, we demonstrate second harmonic generation of blue light on an integrated thin-film lithium niobate waveguide and observe a conversion efficiency of η0 = 33, 000%/W-cm2, significantly exceeding previous demonstrations.

Evidence for line width and carrier screening effects on excitonic valley relaxation in 2D semiconductors.

Monolayers of transition metal dichalcogenides (TMDC) have recently emerged as excellent platforms for exploiting new physics and applications relying on electronic valley degrees of freedom in two-dimensional (2D) systems. Here, we demonstrate that Coulomb screening by 2D carriers plays a critical role in excitonic valley pseudospin relaxation processes in naturally carrier-doped WSe2 monolayers (1L-WSe2). The exciton valley relaxation times were examined using polarization- and time-resolved photoluminescence spectroscopy at temperatures ranging from 10 to 160 K. We show that the temperature-dependent exciton valley relaxation times in 1L-WSe2 under various exciton and carrier densities can be understood using a unified framework of intervalley exciton scattering via momentum-dependent long-range electron-hole exchange interactions screened by 2D carriers that depend on the carrier density and the exciton linewidth. Moreover, the developed framework was successfully applied to engineer the valley polarization of excitons in 1L-WSe2. These findings may facilitate the development of TMDC-based opto-valleytronic devices.

Altering the Anti-inflammatory Lipoxin Microenvironment: a New Insight into Kaposi's Sarcoma-Associated Herpesvirus Pathogenesis.

Lipoxins are host anti-inflammatory molecules that play a vital role in restoring tissue homeostasis. The efficacy of lipoxins and their analog epilipoxins in treating inflammation and its associated diseases has been well documented. Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL) are two well-known inflammation related diseases caused by Kaposi's sarcoma-associated herpesvirus (KSHV). Controlling inflammation is one of the strategies adopted to treat KS and PEL, a primary motivation for exploring and evaluating the therapeutic potential of using lipoxins. This study documents how KSHV manipulates and downregulates the secretion of the anti-inflammatory lipoxin A4 in host cells and the viral factors involved in this process using in vitro KS and PEL cells as models. The presence of the lipoxin A4 receptor/formyl peptidyl receptor (ALX/FPR) in KS patient tissue sections and in vitro KS and PEL cell models offers a novel possibility for treating KS and PEL with lipoxins. Treating de novo KSHV-infected endothelial cells with lipoxin and epilipoxin creates an anti-inflammatory environment by decreasing the levels of NF-κB, AKT, ERK1/2, COX-2, and 5-lipoxygenase. Lipoxin treatment on CRISPR/CAS9 technology-mediated ALX/FPR gene deletion revealed the importance of the lipoxin receptor ALX for effective lipoxin signaling. A viral microRNA (miRNA) cluster was identified as the primary factor contributing to the downregulation of lipoxin A4 secretion in host cells. The KSHV miRNA cluster probably targets enzyme 15-lipoxygenase, which is involved in lipoxin A4 synthesis. This study provides a new insight into the potential treatment of KS and PEL using nature's own anti-inflammatory molecule, lipoxin. IMPORTANCE: KSHV infection has been shown to upregulate several host proinflammatory factors, which aid in its survival and pathogenesis. The influence of KSHV infection on anti-inflammatory molecules is not well studied. Since current treatment methods for KS and PEL are fraught with unwanted side effects and low efficiency, the search for new therapeutics is therefore imperative. The use of nature's own molecule lipoxin as a drug is promising. This study opens up new domains in KSHV research focusing on how the virus modulates lipoxin secretion and warrants further investigation of the therapeutic potential of lipoxin using in vitro cell models for KS and PEL.

The effect of hematocrit on in vitro bilirubin photoalteration.

BACKGROUND: Phototherapy using light in the spectral range of 410-500 nm, which overlaps the absorption of bilirubin, is the common treatment for neonatal hyperbilirubinemia. Hemoglobin (Hb) absorbs light strongly throughout this same range and thus can compete with bilirubin for this light and consequently reduce the efficacy of phototherapy. Here, we determined the effect of hematocrit (Hct) on in vitro bilirubin photoalteration using narrow-band blue (450 nm) light-emitting diodes (LEDs). METHODS: Suspensions with Hcts from 0 to 80% and 16 ± 1 mg/dl bilirubin were prepared by mixing red blood cells (RBCs), bilirubin (30 mg/dl) in 4% human serum albumin, and normal saline. Aliquots of each suspension were exposed to blue light at equal irradiances. Before and after 60 min of exposure, bilirubin levels in supernatants (n = 46) were measured using a diazo-dye method. RESULTS: Bilirubin photoalteration steeply decreased by ~60% as Hct increased from 0 to 10%. Over the clinically relevant range of 30-70% Hct, the decrease was significant, but less drastic, exhibiting a quasi-linear dependence on Hct. CONCLUSION: Bilirubin photoalteration under blue light in vitro is significantly reduced as Hct increases. Clinical studies are warranted to confirm these in vitro observations that Hct can affect the efficacy of phototherapy.

Pouring and running a protein gel by reusing commercial cassettes.

The evaluation of proteins using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis is a common technique used by biochemistry and molecular biology researchers. For laboratories that perform daily analyses of proteins, the cost of commercially available polyacrylamide gels (~$10/gel) can be considerable over time. To mitigate this cost, some researchers prepare their own polyacrylamide gels. Traditional methods of pouring these gels typically utilize specialized equipment and glass gel plates that can be expensive and preclude pouring many gels and storing them for future use. Furthermore, handling of glass plates during cleaning or gel pouring can result in accidental breakage creating a safety hazard, which may preclude their use in undergraduate laboratory classes. Our protocol demonstrates how to pour multiple protein gels simultaneously by recycling Invitrogen Nupage Novex minigel cassettes, and inexpensive materials purchased at a home improvement store. This economical and streamlined method includes a way to store the gels at 4°C for a few weeks. By re-using the plastic gel cassettes from commercially available gels, labs that run frequent protein gels can save significant costs and help the environment. In addition, plastic gel cassettes are extremely resistant to breakage, which makes them ideal for undergraduate laboratory classrooms.