Reducing rail-truck freight intermodal drayage costs

In rail-truck intermodal transport, a highway truck-trailer or container is moved by truck from a shipper to a rail terminal in the shipper\u27s vicinity, and by rail in line haul between rail terminals. Upon being unloaded at the destination rail terminal, the container is delivered to a receiver (consignee) by truck. The highway portion of the move, or drayage, accounts for a relatively high percentage of total origin to destination cost, and it limits severely the competitiveness of intermodal service with door-to-door truck service. The approach used in this thesis is to examine in detail the current costs and potential for improvement at one intermodal terminal for a pre-determined analysis period. The analysis is conducted by first determining the actual cost of container movements and comparing it with the costs of an operation in which movements are scheduled using a proposed heuristic model that reduces the movements of empty containers. The model results indicate a 7.79% reduction in the overall cost of drayage. This reduction is achieved by repositioning and reloading containers, after they have been unloaded at consignees

Seismic stratigraphy of Lago Fagnano sediments (Tierra del Fuego, Argentina) - A potencial archive of paleoclimatic change and tectonic activity since the Late Glacial

Located at 54ºS in the heart of the Island of Tierra del Fuego, Lago Fagnano occupies the deepest of a chain of en-echelon tectonic depressions along the Magallanes-Fagnano Transform system (MFT). A recent geophysical campaign combining 3.5 kHz (pinger) single-channel with 1 in3 airgun multi-channel systems surveyed more than 100 m of glacio-lacustrine sediments filling two main sub-basins. These data provide a unique opportunity to visualize the most recent lacustrine sequence with high-resolution while simultaneously imaging the oldest infill. A preliminary seismic stratigraphic analysis of the high-resolution 3.5 kHz pinger data allowed the identification of three major seismostratigraphic units (A, the oldest and C, the youngest). While unit A is interpreted as glacially derived sediments, the overlying unit B is interpreted as fining upward sequences of proglacial turbidites reflecting sediment pulses released by the retreating Fagnano glacier during the last deglaciation. A major environmental change occurred during deposition of unit C when pelagic style of sedimentation is intercalated by sequences of downslope mass flow events probably triggered by relatively strong tectonic pulses along the MFT system. Gravity cores show a regular alternation of light and dark laminae occasionally interrupted by homogenous sedimentary units interpreted as turbidites. Ultra-high resolution X-ray fluorescence micro-profiles show fluctuations in major trace elements at mm scale that may indicate seasonal variations in the sedimentary influx. These core data provide a unique record of decadal changes in regional climate that can be compared with other marine and continental archives to improve our understanding of the forcing mechanisms behind climate change

Automated High-Content Live Animal Drug Screening Using C. elegans Expressing the Aggregation Prone Serpin α1-antitrypsin Z

The development of preclinical models amenable to live animal bioactive compound screening is an attractive approach to discovering effective pharmacological therapies for disorders caused by misfolded and aggregation-prone proteins. In general, however, live animal drug screening is labor and resource intensive, and has been hampered by the lack of robust assay designs and high throughput work-flows. Based on their small size, tissue transparency and ease of cultivation, the use of C. elegans should obviate many of the technical impediments associated with live animal drug screening. Moreover, their genetic tractability and accomplished record for providing insights into the molecular and cellular basis of human disease, should make C. elegans an ideal model system for in vivo drug discovery campaigns. The goal of this study was to determine whether C. elegans could be adapted to high-throughput and high-content drug screening strategies analogous to those developed for cell-based systems. Using transgenic animals expressing fluorescently-tagged proteins, we first developed a high-quality, high-throughput work-flow utilizing an automated fluorescence microscopy platform with integrated image acquisition and data analysis modules to qualitatively assess different biological processes including, growth, tissue development, cell viability and autophagy. We next adapted this technology to conduct a small molecule screen and identified compounds that altered the intracellular accumulation of the human aggregation prone mutant that causes liver disease in α1-antitrypsin deficiency. This study provides powerful validation for advancement in preclinical drug discovery campaigns by screening live C. elegans modeling α1-antitrypsin deficiency and other complex disease phenotypes on high-content imaging platforms

Aligning for Innovation - Alignment Strategy to Drive Innovation

With the sudden need for innovation that will help the country achieve its long-term space exploration objectives, the question of whether NASA is aligned effectively to drive the innovation that it so desperately needs to take space exploration to the next level should be entertained. Authors such as Robert Kaplan and David North have noted that companies that use a formal system for implementing strategy consistently outperform their peers. They have outlined a six-stage management systems model for implementing strategy, which includes the aligning of the organization towards its objectives. This involves the alignment of the organization from the top down. This presentation will explore the impacts of existing U.S. industrial policy on technological innovation; assess the current NASA organizational alignment and its impacts on driving technological innovation; and finally suggest an alternative approach that may drive the innovation needed to take the world to the next level of space exploration, with NASA truly leading the way

