Photonic chip-based low-noise microwave oscillator.

Numerous modern technologies are reliant on the low-phase noise and exquisite timing stability of microwave signals. Substantial progress has been made in the field of microwave photonics, whereby low-noise microwave signals are generated by the down-conversion of ultrastable optical references using a frequency comb1-3. Such systems, however, are constructed with bulk or fibre optics and are difficult to further reduce in size and power consumption. In this work we address this challenge by leveraging advances in integrated photonics to demonstrate low-noise microwave generation via two-point optical frequency division4,5. Narrow-linewidth self-injection-locked integrated lasers6,7 are stabilized to a miniature Fabry-Pérot cavity8, and the frequency gap between the lasers is divided with an efficient dark soliton frequency comb9. The stabilized output of the microcomb is photodetected to produce a microwave signal at 20 GHz with phase noise of -96 dBc Hz-1 at 100 Hz offset frequency that decreases to -135 dBc Hz-1 at 10 kHz offset-values that are unprecedented for an integrated photonic system. All photonic components can be heterogeneously integrated on a single chip, providing a significant advance for the application of photonics to high-precision navigation, communication and timing systems.

Mimicking lightning-induced electrochemistry on the early Earth.

To test the hypothesis that an abiotic Earth and its inert atmosphere could form chemically reactive carbon- and nitrogen-containing compounds, we designed a plasma electrochemical setup to mimic lightning-induced electrochemistry under steady-state conditions of the early Earth. Air-gap electrochemical reactions at air-water-ground interfaces lead to remarkable yields, with up to 40 moles of carbon dioxide being reduced into carbon monoxide and formic acid, and 3 moles of gaseous nitrogen being fixed into nitrate, nitrite, and ammonium ions, per mole of transmitted electrons. Interfaces enable reactants (e.g., minerals) that may have been on land, in lakes, and in oceans to participate in radical and redox reactions, leading to higher yields compared to gas-phase-only reactions. Cloud-to-ground lightning strikes could have generated high concentrations of reactive molecules locally, establishing diverse feedstocks for early life to emerge and survive globally.

Transforming Growth Factor-ß Signaling Guides the Differentiation of Innate Lymphoid Cells in Salivary Glands.

The signals guiding differentiation of innate lymphoid cells (ILCs) within tissues are not well understood. Salivary gland (SG) ILCs as well as liver and intestinal intraepithelial ILC1 have markers that denote tissue residency and transforming growth factor-ß (TGF-ß) imprinting. We deleted Tgfbr2 in cells expressing the ILC and NK marker NKp46 and found that SG ILCs were reduced in number. They lost distinct tissue markers, such as CD49a, and the effector molecules TRAIL and CD73. Expression of the transcription factor Eomes, which promotes NK cell differentiation, was elevated. Conversely, Eomes deletion in NKp46(+) cells enhanced TGF-ß-imprinting of SG ILCs. Thus, TGF-ß induces SG ILC differentiation by suppressing Eomes. TGF-ß acted through a JNK-dependent, Smad4-independent pathway. Transcriptome analysis demonstrated that SG ILCs had characteristic of both NK cells and ILC1. Finally, TGF-ß imprinting of SG ILCs was synchronized with SG development, highlighting the impact of tissue microenvironment on ILC development.

AlInAsSb Geiger-mode SWIR and eSWIR SPADs with high avalanche probability.

Single-photon avalanche diodes (SPADs) that are sensitive to photons in the Short-wave infrared and extended short-wave infrared (SWIR and eSWIR) spectra are important components for communication, ranging, and low-light level imaging. The high gain, low excess noise factor, and widely tunable bandgap of AlxIn1-xAsySb1-y avalanche photodiodes (APDs) make them a suitable candidate for these applications. In this work, we report single-photon-counting results for a separate absorption, charge, and multiplication (SACM) Geiger-mode SPAD within a gated-quenching circuit. The single-photon avalanche probabilities surpass 80% at 80 K, corresponding with single-photon detection efficiencies of 33% and 12% at 1.55 µm and 2 µm, respectively.

Agricultural insect pests as models for studying stress-induced evolutionary processes.

