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Addressing genome scale design tradeoffs in Pseudomonas putida for bioconversion of an aromatic carbon source
Full text linkGenome-scale metabolic models (GSMM) are commonly used to identify gene deletion sets that result in growth coupling and pairing product formation with substrate utilization and can improve strain performance beyond levels typically accessible using traditional strain engineering approaches. However, sustainable feedstocks pose a challenge due to incomplete high-resolution metabolic data for non-canonical carbon sources required to curate GSMM and identify implementable designs. Here we address a four-gene deletion design in the Pseudomonas putida KT2440 strain for the lignin-derived non-sugar carbon source, p-coumarate (p-CA), that proved challenging to implement. We examine the performance of the fully implemented design for p-coumarate to glutamine, a useful biomanufacturing intermediate. In this study glutamine is then converted to indigoidine, an alternative sustainable pigment and a model heterologous product that is commonly used to colorimetrically quantify glutamine concentration. Through proteomics, promoter-variation, and growth characterization of a fully implemented gene deletion design, we provide evidence that aromatic catabolism in the completed design is rate-limited by fumarase hydratase (FUM) enzyme activity in the citrate cycle and requires careful optimization of another fumarate hydratase protein (PP_0897) expression to achieve growth and production. A double sensitivity analysis also confirmed a strict requirement for fumarate hydratase activity in the strain where all genes in the growth coupling design have been implemented. Metabolic cross-feeding experiments were used to examine the impact of complete removal of the fumarase hydratase reaction and revealed an unanticipated nutrient requirement, suggesting additional functions for this enzyme. While a complete implementation of the design was achieved, this study highlights the challenge of completely inactivating metabolic reactions encoded by under-characterized proteins, especially in the context of multi-gene edits
Mechanically robust surface-degradable implant from fiber silk composites demonstrates regenerative potential.
Full text linkThrough millions of years of evolution, bones have developed a complex and elegant hierarchical structure, utilizing tropocollagen and hydroxyapatite to attain an intricate balance between modulus, strength, and toughness. In this study, continuous fiber silk composites (CFSCs) of large size are prepared to mimic the hierarchical structure of natural bones, through the inheritance of the hierarchical structure of fiber silk and the integration with a polyester matrix. Due to the robust interface between the matrix and fiber silk, CFSCs show maintained stable long-term mechanical performance under wet conditions. During in vivo degradation, this material primarily undergoes host cell-mediated surface degradation, rather than bulk hydrolysis. We demonstrate significant capabilities of CFSCs in promoting vascularization and macrophage differentiation toward repair. A bone defect model further indicates the potential of CFSC for bone graft applications. Our belief is that the material family of CFSCs may promise a novel biomaterial strategy for yet to be achieved excellent regenerative implants
Increasing a Quitline’s Reach to Low-Income Tobacco Users Through 211 Agencies
No full textIntroductionLow-income individuals bear a disproportionate share of the burden of tobacco use. This study tested the feasibility of increasing a quitline's reach to low-income tobacco users by collaborating with 211 information and referral agencies, which primarily serve people experiencing economic hardship.Aims and methodsStudy participants (N = 114 888) were adult tobacco users referred to the California quitline by 211 agencies, referred by healthcare clinics, or self-referred from April 17, 2021 to December 31, 2023. All were offered telephone counseling. Those referred by 211 received $20 for completing one counseling session. A subset (n = 2021) was followed up at 7 months. Referral outcomes, baseline characteristics, counseling and quitting aid utilization, and quitting outcomes were analyzed by referral source in 2024.ResultsOver a 2.7-year period, 211 agencies referred 55 151 clients to the quitline. Participants referred by 211 were more than twice as likely as healthcare-referred participants to enroll in quitline services (34.0% vs. 15.9%, p < .0001). They were more likely than healthcare- and self-referred participants to be female, lesbian, gay, bisexual, transgender, or queer/questioning, Black or multiracial, younger, less educated, and Medicaid-insured; more likely to complete a first counseling session (64.2% vs. 59.7% and 55.7%; both ps < .0001); and completed a similar number of sessions, 2.4. They were less likely to use quitting aids. Quit rates (ie, 30-day point prevalence abstinence) at 7-month follow-up were similar