49 research outputs found
Электрооборудование тепловой насосной станции
В данной работе выполнен расчет электроснабжения тепловой насосной станции №2 города Саяногорска. В работе так же рассмотрен механизм управления сетевым насосом при помощи преобразователя частоты с целью снижения потребляемой электрической энергии.In this paper, the power supply to the heat pump station No. 2 in Sayanogorsk has been calculated. In work the mechanism of management of the network pump by means of the frequency converter with the purpose of decrease in consumed electric energy is also considered
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Rapalink-1 Targets Glioblastoma Stem Cells and Acts Synergistically with Tumor Treating Fields to Reduce Resistance against Temozolomide.
Dysfunctions in brain networks supporting empathy: An fMRI study in adults with autism spectrum disorders
The present study aimed at identifying dysfunctions in brain networks that may underlie disturbed empathic behavior in autism spectrum disorders (ASD). During functional magnetic resonance imaging, subjects were asked to identify the emotional state observed in a facial stimulus (other-task) or to evaluate their own emotional response (self-task). Behaviorally, ASD subjects performed equally to the control group during the other-task, but showed less emotionally congruent responses in the self-task. Activations in brain regions related to theory of mind were observed in both groups. Activations of the medial prefrontal cortex (MPFC) were located in dorsal subregions in ASD subjects and in ventral areas in control subjects. During the self-task, ASD subjects activated an additional network of frontal and inferior temporal areas. Frontal areas previously associated with the human mirror system were activated in both tasks in control subjects, while ASD subjects recruited these areas during the self-task only. Activations in the ventral MPFC may provide the basis for one's “emotional bond” with other persons’ emotions. Such atypical patterns of activation may underlie disturbed empathy in individuals with ASD. Subjects with ASD may use an atypical cognitive strategy to gain access to their own emotional state in response to other people's emotions
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Rapalink-1 Targets Glioblastoma Stem Cells and Acts Synergistically with Tumor Treating Fields to Reduce Resistance against Temozolomide.
Glioblastoma (GBM) is a lethal disease with limited clinical treatment options available. Recently, a new inhibitor targeting the prominent cancer signaling pathway mTOR was discovered (Rapalink-1), but its therapeutic potential on stem cell populations of GBM is unknown. We applied a collection of physiological relevant organoid-like stem cell models of GBM and studied the effect of RL1 exposure on various cellular features as well as on the expression of mTOR signaling targets and stem cell molecules. We also undertook combination treatments with this agent and clinical GBM treatments tumor treating fields (TTFields) and the standard-of-care drug temozolomide, TMZ. Low nanomolar (nM) RL1 treatment significantly reduced cell growth, proliferation, migration, and clonogenic potential of our stem cell models. It acted synergistically to reduce cell growth when applied in combination with TMZ and TTFields. We performed an in silico analysis from the molecular data of diverse patient samples to probe for a relationship between the expression of mTOR genes, and mesenchymal markers in different GBM cohorts. We supported the in silico results with correlative protein data retrieved from tumor specimens. Our study further validates mTOR signaling as a druggable target in GBM and supports RL1, representing a promising therapeutic target in brain oncology
Mutation, selection, and ancestry in branching models: a variational approach
We consider the evolution of populations under the joint action of mutation
and differential reproduction, or selection. The population is modelled as a
finite-type Markov branching process in continuous time, and the associated
genealogical tree is viewed both in the forward and the backward direction of
time. The stationary type distribution of the reversed process, the so-called
ancestral distribution, turns out as a key for the study of mutation-selection
balance. This balance can be expressed in the form of a variational principle
that quantifies the respective roles of reproduction and mutation for any
possible type distribution. It shows that the mean growth rate of the
population results from a competition for a maximal long-term growth rate, as
given by the difference between the current mean reproduction rate, and an
asymptotic decay rate related to the mutation process; this tradeoff is won by
the ancestral distribution.
Our main application is the quasispecies model of sequence evolution with
mutation coupled to reproduction but independent across sites, and a fitness
function that is invariant under permutation of sites. Here, the variational
principle is worked out in detail and yields a simple, explicit result.Comment: 45 pages,8 figure
Imagining transitions in old age through the visual matrix method: thinking about what is hard to bear
Dominant discourses of ageing are often confined to what is less painful to think about and therefore idealise or denigrate ageing and later life. We present findings from an exploratory psychosocial study, in a Nordic context into three later-life transitions: from working life to retirement, from mental health to dementia, and from life to death. Because, for some, these topics are hard to bear, and therefore defended against and routinely excluded from everyday awareness, we used a method led by imagery and affect - the Visual Matrix - to elicit participants’ free associative personal and collective imagination. Through analysis of data extracts, on the three transitions, we illustrate oscillations between defending against the challenges of ageing and realism in facing the anxieties it can provoke. A recurring theme includes the finality of individual life and the inter-generational continuity, which together link life and death, hope and despair, separation and connectedness
The Mitochondrial Chaperone Protein TRAP1 Mitigates α-Synuclein Toxicity
Overexpression or mutation of α-Synuclein is associated with protein aggregation and interferes with a number of cellular processes, including mitochondrial integrity and function. We used a whole-genome screen in the fruit fly Drosophila melanogaster to search for novel genetic modifiers of human [A53T]α-Synuclein–induced neurotoxicity. Decreased expression of the mitochondrial chaperone protein tumor necrosis factor receptor associated protein-1 (TRAP1) was found to enhance age-dependent loss of fly head dopamine (DA) and DA neuron number resulting from [A53T]α-Synuclein expression. In addition, decreased TRAP1 expression in [A53T]α-Synuclein–expressing flies resulted in enhanced loss of climbing ability and sensitivity to oxidative stress. Overexpression of human TRAP1 was able to rescue these phenotypes. Similarly, human TRAP1 overexpression in rat primary cortical neurons rescued [A53T]α-Synuclein–induced sensitivity to rotenone treatment. In human (non)neuronal cell lines, small interfering RNA directed against TRAP1 enhanced [A53T]α-Synuclein–induced sensitivity to oxidative stress treatment. [A53T]α-Synuclein directly interfered with mitochondrial function, as its expression reduced Complex I activity in HEK293 cells. These effects were blocked by TRAP1 overexpression. Moreover, TRAP1 was able to prevent alteration in mitochondrial morphology caused by [A53T]α-Synuclein overexpression in human SH-SY5Y cells. These results indicate that [A53T]α-Synuclein toxicity is intimately connected to mitochondrial dysfunction and that toxicity reduction in fly and rat primary neurons and human cell lines can be achieved using overexpression of the mitochondrial chaperone TRAP1. Interestingly, TRAP1 has previously been shown to be phosphorylated by the serine/threonine kinase PINK1, thus providing a potential link of PINK1 via TRAP1 to α-Synuclein
Bit by bit or all at once?: Splitting up the inquiry task to promote children’s scientific reasoning
This study examined whether and why assigning children to a segmented inquiry task makes their investigations more productive. Sixty-one upper elementary-school pupils engaged in a simulation-based inquiry assignment either received a multivariable inquiry task (n = 21), a segmented version of this task that addressed the variables in successive order (n = 21), or could formulate a task themselves (n = 19). Results showed that children are naturally inclined to pose single-variable inquiry questions. Segmented tasks, in addition, invoked more systematic but equally comprehensive investigations than a single, unsegmented task. More systematic experimentation was associated with more valid inferences and beliefs. These findings demonstrate that dividing a multivariable inquiry task into a series of single-variable subtasks facilitates the control of variables rather than the control of the learning process, and promotes inference performance and conceptual understandin