The Nondeterministic Waiting Time Algorithm: A Review

We present briefly the Nondeterministic Waiting Time algorithm. Our technique for the simulation of biochemical reaction networks has the ability to mimic the Gillespie Algorithm for some networks and solutions to ordinary differential equations for other networks, depending on the rules of the system, the kinetic rates and numbers of molecules. We provide a full description of the algorithm as well as specifics on its implementation. Some results for two well-known models are reported. We have used the algorithm to explore Fas-mediated apoptosis models in cancerous and HIV-1 infected T cells

The dynamic mass spectrometry probe (DMSP) - Advanced process analytics for therapeutic cell manufacturing, health monitoring and biomarker discovery

Spatially and temporally resolved in situ monitoring of biochemical cell culture environments, e.g., in application to therapeutic cell bioreactors, is of critical importance for facilitating the development of new and reliable quality control methodologies for cell therapies. Identifying and monitoring secreted biomolecular critical quality attributes (CQAs) to enable online feedback control will enable large scale, cost-effective manufacturing of therapeutic cells. These CQA biomarkers have varying concentrations within a bioreactor, both in time and space. Current methods for monitoring these diverse biomolecules are generally ex-situ, time consuming, destructive, provide bulk measurements, or lack the ability to reveal the complete secretome/metabolome composition. The Dynamic Mass Spectrometry Probe (DMSP) synergistically incorporates a sampling interface for localized intake of a small fluid volume of the cellular content, a micro-fabricated mass exchanger for sample conditioning and inline separation, and an integrated electrospray ionization (ESI) emitter for softly ionizing (i.e. preserved biochemical structure) extracted biomolecules for mass spectrometry (MS). ESI-MS via DMSP treatment enables both biomarker discovery and transient (~1 min) analysis of biochemical information indicative of cell health and potency. DMSP is manufactured using advanced batch microfabrication techniques, which minimize dead volume (~20 nL) and ensure repeatable operation and precise geometry of each device. DMSP treatment removes 99% of compounds that interfere with mass spectrometry analysis, such as inorganic salts, while retaining biomolecules of interest within the sample for ESI-MS analysis. DMSP has demonstrated the ability to substantially increase signal to noise ratio in MS detection of biomolecules, and to further enhance sensitivity for probing lower biomarker concentrations via introduction of ESI-MS enhancing molecules (i.e. proton donating chemicals, protein denaturing solvents, and supercharging agents) into the sample within the integrated mass exchanger. To exemplify the DMSP’s unique capabilities, Fig. 1 demonstrates detection of multiple low-concentration protein biomarkers sampled from a biochemically-complex cell media solution serving as a proxy to samples taken directly from cell growth bioreactors [1]. Please click Additional Files below to see the full abstract

Low Intensity, High Frequency Vibration Training to Improve Musculoskeletal Function in a Mouse Model of Duchenne Muscular Dystrophy

The objective of the study was to determine if low intensity, high frequency vibration training impacted the musculoskeletal system in a mouse model of Duchenne muscular dystrophy, relative to healthy mice. Three-week old wildtype (n = 26) and mdx mice (n = 22) were randomized to non-vibrated or vibrated (45 Hz and 0.6 g, 15 min/d, 5 d/wk) groups. In vivo and ex vivo contractile function of the anterior crural and extensor digitorum longus muscles, respectively, were assessed following 8 wks of vibration. Mdx mice were injected 5 and 1 days prior to sacrifice with Calcein and Xylenol, respectively. Muscles were prepared for histological and triglyceride analyses and subcutaneous and visceral fat pads were excised and weighed. Tibial bones were dissected and analyzed by micro-computed tomography for trabecular morphometry at the metaphysis, and cortical geometry and density at the mid-diaphysis. Three-point bending tests were used to assess cortical bone mechanical properties and a subset of tibiae was processed for dynamic histomorphometry. Vibration training for 8 wks did not alter trabecular morphometry, dynamic histomorphometry, cortical geometry, or mechanical properties (P≥0.34). Vibration did not alter any measure of muscle contractile function (P≥0.12); however the preservation of muscle function and morphology in mdx mice indicates vibration is not deleterious to muscle lacking dystrophin. Vibrated mice had smaller subcutaneous fat pads (P = 0.03) and higher intramuscular triglyceride concentrations (P = 0.03). These data suggest that vibration training at 45 Hz and 0.6 g did not significantly impact the tibial bone and the surrounding musculature, but may influence fat distribution in mice

Climate warming, marine protected areas and the ocean-scale integrity of coral reef ecosystems

Coral reefs have emerged as one of the ecosystems most vulnerable to climate variation and change. While the contribution of a warming climate to the loss of live coral cover has been well documented across large spatial and temporal scales, the associated effects on fish have not. Here, we respond to recent and repeated calls to assess the importance of local management in conserving coral reefs in the context of global climate change. Such information is important, as coral reef fish assemblages are the most species dense vertebrate communities on earth, contributing critical ecosystem functions and providing crucial ecosystem services to human societies in tropical countries. Our assessment of the impacts of the 1998 mass bleaching event on coral cover, reef structural complexity, and reef associated fishes spans 7 countries, 66 sites and 26 degrees of latitude in the Indian Ocean. Using Bayesian meta-analysis we show that changes in the size structure, diversity and trophic composition of the reef fish community have followed coral declines. Although the ocean scale integrity of these coral reef ecosystems has been lost, it is positive to see the effects are spatially variable at multiple scales, with impacts and vulnerability affected by geography but not management regime. Existing no-take marine protected areas still support high biomass of fish, however they had no positive affect on the ecosystem response to large-scale disturbance. This suggests a need for future conservation and management efforts to identify and protect regional refugia, which should be integrated into existing management frameworks and combined with policies to improve system-wide resilience to climate variation and change

