There are few more powerful questions than, "Where are you from" or "Where do you live?"People feel intensely connected to cities as places and to other people who feel that same connection. In order ...to understand place - and understand human settlements generally - it is important to understand that places are not created by accident. They are created in order to further a political or economic agenda. Better cities emerge when the people who shape them think more broadly and consciously about the places they are creating. In Place and Prosperity: How Cities Help Us to Connect and Innovate, urban planning expert William Fulton takes an engaging look at the process by which these decisions about places are made, how cities are engines of prosperity, and how place and prosperity are deeply intertwined. Fulton has been writing about cities over his forty-year career that includes working as a journalist, professor, mayor, planning director, and the director of an urban think tank in one of America's great cities. Place and Prosperity is a curated collection of his writings with new and updated selections and framing material.Though the essays in Place and Prosperity are in some ways personal, drawing on Fulton's experience in learning and writing about cities, their primary purpose is to show how these two ideas - place and prosperity - lie at the heart of what a city is and, by extension, what our society is all about. Fulton shows how, over time, a successful place creates enduring economic assets that don't go away and lay the groundwork for prosperity in the future. But for urbanism to succeed, all of us have to participate in making cities great places for everybody. Because cities, imposing though they may be as physical environments, don't work without us. Cities are resilient. They've been buffeted over the decades by White flight, decay, urban renewal, unequal investment, increasingly extreme weather events, and now the worst pandemic in a century, and they're still going strong. Fulton shows that at their best, cities not only inspire and uplift us, but they make our daily life more convenient, more fulfilling - and more prosperous.
We use radial velocity (RV) observations to search for long-period gas giant companions in systems hosting inner super-Earth (1-4 R⊕, 1-10 M⊕) planets to constrain formation and migration scenarios ...for this population. We consistently refit published RV data sets for 65 stars and find nine systems with statistically significant trends indicating the presence of an outer companion. We combine these RV data with AO images to constrain the masses and semi-major axes of these companions. We quantify our sensitivity to the presence of long-period companions by fitting the sample with a power-law distribution and find an occurrence rate of 39% 7% for companions 0.5-20 MJup and 1-20 au. Half of our systems were discovered by the transit method, and half were discovered by the RV method. While differences in the RV baselines and number of data points between the two samples lead to different sensitivities to distant companions, we find that occurrence rates of gas giant companions in each sample are consistent at the 0.5 level. We compare the frequency of Jupiter analogs in these systems to the equivalent rate from field star surveys and find that Jupiter analogs are more common around stars hosting super-Earths. We conclude that the presence of outer gas giants does not suppress the formation of inner super-Earths, and that these two populations of planets instead appear to be correlated. We also find that the stellar metallicities of systems with gas giant companions are higher than those without companions, in agreement with the well-established metallicity correlation from RV surveys of field stars.
The nature and role of the intestinal leukocytes in necrotizing enterocolitis (NEC), a severe disease affecting premature infants, remain unknown. We now show that the intestine in mouse and human ...NEC is rich in lymphocytes that are required for NEC development, as recombination activating gene 1–deficient (Rag1–/–) mice were protected from NEC and transfer of intestinal lymphocytes from NEC mice into naive mice induced intestinal inflammation. The intestinal expression of the lipopolysaccharide receptor TLR4, which is higher in the premature compared with full-term human and mouse intestine, is required for lymphocyte influx through TLR4-mediated upregulation of CCR9/CCL25 signaling. TLR4 also mediates a STAT3-dependent polarization toward increased proinflammatory CD3+CD4+IL-17+ and reduced tolerogenic Foxp3+ Treg lymphocytes (Tregs). Th17 lymphocytes were required for NEC development, as inhibition of STAT3 or IL-17 receptor signaling attenuated NEC in mice, while IL-17 release impaired enterocyte tight junctions, increased enterocyte apoptosis, and reduced enterocyte proliferation, leading to NEC. Importantly, TLR4-dependent Th17 polarization could be reversed by the enteral administration of retinoic acid, which induced Tregs and decreased NEC severity. These findings identify an important role for proinflammatory lymphocytes in NEC development via intestinal epithelial TLR4 that could be reversed through dietary modification.
ABSTRACT We conducted a Doppler survey at Keck combined with NIRC2 K-band adaptive optics (AO) imaging to search for massive, long-period companions to 123 known exoplanet systems with one or two ...planets detected using the radial velocity (RV) method. Our survey is sensitive to Jupiter-mass planets out to 20 au for a majority of stars in our sample, and we report the discovery of eight new long-period planets, in addition to 20 systems with statistically significant RV trends that indicate the presence of an outer companion beyond 5 au. We combine our RV observations with AO imaging to determine the range of allowed masses and orbital separations for these companions, and account for variations in our sensitivity to companions among stars in our sample. We estimate the total occurrence rate of companions in our sample to be 52 5% over the range 1-20 MJup and 5-20 au. Our data also suggest a declining frequency for gas giant planets in these systems beyond 3-10 au, in contrast to earlier studies that found a rising frequency for giant planets in the range 0.01-3 au. This suggests either that the frequency of gas giant planets peaks between 3 and 10 au, or that outer companions in these systems have a different semi-major axis distribution than the overall population of gas giant planets. Our results also suggest that hot gas giants may be more likely to have an outer companion than cold gas giants. We find that planets with an outer companion have higher average eccentricities than their single counterparts, suggesting that dynamical interactions between planets may play an important role in these systems.
