Explore the vast range of titles available.

\"Los Angeles has a tantalizing hold on the American imagination. Its self-magnifying myths encompass Hollywood glamour, Arcadian landscapes, and endless summer, but also the apocalyptic undertow of riots, environmental depredation, and natural disaster. This Companion traces the evolution of Los Angeles as the most public staging of the American Dream - and American nightmares. The expert contributors make exciting, innovative connections among the authors and texts inspired by the city, covering the early Spanish settlers, African American writers, the British and German expatriates of the 1930s and 1940s, Latino, and Asian LA literature. The genres discussed include crime novels, science fiction, Hollywood novels, literary responses to urban rebellion, the poetry scene, nature writing, and the most influential non-fiction accounts of the region. Diverse, vibrant, and challenging as the city itself, this Companion is the definitive guide to LA in literature\"--Provided by publisher.

Since the emergence of SARS-CoV-2, vaccines targeting COVID-19 have been developed with unprecedented speed and efficiency. CoronaVac, utilising an inactivated form of the COVID-19 virus and the mRNA26 based Pfizer/BNT162b2 vaccines are widely distributed. Beyond the ability of vaccines to induce production of neutralizing antibodies, they might lead to the generation of antibodies attenuating the disease by recruiting cytotoxic and opsonophagocytic functions. However, the Fc-effector functions of vaccine induced antibodies are much less studied than virus neutralization. Here, using systems serology, we follow the longitudinal Fc-effector profiles induced by CoronaVac and BNT162b2 up until five months following the two-dose vaccine regimen. Compared to BNT162b2, CoronaVac responses wane more slowly, albeit the levels remain lower than that of BNT162b2 recipients throughout the entire observation period. However, mRNA vaccine boosting of CoronaVac responses, including response to the Omicron variant, induce significantly higher peak of antibody functional responses with increased humoral breadth. In summary, we show that vaccine platform-induced humoral responses are not limited to virus neutralization but rather utilise antibody dependent effector functions. We demonstrate that this functionality wanes with different kinetics and can be rescued and expanded via boosting with subsequent homologous and heterologous vaccination. Efficiency of SARS-CoV-2 vaccines has long been attributed to the neutralising capacity of the antibodies that are produced upon prime-boost vaccinations. Here authors show that upon vaccination with CoronaVac and BNT162b2 vaccines in prime-boost regimens, antibodies with Fc-effector functions to enhance cellular and innate immunity are also produced, albeit with different kinetics.

The so-called accretion flow that powers the growth of supermassive black holes in galaxy centres is assumed to be dominated by a smooth, steady flow of very hot plasma, but now observations instead reveal a clumpy accretion of very cold molecular clouds onto a supermassive black hole in the nucleus of a nearby giant elliptical galaxy. Cold gas accretion onto a supermassive black hole The so-called accretion flow that powers the growth of supermassive black holes in galaxy centres is often assumed to be dominated by a smooth, steady flow of very hot plasma, but there is little direct evidence to support this idea. New observations of the Abell 2597 galaxy cluster provide evidence for an alternative model, cold accretion onto black holes, recently predicted by simulations and theory, but not directly observed. The data reveal cold, clumpy molecular clouds falling towards an active supermassive black hole in the nucleus of a nearby giant elliptical galaxy. Supermassive black holes in galaxy centres can grow by the accretion of gas, liberating energy that might regulate star formation on galaxy-wide scales 1 , 2 , 3 . The nature of the gaseous fuel reservoirs that power black hole growth is nevertheless largely unconstrained by observations, and is instead routinely simplified as a smooth, spherical inflow of very hot gas 4 . Recent theory 5 , 6 , 7 and simulations 8 , 9 , 10 instead predict that accretion can be dominated by a stochastic, clumpy distribution of very cold molecular clouds—a departure from the ‘hot mode’ accretion model—although unambiguous observational support for this prediction remains elusive. Here we report observations that reveal a cold, clumpy accretion flow towards a supermassive black hole fuel reservoir in the nucleus of the Abell 2597 Brightest Cluster Galaxy (BCG), a nearby (redshift z  = 0.0821) giant elliptical galaxy surrounded by a dense halo of hot plasma 11 , 12 , 13 . Under the right conditions, thermal instabilities produce a rain of cold clouds that fall towards the galaxy’s centre 14 , sustaining star formation amid a kiloparsec-scale molecular nebula that is found at its core 15 . The observations show that these cold clouds also fuel black hole accretion, revealing ‘shadows’ cast by the molecular clouds as they move inward at about 300 kilometres per second towards the active supermassive black hole, which serves as a bright backlight. Corroborating evidence from prior observations 16 of warmer atomic gas at extremely high spatial resolution 17 , along with simple arguments based on geometry and probability, indicate that these clouds are within the innermost hundred parsecs of the black hole, and falling closer towards it.

