Mode locking in a spatially extended neuron model: active soma and compartmental tree

Understanding the mode-locked response of excitable systems to periodic forcing has important applications in neuroscience. For example it is known that spatially extended place cells in the hippocampus are driven by the theta rhythm to generate a code conveying information about spatial location. Thus it is important to explore the role of neuronal dendrites in generating the response to periodic current injection. In this paper we pursue this using a compartmental model, with linear dynamics for each compartment, coupled to an active soma model that generates action potentials. By working with the piece-wise linear McKean model for the soma we show how the response of the whole neuron model (soma and dendrites) can be written in closed form. We exploit this to construct a stroboscopic map describing the response of the spatially extended model to periodic forcing. A linear stability analysis of this map, together with a careful treatment of the non-differentiability of the soma model, allows us to construct the Arnol'd tongue structure for 1:q states (one action potential for q cycles of forcing). Importantly we show how the presence of quasi-active membrane in the dendrites can influence the shape of tongues. Direct numerical simulations confirm our theory and further indicate that resonant dendritic membrane can enlarge the windows in parameter space for chaotic behavior. These simulations also show that the spatially extended neuron model responds differently to global as opposed to point forcing. In the former case spatio-temporal patterns of activity within an Arnol'd tongue are standing waves, whilst in the latter they are traveling waves.

EGCL: an extended G-Code Language with flow control, functions and mnemonic variables

In the context of computer numerical control (CNC) and computer aided manufacturing (CAM), the capabilities of programming languages such as symbolic and intuitive programming, program portability and geometrical portfolio have special importance -- They allow to save time and to avoid errors during part programming and permit code re-usage -- Our updated literature review indicates that the current state of art presents voids in parametric programming, program portability and programming flexibility -- In response to this situation, this article presents a compiler implementation for EGCL (Extended G-code Language), a new, enriched CNC programming language which allows the use of descriptive variable names, geometrical functions and flow-control statements (if-then-else, while) -- Our compiler produces low-level generic, elementary ISO-compliant Gcode, thus allowing for flexibility in the choice of the executing CNC machine and in portability -- Our results show that readable variable names and flow control statements allow a simplified and intuitive part programming and permit re-usage of the programs -- Future work includes allowing the programmer to define own functions in terms of EGCL, in contrast to the current status of having them as library built-in functions

Why intelligent travel system is a good organizing trips tool for Polish tourists?

Paper based on the report for the unit on “Sociology of New Information Technologies” at the MSc Industrial Management and Engineering at the Universidade Nova Lisbon, Faculty of Sciences and Technology, under supervision of Prof. António B. Moniz. The report had the support from the ERASMUS program.

EXISTENCE OF UNUSED MANAGED CAPACITY ON DEDICATED LANES AND AN ALTERNATIVE ON HOW TO SELL IT VIA AUCTIONS

This dissertation verifies whether the following two hypotheses are true: (1) High-occupancy/toll lanes (and therefore other dedicated lanes) have capacity that could still be used; (2) such unused capacity (or more precisely, “unused managed capacity”) can be sold successfully through a real-time auction. To show that the second statement is true, this dissertation proposes an auction-based metering (ABM) system, that is, a mechanism that regulates traffic that enters the dedicated lanes. Participation in the auction is voluntary and can be skipped by paying the toll or by not registering to the new system. This dissertation comprises the following four components: a measurement of unused managed capacity on an existing HOT facility, a game-theoretic model of an ABM system, an operational description of the ABM system, and a simulation-based evaluation of the system. Some other and more specific contributions of this dissertation include the following: (1) It provides a definition and a methodology for measuring unused managed capacity and another important variable referred as “potential volume increase”. (2) It proves that the game-theoretic model has a unique Bayesian Nash equilibrium. (3) And it provides a specific road design that can be applied or extended to other facilities. The results provide evidence that the hypotheses are true and suggest that the ABM system would benefit a public operator interested in reducing traffic congestion significantly, would benefit drivers when making low-reliability trips (such as work-to-home trips), and would potentially benefit a private operator interested in raising revenue.

Synchronous products of rewrite systems (extended version)

We present and formalize a concept of synchronous product for rewrite systems, and also a corresponding concept for general transition systems, used as semantics for the former. A series of examples shows their practical usefulness: for the strategic control of systems, and for modular specification and verification.