Agricultural insect pests (AIPs) are widely successful in adapting to natural and anthropogenic stressors, repeatedly overcoming population bottlenecks and acquiring resistance to intensive management practices. Although they have been largely overlooked in evolutionary studies, AIPs are ideal systems for understanding rapid adaptation under novel environmental conditions. Researchers have identified several genomic mechanisms that likely contribute to adaptive stress responses, including positive selection on de novo mutations, polygenic selection on standing allelic variation and phenotypic plasticity (e.g., hormesis). However, new theory suggests that stress itself may induce epigenetic modifications, which may confer heritable physiological changes (i.e., stress-resistant phenotypes). In this perspective, we discuss how environmental stress from agricultural management generates the epigenetic and genetic modifications that are associated with rapid adaptation in AIPs. We summarise existing evidence for stress-induced evolutionary processes in the context of insecticide resistance. Ultimately, we propose that studying AIPs offers new opportunities and resources for advancing our knowledge of stress-induced evolution.

Genetic diversity of astroviruses detected in wild aquatic birds in Hong Kong.

Wild waterfowl serve as a reservoir of some astroviruses. Fecal samples from wild waterfowl collected at Hong Kong's Marshes were tested using pan-astrovirus reverse transcription-PCR. Positive samples underwent subsequent host identification using DNA barcoding. Based on deduced partial sequences, noteworthy samples from three astrovirus groups (mammalian, avian and unclassified astroviruses) were further analyzed by next-generation sequencing. One sample of Avastrovirus 4 clade, MP22-196, had a nearly complete genome identified. The results of ORF2 phylogenetic analysis and genetic distance analysis indicate that Avastrovirus 4 is classified as a distinct subclade within Avastrovirus. MP22-196 has typical astrovirus genome characteristics. The unique characteristics and potential differences of this genome, compared to other avian astrovirus sequences, involve the identification of a modified sgRNA sequence situated near the ORF2 start codon, which precedes the ORF1b stop codon. Additionally, the 3' UTR of MP22-196 is shorter than other avian astroviruses. This study expands our understanding of the Avastrovirus 4 clade.

A de novo mutation in CACNA1A is associated with autosomal dominant bovine familial convulsions and ataxia in Angus cattle.

Bovine familial convulsions and ataxia (BFCA) is considered an autosomal dominant syndrome with incomplete penetrance. Nine Angus calves from the same herd were diagnosed with BFCA within days of birth. Necropsy revealed cerebellar and spinal cord lesions associated with the condition. Parentage testing confirmed that all affected calves had a common sire. The sire was then bred to 36 cows across two herds using artificial insemination, producing an additional 14 affected calves. The objective of this investigation was to identify hypothesized dominant genetic variation underlying the condition. Whole-genome sequencing was performed on the sire, six affected and seven unaffected paternal half-sibling calves and combined with data from 135 unrelated controls. The sire and five of the six affected calves were heterozygous for a nonsense variant (Chr7 g.12367906C>T, c.5073C>T, p.Arg1681*) in CACNA1A. The other affected calves (N = 8) were heterozygous for the variant but it was absent in the other unaffected calves (N = 7) and parents of the sire. This variant was also absent in sequence data from over 6500 other cattle obtained via public repositories and collaborator projects. The variant in CACNA1A is expressed in the cerebellum of the ataxic calves as detected in the transcriptome and was not differentially expressed compared with controls. The CACNA1A protein is part of a highly expressed cerebellar calcium voltage gated channel. The nonsense variant is proposed to cause haploinsufficiency, preventing proper transmission of neuronal signals through the channel and resulting in BFCA.

Efficacy of root-end filling techniques using premixed putty type bioceramic cements: an ex vivo study.

