1,236 research outputs found
Дотик до вічності. Про розроблення нового історико/архітектурного плану м. Керчі
У 2009 р. автору статті було доручено очолити історико-містобудівні дослідження одного з найцікавіших стародавніх міст нашої країни Керчі. Метою досліджень було складання нового історико/архітектурного опорного плану з визначенням історичного ареалу і зони охорони найбільш цінних територій в межах сучасного міста
Fast DNA translocation through a solid-state nanopore
We report translocation experiments on double-strand DNA through a silicon
oxide nanopore. Samples containing DNA fragments with seven different lengths
between 2000 to 96000 basepairs have been electrophoretically driven through a
10 nm pore. We find a power-law scaling of the translocation time versus
length, with an exponent of 1.26 0.07. This behavior is qualitatively
different from the linear behavior observed in similar experiments performed
with protein pores. We address the observed nonlinear scaling in a theoretical
model that describes experiments where hydrodynamic drag on the section of the
polymer outside the pore is the dominant force counteracting the driving. We
show that this is the case in our experiments and derive a power-law scaling
with an exponent of 1.18, in excellent agreement with our data.Comment: 5 pages, 2 figures. Submitted to PR
Applied design thinking in urban air mobility: creating the airtaxi cabin design of the future from a user perspective
In the course of developing digital and future aviation cabin concepts at the
German Aerospace Center, the exploration of user-centered and
acceptance-enhancing methods plays a central role. The challenge here is to
identify the flexible range of requirements of different user groups for a
previously non-existent transport concept, to translate these into a concept
and to generate a rapid evaluation process by the user groups. Therefore, this
paper aims to demonstrate the application of the user-centered Design Thinking
method in the design of cabin for future air taxis. Based on the Design
Thinking approach and its iterative process steps, the direct implementation is
described on the combined airport shuttle and intracity UAM concept. The main
focus is on the identification of key user requirements by means of a focus
group study and the evaluation of initial cabin designs and key ideas by means
of an online survey. Consequently, the creative design process of a digital
prototype will be presented. In addition to an increased awareness and
acceptance among the population towards a novel mode of transportation, the
application of the Design Thinking methodology offers a flexible and
user-centered approach for further testing and simulation scenarios.Comment: 13 page
Rational Design of Small Molecule Inhibitors Targeting the Ras GEF, SOS1
SummaryRas GTPases regulate intracellular signaling involved in cell proliferation. Elevated Ras signaling activity has been associated with human cancers. Ras activation is catalyzed by guanine nucleotide exchange factors (GEFs), of which SOS1 is a major member that transduces receptor tyrosine kinase signaling to Ras. We have developed a rational approach coupling virtual screening with experimental screening in identifying small-molecule inhibitors targeting the catalytic site of SOS1 and SOS1-regulated Ras activity. A lead inhibitor, NSC-658497, was found to bind to SOS1, competitively suppress SOS1-Ras interaction, and dose-dependently inhibit SOS1 GEF activity. Mutagenesis and structure-activity relationship studies map the NSC-658497 site of action to the SOS1 catalytic site, and define the chemical moieties in the inhibitor essential for the activity. NSC-658497 showed dose-dependent efficacy in inhibiting Ras, downstream signaling activities, and associated cell proliferation. These studies establish a proof of principle for rational design of small-molecule inhibitors targeting Ras GEF enzymatic activity
Traumatic Brain Injury Induces Alterations in Cortical Glutamate Uptake without a Reduction in Glutamate Transporter-1 Protein Expression
We hypothesize that the primary mechanism for removal of glutamate from the extracellular space is altered after traumatic brain injury (TBI). To evaluate this hypothesis, we initiated TBI in adult male rats using a 2.0 atm lateral fluid percussion injury (LFPI) model. In the ipsilateral cortex and hippocampus, we found no differences in expression of the primary glutamate transporter in the brain (GLT-1) 24 h after TBI. In contrast, we found a decrease in glutamate uptake in the cortex, but not the hippocampus, 24 h after injury. Because glutamate uptake is potently regulated by protein kinases, we assessed global serine-threonine protein kinase activity using a kinome array platform. Twenty-five kinome array peptide substrates were differentially phoshorylated between LFPI and controls in the cortex, whereas 19 peptide substrates were differentially phosphorylated in the hippocampus (fold change ≥ ± 1.15). We identified several kinases as likely to be involved in acute TBI, including protein kinase B (Akt) and protein kinase C (PKC), which are well-characterized modulators of GLT-1. Exploratory studies using an inhibitor of Akt suggest selective activation of kinases in LFPI versus controls. Ingenuity pathway analyses of implicated kinases from our network model found apoptosis and cell death pathways as top functions in acute LFPI. Taken together, our data suggest diminished activity of glutamate transporters in the prefrontal cortex, with no changes in protein expression of the primary glutamate transporter GLT-1, and global alterations in signaling networks that include serine-threonine kinases that are known modulators of glutamate transport activity
Does Young's equation hold on the nanoscale? A Monte Carlo test for the binary Lennard-Jones fluid
When a phase-separated binary () mixture is exposed to a wall, that
preferentially attracts one of the components, interfaces between A-rich and
B-rich domains in general meet the wall making a contact angle .
Young's equation describes this angle in terms of a balance between the
interfacial tension and the surface tensions ,
between, respectively, the - and -rich phases and the wall,
. By Monte Carlo simulations
of bridges, formed by one of the components in a binary Lennard-Jones liquid,
connecting the two walls of a nanoscopic slit pore, is estimated from
the inclination of the interfaces, as a function of the wall-fluid interaction
strength. The information on the surface tensions ,
are obtained independently from a new thermodynamic integration method, while
is found from the finite-size scaling analysis of the
concentration distribution function. We show that Young's equation describes
the contact angles of the actual nanoscale interfaces for this model rather
accurately and location of the (first order) wetting transition is estimated.Comment: 6 pages, 6 figure
- …