Direct continuities between cisternae at different levels of the Golgi complex in glucose-stimulated mouse islet beta cells

Direct continuity between the membranes of cisternae in the Golgi complex in mammalian cells rarely has been observed; when seen, its documentation has been equivocal. Here we have used dual-axis electron microscope tomography to examine the architecture of the Golgi in three dimensions at approximate to6-nm resolution in rapidly frozen, freeze-substituted murine cells that make and secrete insulin in response to glucose challenge. Our data show three types of direct connections between Golgi cisternae that are normally distinct from one another. These connections all bypass interceding cisternae. We propose that when pancreatic beta cells are stimulated to synthesize and secrete insulin rapidly in vivo, such connections provide a continuous lumen that facilitates the rapid transit of large amounts of newly made protein for secretion. The heterotypic fusion of cisternae, even transiently, raises important questions about the molecular mechanisms that (i) facilitate the fusion/fission of cisternal membranes and control the directionality and specificity of such events, and (it) retain Golgi processing enzymes at specific places within individual cisternae when two cisternae at different levels in the Golgi have fused, maintaining the sequential processing hierarchy that is a hallmark of Golgi organization.

Strategies and therapeutic opportunities for the delivery of drugs to the esophagus

Targeting of drugs and therapies locally to the esophagus is an important objective in the development of new and more effective dosage forms. Therapies that are retained within the oral cavity for both local and systemic action have been utilized for many years, although delivery to the esophagus has been far less reported. Esophageal disease states, including infections, motility disorders, gastric reflux, and cancers, would all benefit from localized drug delivery. Therefore, research in this area provides significant opportunities. The key limitation to effective drug delivery within the esophagus is sufficient retention at this site coupled with activity profiles to correspond with these retention times; therefore, a suitable formulation needs to provide the drug in a ready-to-work form at the site of action during the rapid transit through this organ. A successfully designed esophageal-targeted system can overcome these obstacles. This review presents a range of dosage form approaches for targeting the esophagus, including bioadhesive liquids and orally retained lozenges, chewing gums, gels, and films, as well as endoscopically delivered therapeutics. The techniques used to measure efficacy both in vitro and in vivo are also discussed. Drug delivery is a growing driver within the pharmaceutical industry and offers benefits both in terms of clinical efficacy, as well as in market positioning, as a means of extending a drug's exclusivity and profitability. Emerging systems that can be used to target the esophagus are reported within this review, as well as the potential of alternative formulations that offer benefits in this exciting area.

Metropolitan Governance and Institutional Design: Transportation in the Jakarta Metropolitan Region

In the Jakarta Metropolitan Region (JMR), the lack of co-ordination and appropriate governance has resulted in paralyzing traffic jams at the metropolitan scale that cannot be resolved by a single government entity. The issue of metropolitan governance is especially crucial here as the JMR lacks an established and formally pre-designed system of governance (e.g., in a constitution or other legal regulations). Instead, it relies on the interaction, coordination and cooperation of a multitude of different stakeholders, ranging from local and regional authorities to private entities and citizens. This chapter offers a discussion on the various governance approaches relating to an appropriate institutional design required for transportation issues at the metropolitan scale. The case used is a regional Bus Rapid Transit (BRT) system as an extension to the metropolitan transport system. Institutional design analysis is applied to the case and three possible improvements - i) a ‘Megapolitan’ concept, ii) a regional spatial plan and iii) inter-local government cooperation; were identified that correspond to current debates on metropolitan governance approaches of regionalism, localism and new regionalism. The findings, which are relevant to similar metropolitan regions, suggest that i) improvements at the meso-level of institutional design are more readily accepted and effective than improvements at the macro-level and ii) that the appropriate institutional design for governing metropolitan transportation in the JMR requires enhanced coordination and cooperation amongst four important actors - local governments, the regional agency, the central government, and private companies.

Letter from the Editors

[Excerpt] The Editorial Team is proud to release this 2016 14th Annual Volume of the Cornell Real Estate Review. This year’s issue explores a wide range of topics, including the deployment of new technologies in multifamily properties, the effects of autonomous vehicles on real estate, and the continued ramifications of the housing crisis through the legal tactics of certain mortgage lenders. Also included, a recent repositioning project– the unique turnaround of a former casino hotel property in Reno, Nevada. Furthermore, this release includes a discussion of value-added multifamily investment strategy, an analysis of the impact of rapid transit on the residential market in Hudson County, New Jersey, and a summary of federal affordable housing incentive programs in the United States. This year’s Pathways features an interview with Toll Brothers Division President Karl Mistry (Baker ’04), and the Baker Viewpoint piece explores the concept of curtailment mortgages.

O interface do Campo Grande

Dissertação para obtenção do grau de Mestre em Arquitectura com Especialização em Urbanismo, apresentada na Universidade de Lisboa - Faculdade de Arquitectura.