OBJECTIVES: Currently, premixed putty-type bioceramic cements (PPBCs) have become popular materials for root-end fillings. This study investigated three root-end filling techniques using PPBCs and calcium silicate-based sealers including EDTA pretreatment. MATERIALS AND METHODS: Ninety root segments were prepared and standardized with an artificial fin and lateral canal, and assigned to three groups (n = 30). Root-end fillings were placed using BC-RRM Putty alone (Group PA), injection of BC sealer followed by BC-RRM Putty (Lid Technique: Group LT) or BC-RRM Putty with BC sealer coating (Deep putty packing technique: Group DP). Half of each group was pretreated with 17% EDTA. The radiographic images of the specimens were assessed by five graders and push-out bond strength tests were conducted. The data were analyzed with a general linear model including two-way ANOVA and chi-square test at a significance level of 5%. RESULTS: DP approach demonstrated significantly higher bond strength than LT (P < 0.05). However, there was no statistically significant difference in bond strength between PA and either DP or LT. EDTA pretreatment had no significant effect on push-out bond strength. Radiographically, for the main canal, PA and DP scored significantly higher than LT. In the fin, PA scored significantly higher than others (P < 0.05). CONCLUSION: Our study highlights variations in root-end filling techniques. Injecting a bulk of bioceramic sealer before the placement of PPBCs may reduce bond strength and radiopacity. The application of PPBCs alone or in the deep putty technique demonstrates potential for favorable outcomes. EDTA pretreatment did not enhance bond-strength. CLINICAL RELEVANCE: Careful selection and application of bioceramic materials and techniques in root-end fillings may influence the outcome of endodontic root-end surgery. When PPBCs and calcium silicate-based sealers are used together for root-end fillings, sealer followed by deep putty application may offer improved bond strength and radiographic fill compared to the lid technique.

Thermal dissipation enhancement in flip-chip bonded uni-traveling carrier photodiodes.

The thermal properties of modified uni-traveling carrier (MUTC) photodiode flip-chip bonded to AlN and diamond are simulated. The thermal impedance of InGaAs is the primary source of internal heating. An n-down epitaxial structure is designed to improve thermal dissipation. Compared to the conventional p-down configuration, the n-down MUTCs bonded to diamond, or AlN submounts achieved 145% and 110% improvement in dissipated power density at thermal failure, respectively. The improved thermal characteristics presage higher RF output power before thermal failure.

Dehydropolymerization of Amine-Boranes using Bis(imino)pyridine Rhodium Pre-Catalysis: σ-Amine-Borane Complexes, Nanoparticles, and Low Residual-Metal BN-Polymers that can be Chemically Repurposed.

The sigma amine-borane complexes [Rh(L1)(η2 :η2 -H3 B⋅NRH2 )][OTf] (L1=2,6-bis-[1-(2,6-diisopropylphenylimino)ethyl]pyridine, R=Me, Et, n Pr) are described, alongside [Rh(L1)(NMeH2 )][OTf]. Using R=Me as a pre-catalyst (1 mol %) the dehydropolymerization of H3 B ⋅ NMeH2 gives [H2 BNMeH]n selectively. Added NMeH2 , or the direct use of [Rh(L1)(NMeH2 )][OTf], is required for initiation of catalysis, which is suggested to operate through the formation of a neutral hydride complex, Rh(L1)H. The formation of small (1-5 nm) nanoparticles is observed at the end of catalysis, but studies are ambiguous as to whether the catalysis is solely nanoparticle promoted or if there is a molecular homogeneous component. [Rh(L1)(NMeH2 )][OTf] is shown to operate at 0.025 mol % loadings on a 2 g scale of H3 B ⋅ NMeH2 to give polyaminoborane [H2 BNMeH]n [Mn =30,900 g/mol, Ð=1.8] that can be purified to a low residual [Rh] (6 µg/g). Addition of Na[N(SiMe3 )2 ] to [H2 BNMeH]n results in selective depolymerization to form the eee-isomer of N,N,N-trimethylcyclotriborazane [H2 BNMeH]3 : the chemical repurposing of a main-group polymer.

Considerations for excess noise measurements of low-k-factor Sb-based avalanche photodiodes.