for all three groups.ConclusionsA collaboration between a quitline and 211 agencies connected large numbers of underserved, low-income tobacco users to evidence-based cessation treatment.ImplicationsThe study shows that quitlines and 211 agencies can collaborate effectively to help low-income tobacco users quit. It shows that when offered a modest incentive, 211-referred participants engage in counseling as much as healthcare- and self-referred participants and are as likely to quit. If 211 agencies across the US referred at the same rate as agencies in this study, an estimated 65 000 additional tobacco users annually would receive treatment. Total reach at full implementation would likely be much higher. Quitline and 211 funders and other supporters should find ways to sustain these gains and expand their reach
Nicandro Tamez: compositor vanguardista y pionero de la enseñanza multidisciplinaria de la música
Full text linkPor medio de bibliografía, hemerografía, historia oral, y documentos inéditos, en este artículo busco reconstruir una parte fundamental de la historia de la enseñanza musical en Monterrey, Nuevo León: la contribución pedagógica del filósofo, pianista, compositor y maestro Nicandro Emilio Tamez Tamez (1931-1985), pionero de la educación multidisciplinaria de la música en México. Discípulo de algunos de los más prominentes pedagogos musicales y compositores del siglo XX—como Domingo Lobato, Miguel Bernal Jiménez, y el alemán Gerhart Muench—, Tamez desarrolló una pedagogía musical innovadora, que combinó la enseñanza del arte de los sonidos con la filosofía y las artes, impulsando la participación de sus alumnos en grupos de cámara y estimulando su creatividad por medio del estudio de la composición. Su aproximación multidisciplinaria al estudio de la música se vio consolidada con la creación del programa de licenciatura en música en la Universidad Regiomontana, que modeló a una generación de influyentes músicos de la región
Attosecond time delays in the body frame for photodetachment from molecular anions
Full text linkAttosecond time delays in molecular photoionization at low energies are dominated by the contribution of the Coulomb phase, which diverges as the energy of the photoelectron decreases towards zero. With calculations on core-electron ejection from CN− and C2− we demonstrate that in photodetachment of molecular anions the absence of the long-range Coulomb interaction in the final state can reveal the delays of narrow low-energy shape resonances that do not generally occur in photoionization. Delays of several femtoseconds can be associated with such resonances. The angular dependence of photodetachment time delays in the body frame is highly sensitive to short-range anisotropies in the electron-molecule interaction as well as to the initial state
Salience maps for judgments of frontal plane distance, centroids, numerosity, and letter identity inferred from substance-invariant processing.
Full text linkA salience map is a topographic map that has inputs at each x,y location from many different feature maps and summarizes the combined salience of all those inputs as a real number, salience, which is represented in the map. Of the more than 1 million Google references to salience maps, nearly all use the map for computing the relative priority of visual image components for subsequent processing. We observe that salience processing is an instance of substance-invariant processing, analogous to household measuring cups, weight scales, and measuring tapes, all of which make single-number substance-invariant measurements. Like these devices, the brain also collects material for substance-invariant measurements but by a different mechanism: salience maps that collect visual substances for subsequent measurement. Each salience map can be used by many different measurements. The instruction to attend is implemented by increasing the salience of the to-be-attended items so they can be collected in a salience map and then further processed. Here we show that, beyond processing priority, the following measurement tasks are substance invariant and therefore use salience maps: computing distance in the frontal plane, computing centroids (center of a cluster of items), computing the numerosity of a collection of items, and identifying alphabetic letters. We painstakingly demonstrate that defining items exclusively by color or texture not only is sufficient for these tasks, but that light-dark luminance information significantly improves performance only for letter recognition. Obviously, visual features are represented in the brain but their salience alone is sufficient for these four judgments
Associations of Partnership Types and Quality on Cognitive Performance Among Midlife and Older Sexual Minority Men With or Without HIV
