1,692 research outputs found
A People's History Of Recent Urban Transportation Innovation
Who are the people leading the charge in urban transportation? As our report explains, the short answer is that it takes leaders from three different sectors of urban society to make change happen quickly.First, there needs to be a robust civic vanguard, the more diverse their range of skills and participation, the better. Second, mayors, commissioners and other city leaders need to create the mandate and champion the change. The third sector is the agency staff. When these three sectors align, relatively quick transformation is possible. Several cities, including New York and Pittsburgh, recently experienced this alignment of a healthy civic community, a visionary and bold mayor and transportation head, and internal agency champions. Our report also highlighted the potential of other cities, such as Charlotte, where the civic sector continues to build on and widen their base
Two paths of cluster evolution: global expansion versus core collapse
All gravitationally bound clusters expand, due to both gas loss from their
most massive members and binary heating. All are eventually disrupted tidally,
either by passing molecular clouds or the gravitational potential of their host
galaxies. However, their interior evolution can follow two very different
paths. Only clusters of sufficiently large initial population and size undergo
the combined interior contraction and exterior expansion that leads eventually
to core collapse. In all other systems, core collapse is frustrated by binary
heating. These clusters globally expand for their entire lives, up to the point
of tidal disruption.
Using a suite of direct N-body calculations, we trace the "collapse line" in
r_v-N space that separates these two paths. Here, r_v and N are the cluster's
initial virial radius and population, respectively. For realistic starting
radii, the dividing N-value is from 10^4 to over 10^5. We also show that there
exists a minimum population, N_min, for core collapse. Clusters with N < N_min
tidally disrupt before core collapse occurs. At the Sun's Galactocentric
radius, R_G = 8.5 kpc, we find N_min >~ 300. The minimum population scales with
Galactocentric radius as R_G^{-9/8}.
The position of an observed cluster relative to the collapse line can be used
to predict its future evolution. Using a small sample of open clusters, we find
that most lie below the collapse line, and thus will never undergo core
collapse. Most globular clusters, on the other hand, lie well above the line.
In such a case, the cluster may or may not go through core collapse, depending
on its initial size. We show how an accurate age determination can help settle
this issue.Comment: Accepted for publication in MNRAS. 14 Pages, 9 Figures, 2 Table
Two-dimensional molecular-based ferrimamagnets incorporating decamethylmetallocenium cations
Journal ArticleFour new molecular-based magnets have been synthesized, and their magnetic properties have been investigated in detail. Their formulae are [M'(C5Me5)2]2M2[Cu(opba)]3.(DMSO)x(H20)y with M' = Fe, M = Mn, x = 5, y = 4 (1), M' = Fe, M = Co, x = 6, y = 4 (2), M' = Co, M = Mn, x = 5.5, y = 4 (3) and M' = Co, M = Co, x = 5.5, y = 4 (4) [opba = ortfro-phenylenebis (oxamato)]. The decamethylmetallocenium cations [Fe(C5Me5)2]+ and [Co(C5Me5)2]+ are most probably located between the anionic honeycomb-like networks Mn2[Cu(opba)]3 and Co2[Cu(opba)]3
Identifying targets of the Sox domain protein Dichaete in the Drosophila CNS via targeted expression of dominant negative proteins.
BACKGROUND: Group B Sox domain transcription factors play important roles in metazoan central nervous system development. They are, however, difficult to study as mutations often have pleiotropic effects and other Sox family members can mask phenotypes due to functional compensation. In Drosophila melanogaster, the Sox gene Dichaete is dynamically expressed in the embryonic CNS, where it is known to have functional roles in neuroblasts and the ventral midline. In this study, we use inducible dominant negative proteins in combination with ChIP, immunohistochemistry and genome-wide expression profiling to further dissect the role of Dichaete in these two tissues. RESULTS: We generated two dominant negative Dichaete constructs, one lacking a DNA binding domain and the other fused to the Engrailed transcriptional repressor domain. We expressed these tissue-specifically in the midline and in neuroblasts using the UAS/GAL4 system, validating their use at the phenotypic level and with known target genes. Using ChIP and immunohistochemistry, we identified two new likely direct Dichaete target genes, commisureless in the midline and asense in the neuroectoderm. We performed genome-wide expression profiling in stage 8-9 embryos, identifying almost a thousand potential tissue-specific Dichaete targets, with half of these genes showing evidence of Dichaete binding in vivo. These include a number of genes with known roles in CNS development, including several components of the Notch, Wnt and EGFR signalling pathways. CONCLUSIONS: As well as identifying commisureless as a target, our data indicate that Dichaete helps establish its expression during early midline development but has less effect on its established later expression, highlighting Dichaete action on tissue specific enhancers. An analysis of the broader range of candidate Dichaete targets indicates that Dichaete plays diverse roles in CNS development, with the 500 or so Dichaete-bound putative targets including a number of transcription factors, signalling pathway components and terminal differentiation genes. In the early neurectoderm we implicate Dichaete in the lateral inhibition pathway and show that Dichaete acts to repress the proneural gene asense. Our analysis also reveals that dominant negatives cause off-target effects, highlighting the need to use other experimental data for validating findings from dominant negative studies.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are
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Stemness factor Sall4 is required for DNA damage response in embryonic stem cells.