In applications where high sensitivity is required, the internal gain mechanism of avalanche photodiodes can provide a performance advantage relative to p-i-n photodiodes. However, this internal gain mechanism leads to an excess noise that scales with gain. This excess noise term can be minimized by using materials systems in which impact ionization is initiated primarily by one carrier type. Recently, two Sb-based materials systems, AlInAsSb and AlGaAsSb, have exhibited exceptionally low excess noise, particularly for III-V compound materials. There are four important considerations that can impact the excess noise measurements in such low-noise materials. These considerations deal with the excess noise factor calculation method, measurement RF frequency, measurement wavelength, and the gain calculation method. In this paper, each of these factors is discussed, and their implications on excess noise are considered.

Effect of Material and Pad Abrasion on Shear Bond Strength of 3D-Printed Orthodontic Brackets.

OBJECTIVE: To investigate the effect of printing material and air abrasion of bracket pads on the shear bond strength of 3D-printed plastic orthodontic brackets when bonded to the enamel of extracted human teeth. MATERIALS AND METHODS: Premolar brackets were 3D-printed using the design of a commercially available plastic bracket in two biocompatible resins: Dental LT Resin and Dental SG Resin (n = 40/material). 3D-printed brackets and commercially manufactured plastic brackets were divided into two groups (n = 20/group), one of which was air abraded. All brackets were bonded to extracted human premolars, and shear bond strength tests were performed. The failure types of each sample were classified using a 5-category modified adhesive remnant index (ARI) scoring system. RESULTS: Bracket material and bracket pad surface treatment presented statistically significant effects for shear bond strengths, and a significant interaction effect between bracket material and bracket pad surface treatment was observed. The non-air abraded (NAA) SG group (8.87 ± 0.64 MPa) had a statistically significantly lower shear bond strength than the air abraded (AA) SG group (12.09 ± 1.23 MPa). In the manufactured brackets and LT Resin groups, the NAA and AA groups were not statistically significantly different within each resin. A significant effect of bracket material and bracket pad surface treatment on ARI score was observed, but no significant interaction effect between bracket material and pad treatment was found. CONCLUSION: 3D-printed orthodontic brackets presented clinically sufficient shear bond strengths both with and without AA prior to bonding. The effect of bracket pad AA on shear bond strength depends on the bracket material.

Narrow bandgap Al0.15In0.85As0.77Sb0.23 for mid-infrared photodetectors.

Mid-IR is a useful wavelength range for both science and military applications due to its low atmospheric attenuation and ability to be used for passive detection. However, many solutions for detecting light in this spectral region need to be operated at cryogenic temperatures as their required narrow bandgaps suffer from carrier recombination and band-to-band tunneling at room temperature leading to high dark currents. These problems can be alleviated by using a separate absorption, charge, and multiplication avalanche photodiode. We have recently demonstrated such a device with a 3-µm cutoff using Al0.15In0.85As0.77Sb0.23, as the absorber, grown on GaSb. Here we investigate Al0.15In0.85As0.77Sb0.23 as a simple PIN homojunction and provide metrics to aid in future designs using this material. PL spectrum measurements indicate a bandgap of 2.94 µm at 300 K. External quantum efficiencies of 39% and 33% are achieved at 1.55 µm and 2 µm respectively. Between 180 K and 280 K the activation energy is ∼0.22 eV, roughly half the bandgap of Al0.15In0.85As0.77Sb0.23, indicating thermal generation is dominant.

Frequency behavior of AlInAsSb nBn photodetectors and the development of an equivalent circuit model.

We report the frequency response of Al0.3InAsSb/Al0.7InAsSb nBn photodetectors. The 3-dB bandwidth of the devices varies from ∼ 150 MHz to ∼ 700 MHz with different device diameters and saturates with bias voltage immediately after the device turn on. A new equivalent circuit model is developed to explain the frequency behavior of nBn photodetectors. The simulated bandwidth based on the new equivalent circuit model agrees well with the bandwidth and the microwave scattering parameter measurements. The analysis reveals that the limiting factor of the bandwidth of the nBn photodetector is the large diffusion capacitance caused by the minority carrier lifetime and the device area. Additionally, the bandwidth of the nBn photodetector is barely affected by the photocurrent, which is found to be caused by the barrier structure in the nBn photodetector.

Near 100% external quantum efficiency 1550-nm broad spectrum photodetector.