Angiotensin-converting enzyme 2 (ACE2) is a potent negative regulator capable of restraining overactivation of the renin-angiotensin system, which contributes to exuberant inflammation after ...bacterial infection. However, the mechanism through which ACE2 modulates this inflammatory response is not well understood. Accumulating evidence indicates that infectious insults perturb ACE2 activity, allowing for uncontrolled inflammation. In the current study, we demonstrate that pulmonary ACE2 levels are dynamically varied during bacterial lung infection, and the fluctuation is critical in determining the severity of bacterial pneumonia. Specifically, we found that a pre-existing and persistent deficiency of active ACE2 led to excessive neutrophil accumulation in mouse lungs subjected to bacterial infection, resulting in a hyperinflammatory response and lung damage. In contrast, pre-existing and persistent increased ACE2 activity reduces neutrophil infiltration and compromises host defense, leading to overwhelming bacterial infection. Further, we found that the interruption of pulmonary ACE2 restitution in the model of bacterial lung infection delays the recovery process from neutrophilic lung inflammation. We observed the beneficial effects of recombinant ACE2 when administered to bacterially infected mouse lungs following an initial inflammatory response. In seeking to elucidate the mechanisms involved, we discovered that ACE2 inhibits neutrophil infiltration and lung inflammation by limiting IL-17 signaling by reducing the activity of the STAT3 pathway. The results suggest that the alteration of active ACE2 is not only a consequence of bacterial lung infection but also a critical component of host defense through modulation of the innate immune response to bacterial lung infection by regulating neutrophil influx.
Necrotising enterocolitis (NEC) is a common disease in premature infants characterised by intestinal ischaemia and necrosis. The only effective preventative strategy against NEC is the administration ...of breast milk, although the protective mechanisms remain unknown. We hypothesise that an abundant human milk oligosaccharide (HMO) in breast milk, 2'-fucosyllactose (2'FL), protects against NEC by enhancing intestinal mucosal blood flow, and we sought to determine the mechanisms underlying this protection. Administration of HMO-2'FL protected against NEC in neonatal wild-type mice, resulted in a decrease in pro-inflammatory markers and preserved the small intestinal mucosal architecture. These protective effects occurred via restoration of intestinal perfusion through up-regulation of the vasodilatory molecule endothelial nitric oxide synthase (eNOS), as administration of HMO-2'FL to eNOS-deficient mice or to mice that received eNOS inhibitors did not protect against NEC, and by 16S analysis HMO-2'FL affected the microbiota of the neonatal mouse gut, although these changes do not seem to be the primary mechanism of protection. Induction of eNOS by HMO-2'FL was also observed in cultured endothelial cells, providing a link between eNOS and HMO in the endothelium. These data demonstrate that HMO-2'FL protects against NEC in part through maintaining mesenteric perfusion via increased eNOS expression, and suggest that the 2'FL found in human milk may be mediating some of the protective benefits of breast milk in the clinical setting against NEC.
Neurobiology of Photophobia Burstein, Rami; Noseda, Rodrigo; Fulton, Anne B
Journal of neuro-ophthalmology,
03/2019, Letnik:
39, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Photophobia is commonly associated with migraine, meningitis, concussion, and a variety of ocular diseases. Advances in our ability to trace multiple brain pathways through which light information is ...processed have paved the way to a better understanding of the neurobiology of photophobia and the complexity of the symptoms triggered by light.
The purpose of this review is to summarize recent anatomical and physiological studies on the neurobiology of photophobia with emphasis on migraine.
Observations made in blind and seeing migraine patients, and in a variety of animal models, have led to the discovery of a novel retino-thalamo-cortical pathway that carries photic signal from melanopsinergic and nonmelanopsinergic retinal ganglion cells (RGCs) to thalamic neurons. Activity of these neurons is driven by migraine and their axonal projections convey signals about headache and light to multiple cortical areas involved in the generation of common migraine symptoms. Novel projections of RGCs into previously unidentified hypothalamic neurons that regulate parasympathetic and sympathetic functions have also been discovered. Finally, recent work has led to a novel understanding of color preference in migraine-type photophobia and of the roles played by the retina, thalamus, and cortex.
The findings provide a neural substrate for understanding the complexity of aversion to light in patients with migraine and neuro-ophthalmologic other disorders.
Migraine headache is uniquely exacerbated by light. Using psychophysical assessments in patients with normal eyesight we found that green light exacerbates migraine headache significantly less than ...white, blue, amber or red lights. To delineate mechanisms, we used electroretinography and visual evoked potential recording in patients, and multi-unit recording of dura- and light-sensitive thalamic neurons in rats to show that green activates cone-driven retinal pathways to a lesser extent than white, blue and red; that thalamic neurons are most responsive to blue and least responsive to green; and that cortical responses to green are significantly smaller than those generated by blue, amber and red lights. These findings suggest that patients' experience with colour and migraine photophobia could originate in cone-driven retinal pathways, fine-tuned in relay thalamic neurons outside the main visual pathway, and preserved by the cortex. Additionally, the findings provide substrate for the soothing effects of green light.
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