Artificial photosynthesis (AP) is a promising method of converting solar energy into fuel (H ₂). Harnessing solar energy to generate H ₂ from H ⁺ is a crucial process in systems for artificial photosynthesis. Widespread application of a device for AP would rely on the use of platinum-free catalysts due to the scarcity of noble metals. Here we report a series of cobalt dithiolene complexes that are exceptionally active for the catalytic reduction of protons in aqueous solvent mixtures. All catalysts perform visible-light-driven reduction of protons from water when paired with [Formula] as the photosensitizer and ascorbic acid as the sacrificial donor. Photocatalysts with electron withdrawing groups exhibit the highest activity with turnovers up to 9,000 with respect to catalyst. The same complexes are also active electrocatalysts in 1∶1 acetonitrile/water. The electrocatalytic mechanism is proposed to be ECEC, where the Co dithiolene catalysts undergo rapid protonation once they are reduced to [Formula]. Subsequent reduction and reaction with H ⁺ lead to H ₂ formation. Cobalt dithiolene complexes thus represent a new group of active catalysts for the reduction of protons.

To determine the effects of long-chain omega-3 (LCn-3) fatty acids found in fish oil, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on cortical blood oxygen level-dependent (BOLD) activity during a working memory task in older adults with subjective memory impairment. Randomized, double-blind, placebo-controlled study. Academic medical center. Healthy older adults (62–80 years) with subjective memory impairment, but not meeting criteria for mild cognitive impairment or dementia. Fish oil (EPA+DHA: 2.4 g/d, n=11) or placebo (corn oil, n=10) for 24 weeks. Cortical BOLD response patterns during performance of a sequential letter n-back working memory task were determined at baseline and week 24 by functional magnetic resonance imaging (fMRI). At 24 weeks erythrocyte membrane EPA+DHA composition increased significantly from baseline in participants receiving fish oil (+31%, p≤0.0001) but not placebo (−17%, p=0.06). Multivariate modeling of fMRI data identified a significant interaction among treatment, visit, and memory loading in the right cingulate (BA 23/24), and in the right sensorimotor area (BA 3/4). In the fish oil group, BOLD increases at 24 weeks were observed in the right posterior cingulate and left superior frontal regions during memory loading. A region-of-interest analysis indicated that the baseline to endpoint change in posterior cingulate cortex BOLD activity signal was significantly greater in the fish oil group compared with the placebo group during the 1-back (p=0.0003) and 2-back (p=0.0005) conditions. Among all participants, the change in erythrocyte EPA+DHA during the intervention was associated with performance in the 2-back working memory task (p = 0.01), and with cingulate BOLD signal during the 1-back (p = 0.005) with a trend during the 2-back (p = 0.09). Further, cingulate BOLD activity was related to performance in the 2-back condition. Dietary fish oil supplementation increases red blood cell omega-3 content, working memory performance, and BOLD signal in the posterior cingulate cortex during greater working memory load in older adults with subjective memory impairment suggesting enhanced neuronal response to working memory challenge.

The formalin model is widely used for evaluating the effects of analgesic compounds in laboratory animals. Injection of formalin into the hind paw induces a biphasic pain response; the first phase is thought to result from direct activation of primary afferent sensory neurons, whereas the second phase has been proposed to reflect the combined effects of afferent input and central sensitization in the dorsal horn. Here we show that formalin excites sensory neurons by directly activating TRPA1, a cation channel that plays an important role in inflammatory pain. Formalin induced robust calcium influx in cells expressing cloned or native TRPA1 channels, and these responses were attenuated by a previously undescribed TRPA1-selective antagonist. Moreover, sensory neurons from TRPA1-deficient mice lacked formalin sensitivity. At the behavioral level, pharmacologic blockade or genetic ablation of TRPA1 produced marked attenuation of the characteristic flinching, licking, and lifting responses resulting from intraplantar injection of formalin. Our results show that TRPA1 is the principal site of formalin's pain-producing action in vivo, and that activation of this excitatory channel underlies the physiological and behavioral responses associated with this model of pain hypersensitivity.

