On the capacity of isolated, curbside bus stops Gu, Weihua; Li, Yuwei; Cassidy, Michael J. ...
Transportation research. Part B: methodological,
05/2011, Letnik:
45, Številka:
4
Journal Article
Recenzirano
Odprti dostop
► Models are developed to predict bus discharge capacity of isolated, curbside stops. ► Influences include the bus arrival process and service time distribution. ► Findings are at odds with ...information presented in professional handbooks. ► The models can determine a stop’s suitable number of bus berths.
The maximal rates that buses can discharge from bus stops are examined. Models were developed to estimate these capacities for curbside stops that are isolated from the effects of traffic signals. The models account for key features of the stops, including their target service levels assigned to them by a transit agency. Among other things, the models predict that adding bus berths to a stop can sometimes return disproportionally high gains in capacity. This and other of our findings are at odds with information furnished in professional handbooks.
Traffic signal plans to decongest street grids Sadek, Bassel; Doig Godier, Jean; Cassidy, Michael J ...
Transportation research. Part B: methodological,
August 2022, 2022-08-00, Letnik:
162
Journal Article
Recenzirano
Odprti dostop
Two new synchronization strategies are developed for signalized grids of two-directional streets. Both strategies are found to reduce congestion significantly more than do other approaches. One of ...the strategies is static and the other adaptive. Both use a common timing pattern for all signals on the grid but use a different offset for each. The static strategy serves the morning rush by providing perfect forward progression on all streets in the directions that point toward a reference intersection, one that is located near the center of gravity of all workplaces. For the evening rush, perfect progression is achieved for all travel directions that point away from the reference intersection. The adaptive strategy toggles between this forward synchronization mode and a second mode suited for congestion, but only in a pre-determined district surrounding the reference intersection. Toggling is based on the district's real-time traffic density.
The paper shows how to switch quickly between the two synchronization modes without resorting to unacceptably short phases. It also shows that if the grid is formed by two intersecting sets of parallel streets, even if unevenly spaced, then every street can be perfectly synchronized in one of its directions. As a result, an inbound driver in the morning, or an outbound driver in the evening, is guaranteed to encounter synchronized signals over the full length of her trip. Although this is not possible for more irregular grids, the paper shows how to modify the two strategies for this case, so that they still perform well.
The strategies were benchmarked with simulations against a fixed, zero-offset strategy for many scenarios, because zero-offsets are known to work well under congestion. In one important scenario representing a severely congested morning rush, both strategies were also benchmarked against a state-of-the-practice computer program. While the state-of-the-practice program reduced the zero-offset delay by a modest 7%, the proposed strategies reduced it by 21% (static) and 32% (adaptive); i.e., improving on the state-of-the-practice program by 14% and 25%. These improvements considerably exceed the 1% to 5% reductions typically reported in the literature for other state-of-the-art methods that have been compared with state-of-the-practice programs. Similarly good results were obtained for the other scenarios, which included the morning and evening rushes, various distributions of workplaces, and both regular and irregular grids.
Significance Mutations in the catalytic subunit of protein kinase A (PKA) have been found in tumors associated with the kidney disorder Cushing’s syndrome and with the rare liver cancer fibrolamellar ...hepatocellular carcinoma (FL-HCC). Crystal structures and biochemical characterizations of the relevant PKA mutants clarify the molecular basis for disease caused by these mutations. We find contrasting underlying mechanisms for increased PKA signaling in these cancers. In Cushing’s syndrome, the L205R PKA mutation abolishes regulatory-subunit binding, whereas in FL-HCC, the recurring DnaJ–PKA fusion that results from a chromosomal deletion exhibits wild-type characteristics, but is overproduced by a more active promoter. Our findings provide a structural basis for designing selective drugs that may lead to effective treatments for these diseases.