TRIPS and Special & Differential Treatment – Revisiting the Case for Derogations in Applying Patent Protection for Pharmaceuticals in Developing Count

In this paper we apply an implicit threshold approach, malleable to the principle of graduation, to identify countries that should benefit from derogations from WTO TRIPS commitments for pharmaceutical patents under the tenets of Special and Differential Treatment. This is based on the identification of four broad constraints loosely classified as; economic constraints; access topharmaceuticals; capacity constraints; and incidence of health outcomes. We identify these by means of analytical criteria and create a composite index that ranks countries according to the observed constraints which delimit the capabilities and desirability of implementing TRIPs disciplines. We discuss the use of negotiated weights and thresholds in determining participation and graduation into general provisions of the agreement. It follows that countries below the chosen threshold should be exempt from these hence receiving Special and Differential Treatment.

Children with Special Health Care Needs: Comparison of the Effects of Home Care Setting, Prescribed Pediatric Extended Care Setting, and Long-Term Care Setting on Child and Family Health Outcomes and Health Care Service Use

Technological advances during the past 30 years have dramatically improved survival rates for children with life-threatening conditions (preterm births, congenital anomalies, disease, or injury) resulting in children with special health care needs (CSHCN), children who have or are at increased risk for a chronic physical, developmental, behavioral, or emotional condition and who require health and related services beyond that required by children generally. There are approximately 10.2 million of these children in the United States or one in five households with a child with special health care needs. Care for these children is limited to home care, medical day care (Prescribed Pediatric Extended Care; P-PEC) or a long term care (LTC) facility. There is very limited research examining health outcomes of CSHCN and their families. The purpose of this research was to compare the effects of home care settings, P-PEC settings, and LTC settings on child health and functioning, family health and function, and health care service use of families with CSHCN. Eighty four CSHCN ages 2 to 21 years having a medically fragile or complex medical condition that required continual monitoring were enrolled with their parents/guardians. Interviews were conducted monthly for five months using the PedsQL TM Generic Core Module for child health and functioning, PedsQL TM Family Impact Module for family health and functioning, and Access to Care from the NS-CSHCN survey for health care services. Descriptive statistics, chi square, and ANCOVA were conducted to determine differences across care settings. Children in the P-PEC settings had a highest health care quality of life (HRQL) overall including physical and psychosocial functioning. Parents/guardians with CSHCN in LTC had the highest HRQL including having time and energy for a social life and employment. Parents/guardians with CSHCN in home care settings had the poorest HRQL including physical and psychosocial functioning with cognitive difficulties, difficulties with worry, communication, and daily activities. They had the fewest hours of employment and the most hours providing direct care for their children. Overall health care service use was the same across the care settings.

Rapid detection of β-lactamase-hydrolyzing extended-spectrum cephalosporins in Enterobacteriaceae by use of the new chromogenic βLacta test

The chromogenic βLacta test developed for the rapid detection of β-lactamase-hydrolyzing extended-spectrum cephalosporins in Enterobacteriaceae revealed good performance with extended-spectrum β-lactamase (ESBL) producers (97.5% true-positive results). However, false-negative results occurred with chromosomal AmpC hyperproducers and plasmid AmpC producers, whereas uninterpretable results were mostly due to VIM-1 carbapenemase producers and possibly low levels of expressed ESBLs.

Association of extended-spectrum β-lactamase VEB-5 and 16S rRNA methyltransferase armA in Salmonella enterica from the United Kingdom

Aminoglycosides and beta-lactams are used for the treatment of a wide range of infections due to both Gram-negative and Gram-positive. An emerging aminoglycoside resistance mechanism, methylation of the aminoacyl site of the 16S rRNA, confers high-level resistance to clinically important aminoglycosides such as amikacin, tobramycin and gentamicin. Eight 16S rRNA methyltransferase genes, armA, rmtA, rmtB, rmtC, rmtD, rmtE, rmtF and npmA, have been identified in several species of enterobacteria worldwide (2, 6, 7, 9, 11, 13, 14). Resistance to extended spectrum β-lactams remains additionally an important clinical problem. Apart from the large TEM, SHV, and CTX-M families, several other extended-spectrum β-lactamases (ESBLs) have been identified, including VEB enzymes, which confer high-level resistance to cephalosporins and monobactams. Although 16S rRNA methyltransferases have been frequently identified associated with different ESBLs, there has been no report of association of a 16S rRNA methyltransferase with a VEB enzyme, except for the identification of rmtC with blaVEB-6 (14)

