Global and Local Information in Traffic Congestion

A generic network flow model of transport (of relevance to information transport as well as physical transport) is studied under two different control protocols. The first involves information concerning the global state of the network, the second only information about nodes' nearest neighbors. The global protocol allows for a larger external drive before jamming sets in, at the price of significant larger flow fluctuations. By triggering jams in neighboring nodes, the jamming perturbation grows as a pulsating core. This feature explains the different results for the two information protocols.Comment: 4 pages, 5 figures, preprint; corrected typos and minor format issue

Case report: Unusual complication during outpatient continuous regional popliteal analgesia

Purpose: Continuous regional anesthesia applied as pain therapy at home is clinically established standard practice after upper and lower limb surgery. Persistent motor block at discharge or after continuous infusion of local anesthetics, however, might lead to complications related to the insensate extremity. We report a rare case of a foot fracture due to stumbling after continuous sciatic nerve block at home and discuss the related clinical implications. Clinical features: After uncomplicated ambulatory foot surgery under regional anesthesia, a patient was discharged with a continuous sciatic popliteal nerve block for pain therapy at home. After stumbling, the patient remained symptom-free even until catheter removal three days after surgery. Radiography done one week after surgery revealed a styloid fracture of the fifth metatarsal bone. Her subsequent recovery was uneventful. Conclusions: The true incidence of complications related to falls at home associated with lower extremity blockade remains unknown, as symptoms of possible complications may be masked by the effects of the local anesthetic. However, with increasing use of postoperative regional anesthesia, it is mandatory to develop and adhere to clinical care maps, and to elaborate and teach strategies to further enhance patient safet

CodeProcess Charts: Visualizing the Process of Writing Code

Instructors of computer programming courses evaluate student progress on code submissions, exams, and other activities. The evaluation of code submissions is typically a summative assessment that gives very little insight into the process the student used when designing and writing the code. Thus, a tool that offers instructors a view into how students actually write their code could have broad impacts on assessment, intervention, instructional design, and plagiarism detection. In this article we propose an interactive software tool with a novel visualization that includes both static and dynamic views of the process that students take to complete computer programming assignments. We report results of an exploratory think-aloud study in which instructors offer thoughts as to the utility and potential of the tool. In the think-aloud study, we observed that the instructors easily identified multiple coding strategies (or the lack of thereof), were able to recognize plagiarism, and noticed a clear need for wider dissemination of tools for visualizing the programming process.Peer reviewe

Structure of the ATP synthase from Mycobacterium smegmatis provides targets for treating tuberculosis.

The structure has been determined by electron cryomicroscopy of the adenosine triphosphate (ATP) synthase from Mycobacterium smegmatis This analysis confirms features in a prior description of the structure of the enzyme, but it also describes other highly significant attributes not recognized before that are crucial for understanding the mechanism and regulation of the mycobacterial enzyme. First, we resolved not only the three main states in the catalytic cycle described before but also eight substates that portray structural and mechanistic changes occurring during a 360° catalytic cycle. Second, a mechanism of auto-inhibition of ATP hydrolysis involves not only the engagement of the C-terminal region of an α-subunit in a loop in the γ-subunit, as proposed before, but also a "fail-safe" mechanism involving the b'-subunit in the peripheral stalk that enhances engagement. A third unreported characteristic is that the fused bδ-subunit contains a duplicated domain in its N-terminal region where the two copies of the domain participate in similar modes of attachment of the two of three N-terminal regions of the α-subunits. The auto-inhibitory plus the associated "fail-safe" mechanisms and the modes of attachment of the α-subunits provide targets for development of innovative antitubercular drugs. The structure also provides support for an observation made in the bovine ATP synthase that the transmembrane proton-motive force that provides the energy to drive the rotary mechanism is delivered directly and tangentially to the rotor via a Grotthuss water chain in a polar L-shaped tunnel

Wildfire-Related Catastrophes : The Need for a Modern International Safety Investigation Procedure

Publisher Copyright: Copyright © 2021 Vuorio, Kovanen, Budowle, Sajantila, Palo and Stoop.Despite the increased frequency and scale of wildfire-related catastrophes, there has been little or no effective and coordinated international policy to address their highly negative impact. Possibly a generalized approach to respond to such major events could be modeled on existing international safety investigation policies and agreements that already have proved successful. The International Civil Aviation Organization (ICAO) outlines safety investigations after international fatal aviation accidents. Although this well-established safety investigation protocol cannot be directly applied in acute wildfire-related accidents, it can offer a useful framework for establishing international guidelines to reduce risk of future wildfire catastrophes. The co-operation between safety investigation authorities has been shown to be fruitful especially for those less developed countries that have limited resources and experience related to accident investigations. While primarily an adaptive measure that can set practices to reduce vulnerability and fragility of ecosystems and human societies, the same policies could be seen as a climate change mitigation measure, as wildfires can contribute significantly to global CO2 emissions. Finally, the concept of independent and qualified safety investigations represents the principle of serendipity: disclosing by accident something that has not been foreseen. Feedback from reality compensates assumptions and limitations of feedforward analysis of complex systems that can only reveal their dynamics and performance in reality and over time.Peer reviewe