Superposition rules for higher-order systems and their applications

Superposition rules form a class of functions that describe general solutions of systems of first-order ordinary differential equations in terms of generic families of particular solutions and certain constants. In this work we extend this notion and other related ones to systems of higher-order differential equations and analyse their properties. Several results concerning the existence of various types of superposition rules for higher-order systems are proved and illustrated with examples extracted from the physics and mathematics literature. In particular, two new superposition rules for second- and third-order Kummer--Schwarz equations are derived.Comment: (v2) 33 pages, some typos corrected, added some references and minor commentarie

Actions to halt biodiversity loss generally benefit the climate

The two most urgent and interlinked environmental challenges humanity faces are climate change and biodiversity loss. We are entering a pivotal decade for both the international biodiversity and climate change agendas with the sharpening of ambitious strategies and targets by the Convention on Biological Diversity and the United Nations Framework Convention on Climate Change. Within their respective Conventions, the biodiversity and climate interlinked challenges have largely been addressed separately. There is evidence that conservation actions that halt, slow or reverse biodiversity loss can simultaneously slow anthropogenic mediated climate change significantly. This review highlights conservation actions which have the largest potential for mitigation of climate change. We note that conservation actions have mainly synergistic benefits and few antagonistic trade-offs with climate change mitigation. Specifically, we identify direct co-benefits in 14 out of the 21 action targets of the draft post-2020 global biodiversity framework of the Convention on Biological Diversity, notwithstanding the many indirect links that can also support both biodiversity conservation and climate change mitigation. These relationships are context and scale-dependent; therefore, we showcase examples of local biodiversity conservation actions that can be incentivized, guided and prioritized by global objectives and targets. The close interlinkages between biodiversity, climate change mitigation, other nature\u27s contributions to people and good quality of life are seldom as integrated as they should be in management and policy. This review aims to re-emphasize the vital relationships between biodiversity conservation actions and climate change mitigation in a timely manner, in support to major Conferences of Parties that are about to negotiate strategic frameworks and international goals for the decades to come

Understanding signaling cascades in melanoma

Understanding regulatory pathways involved in melanoma development and progression has advanced significantly in recent years. It is now appreciated that melanoma is the result of complex changes in multiple signaling pathways that affect growth control, metabolism, motility and the ability to escape cell death programs. Here we review the major signaling pathways currently known to be deregulated in melanoma with an implication to its development and progression. Among these pathways are Ras, B-Raf, MEK, PTEN, phosphatidylinositol-3 kinase (PI3Ks) and Akt which are constitutively activated in a significant number of melanoma tumors, in most cases due to genomic change. Other pathways discussed in this review include the [Janus kinase/signal transducer and activator of transcription (JAK/STAT), transforming growth factor-beta pathways which are also activated in melanoma, although the underlying mechanism is not yet clear. As a paradigm for remodeled signaling pathways, melanoma also offers a unique opportunity for targeted drug development.Fil: Lopez Bergami, Pablo Roberto. Sanford-burnham Medical Research Institute; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Fitchmann, B. Sanford-burnham Medical Research Institute; Estados UnidosFil: Ronai, Ze´ev. Sanford-burnham Medical Research Institute; Estados Unido

Integrability of Lie systems through Riccati equations

Integrability conditions for Lie systems are related to reduction or transformation processes. We here analyse a geometric method to construct integrability conditions for Riccati equations following these approaches. This approach provides us with a unified geometrical viewpoint that allows us to analyse some previous works on the topic and explain new properties. Moreover, this new approach can be straightforwardly generalised to describe integrability conditions for any Lie system. Finally, we show the usefulness of our treatment in order to study the problem of the linearisability of Riccati equations.Comment: Corrected typo

Методологія вітчизняної кримінально-правової науки: становлення історичного методу та проблеми наступності

Аналізуються методологічні проблеми кримінально-правової науки, зокрема процес становлення історичного методу та його ролі у вивченні питань наступності в кримінальному праві.Анализируются методологические проблемы уголовно-правовой науки, в частности процесс становления исторического метода и его роли в изучении вопросов преемственности в уголовном праве.The paper is devoted to an analysis of methodological problems of a criminal legal sci­ence, namely, an establishing process of historical method and its role in studying succession issues in a criminal law

Environmental drivers of distribution and reef development of the Mediterranean coral Cladocora caespitosa

Cladocora caespitosa is the only Mediterranean scleractinian similar to tropical reef-building corals. While this species is part of the recent fossil history of the Mediterranean Sea, it is currently considered endangered due to its decline during the last decades. Environmental factors affecting the distribution and persistence of extensive bank reefs of this endemic species across its whole geographic range are poorly understood. In this study, we examined the environmental response of C. caespitosa and its main types of assemblages using ecological niche modeling and ordination analysis. We also predicted other suitable areas for the occurrence of the species and assessed the conservation effectiveness of Mediterranean marine protected areas (MPAs) for this coral. We found that phosphate concentration and wave height were factors affecting both the occurrence of this versatile species and the distribution of its extensive bioconstructions in the Mediterranean Sea. A set of factors (diffuse attenuation coefficient, calcite and nitrate concentrations, mean wave height, sea surface temperature, and shape of the coast) likely act as environmental barriers preventing the species from expansion to the Atlantic Ocean and the Black Sea. Uncertainties in our large-scale statistical results and departures from previous physiological and ecological studies are also discussed under an integrative perspective. This study reveals that Mediterranean MPAs encompass eight of the ten banks and 16 of the 21 beds of C. caespitosa. Preservation of water clarity by avoiding phosphate discharges may improve the protection of this emblematic species.Spanish Ministry of Economy and Competitiveness [CTM2014-57949-R]info:eu-repo/semantics/publishedVersio