854 research outputs found
Angular Dependence of the Dipole-Dipole Interaction in a Nearly One-Dimensional Sample of Rydberg Atoms
Atoms in an ultracold highly excited sample are strongly coupled through the dipole-dipole interaction. In an effort to understand and manipulate the complicated interactions in this system we are investigating their dependence on the relative orientation of the dipoles. By focusing a 480 nm beam from a tunable dye laser into a magneto-optical trap, we produce a nearly one-dimensional sample of Rydberg atoms. The trap lies at the center of four conducting rods with which we can vary the magnitude and direction of the electric field at the trap, thus controlling the orientation of the dipoles with respect to the sample axis.We have measured the strength of the interaction for a variety of relative orientations
Empirical entropic contributions in computational docking: Evaluation in APS reductase complexes
The results from reiterated docking experiments may be used to evaluate an empirical vibrational entropy of binding in ligand–protein complexes. We have tested several methods for evaluating the vibrational contribution to binding of 22 nucleotide analogues to the enzyme APS reductase. These include two cluster size methods that measure the probability of finding a particular conformation, a method that estimates the extent of the local energetic well by looking at the scatter of conformations within clustered results, and an RMSD-based method that uses the overall scatter and clustering of all conformations. We have also directly characterized the local energy landscape by randomly sampling around docked conformations. The simple cluster size method shows the best performance, improving the identification of correct conformations in multiple docking experiments. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2008Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/60220/1/20936_ftp.pd
The mRNA expression of SETD2 in human breast cancer: Correlation with clinico-athological parameters
BACKGROUND: SET domain containing protein 2 (SETD2) is a histone methyltransferase that is involved in transcriptional elongation. There is evidence that SETD2 interacts with p53 and selectively regulates its downstream genes. Therefore, it could be implicated in the process of carcinogenesis. Furthermore, this gene is located on the short arm of chromosome 3p and we previously demonstrated that the 3p21.31 region of chromosome 3 was associated with permanent growth arrest of breast cancer cells. This region includes closely related genes namely: MYL3, CCDC12, KIF9, KLHL18 and SETD2. Based on the biological function of these genes, SETD2 is the most likely gene to play a tumour suppressor role and explain our previous findings. Our objective was to determine, using quantitative PCR, whether the mRNA expression levels of SETD2 were consistent with a tumour suppressive function in breast cancer. This is the first study in the literature to examine the direct relationship between SETD2 and breast cancer. METHODS: A total of 153 samples were analysed. The levels of transcription of SETD2 were determined using quantitative PCR and normalized against (CK19). Transcript levels within breast cancer specimens were compared to normal background tissues and analyzed against conventional pathological parameters and clinical outcome over a 10 year follow-up period. RESULTS: The levels of SETD2 mRNA were significantly lower in malignant samples (p = 0.0345) and decreased with increasing tumour stage. SETD2 expression levels were significantly lower in samples from patients who developed metastasis, local recurrence, or died of breast cancer when compared to those who were disease free for > 10 years (p = 0.041). CONCLUSION: This study demonstrates a compelling trend for SETD2 transcription levels to be lower in cancerous tissues and in patients who developed progressive disease. These findings are consistent with a possible tumour suppressor function of this gene in breast cancer
The RCSB Protein Data Bank: views of structural biology for basic and applied research and education.
The RCSB Protein Data Bank (RCSB PDB, http://www.rcsb.org) provides access to 3D structures of biological macromolecules and is one of the leading resources in biology and biomedicine worldwide. Our efforts over the past 2 years focused on enabling a deeper understanding of structural biology and providing new structural views of biology that support both basic and applied research and education. Herein, we describe recently introduced data annotations including integration with external biological resources, such as gene and drug databases, new visualization tools and improved support for the mobile web. We also describe access to data files, web services and open access software components to enable software developers to more effectively mine the PDB archive and related annotations. Our efforts are aimed at expanding the role of 3D structure in understanding biology and medicine
Palmitic Acid Analogs Exhibit Nanomolar Binding Affinity for the HIV-1 CD4 Receptor and Nanomolar Inhibition of gp120-to-CD4 Fusion
Background: We recently reported that palmitic acid (PA) is a novel and efficient CD4 fusion inhibitor to HIV-1 entry and infection. In the present report, based on in silico modeling of the novel CD4 pocket that binds PA, we describe discovery of highly potent PA analogs with increased CD4 receptor binding affinities (Kd) and gp120-to-CD4 inhibition constants (Ki). The PA analogs were selected to satisfy Lipinski’s rule of drug-likeness, increased solubility, and to avoid potential cytotoxicity. Principal Findings: PA analog 2-bromopalmitate (2-BP) was most efficacious with Kd,74 nM and Ki,122 nM, ascorbyl palmitate (6-AP) exhibited slightly higher Kd,140 nM and Ki,354 nM, and sucrose palmitate (SP) was least efficacious binding to CD4 with Kd,364 nM and inhibiting gp120-to-CD4 binding with Ki,1486 nM. Importantly, PA and its analogs specifically bound to the CD4 receptor with the one to one stoichiometry. Significance: Considering observed differences between K i and K d values indicates clear and rational direction for improving inhibition efficacy to HIV-1 entry and infection. Taken together this report introduces a novel class of natural small molecules fusion inhibitors with nanomolar efficacy of CD4 receptor binding and inhibition of HIV-1 entry
The kinetic dark-mixing in the light of CoGENT and XENON100
Several string or GUT constructions motivate the existence of a dark U(1)_D
gauge boson which interacts with the Standard Model only through its kinetic
mixing. We compute the dark matter abundance in such scenario and the
constraints in the light of the recent data from CoGENT, CDMSII and XENON100.