Land & Stream Management, June 2, 2010

Iowa’s rivers are constantly shifting and changing and can be challenging places to design, construct, and maintain water trails. This section discusses aspects you will immediately encounter when developing a water trail: launches, parking areas, and trails. The intended users and expected use suggest how these amenities are designed and constructed. Water trails intended for extended families, for example, are designed differently from those intended for experienced paddlers on multi-day trips.

PRISM (Polarized Radiation Imaging and Spectroscopy Mission): an extended white paper

PRISM (Polarized Radiation Imaging and Spectroscopy Mission) was proposed to ESA in May 2013 as a large-class mission for investigating within the framework of the ESA Cosmic Vision program a set of important scientific questions that require high res- olution, high sensitivity, full-sky observations of the sky emission at wavelengths ranging from millimeter-wave to the far-infrared. PRISM’s main objective is to explore the distant universe, probing cosmic history from very early times until now as well as the structures, distribution of matter, and velocity flows throughout our Hubble volume. PRISM will survey the full sky in a large number of frequency bands in both intensity and polarization and will measure the absolute spectrum of sky emission more than three orders of magnitude bet- ter than COBE FIRAS. The data obtained will allow us to precisely measure the absolute sky brightness and polarization of all the components of the sky emission in the observed frequency range, separating the primordial and extragalactic components cleanly from the galactic and zodiacal light emissions. The aim of this Extended White Paper is to provide a more detailed overview of the highlights of the new science that will be made possible by PRISM, which include: (1) the ultimate galaxy cluster survey using the Sunyaev-Zeldovich (SZ) e↵ect, detecting approximately 106 clusters extending to large redshift, including a char- acterization of the gas temperature of the brightest ones (through the relativistic corrections to the classic SZ template) as well as a peculiar velocity survey using the kinetic SZ e↵ect that comprises our entire Hubble volume; (2) a detailed characterization of the properties and evolution of dusty galaxies, where the most of the star formation in the universe took place, the faintest population of which constitute the di↵use CIB (Cosmic Infrared Background); (3) a characterization of the B modes from primordial gravity waves generated during inflation and from gravitational lensing, as well as the ultimate search for primordial non-Gaussianity using CMB polarization, which is less contaminated by foregrounds on small scales than thetemperature anisotropies; (4) a search for distortions from a perfect blackbody spectrum, which include some nearly certain signals and others that are more speculative but more informative; and (5) a study of the role of the magnetic field in star formation and its inter- action with other components of the interstellar medium of our Galaxy. These are but a few of the highlights presented here along with a description of the proposed instrument.

Plasticity and neuromodulation of the extended recurrent visual network

The extended visual network, which includes occipital, temporal and parietal posterior cortices, is a system characterized by an intrinsic connectivity consisting of bidirectional projections. This network is composed of feedforward and feedback projections, some hierarchically arranged and others bypassing intermediate areas, allowing direct communication across early and late stages of processing. Notably, the early visual cortex (EVC) receives considerably more feedback and lateral inputs than feedforward thalamic afferents, placing it at the receiving end of a complex cortical processing cascade, rather than just being the entrance stage of cortical processing of retinal input. The critical role of back-projections to visual cortices has been related to perceptual awareness, amplification of neural activity in lower order areas and improvement of stimulus processing. Recently, significant results have shown behavioural evidence suggesting the importance of reentrant projections in the human visual system, and demonstrated the feasibility of inducing their reversible modulation through a transcranial magnetic stimulation (TMS) paradigm named cortico-cortical paired associative stimulation (ccPAS). Here, a novel research line for the study of recurrent connectivity and its plasticity in the perceptual domain was put forward. In the present thesis, we used ccPAS with the aim of empowering the synaptic efficacy, and thus the connectivity, between the nodes of the visuocognitive system to evaluate the impact on behaviour. We focused on driving plasticity in specific networks entailing the elaboration of relevant social features of human faces (Chapters I & II), alongside the investigation of targeted pathways of sensory decisions (Chapter III). This allowed us to characterize perceptual outcomes which endorse the prominent role of the EVC in visual awareness, fulfilled by the activity of back-projections originating from distributed functional nodes.