The extensively studied cAMP-dependent protein kinase A (PKA) is involved in the regulation of critical cell processes, including metabolism, gene expression, and cell proliferation; consequentially, mis-regulation of PKA signaling is implicated in tumorigenesis. Recent genomic studies have identified recurrent mutations in the catalytic subunit of PKA in tumors associated with Cushing’s syndrome, a kidney disorder leading to excessive cortisol production, and also in tumors associated with fibrolamellar hepatocellular carcinoma (FL-HCC), a rare liver cancer. Expression of a L205R point mutant and a DnaJ–PKA fusion protein were found to be linked to Cushing's syndrome and FL-HCC, respectively. Here we reveal contrasting mechanisms for increased PKA signaling at the molecular level through structural determination and biochemical characterization of the aberrant enzymes. In the Cushing’s syndrome disorder, we find that the L205R mutation abolishes regulatory-subunit binding, leading to constitutive, cAMP-independent signaling. In FL-HCC, the DnaJ–PKA chimera remains under regulatory subunit control; however, its overexpression from the DnaJ promoter leads to enhanced cAMP-dependent signaling. Our findings provide a structural understanding of the two distinct disease mechanisms and they offer a basis for designing effective drugs for their treatment.
Coastal sharks are challenging to manage in the United States due to their slow life history, limited data availability, history of overexploitation, and competing stakeholder interests. Furthermore, ...species like the sandbar shark (Carcharhinus plumbeus) are subjected to international exploitation unmanaged by the US. We conducted a management strategy evaluation using Stock Synthesis on the sandbar shark to test the performance of various configurations of a threshold harvest control rule. In addition to uncertainties addressed in the operating model (OM), we built multiple implementation models to address uncertainties related to future levels of a partially unmanaged source of removals, the combined Mexican and US recreational (MexRec) fleet. We found that the presence of unregulated removals had the potential to significantly influence the success of the various management procedures (MPs) tested. Notably, if MexRec catches continue to increase with total stock abundance following historical trends, the rate of MexRec removals will be too large to allow the sandbar shark to recover across OMs. We present trade-offs between performance metrics across a range of 24 MPs and three implementation models.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objectives To assess psychiatric disorders and function in adolescents with repaired tetralogy of Fallot (TOF) without and with a genetic diagnosis and to evaluate associations of functioning with ...medical factors, IQ, and demographics. Study design Adolescents with TOF (n = 91) and 87 healthy referents completed a clinician-rated structured psychiatric interview, parent-/self-report measures of psychopathology, and brain magnetic resonance imaging. Twenty-three of the adolescents with TOF had a known genetic diagnosis. Results The prevalence of anxiety disorders did not differ significantly between adolescents with TOF without genetic diagnosis (n = 68) and referents. Adolescents with TOF and a genetic diagnosis showed an increased lifetime prevalence of anxiety disorder (43%) and lower global psychosocial functioning (median, 70; IQR, 63-75) compared with adolescents with TOF without genetic diagnosis (15% and 83; IQR, 79-87, respectively; P = .04 and <.001, respectively) and referents (6% and 85; IQR, 76-90, respectively; P = .001 and <.001, respectively). Adolescents with TOF without and with a genetic diagnosis had a higher lifetime prevalence of attention deficit-hyperactivity disorder (ADHD) than referents (19% and 39%, respectively, vs 5%; P = .04 and .002, respectively) and worse outcomes on parent-/self-report ratings of anxiety and disruptive behavior compared with referents. Risk factors for anxiety, ADHD, and lower psychosocial functioning for adolescents with TOF without a genetic diagnosis included older age, male sex, and low IQ. Medical variables were not predictive of psychiatric outcomes. Conclusion Adolescents with TOF, particularly those with a genetic diagnosis, show increased rates of psychiatric disorder and dysfunction. Continued mental health screening and surveillance into young adulthood is warranted for adolescents with TOF.
Ricin toxin is a heterodimer consisting of RTA, a ribosome-inactivating protein, and RTB, a lectin that facilitates receptor-mediated uptake into mammalian cells. In previous studies, we demonstrated ...that toxin-neutralizing antibodies target four spatially distinct hot spots on RTA, which we refer to as epitope clusters I–IV. In this report, we identified and characterized three single domain camelid antibodies (VHH) against cluster II. One of these VHHs, V5E1, ranks as one of the most potent ricin-neutralizing antibodies described to date. We solved the X-ray crystal structures of each of the three VHHs (E1, V1C7, and V5E1) in complex with RTA. V5E1 buries a total of 1,133 Å2 of surface area on RTA and makes primary contacts with α-helix A (residues 18–32), α-helix F (182–194), as well as the F-G loop. V5E1, by virtue of complementarity determining region 3 (CDR3), may also engage with RTB and potentially interfere with the high affinity galactose-recognition element that plays a critical role in toxin attachment to cell surfaces and intracellular trafficking. The two other VHHs, E1 and V1C7, bind epitopes adjacent to V5E1 but display only weak toxin neutralizing activity, thereby providing structural insights into specific residues within cluster II that may be critical contact points for toxin inactivation.
