425 research outputs found
Research of academic motivation at the stage of forming a threshold level of mastering competences
The relevance of researched problem is caused by the society requirement to form and implement educational and creative potential of a student as a conductor of changes that set a high level of motivational behavior. The aim of this article is to develop a structural model of motivational behavior of students that allow carrying out modeling of specific characteristics and their practical application. The leading approach to the research of this problem is the provision of the theory of self-determination on basic needs that allow considering basics of intrinsic motivation. The results of the research are: the structural model of motivational behavior is considered in the article, the questions are selected and the questionnaire on educational motivation is developed for the poll of student's groups “Economy and Management”. The development and approbation of multi-profile software programs are “Students’ Questionnaire” to implement on-line poll or interviews with students on academic motivation. The results of the research can be useful for specialized structural divisions of the university, teachers, and also for the students in case of further research of the issues of academic motivation and individual educational paths. © 2016 Eremicheva et al
Optimizing Combination Therapies with Existing and Future CML Drugs
Small-molecule inhibitors imatinib, dasatinib and nilotinib have been developed to treat Chromic Myeloid Leukemia (CML). The existence of a triple-cross-resistant mutation, T315I, has been a challenging problem, which can be overcome by finding new inhibitors. Many new compounds active against T315I mutants are now at different stages of development. In this paper we develop an algorithm which can weigh different combination treatment protocols according to their cross-resistance properties, and find the protocols with the highest probability of treatment success. This algorithm also takes into account drug toxicity by minimizing the number of drugs used, and their concentration. Although our methodology is based on a stochastic model of CML microevolution, the algorithm itself does not require measurements of any parameters (such as mutation rates, or division/death rates of cells), and can be used by medical professionals without a mathematical background. For illustration, we apply this algorithm to the mutation data obtained in [1], [2]
Niche as a determinant of word fate in online groups
Patterns of word use both reflect and influence a myriad of human activities
and interactions. Like other entities that are reproduced and evolve, words
rise or decline depending upon a complex interplay between {their intrinsic
properties and the environments in which they function}. Using Internet
discussion communities as model systems, we define the concept of a word niche
as the relationship between the word and the characteristic features of the
environments in which it is used. We develop a method to quantify two important
aspects of the size of the word niche: the range of individuals using the word
and the range of topics it is used to discuss. Controlling for word frequency,
we show that these aspects of the word niche are strong determinants of changes
in word frequency. Previous studies have already indicated that word frequency
itself is a correlate of word success at historical time scales. Our analysis
of changes in word frequencies over time reveals that the relative sizes of
word niches are far more important than word frequencies in the dynamics of the
entire vocabulary at shorter time scales, as the language adapts to new
concepts and social groupings. We also distinguish endogenous versus exogenous
factors as additional contributors to the fates of words, and demonstrate the
force of this distinction in the rise of novel words. Our results indicate that
short-term nonstationarity in word statistics is strongly driven by individual
proclivities, including inclinations to provide novel information and to
project a distinctive social identity.Comment: Supporting Information is available here:
http://www.plosone.org/article/fetchSingleRepresentation.action?uri=info:doi/10.1371/journal.pone.0019009.s00
New Studies of the Pulsar Wind Nebula in the Supernova Remnant CTB 80
We investigated the kinematics of the pulsar wind nebula (PWN) associated
with PSR B1951+32 in the old supernova remnant CTB 80 using the Fabry-Perot
interferometer of the 6m Special Astrophysical Observatory telescope. In
addition to the previously known expansion of the system of bright filaments
with a velocity of 100-200km/s, we detected weak high-velocity features in the
H-alpha line at least up to velocities of 400-450km/s. We analyzed the
morphology of the PWN in the H-alpha, [SII], and [OIII] lines using HST data
and discuss its nature. The shape of the central filamentary shell, which is
determined by the emission in the [OIII] line and in the radio continuum, is
shown to be consistent with the bow-shock model for a significant (about 60
degrees) inclination of the pulsar's velocity vector to the plane of the sky.
In this case, the space velocity of the pulsar is twice higher than its
tangential velocity, i.e., it reaches ~500 km/s, and PSR B1951+32 is the first
pulsar whose line-of-sight velocity (of about 400 km/s) has been estimated from
the PWN observations. The shell-like H-alpha-structures outside the bow shock
front in the east and the west may be associated with both the pulsar's jets
and the pulsar-wind breakthrough due to the layered structure of the extended
CTB 80 shell.Comment: to appear in Astronomy Letters, 12 pages, 6 postscript figures, two
in colour; for a version with high resolution figures see
http://www.sao.ru/hq/grb/team/vkom/CTB80_fine.pd
Ectopic A-lattice seams destabilize microtubules
Natural microtubules typically include one A-lattice seam within an otherwise helically symmetric B-lattice tube. It is currently unclear how A-lattice seams influence microtubule dynamic instability. Here we find that including extra A-lattice seams in GMPCPP microtubules, structural analogues of the GTP caps of dynamic microtubules, destabilizes them, enhancing their median shrinkage rate by >20-fold. Dynamic microtubules nucleated by seeds containing extra A-lattice seams have growth rates similar to microtubules nucleated by B-lattice seeds, yet have increased catastrophe frequencies at both ends. Furthermore, binding B-lattice GDP microtubules to a rigor kinesin surface stabilizes them against shrinkage, whereas microtubules with extra A-lattice seams are stabilized only slightly. Our data suggest that introducing extra A-lattice seams into dynamic microtubules destabilizes them by destabilizing their GTP caps. On this basis, we propose that the single A-lattice seam of natural B-lattice MTs may act as a trigger point, and potentially a regulation point, for catastrophe
Evolution of Resistance to Targeted Anti-Cancer Therapies during Continuous and Pulsed Administration Strategies
The discovery of small molecules targeted to specific oncogenic pathways has revolutionized anti-cancer therapy. However, such therapy often fails due to the evolution of acquired resistance. One long-standing question in clinical cancer research is the identification of optimum therapeutic administration strategies so that the risk of resistance is minimized. In this paper, we investigate optimal drug dosing schedules to prevent, or at least delay, the emergence of resistance. We design and analyze a stochastic mathematical model describing the evolutionary dynamics of a tumor cell population during therapy. We consider drug resistance emerging due to a single (epi)genetic alteration and calculate the probability of resistance arising during specific dosing strategies. We then optimize treatment protocols such that the risk of resistance is minimal while considering drug toxicity and side effects as constraints. Our methodology can be used to identify optimum drug administration schedules to avoid resistance conferred by one (epi)genetic alteration for any cancer and treatment type
Nonlinear deterministic equations in biological evolution
We review models of biological evolution in which the population frequency
changes deterministically with time. If the population is self-replicating,
although the equations for simple prototypes can be linearised, nonlinear
equations arise in many complex situations. For sexual populations, even in the
simplest setting, the equations are necessarily nonlinear due to the mixing of
the parental genetic material. The solutions of such nonlinear equations
display interesting features such as multiple equilibria and phase transitions.