We show in particular that a region with relatively light WIMPS, M_{Z_D}< 40
GeV and a kinetic mixing 10^-4 < delta < 10^-3 is not yet excluded by the last
experimental data and seems to give promising signals in a near future. We also
compute the value of the kinetic mixing needed to explain the
DAMA/CoGENT/CRESST excesses and find that for M_{Z_D}< 30 GeV, delta ~ 10^-3 is
sufficient to fit with the data.Comment: 6 pages, 5figure
The ZZ' kinetic mixing in the light of the recent direct and indirect dark matter searches
Several constructions, of stringy origins or not, generate abelian gauge
extensions of the Standard Model (SM). Even if the particles of the SM are not
charged under this extra , one cannot avoid the presence of a kinetic
mixing between and the hypercharge . In this work, we
constraint drastically this kinetic mixing, taking into account the recent
experimental data from accelerator physics, direct detection and indirect
detection of dark matter. We show that the region respecting WMAP and
experimental constraints is now very narrowed along the pole line where
, being the gauge boson associated to the extra
.Comment: 9 pages, 3 figures, final version to appear in JCA
The RCSB Protein Data Bank: redesigned web site and web services
The RCSB Protein Data Bank (RCSB PDB) web site (http://www.pdb.org) has been redesigned to increase usability and to cater to a larger and more diverse user base. This article describes key enhancements and new features that fall into the following categories: (i) query and analysis tools for chemical structure searching, query refinement, tabulation and export of query results; (ii) web site customization and new structure alerts; (iii) pair-wise and representative protein structure alignments; (iv) visualization of large assemblies; (v) integration of structural data with the open access literature and binding affinity data; and (vi) web services and web widgets to facilitate integration of PDB data and tools with other resources. These improvements enable a range of new possibilities to analyze and understand structure data. The next generation of the RCSB PDB web site, as described here, provides a rich resource for research and education
The effective action of D6-branes in N=1 type IIA orientifolds
We use a Kaluza-Klein reduction to compute the low-energy effective action
for the massless modes of a spacetime-filling D6-brane wrapped on a special
Lagrangian 3-cycle of a type IIA Calabi-Yau orientifold. The modifications to
the characteristic data of the N=1 bulk orientifold theory in the presence of a
D6-brane are analysed by studying the underlying Type IIA supergravity coupled
to the brane worldvolume in the democratic formulation and performing a
detailed dualisation procedure. The N=1 chiral coordinates are found to be in
agreement with expectations from mirror symmetry. We work out the Kahler
potential for the chiral superfields as well as the gauge kinetic functions for
the bulk and the brane gauge multiplets including the kinetic mixing between
the two. The scalar potential resulting from the dualisation procedure can be
formally interpreted in terms of a superpotential. Finally, the gauging of the
Peccei-Quinn shift symmetries of the complex structure multiplets reproduces
the D-term potential enforcing the calibration condition for special Lagrangian
3-cycles.Comment: 48 pages, v2: typos corrected, references adde
A precision study of the fine tuning in the DiracNMSSM
Recently the DiracNMSSM has been proposed as a possible solution to reduce
the fine tuning in supersymmetry. We determine the degree of fine tuning needed
in the DiracNMSSM with and without non-universal gaugino masses and compare it
with the fine tuning in the GNMSSM. To apply reasonable cuts on the allowed
parameter regions we perform a precise calculation of the Higgs mass. In
addition, we include the limits from direct SUSY searches and dark matter
abundance. We find that both models are comparable in terms of fine tuning,
with the minimal fine tuning in the GNMSSM slightly smaller.Comment: 20 pages + appendices, 10 figure
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