► Strategies are proposed for using bus lanes when bus flows are low. ► The strategies prioritize bus travel while maximizing car-carrying capacity. ► Models show that the ideas can enjoy broad ...application. ► A case study illustrates potential benefits.
In urban settings where space is at a premium, bus lanes can often times be created only via the conversion of existing general-use lanes. If buses are dispatched at low rates, the converted lanes will be under-utilized and squander road space. The bottlenecks within the city’s road network would then impart even greater delays to cars.
The present paper addresses this problem by exploring novel ways in which buses and cars can share lanes within select bottlenecks. The details of a shared-lane strategy vary, depending upon certain details of its bottleneck. In all cases, the idea is to insert cars into a shared lane so as to put available road space to use without delaying buses. Ordinary lane conversions would occur elsewhere throughout the road network, and these would connect to the shared lanes within the bottlenecks.
Analytical assessments unveil a wide range of cases for which the proposed strategies increase a bottleneck’s car-carrying capacity, as compared against reserving one of its lanes for buses only. Simulations of a real site indicate that significant reductions in car delays can result.
CONTEXT:Recombinant human GH (rhGH) therapy in Prader-Willi syndrome (PWS) has been used by the medical community and advocated by parental support groups since its approval in the United States in ...2000 and in Europe in 2001. Its use in PWS represents a unique therapeutic challenge that includes treating individuals with cognitive disability, varied therapeutic goals that are not focused exclusively on increased height, and concerns about potential life-threatening adverse events.
OBJECTIVE:The aim of the study was to formulate recommendations for the use of rhGH in children and adult patients with PWS.
EVIDENCE:We performed a systematic review of the clinical evidence in the pediatric population, including randomized controlled trials, comparative observational studies, and long-term studies (>3.5 y). Adult studies included randomized controlled trials of rhGH treatment for ≥ 6 months and uncontrolled trials. Safety data were obtained from case reports, clinical trials, and pharmaceutical registries.
METHODOLOGY:Forty-three international experts and stakeholders followed clinical practice guideline development recommendations outlined by the AGREE Collaboration (www.agreetrust.org). Evidence was synthesized and graded using a comprehensive multicriteria methodology (EVIDEM) (http://bit.ly.PWGHIN).
CONCLUSIONS:Following a multidisciplinary evaluation, preferably by experts, rhGH treatment should be considered for patients with genetically confirmed PWS in conjunction with dietary, environmental, and lifestyle interventions. Cognitive impairment should not be a barrier to treatment, and informed consent/assent should include benefit/risk information. Exclusion criteria should include severe obesity, uncontrolled diabetes mellitus, untreated severe obstructive sleep apnea, active cancer, or psychosis. Clinical outcome priorities should vary depending upon age and the presence of physical, mental, and social disability, and treatment should be continued for as long as demonstrated benefits outweigh the risks.
Background. The purpose of this study was to describe the prevalence and extent of coronary artery calcification (CAC) in subjects with chronic kidney disease (CKD) stages 3 and 4 comparing those ...with and without diabetes. We also wished to determine if the presence of peripheral artery calcification (PAC) would assist in identifying patients positive for CAC. Methods. CAC was detected by multi-slice computed tomography and PAC was detected by plain foot radiography. Study population was 112 patients, 54 with diabetes and 58 without, all asymptomatic for heart disease. Demographic and laboratory data were collected and analysed. Results. The prevalence of CAC in CKD patients was 76 and 46.5% with and without diabetes, respectively. Patients with diabetes had higher CAC scores with more vessels affected, and in the presence of diabetes men and women had the same risk for CAC. In patients with diabetes, age was the unique explanatory variable for detecting the presence of CAC, while age and smoking history predicted severity. In patients without diabetes, age, male gender, body mass index, estimated glomerular filtration rate and serum phosphate levels predicted the presence of CAC, while parathyroid hormone predicted severity. Prevalence of PAC was 63 and 12% in subjects with and without diabetes. PAC detected by foot radiography was not an adequate alternative-screening marker for identifying patients with CAC. Conclusions. CAC is common in CKD stages 3 and 4 patients, especially in men and women with diabetes.
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