355 research outputs found
Design Equation: A Novel Approach to Heteropolymer Design
A novel approach to heteropolymer design is proposed. It is based on the
criterion by Kurosky and Deutsch, with which the probability of a target
conformation in a conformation space is maximized at low but finite
temperature. The key feature of the proposed approach is the use of soft spins
(fuzzy monomers) that leads to a design equation, which is an analog of the
Boltzmann machine learning equation in the design problem. We implement an
algorithm based on the design equation for the generalized HP model on the
3x3x3 cubic lattice and check its performance.Comment: 7 pages, 3 tables, 1 figures, uses jpsj.sty, jpsjbs1.sty, epsf.sty,
Submitted to J. Phys. Soc. Jp
development of adaptive immune effector therapies in solid tumors
Abstract State-of-the-art treatment strategies have drastically ameliorated the outcome of patients affected by cancer. However, resistant and recurrent solid tumors are generally nonresponsive to conventional therapies. A central factor in the sequence of events that lead to cancer is an alteration in antitumor immune surveillance, which results in failure to recognize and eliminate the transformed tumor cell. A greater understanding of the dysregulation and evasion of the immune system in the evolution and progression of cancer provides the basis for improved therapies. Targeted strategies, such as T-cell therapy, not only generally spare normal tissues, but also use alternative antineoplastic mechanisms that synergize with other therapeutics. Despite encouraging success in hematologic malignancies, adaptive cellular therapies for solid tumors face unique challenges because of the immunosuppressive tumor microenvironment, and the hurdle of T-cell trafficking within scarcely accessible tumor sites. This review provides a brief overview of current cellular therapeutic strategies for solid tumors, research carried out to increase efficacy and safety, and results from ongoing clinical trials
Spin effects in single electron tunneling
An important consequence of the discovery of giant magnetoresistance in
metallic magnetic multilayers is a broad interest in spin dependent effects in
electronic transport through magnetic nanostructures. An example of such
systems are tunnel junctions -- single-barrier planar junctions or more complex
ones. In this review we present and discuss recent theoretical results on
electron and spin transport through ferromagnetic mesoscopic junctions
including two or more barriers. Such systems are also called ferromagnetic
single-electron transistors. We start from the situation when the central part
of a device has the form of a magnetic (or nonmagnetic) metallic nanoparticle.
Transport characteristics reveal then single-electron charging effects,
including the Coulomb staircase, Coulomb blockade, and Coulomb oscillations.
Single-electron ferromagnetic transistors based on semiconductor quantum dots
and large molecules (especially carbon nanotubes) are also considered. The main
emphasis is placed on the spin effects due to spin-dependent tunnelling through
the barriers, which gives rise to spin accumulation and tunnel
magnetoresistance. Spin effects also occur in the current-voltage
characteristics, (differential) conductance, shot noise, and others. Transport
characteristics in the two limiting situations of weak and strong coupling are
of particular interest. In the former case we distinguish between the
sequential tunnelling and cotunneling regimes. In the strong coupling regime we
concentrate on the Kondo phenomenon, which in the case of transport through
quantum dots or molecules leads to an enhanced conductance and to a pronounced
zero-bias Kondo peak in the differential conductance.Comment: topical review (36 figures, 65 pages), to be published in J. Phys.:
Condens. Matte
Consensus of German Transplant Centers on Hematopoietic Stem Cell Transplantation in Fanconi Anemia
Allogeneic hematopoietic stem cell transplantation (HSCT) is currently the only curative therapy for the severe hematopoietic complications associated with Fanconi anemia (FA). In Germany, it is estimated that 10–15 transplants are performed annually for FA. However, because FA is a DNA repair disorder, standard conditioning regimens confer a high risk of excessive regimen-related toxicities and mortality, and reduced intensity regimens are linked with graft failure in some FA patients. Moreover, development of graft-versus-host disease is a major contributing factor for secondary solid tumors. The relative rarity of the disorder limits HSCT experience at any single center. Consensus meetings were convened to develop a national approach for HSCT in FA. This manuscript outlines current experience and knowledge about HSCT in FA and, based on this analysis, general recommendations reached at these meetings
Fourier Magnetic Imaging with Nanoscale Resolution and Compressed Sensing Speed-up using Electronic Spins in Diamond
Optically-detected magnetic resonance using Nitrogen Vacancy (NV) color
centres in diamond is a leading modality for nanoscale magnetic field imaging,
as it provides single electron spin sensitivity, three-dimensional resolution
better than 1 nm, and applicability to a wide range of physical and biological
samples under ambient conditions. To date, however, NV-diamond magnetic imaging
has been performed using real space techniques, which are either limited by
optical diffraction to 250 nm resolution or require slow, point-by-point
scanning for nanoscale resolution, e.g., using an atomic force microscope,
magnetic tip, or super-resolution optical imaging. Here we introduce an
alternative technique of Fourier magnetic imaging using NV-diamond. In analogy
with conventional magnetic resonance imaging (MRI), we employ pulsed magnetic
field gradients to phase-encode spatial information on NV electronic spins in
wavenumber or k-space followed by a fast Fourier transform to yield real-space
images with nanoscale resolution, wide field-of-view (FOV), and compressed
sensing speed-up.Comment: 31 pages, 10 figure
Changes of solar cell parameters during damp-heat exposure
The degradation of PV modules during damp-heat exposure is investigated. Power degradation is analysed in dependence of temperature and humidity during exposure. The module’s equivalent circuit parameters are calculated from I-V characteristics measured during ageing. A dose function is developed and degradations of power as well as equivalent circuit parameters can be analysed against the dose, which provides a better understanding of the module ageing behaviour. EL images of modules before and after ageing support the changes of solar cell parameters
Fr-TM-align: a new protein structural alignment method based on fragment alignments and the TM-score
©2008 Pandit and Skolnick; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. This article is available from: http://www.biomedcentral.com/1471-2105/9/531doi:10.1186/1471-2105-9-531Background: Protein tertiary structure comparisons are employed in various fields of
contemporary structural biology. Most structure comparison methods involve generation of an
initial seed alignment, which is extended and/or refined to provide the best structural superposition
between a pair of protein structures as assessed by a structure comparison metric. One such
metric, the TM-score, was recently introduced to provide a combined structure quality measure
of the coordinate root mean square deviation between a pair of structures and coverage. Using the
TM-score, the TM-align structure alignment algorithm was developed that was often found to have
better accuracy and coverage than the most commonly used structural alignment programs;
however, there were a number of situations when this was not true.