The Digital Disruption and its Societal Impacts

Deepening digitalization and globalization has induced an ongoing societal transformation that may ultimately prove to be as significant as the original industrial revolution. Even as the ICT industry is being restructured, global competition is being transformed. Previously dominant firms—including telecommunications carriers, equipment providers, and powerful legacy software firms—are under assault from the move to cloud computing, in the network center, and mobile computing, on the network periphery. This transformation of the computing and communication infrastructure has been occurring simultaneously with the spread of ever more complicated and sophisticated global value chains. The articles in this special issue explore a number of the key facets of this transformation in a comparative lens. The authors find that the social, legal, and economic arrangements will impact how these changes affect nation-states. For policy-makers there will be serious dilemmas, as they will have to simultaneously nurture and support many aspects of these changes, while also mitigating or channeling some of the outcomes so as to protect privacy, income equality, and fair taxation.</p

Habitat preferences, estimated abundance and behavior of tree hyrax (Dendrohyrax sp.) in fragmented montane forests of Taita Hills, Kenya

We studied a previously almost unknown nocturnal mammal, an apparently undescribed species of tree hyrax (Dendrohyrax sp.) in the moist montane forests of Taita Hills, Kenya. We used thermal imaging to locate tree hyraxes, observe their behavior, and to identify woody plants most frequently visited by the selective browsers. We also documented acoustic behavior in forest fragments of different sizes. Data on calling type and frequency were analyzed together with lidar data to estimate population densities and to identify forest stand characteristics associated with large populations. Viable populations were found only in the largest forest fragments (> 90 ha), where tree hyraxes preferred most pristine forest stands with high, multilayered canopies. The estimated population sizes in smaller forest fragments were very limited, and hyraxes were heard to call only during late night and early morning hours, presumably in order to avoid detection. While we frequently recorded tree hyrax songs in the largest forest fragments, we almost never heard songs in the small ones. All remaining subpopulations of the Taita tree hyrax are under threat of human disturbance and further habitat deterioration. Conservation efforts should include protection of all remaining habitat patches, but also reforestation of former habitat is urgently needed.Peer reviewe

Structural and Biochemical Studies of Human 4-hydroxy-2-oxoglutarate Aldolase: Implications for Hydroxyproline Metabolism in Primary Hyperoxaluria

4-hydroxy-2-oxoglutarate (HOG) aldolase is a unique enzyme in the hydroxyproline degradation pathway catalyzing the cleavage of HOG to pyruvate and glyoxylate. Mutations in this enzyme are believed to be associated with the excessive production of oxalate in primary hyperoxaluria type 3 (PH3), although no experimental data is available to support this hypothesis. Moreover, the identity, oligomeric state, enzymatic activity, and crystal structure of human HOGA have not been experimentally determined.In this study human HOGA (hHOGA) was identified by mass spectrometry of the mitochondrial enzyme purified from bovine kidney. hHOGA performs a retro-aldol cleavage reaction reminiscent of the trimeric 2-keto-3-deoxy-6-phosphogluconate aldolases. Sequence comparisons, however, show that HOGA is related to the tetrameric, bacterial dihydrodipicolinate synthases, but the reaction direction is reversed. The 1.97 Å resolution crystal structure of hHOGA bound to pyruvate was determined and enabled the modeling of the HOG-Schiff base intermediate and the identification of active site residues. Kinetic analyses of site-directed mutants support the importance of Lys196 as the nucleophile, Tyr168 and Ser77 as components of a proton relay, and Asn78 and Ser198 as unique residues that facilitate substrate binding.The biochemical and structural data presented support that hHOGA utilizes a type I aldolase reaction mechanism, but employs novel residue interactions for substrate binding. A mapping of the PH3 mutations identifies potential rearrangements in either the active site or the tetrameric assembly that would likely cause a loss in activity. Altogether, these data establish a foundation to assess mutant forms of hHOGA and how their activity could be pharmacologically restored

First-in-human Phase 1 open label study of the BET inhibitor ODM-207 in patients with selected solid tumours

Background Bromodomain and extra-terminal domain (BET) proteins are reported to be epigenetic anti-cancer drug targets. This first-in-human study evaluated the safety, pharmacokinetics and preliminary anti-tumour activity of the BET inhibitor ODM-207 in patients with selected solid tumours. Methods This was an open-label Phase 1 study comprised of a dose escalation part, and evaluation of the effect of food on pharmacokinetics. ODM-207 was administered orally once daily. The dose escalation part was initiated with a dose titration in the initial cohort, followed by a 3 + 3 design. Results Thirty-five patients were treated with ODM-207, of whom 12 (34%) had castrate-resistant prostate cancer. One dose-limiting toxicity of intolerable fatigue was observed. The highest studied dose achieved was 2 mg/kg due to cumulative toxicity observed beyond the dose-limiting toxicity (DLT) treatment window. Common AEs included thrombocytopenia, asthenia, nausea, anorexia, diarrhoea, fatigue, and vomiting. Platelet count decreased proportionally to exposure with rapid recovery upon treatment discontinuation. No partial or complete responses were observed. Conclusions ODM-207 shows increasing exposure in dose escalation and was safe at doses up to 2 mg/kg but had a narrow therapeutic window.Peer reviewe