We report InGaAs/InP based p-i-n photodiodes with an external quantum efficiency (EQE) above 98% from 1510 nm to 1575 nm. For surface normal photodiodes with a diameter of 80 µm, the measured 3-dB bandwidth is 3 GHz. The saturation current is 30.5 mA, with an RF output power of 9.3 dBm at a bias of -17 V at 3 GHz.

Comparison of Preoperative Alpha-blockade for Resection of Paraganglioma and Pheochromocytoma.

OBJECTIVE: Phenoxybenzamine (nonselective, noncompetitive alpha-blocker) is the preferred drug for preoperative treatment of pheochromocytoma, but doxazosin (selective, competitive alpha-blocker) may be equally effective. We compared the efficacy of doxazosin vs phenoxybenzamine. METHODS: We conducted a prospective study of patients undergoing pheochromocytoma or paraganglioma resection by randomizing pretreatment with phenoxybenzamine or doxazosin at a single tertiary referral center. The high cost of phenoxybenzamine led to high crossover to doxazosin. Randomization was halted, and a consecutive historical cohort of phenoxybenzamine patients was included for a case-control study design. The efficacy of alpha-blockade was assessed with preinduction infusion of incremental doses of phenylephrine. The primary outcomes were mortality, cardiovascular complications, and intensive care unit admission. The secondary outcomes were hemodynamic instability index (proportion of operation outside of hemodynamic goals), adequacy of blockade by the phenylephrine titration test, and drug costs. RESULTS: Twenty-four patients were prospectively enrolled (doxazosin, n = 20; phenoxybenzamine, n = 4), and 15 historical patients treated with phenoxybenzamine were added (total phenoxybenzamine, n = 19). No major cardiovascular complications occurred in either group. The phenylephrine dose-response curves showed less blood pressure rise in the phenoxybenzamine than in the doxazosin group (linear regression coefficient = 0.008 vs 0.018, P = .01), suggesting better alpha-blockade in the phenoxybenzamine group. The median hemodynamic instability index was 14% vs 13% in the phenoxybenzamine and doxazosin groups, respectively (P = .56). The median highest daily cost of phenoxybenzamine was $442.20 compared to $5.06 for doxazosin. CONCLUSION: Phenoxybenzamine may blunt intraoperative hypertension better than doxazosin, but this difference did not translate to fewer cardiovascular complications and is offset by a considerably increased cost.

Fracture resistance of cement-retained and screw-cement-retained milled posterior crowns with screw-access hole preparations before and after firing: An in vitro study.

STATEMENT OF PROBLEM: When a cement-retained lithium disilicate crown needs to be removed, perforation is needed to reach the abutment screw. How this process affects its strength is unclear. PURPOSE: The purpose of this in vitro study was to evaluate the fracture strength of milled lithium disilicate implant crowns with screw-access holes created before and after the firing stages. MATERIAL AND METHODS: Nine implant replicas with stock abutments were embedded in acrylic resin. Forty-five lithium disilicate (IPS e.max CAD) crowns were designed, milled, and divided into groups. The control group had no screw access, the blue state group had the screw access created in the intermediate phase of the ceramic, and the postfiring group had the screw access created after firing. The crowns were cemented with a self-adhesive resin cement, placed in an incubator for 24 hours and then thermocycled. The screw-access holes were sealed with composite resin. The crowns were loaded to failure with a universal testing machine using a 1- mm-diameter ball at a crosshead speed of 0.5 mm/min and a 5-kN cell load. Data were analyzed by ANOVA and the Tukey post hoc test (α=.05). RESULTS: Screw-access holes created before and after firing stages had a significant effect on the fracture resistance of lithium disilicate crowns (P=.002). No difference in fracture resistance was observed between the control group and the blue state group (P>.05), while the fracture resistance of the postfiring group was significantly lower than that of the control group and the blue state group (P<.05). CONCLUSIONS: The fracture strength of lithium disilicate crowns was not affected by a screw-access hole created during the blue state of the ceramic followed by repair with composite resin. Creating a screw-access hole after firing the ceramic reduced fracture strength.

Room-temperature bandwidth of 2-µm AlInAsSb avalanche photodiodes.