Characterisation, prevalence and severity of skin lesions caused by ophidiomycosis in a population of wild snakes

Ophidiomycosis is an emerging infectious disease affecting wild snakes in the Northern Hemisphere. Recently confirmed in Great Britain, the prevalence, severity and significance of ophidiomycosis has yet to be characterised in free-living snakes at a population level in Europe. Therefore, a population of barred grass snakes (Natrix helvetica) in eastern England was monitored for three seasons (May 2019 to October 2021), to investigate the prevalence (25.5%; 191/750 snakes) and severity of skin lesions and their aetiology. The most frequently observed skin lesion characteristics were changes in scale colour, crusting, and scale margin erosion. The majority of such lesions (96.9%; 185/191 snakes) was observed on the ventral surface along the length of the body. The severity of skin lesions was considered mild in more than half of the cases (53.1%; 98/191 snakes). Predominantly, skin lesions were observed in adult snakes (72.8%; 139/191 snakes). Combined histological examinations and qPCR tests of skin lesions from N. helvetica sloughs and/or carcasses confirmed a diagnosis of ophidiomycosis. Further targeted surveillance, supported by molecular and histological examinations to confirm skin lesion aetiology, is required to determine the extent to which our findings reflect the occurrence of ophidiomycosis in populations within wider landscapes.</p

The AtRial Cardiopathy and Antithrombotic Drugs In prevention After cryptogenic stroke randomized trial: Rationale and methods

Recent data suggest that a thrombogenic atrial substrate can cause stroke in the absence of atrial fibrillation. Such an atrial cardiopathy may explain some proportion of cryptogenic strokes. The aim of the ARCADIA trial is to test the hypothesis that apixaban is superior to aspirin for the prevention of recurrent stroke in subjects with cryptogenic ischemic stroke and atrial cardiopathy. 1100 participants. Biomarker-driven, randomized, double-blind, active-control, phase 3 clinical trial conducted at 120 U.S. centers participating in NIH StrokeNet. Patients ≥ 45 years of age with embolic stroke of undetermined source and evidence of atrial cardiopathy, defined as ≥ 1 of the following markers: P-wave terminal force >5000 µV × ms in ECG lead V , serum NT-proBNP > 250 pg/mL, and left atrial diameter index ≥ 3 cm/m on echocardiogram. Exclusion criteria include any atrial fibrillation, a definite indication or contraindication to antiplatelet or anticoagulant therapy, or a clinically significant bleeding diathesis. Intervention: Apixaban 5 mg twice daily versus aspirin 81 mg once daily. Analysis: Survival analysis and the log-rank test will be used to compare treatment groups according to the intention-to-treat principle, including participants who require open-label anticoagulation for newly detected atrial fibrillation. The primary efficacy outcome is recurrent stroke of any type. The primary safety outcomes are symptomatic intracranial hemorrhage and major hemorrhage other than intracranial hemorrhage. ARCADIA is the first trial to test whether anticoagulant therapy reduces stroke recurrence in patients with atrial cardiopathy but no known atrial fibrillation

Ketogenic diet improves behaviors in a maternal immune activation model of autism spectrum disorder

Prenatal factors influence autism spectrum disorder (ASD) incidence in children and can increase ASD symptoms in offspring of animal models. These may include maternal immune activation (MIA) due to viral or bacterial infection during the first trimesters. Unfortunately, regardless of ASD etiology, existing drugs are poorly effective against core symptoms. For nearly a century a ketogenic diet (KD) has been used to treat seizures, and recent insights into mechanisms of ASD and a growing recognition that immune/inflammatory conditions exacerbate ASD risk has increased interest in KD as a treatment for ASD. Here we studied the effects of KD on core ASD symptoms in offspring exposed to MIA. To produce MIA, pregnant C57Bl/6 mice were injected with the viral mimic polyinosinic-polycytidylic acid; after weaning offspring were fed KD or control diet for three weeks. Consistent with an ASD phenotype of a higher incidence in males, control diet-fed MIA male offspring were not social and exhibited high levels of repetitive self-directed behaviors; female offspring were unaffected. However, KD feeding partially or completely reversed all MIA-induced behavioral abnormalities in males; it had no effect on behavior in females. KD-induced metabolic changes of reduced blood glucose and elevated blood ketones were quantified in offspring of both sexes. Prior work from our laboratory and others demonstrate KDs improve relevant behaviors in several ASD models, and here we demonstrate clear benefits of KD in the MIA model of ASD. Together these studies suggest a broad utility for metabolic therapy in improving core ASD symptoms, and support further research to develop and apply ketogenic and/or metabolic strategies in patients with ASD