Galactic clusters on heat Astronomers using the latest generation of orbiting X-ray observatories are making some surprising discoveries, one of which is the relatively slow rate of cooling of gas in the cores of galaxy clusters. The Chandra X-ray observatory is now routinely observing giant cavities in the centre of galaxy clusters, and these may hold the key to this phenomenon. The gaseous halo of the galaxy cluster MS0735.6+7421 has been found to contain two such cavities, caused by interaction between a radio source and the hot gas surrounding it. This is producing the most powerful radio outburst known, and sufficient heat to counteract the expected cooling. The most likely power source is a supermassive black hole. Most of the baryons in galaxy clusters reside between the galaxies in a hot, tenuous gas 1 . The densest gas in their centres should cool and accrete onto giant central galaxies at rates of 10–1,000 solar masses per year 1 . No viable repository for this gas, such as clouds or new stars, has been found 1 . New X-ray observations, however, have revealed far less cooling below X-ray temperatures than expected 2 , altering the previously accepted picture of cooling flows. As a result, most of the gas must be heated to and maintained at temperatures above ∼2 keV (ref. 3 ). The most promising heating mechanism is powerful radio jets emanating from supermassive black holes in the central galaxies of clusters 4 . Here we report the discovery of giant cavities and shock fronts in a distant ( z = 0.22) cluster caused by an interaction between a radio source and the hot gas surrounding it. The energy involved is ∼6 × 10 61 erg, the most powerful radio outburst known. This is enough energy to quench a cooling flow for several Gyr, and to provide ∼1/3 keV per particle of heat to the surrounding cluster.

Reduced functional bladder capacity and concomitant increased micturition frequency (pollakisuria) are common lower urinary tract symptoms associated with conditions such as cystitis, prostatic hyperplasia, neurological disease, and overactive bladder syndrome. These symptoms can profoundly affect the quality of life of afflicted individuals, but available pharmacological treatments are often unsatisfactory. Recent work has demonstrated that the cation channel TRPV4 is highly expressed in urothelial cells and plays a role in sensing the normal filling state of the bladder. In this article, we show that the development of cystitis-induced bladder dysfunction is strongly impaired in Trpv4 -/- mice. Moreover, we describe HC-067047, a previously uncharacterized, potent, and selective TRPV4 antagonist that increases functional bladder capacity and reduces micturition frequency in WT mice and rats with cystitis. HC-067047 did not affect bladder function in Trpv4 -/- mice, demonstrating that its in vivo effects are on target. These results indicate that TRPV4 antagonists may provide a promising means of treating bladder dysfunction.

Background Hypertension management in rural, resource-poor settings is difficult. Detailed understanding of patient, clinician and logistic factors which pose barriers to effective blood pressure control could enable strategies to improve control to be implemented. Methods This cross-sectional, multifactorial, observational study was conducted at four rural Rwandan district hospitals, examining patient, clinician and logistic factors. Questionnaires were administered to consenting adult outpatient hypertensive patients, obtaining information on sociodemographic factors, past management for hypertension, and adherence (by Morisky Medication Adherence 8-item Scale (MMAS-8). Treating clinicians identified local difficulties in providing hypertension management from a standard World Health Organisation list and nominated their preferred treatment regimens. Blood pressure measurements and other clinical data were collected during the study visit and used to determine blood pressure control, according to goals from JNC-8 guidelines. Medication availability and cost at each hospital’s pharmacy were reviewed as logistic barriers to treatment. Results The 112 participating patients were 80% female, with only 41% having completed primary education. Self-reported adherence by the MMAS-8 was high in 77% (86/112) and significantly associated) with literacy, lack of medication side effects and the particular hospital and pharmacy attended (all p  < 0.05). However, of 89 patients with blood pressure data, only 26 (29%) had achieved goal blood pressure. No patient factor were statistically associated with poor blood pressure control. Among 30 participating clinicians, deficiencies in knowledge were evident; 43% (13/30) and 37% (11/30) chose a loop diuretic as their prescribed medication and as an ideal medication, respectively, for a newly diagnosed hypertensive patient without comorbidities, counter to JNC 8 recommendations, and 50% (15/30) identified clinician non-adherence to hypertension guidelines as a barrier. In the pharmacies, common anti-hypertensive medications were affordably available (> 6 out of 8 examined medications available in all pharmacies, cost

Journal Article

Share this book

Add to My Shelf