We mainly discuss those models for which an analytical understanding of such
nonlinear equations is available.Comment: Invited review for J. Nonlin. Math. Phy
Adenine, guanine and pyridine nucleotides in blood during physical exercise and restitution in healthy subjects
Maximal physical exertion is accompanied by increased degradation of purine nucleotides in muscles with the products of purine catabolism accumulating in the plasma. Thanks to membrane transporters, these products remain in an equilibrium between the plasma and red blood cells where they may serve as substrates in salvage reactions, contributing to an increase in the concentrations of purine nucleotides. In this study, we measured the concentrations of adenine nucleotides (ATP, ADP, AMP), inosine nucleotides (IMP), guanine nucleotides (GTP, GDP, GMP), and also pyridine nucleotides (NAD, NADP) in red blood cells immediately after standardized physical effort with increasing intensity, and at the 30th min of rest. We also examined the effect of muscular exercise on adenylate (guanylate) energy charge—AEC (GEC), and on the concentration of nucleosides (guanosine, inosine, adenosine) and hypoxanthine. We have shown in this study that a standardized physical exercise with increasing intensity leads to an increase in IMP concentration in red blood cells immediately after the exercise, which with a significant increase in Hyp concentration in the blood suggests that Hyp was included in the IMP pool. Restitution is accompanied by an increase in the ATP/ADP and ADP/AMP ratios, which indicates an increase in the phosphorylation of AMP and ADP to ATP. Physical effort applied in this study did not lead to changes in the concentrations of guanine and pyridine nucleotides in red blood cells
Agrobacterium tumefaciens-Induced Bacteraemia Does Not Lead to Reporter Gene Expression in Mouse Organs
Agrobacterium tumefaciens is the main plant biotechnology gene transfer tool with host range which can be extended to non-plant eukaryotic organisms under laboratory conditions. Known medical cases of Agrobacterium species isolation from bloodstream infections necessitate the assessment of biosafety-related risks of A. tumefaciens encounters with mammalian organisms. Here, we studied the survival of A. tumefaciens in bloodstream of mice injected with bacterial cultures. Bacterial titers of 108 CFU were detected in the blood of the injected animals up to two weeks after intravenous injection. Agrobacteria carrying Cauliflower mosaic virus (CaMV) 35S promoter-based constructs and isolated from the injected mice retained their capacity to promote green fluorescent protein (GFP) synthesis in Nicotiana benthamiana leaves. To examine whether or not the injected agrobacteria are able to express in mouse organs, we used an intron-containing GFP (GFPi) reporter driven either by a cytomegalovirus (CMV) promoter or by a CaMV 35S promoter. Western and northern blot analyses as well as RT-PCR analysis of liver, spleen and lung of mice injected with A. tumefaciens detected neither GFP protein nor its transcripts. Thus, bacteraemia induced in mice by A. tumefaciens does not lead to detectible levels of genetic transformation of mouse organs
Evolutionary dynamics of imatinib-treated leukemic cells by stochastic approach
The evolutionary dynamics of a system of cancerous cells in a model of
chronic myeloid leukemia (CML) is investigated by a statistical approach.
Cancer progression is explored by applying a Monte Carlo method to simulate the
stochastic behavior of cell reproduction and death in a population of blood
cells which can experience genetic mutations. In CML front line therapy is
represented by the tyrosine kinase inhibitor imatinib which strongly affects
the reproduction of leukemic cells only. In this work, we analyze the effects
of a targeted therapy on the evolutionary dynamics of normal, first-mutant and
cancerous cell populations. Several scenarios of the evolutionary dynamics of
imatinib-treated leukemic cells are described as a consequence of the efficacy
of the different modeled therapies. We show how the patient response to the
therapy changes when an high value of the mutation rate from healthy to
cancerous cells is present. Our results are in agreement with clinical
observations. Unfortunately, development of resistance to imatinib is observed
in a proportion of patients, whose blood cells are characterized by an
increasing number of genetic alterations. We find that the occurrence of
resistance to the therapy can be related to a progressive increase of
deleterious mutations.Comment: Submitted to Central European Journal of Physic
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