Full text linkPartnership status among sexual minority men (SMM) is a potentially important yet underexplored predictor of cognitive functioning. Using data from the understanding patterns of healthy aging among men who have sex with men substudy of the Multicenter AIDS Cohort Study, we assessed the associations of partnership status and quality with cognitive performance in middle-aged and older SMM, adjusting for sociodemographic and clinical covariates. Partnership status was classified into four types: “only a primary partnership,” “only a secondary partnership,” “both a primary and secondary relationship,” and “neither a primary nor secondary relationship.” Partnership quality was assessed based on perceived support or strain from partners. Cognitive performance was evaluated using the z-scores on the Symbol Digit Modalities Test (SDMT), Trail Making Test Parts A (TMT-A) and B (TMT-B), and a composite Z-score that summed the SDMT, TMT-A, and TMT-B z-scores. Among 1067 participants (median age 60, 85.7% college educated), having a primary partner was associated with better cognitive performance (Z-score composite β^\widehat{\upbeta }= 0.41 [95% CI 0.12–0.70]), TMT-A (β^\widehat{\upbeta }= 0.16 [95% CI 0.02–0.30]), and TMT-B (β^\widehat{\upbeta }= 0.19 [95% CI 0.06–0.33]). Support from secondary partners was also linked to better cognition. Additionally, there was a significant interaction between partnership and HIV status, indicating that SMM with HIV and both primary and secondary partners showed better cognitive outcomes than unpartnered SMM with HIV. These findings suggest that having a primary partner and receiving support from secondary partners may contribute to better cognitive health among middle-aged and older SMM, especially those with HIV
Polariton Condensation in Gap-Confined States of Photonic Crystal Waveguides
Full text linkThe development of patterned multiquantum well heterostructures in GaAs/AlGaAs waveguides has recently made it possible to achieve exciton-polariton condensation in a topologically protected bound state in the continuum (BIC). Polariton condensation was shown to occur above a saddle point of the two-dimensional polariton dispersion in a one-dimensional photonic crystal waveguide. A rigorous analysis of the condensation phenomenon in these systems, as well as the role of the BIC, is still missing. In the present Letter, we theoretically and experimentally fill this gap by showing that polariton confinement resulting from the negative effective mass and the photonic energy gap in the dispersion play a key role in enhancing the relaxation toward the condensed state. In fact, our results show that low-threshold polariton condensation is achieved within the effective trap created by the exciting laser spot, regardless of whether the resulting confined mode is long-lived (polariton BIC) or short-lived (lossy mode). In both cases, the spatial quantization of the polariton condensate and the threshold differences associated to the corresponding state lifetime are measured and characterized. For a given negative mass, a slightly lower condensation threshold from the polariton BIC mode is found and associated to its reduced radiative losses, as compared to the lossy one
Injection mechanisms in a III-nitride light-emitting diode as seen by self-emissive electron microscopy
Full text linkWe report on the investigation of an electrically biased high efficiency green III-nitride light-emitting diode (LED) by electron emission microscopy (EEM) using a low-energy electron microscope (LEEM). The surface of the LED was activated to negative electron affinity via deposition of a submonolayer of Cs. With the illumination column of the LEEM turned off, upon electrical injection of the LED, we directly image the hot electrons generated by eeh Auger-Meitner nonradiative processes that diffuse through the top p-GaN layer and emit out the surface of the biased LED. By determining the source of emitted electrons using complementary electron emission spectroscopy measurements, EEM allows us to effectively map the carrier density within the LED. Using EEM, we observed nonelectron emitting regions with a density of approximately 3×108cm−2, identified as V-shaped defects (V-defects). This is confirmed through the corresponding dark spots of panchromatic cathodoluminescence measurements of the same sample and by plan-view transmission electron microscopy. The absence of electron emission at the sidewall of the V-defects can be attributed to several factors, including reduced carrier density in the sidewall quantum wells due to carriers traveling fast through the semipolar sidewalls before being injected into the planar quantum wells, the reduced population of hot electrons surviving diffusion through the thicker p-GaN filling in the V-defect before emission onto vacuum, and a smaller Auger-Meitner coefficient for the low In content semipolar sidewall quantum wells. The stronger electron emission observed at the ridges of most V-defects compared to the planar quantum well regions indicates larger local injected carrier densities, confirming that V-defect sidewalls allow for strong lateral carrier injection when compared to the weaker vertical injection away from the V-defect as evidenced by the weaker electron emission intensity away from the V-defects