Aproximación al desarrollo de un sistema de transporte masivo a través de la dinámica de sistemas

El porvenir social y económico de una ciudad depende, en gran medida, de la eficiencia de su sistema de transporte; esto se ve reflejado en la capacidad de transportar personas y bienes de una forma sostenible, con los recursos disponibles. En la actualidad se encuentran en desarrollo sistemas de transporte masivo tipo Bus Rapid Transit [BRT] en siete ciudades colombianas, situación que genera la necesidad de dar seguimiento a su progreso y al crecimiento de su participación en la demanda de viajes unipersonales. El siguiente trabajo busca, a través de una simulación en dinámica de sistemas, describir el desarrollo de un sistema de transporte masivo, con el fin de otorgar una visión acerca del impacto de los parámetros operativos y la reinversión en el sistema y en el desarrollo e incremento de su demanda. Se plantean tres escenarios para evaluar diferentes políticas operativas y de reinversión en el sistema, analizando el comportamiento en su desarrollo.

British railways and the challenge from road haulage: 1919-39

Interwar Britain witnessed the rapid rise of road transport as a serious competitor to the railways. This article examines road–rail competition for freight traffic. It demonstrates that, contrary to previous accounts—which have been highly critical of the railway companies—their failure to prevent rapid loss of traffic to the roads was the inevitable consequence of the regulatory framework under which the railways had been returned to private control in 1921. Given the constraints imposed by this framework, price competition with road hauliers would have further depressed railway company profits. Railway policy thus concentrated on pressing for a revision of the legislative framework governing road–rail competition.

Melhoria do nível de serviço no atendimento ao cliente por meio da estrutura direta de distribuição Transit Point

Increasingly competitive markets have driven the search for companies in many different ways to win and keep customers. The service level is basically the performance of companies in fulfilling the orders made, or how companies demonstrate to their clients efforts in their behalf. This work aims to solve the difficulties faced by a multinational company present in Brazil, in the distribution of its products in the category Ice Cream in order to improve the service level of their customers. Review the logistics network and concepts related to the distribution system of products is one of several ways to achieve this goal, as well as the use of IT and tools to assist in planning and programming of the physical distribution of products. In this study we used the concept of direct distribution system called Transit Point (TP). The TP provides at the same time, a strategy of rapid response, flexibility, low transportation costs and no inventory. A router - software capable of simulating the actual conditions experienced in the daily distribution - was used to assist in calculations. Results showed reductions of up to 47.5% in transportation costs and better conditions were provided in the distribution of products, positively impacting on service levels and in the maintenance of products quality, with a reduction of 1.6% of the total costs involve

Sleeve Gastrectomy With Transit Bipartition A Potent Intervention for Metabolic Syndrome and Obesity

Objective: To present 5-year results of sleeve gastrectomy (SG) with transit bipartition (TB) as a metabolic intervention for obesity. Background: Recent data suggest that high glycemic index foods may lead to a hormonally hyperactive proximal gut and a hypoactivate distal gut, which are linked to metabolic syndrome. TB was designed to counterbalance these effects. Methods: A total of 1020 obese patients with body mass index (BMI) ranging from 33 to 72 Kg/m(2) underwent SG and TB (SG + TB). TB creates a gastroileal anastomosis in the antrum after the SG; nutrient transit is maintained in the duodenum, avoiding blind loops and minimizing malabsorption. The stomach retains 2 outflow pathways. A lateral enteroanastomosis connects both segments at 80 cm proximal to the cecum. Results: Adequate follow-up data were collected in 59.1% of patients from 4 months to 5 years. The average percent of excess BMI loss was 91%, 94%, 85%, 78%, and 74% in the first, second, third, fourth, and fifth year, respectively. Patients experienced early satiety and major improvement in presurgical comorbidities, including diabetes (86% in remission), following surgery. Two deaths occurred (0.2%). Other surgical complications occurred in 6% of patients. Signs of malabsorption were rare. Conclusions: SG + TB is a simple procedure that results in rapid weight loss and remission or major improvement of comorbidities. Strictly aiming at physiological correction, TB avoids prostheses, narrow anastomoses, excluded segments, and malabsorption. Weight and comorbidities are much improved. Diabetes is improved without duodenal exclusion. TB is an excellent complement to an SG.

Cessation of rapid late endosomal tubulovesicular trafficking in Niemann–Pick type C1 disease

Niemann–Pick type C1 (NPC1) disease results from a defect in the NPC1 protein and is characterized by a pathological accumulation of cholesterol and glycolipids in endocytic organelles. We followed the biosynthesis and trafficking of NPC1 with the use of a functional green fluorescent protein-fused NPC1. Newly synthesized NPC1 is exported from the endoplasmic reticulum and requires transit through the Golgi before it is targeted to late endosomes. NPC1-containing late endosomes then move by a dynamic process involving tubulation and fission, followed by rapid retrograde and anterograde migration along microtubules. Cell fusion studies with normal and mutant NPC1 cells show that exchange of contents between late endosomes and lysosomes depends upon ongoing tubulovesicular late endocytic trafficking. In turn, rapid endosomal tubular movement requires an intact NPC1 sterol-sensing domain and is retarded by an elevated endosomal cholesterol content. We conclude that the neuropathology and cellular lysosomal lipid accumulation in NPC1 disease results, at least in part, from striking defects in late endosomal tubulovesicular trafficking.