Mouse embryonic stem cells (ESCs) are genetically more stable than somatic cells, thereby preventing the passage of genomic abnormalities to their derivatives including germ cells. The underlying mechanisms, however, remain largely unclear. In this paper, we show that the stemness factor Sall4 is required for activating the critical Ataxia Telangiectasia Mutated (ATM)-dependent cellular responses to DNA double-stranded breaks (DSBs) in mouse ESCs and confer their resistance to DSB-induced cytotoxicity. Sall4 is rapidly mobilized to the sites of DSBs after DNA damage. Furthermore, Sall4 interacts with Rad50 and stabilizes the Mre11-Rad50-Nbs1 complex for the efficient recruitment and activation of ATM. Sall4 also interacts with Baf60a, a member of the SWI/SNF (switch/sucrose nonfermentable) ATP-dependent chromatin-remodeling complex, which is responsible for recruiting Sall4 to the site of DNA DSB damage. Our findings provide novel mechanisms to coordinate stemness of ESCs with DNA damage response, ensuring genomic stability during the expansion of ESCs
Subsidence in Coastal Cities Throughout the World Observed by InSAR
We measured subsidence rates in 99 coastal cities around the world between 2015 and 2020 using the PS Interferometric Synthetic Aperture Radar method and Sentinel-1 data. In most cities, part of the land is subsiding faster than sea level is rising. If subsidence continues at present rates, these cities will be challenged by flooding much sooner than projected by sea level rise models. The most rapid subsidence is occurring in South, Southeast, and East Asia. However, rapid subsidence is also happening in North America, Europe, Africa, and Australia. Human activity—primarily groundwater extraction—is likely the main cause of this subsidence. Expanded monitoring and policy interventions are required to reduce subsidence rates and minimize their consequences
Economic implications of comorbid conditions among Medicaid beneficiaries with COPD
SummaryObjectivesTo characterize a comprehensive comorbidity profile and to explore the economic implications of comorbidity among patients with chronic obstructive pulmonary disease (COPD).MethodsThis retrospective cohort study analyzed medical claims from the Maryland Medicaid database. We employed a 1:2 case–control design to select COPD patients (n=1388) and demographically matched controls (n=2776) aged 40 to 64 years with 24 months of continuous enrollment. Odds ratios were employed to compare comorbidity differences, including 17 conditions defined by the Charlson Comorbidity Index (CCI) and 6 additional conditions commonly observed in COPD patients. We estimated the incremental medical utilization and medical cost by specific condition.ResultsCompared with the controls, Medicaid COPD patients had higher comorbidity burden and were more likely to have myocardial infarction, congestive heart failure, cerebrovascular disease, peptic ulcer, mild liver disease, hypertension, sleep apnea, tobacco use, and edema. COPD patients on average had 24% more medical claims (81.4 vs. 65.4, p<0.001) and were 33% more expensive than controls (5732, p<0.001). Ten conditions defined by the CCI as well as hypertension, tobacco use, and edema were associated with incremental medical utilization and cost in COPD patients; depression was associated with incremental medical utilization but not cost.ConclusionsThe high burden of comorbidity in COPD patients translates into additional medical utilization and cost. Effective disease management and treatment protocols are needed to reduce comorbidity burden. The development of a COPD-specific comorbidity measure may be used to identify high-risk subgroups and to predict utilization and cost
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