Results: To further improve structure alignment quality, the Fr-TM-align algorithm has been
developed where aligned fragment pairs are used to generate the initial seed alignments that are
then refined using dynamic programming to maximize the TM-score. For the assessment of the
structural alignment quality from Fr-TM-align in comparison to other programs such as CE and TMalign,
we examined various alignment quality assessment scores such as PSI and TM-score. The
assessment showed that the structural alignment quality from Fr-TM-align is better in comparison
to both CE and TM-align. On average, the structural alignments generated using Fr-TM-align have
a higher TM-score (~9%) and coverage (~7%) in comparison to those generated by TM-align. Fr-
TM-align uses an exhaustive procedure to generate initial seed alignments. Hence, the algorithm is
computationally more expensive than TM-align.
Conclusion: Fr-TM-align, a new algorithm that employs fragment alignment and assembly provides
better structural alignments in comparison to TM-align. The source code and executables of Fr-
TM-align are freely downloadable at: http://cssb.biology.gatech.edu/skolnick/files/FrTMalign/
A climate-sensitive forest model for assessing impacts of forest management in Europe
FORMIT-M is a widely applicable, open-access, simple and flexible, climate-sensitive forest management simulator requiring only standard forest inventory data as input. It combines a process-based carbon balance approach with a strong inventory-based empirical component. The model has been linked to the global forest sector model EFI-GTM to secure consistency between timber cutting and demand, although prescribed harvest scenarios can also be used. Here we introduce the structure of the model and demonstrate its use with example simulations until the end of the 21st century in Europe, comparing different management scenarios in different regions under climate change. The model was consistent with country-level statistics of growing stock volumes (R-2=0.938) and its projections of climate impact on growth agreed with other studies. The management changes had a greater impact on growing stocks, harvest potential and carbon balance than projected climate change, at least in the absence of increased disturbance rates.Peer reviewe
Neurochemical Changes in the Mouse Hippocampus Underlying the Antidepressant Effect of Genetic Deletion of P2X7 Receptors.
Recent investigations have revealed that the genetic deletion of P2X7 receptors (P2rx7) results in an antidepressant phenotype in mice. However, the link between the deficiency of P2rx7 and changes in behavior has not yet been explored. In the present study, we studied the effect of genetic deletion of P2rx7 on neurochemical changes in the hippocampus that might underlie the antidepressant phenotype. P2X7 receptor deficient mice (P2rx7-/-) displayed decreased immobility in the tail suspension test (TST) and an attenuated anhedonia response in the sucrose preference test (SPT) following bacterial endotoxin (LPS) challenge. The attenuated anhedonia was reproduced through systemic treatments with P2rx7 antagonists. The activation of P2rx7 resulted in the concentration-dependent release of [3H]glutamate in P2rx7+/+ but not P2rx7-/- mice, and the NR2B subunit mRNA and protein was upregulated in the hippocampus of P2rx7-/- mice. The brain-derived neurotrophic factor (BDNF) expression was higher in saline but not LPS-treated P2rx7-/- mice; the P2rx7 antagonist Brilliant blue G elevated and the P2rx7 agonist benzoylbenzoyl ATP (BzATP) reduced BDNF level. This effect was dependent on the activation of NMDA and non-NMDA receptors but not on Group I metabotropic glutamate receptors (mGluR1,5). An increased 5-bromo-2-deoxyuridine (BrdU) incorporation was also observed in the dentate gyrus derived from P2rx7-/- mice. Basal level of 5-HT was increased, whereas the 5HIAA/5-HT ratio was lower in the hippocampus of P2rx7-/- mice, which accompanied the increased uptake of [3H]5-HT and an elevated number of [3H]citalopram binding sites. The LPS-induced elevation of 5-HT level was absent in P2rx7-/- mice. In conclusion there are several potential mechanisms for the antidepressant phenotype of P2rx7-/- mice, such as the absence of P2rx7-mediated glutamate release, elevated basal BDNF production, enhanced neurogenesis and increased 5-HT bioavailability in the hippocampus
Experimental evidence of the ferroelectric phase transition near the point in liquid water
We studied dielectric properties of nano-sized liquid water samples confined
in polymerized silicates MCM-41 characterized by the porous sizes \sim 3-10nm.
We report the direct measurements of the dielectric constant by the dielectric
spectroscopy method at frequencies 25Hz-1MHz and demonstrate clear signatures
of the second-order phase transition of ferroelectric nature at temperatures
next to the \lambda- point in the bulk supercooled water. The presented results
support the previously developed polar liquid phenomenology and hence establish
its applicability to model actual phenomena in liquid water.Comment: 4 pages, single figur
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