Handbook of modern electric railway methods and practices. A compilation of methods, practices, experiences, and policies of electric railways in the United States,

Mode of access: Internet.

A simple, rapid method for mapping bathymetry of small wetland basins

Many tools exist for determining and mapping the bathymetry and topography of aquatic systems, such as freshwater wetlands. However, these tools often require time-consuming survey work to produce accurate maps. In particular, the large quantity of data necessary may be prohibitive for projects where determining bathymetry is not a central focus, but instead a necessary step in achieving some other goal. We present a method to produce bathymetric surface maps with a minimum amount of effort using global positioning system receiver and laser transit survey data. We also demonstrate that this method is surprisingly accurate, given the small amount of data we use to generate the bathymetry maps.

Differentiating responses to obstructive sleep apnoea using pulse transit time

Conventional overnight polysomnography (PSG) used to determine the respiratory behaviour during sleep can be a complex and expensive procedure. Pulse transit time analysis (PTT) has shown potential to detect obstructive apnoeic and hypopnoeic events in adults. This study was undertaken to determine the potential of PTT to differentiate responses to upper airway obstruction. 103 obstructive respiratory events occurred in PSG studies performed on 11 children (10 male and 1 female, mean age 7.5years). PTT measurements were evaluated against the corresponding PSG results pre-scored by 2 blinded observers. Broadly, there were 2 types of responses. They can be either short period of rapid PTT decreases (Type 1) or prolonged but gradual PTT decreases (Type 2). Type 1 obstructive events showed a mean change of 51.77% (p

Development of a medium-capacity guideway transit planning guide

Rapid population increase and booming economic growth have caused a significant escalation in car ownership in many cities, leading to additional or, multiple traffic problems on congested roadways. The increase of automobiles is generating a significant amount of congestion and pollution in many cities. It has become necessary to find a solution to the ever worsening traffic problems in our cities. Building more roadways is nearly impossible due to the limitations of right-of-way in cities. Studies have shown that guideway transit could provide effective transportation and could stimulate land development. The Medium-Capacity Guideway Transit (MCGT) is one of the alternatives to solve this problem. The objective of this research was to better understand the characteristics of MCGT systems, to investigate the existing MCGT systems around the world and determine the main factors behind the planning of successful systems, and to develop a MCGT planning guide. The factors utilized in this study were determined and were analyzed using Excel. A MCGT Planning Guide was developed using Microsoft Visual Basic. ^ A MCGT was defined as a transit system whose capacity can carry up to 20,000 passengers per hour per direction (pphpd). The results shown that Light Rail Transit (LRT) is favored when peak hour demand is less than 13,000 pphpd. Automated People Mover (APM) is favored when the peak hour demand is more than 18,000 pphpd. APM systems could save up to three times the waiting time cost compared to that of the LRT. If comfort and convenience are important, then using an APM does make sense. However, if cost is the critical factor, then LRT will make more sense because it is reasonable service at a reasonable price. If travel time and safety (accident/crush) costs were included in calculating life-cycle “total” costs, the capital cost advantage of LRT disappeared and APM could become very competitive. The results also included a range of cost-performance criteria for MCGT systems that help planners, engineers, and decision-makers to select the most feasible system for their respective areas. ^

A Rapid And Simple Capillary Electrophoresis Method For Indirect Determination Of The Biocide 2,2-dibromo-3-nitrilo-propionamide (dbnpa) In Cooling Waters.

A capillary zone electrophoresis (CE) method was developed for the determination of the biocide 2,2-dibromo-3-nitrilo-propionamide (DBNPA) in water used in cooling systems. The biocide is indirectly determined by CE measurement of the concentration of bromide ions produced by the reaction between the DBNPA and bisulfite. The relationship between the bromide peak areas and the DBNPA concentrations showed a good linearity and a coefficient of determination (R(2)) of 0.9997 in the evaluated concentration range of 0-75 μmol L(-1). The detection and quantification limits for DBNPA were 0.23 and 0.75 μmol L(-1), respectively. The proposed CE method was successfully applied for the analysis of samples of tap water and cooling water spiked with DBNPA. The intra-day and inter-day (intermediary) precisions were lower than 2.8 and 6.2%, respectively. The DBNPA concentrations measured by the CE method were compared to the values obtained by a spectrophotometric method and were found to agree well.