A phase II, single arm study of CarbopLatin plus Etoposide with Bevacizumab and Atezolizumab in patients with exTEnded-disease small-cell lung cancer (SCLC) – CeLEBrATE trial

Small cell lung cancer (SCLC) is an aggressive neuroendocrine tumor diagnosed at extended disease SCLC (ES-SCLC) stage in about 70% of cases. The new standard of treatment for patients with ES-SCLC is a combination of platinum-etoposide chemotherapy and atezolizumab or durvalumab, two programmed cell death ligand 1 (PD-L1) inhibitory monoclonal antibodies (mAb). However, the benefit derived from the addition of PD-L1 inhibitors to chemotherapy in ES-SCLC was limited and restricted to a subset of patients. The vascular endothelial growth factor (VEGF) is the most important pro-angiogenic factor implicated in cancer angiogenesis, which is abundant in SCLC and associated with poor prognosis. Antiangiogenic agents, such as bevacizumab, a humanized mAb against VEGF, added to platinum-etoposide chemotherapy improved progression-free survival in SCLC in two trials, but it did not translate into a benefit in overall survival. Nevertheless, VEGF has also acts as a mediator of an immunosuppressive microenvironment and its inhibition can revert the immune-suppressive tumor microenvironment and potentially enhance the efficacy of immunotherapies. Based on available preclinical data, we hypothesized that VEGF inhibition by bevacizumab could improve atezolizumab efficacy in a synergistic way and designed a phase II single-arm trial of bevacizumab in combination with carboplatin, etoposide, and atezolizumab as first-line treatment in ES-SCLC. The trial, which is still ongoing, enrolled 53 patients, including those with treated or untreated asymptomatic brain metastases (provided criteria are met), who received atezolizumab, bevacizumab, carboplatin and etoposide for 4-6 cycles (induction phase), followed by maintenance with atezolizumab and bevacizumab for a maximum of 18 total cycles or until disease progression, patient refusal, unacceptable toxicity. The evaluation of efficacy of the experimental combination in terms of 1-year overall survival rate is not yet mature (primary objective of the trial). The combination was feasible and the toxicity profile manageable (secondary objective of the trial).

Developing a methodology for co-creation using extended reality technologies.

Amid the remarkable growth of innovative technologies, particularly immersive technologies like Extended Reality (XR) (comprising of Virtual Reality (VR), Augmented Reality (AR) & Mixed Reality (MR)), a transformation is unfolding in the way we collaborate and interact. The current research takes the initiative to explore XR’s potential for co-creation activities and proposes XR as a future co-creation platform. It strives to develop a XR-based co-creation system, actively engage stakeholders in the co-creation process, with the goal of enhancing their creative businesses. The research leverages XR tools to investigate how they can enhance digital co-creation methods and determine if the system facilitates efficient and effective value creation during XR-based co-creation sessions. In specific terms, the research probes into whether the XR-based co-creation method and environment enhances the quality and novelty of ideas, reduce communication challenges by providing better understanding of the product, problem or process and optimize the process in terms of reduction in time and costs. The research introduces a multi-user, multi-sensory collaborative and interactive XR platform that adapts to various use-case scenarios. This thesis also presents the user testing performed to collect both qualitative and quantitative data, which serves to substantiate the hypothesis. What sets this XR system apart is its incorporation of fully functional prototypes into a mixed reality environment, providing users with a unique dimension within an immersive digital landscape. The outcomes derived from the experimental studies demonstrate that XR-based co-creation surpasses conventional desktop co-creation methods and remarkably, the results are even comparable to a full mock-up test. In conclusion, the research underscores that the utilization of XR as a tool for co-creation generates substantial value. It serves as a method that enhances the process, an environment that fosters interaction and collaboration, and a platform that equips stakeholders with the means to engage effectively.