We investigate the room-temperature bandwidth performance of AlInAsSb avalanche photodiodes under 2-µm illumination. Parameter characterization denotes RC-limited performance. While measurements indicate a maximum gain-bandwidth product of 44 GHz for a 60-µm-diameter device, we scale this performance to smaller device sizes based on the RC response. For a 15-µm-diameter device, we predict a maximum gain-bandwidth product of approximately 144 GHz based on the reported measurements.

Lineage Switch in an Infant B-Lymphoblastic Leukemia With t(1;11)(p32;q23); KMT2A/EPS15, Following Blinatumomab Therapy.

We report a 6 month-old infant girl with t(1;11)(p32;q23), KMT2A/EPS15-rearranged B-acute lymphoblastic leukemia (B-ALL) that was refractory to traditional ALL-directed chemotherapy. Following administration of blinatumomab, she experienced lineage switch from B-ALL to acute myeloid leukemia (AML). Myeloid-directed chemotherapy resulted in clearance of AML by flow cytometry, though a residual CD19+ B-ALL population persisted (0.14%). Following bridging blinatumomab, the patient achieved B-ALL and AML remission, as measured by flow cytometry. The patient subsequently underwent allogeneic hematopoietic stem cell transplant. Unfortunately, she relapsed with CD19+ B-ALL one-month post-transplantation. Next generation sequencing study of IGH/IGL using ClonoSEQ® analysis detected 3 dominant sequences all present in her original B-ALL, lineage switched AML, and post-transplant relapsed B-ALL, though the latter showed an additional 4 sequences, three of which were present at low abundance in the original diagnostic sample. The presence of the same clones throughout her disease course suggests cellular reprogramming and differentiation following chemotherapy and immunotherapy. This is the first reported case of lineage switch of B-ALL with t(1;11) and also the first report of a lineage switch case that used ClonoSEQ® to define the clonality of the original B-ALL, lineage switched AML, and relapsed B-ALL.

Wear Resistance of 3D Printed and Prefabricated Denture Teeth Opposing Zirconia.

PURPOSE: To evaluate the wear resistance of a recently developed three-dimensional (3D) printed denture teeth resin compared to three commercially available prefabricated denture teeth. MATERIALS AND METHODS: A total of 88 maxillary first molar denture teeth were evaluated: C (Classic; Dentsply Sirona, York, PA), DCL (SR Postaris DCL; Ivoclar Vivadent, Schaan, Liechtenstein), IPN (Portrait IPN; Dentsply Sirona, York, PA), and F (Denture Teeth A2 Resin 1 L; Formlabs, Somerville, MA). The 3D printed denture tooth specimens were fabricated from a methacrylate-based photopolymerizing resin using stereolithography (SLA). Denture teeth were subjected to a three-body wear test with a poly(methylmethacrylate) (PMMA) abrasive slurry. A Leinfelder-style four station wear apparatus with custom bullet-shaped milled zirconia styli was utilized with a load force of 36-40 N at 1.7 Hz for 200,000 cycles. Maximum depth of wear was measured using a lab grade scanner and analyzing software program. Data were analyzed using a one-way ANOVA followed by the Tukey's Multiple Comparisons post hoc test (α = 0.05). RESULTS: A statistically significant difference in depth of wear was found between denture tooth materials (p < 0.001). The mean vertical depth of wear for the 3D printed denture teeth (0.016 ± 0.010 mm) was statistically significantly less than the prefabricated denture teeth. The highly cross-linked denture teeth, DCL (0.036 ± 0.011 mm) and IPN (0.035 ± 0.014 mm), exhibited statistically significantly less wear than the conventional acrylic denture teeth. The conventional acrylic denture teeth demonstrated the greatest wear (0.058 ± 0.014 mm). No significant difference in depth of wear was found between DCL and IPN (p > 0.001). CONCLUSIONS: Denture tooth material significantly influences the depth of wear. The 3D printed denture teeth demonstrated superior wear resistance compared to the commercially available prefabricated denture teeth when opposed to zirconia. Denture teeth fabricated with SLA technology may have a promising future in prosthetic dentistry.