10,101 research outputs found
Effects of Epac1 on Diabetic Retinal Inflammation
An ever-growing body of research suggests that inflammation is one of the primary causes of diabetic retinopathy, as the inflammation can lead to insulin resistance. Beta-adrenergic receptor agonists can reduce the inflammation in human retinal endothelial cells (HRECs), but are not a viable treatment due to systemic effects. Epac1 lies downstream of beta-adrenergic receptor signaling, and it may have the capability to reduce inflammation by acting as an alternative pathway for beta-adrenergic receptor agonists to block inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1B). We hypothesized that the Epac1 agonist will decrease cytokine levels, leading to improved insulin signal transduction in the retina.
HRECs were grown in normal (5mM) or high glucose (25mM). Some cells were not treated with the Epac1 agonist and serve as controls. Western blotting was done using primary antibodies for total and phosphorylated insulin receptor substrate-1 (IRS-1), insulin receptor (IR) and Akt, as well as beta actin as a control for loading. Anti-Rabbit IgG/HRP was used for secondary antibodies. ELISA analyses were done for protein levels of TNF-alpha and IL-1B. We are not done with data analyses, but we expect to find that Epac1 will increase insulin receptor and Akt phosphorylation, while reducing TNF-alpha and IL-1B levels
Counting, generating and sampling tree alignments
Pairwise ordered tree alignment are combinatorial objects that appear in RNA
secondary structure comparison. However, the usual representation of tree
alignments as supertrees is ambiguous, i.e. two distinct supertrees may induce
identical sets of matches between identical pairs of trees. This ambiguity is
uninformative, and detrimental to any probabilistic analysis.In this work, we
consider tree alignments up to equivalence. Our first result is a precise
asymptotic enumeration of tree alignments, obtained from a context-free grammar
by mean of basic analytic combinatorics. Our second result focuses on
alignments between two given ordered trees and . By refining our grammar
to align specific trees, we obtain a decomposition scheme for the space of
alignments, and use it to design an efficient dynamic programming algorithm for
sampling alignments under the Gibbs-Boltzmann probability distribution. This
generalizes existing tree alignment algorithms, and opens the door for a
probabilistic analysis of the space of suboptimal RNA secondary structures
alignments.Comment: ALCOB - 3rd International Conference on Algorithms for Computational
Biology - 2016, Jun 2016, Trujillo, Spain. 201
Antibiotics Increase Gut Metabolism and Antioxidant Proteins and Decrease Acute Phase Response and Necrotizing Enterocolitis in Preterm Neonates
Background: The appropriate use of antibiotics for preterm infants, which are highly susceptible to develop necrotizing enterocolitis (NEC), is not clear. While antibiotic therapy is commonly used in neonates with NEC symptoms and sepsis, it remains unknown how antibiotics may affect the intestine and NEC sensitivity. We hypothesized that broad-spectrum antibiotics, given immediately after preterm birth, would reduce NEC sensitivity and support intestinal protective mechanisms. Methodology/Principal Findings: Preterm pigs were treated with antibiotics for 5 d (oral and systemic doses of gentamycin, ampicillin and metrodinazole; AB group) and compared with untreated pigs. Only the untreated pigs showed evidence of NEC lesions and reduced digestive function, as indicated by lowered villus height and activity of brush border enzymes. In addition, 53 intestinal and 22 plasma proteins differed in expression between AB and untreated pigs. AB treatment increased the abundance of intestinal proteins related to carbohydrate and protein metabolism, actin filaments, iron homeostasis and antioxidants. Further, heat shock proteins and the complement system were affected suggesting that all these proteins were involved in the colonization-dependent early onset of NEC. In plasma, acute phase proteins (haptoglobin, complement proteins) decreased, while albumin, cleaved C3, ficolin and transferrin increased. Conclusions/Significance: Depressed bacterial colonization following AB treatment increases mucosal integrity and reduces bacteria-associated inflammatory responses in preterm neonates. The plasma proteins C3, ficolin, and transferrin are potential biomarkers of the colonization-dependent NEC progression in preterm neonates. © 2012 Jiang et al.published_or_final_versio
A new mib allele with a chromosomal deletion covering foxc1a exhibits anterior somite specification defect
mibnn2002, found from an allele screen, showed early segmentation defect and severe cell death phenotypes, which are different from previously known mib mutants. Despite distinct morphological phenotypes, the typical mib molecular phenotypes: her4 down-regulation, neurogenic phenotype and cold sensitive dlc expression pattern, still remained. The linkage analysis also indicated that mibnn2002 is a new mib allele. Failure of specification in anterior 7-10 somites is likely due to lack of foxc1a expression in mibnn2002 homozygotes. Somites and somite markers gradually appeared after 7-10 somite stage, suggesting that foxc1a is only essential for the formation of anterior 7-10 somites. Apoptosis began around 16-somite stage with p53 up-regulation. To find the possible links of mib, foxc1a and apoptosis, transcriptome analysis was employed. About 140 genes, including wnt3a, foxc1a and mib, were not detected in the homozygotes. Overexpression of foxc1a mRNA in mibnn2002 homozygotes partially rescued the anterior somite specification. In the process of characterizing mibnn2002 mutation, we integrated the scaffolds containing mib locus into chromosome 2 (or linkage group 2, LG2) based on synteny comparison and transcriptome results. Genomic PCR analysis further supported the conclusion and showed that mibnn2002 has a chromosomal deletion with the size of about 9.6 Mbp.published_or_final_versio
Unconventional quantum Hall effect and Berry’s phase 2pi in bilayer graphene.
There are known two distinct types of the integer quantum Hall effect. One is the conventional quantum Hall effect, characteristic of two-dimensional semiconductor systems, and the other is its relativistic counterpart recently observed in graphene, where charge carriers mimic Dirac fermions characterized by Berry’s phase pi, which results in a shifted positions of Hall plateaus. Here we report a third type of the integer quantum Hall effect. Charge carriers in bilayer graphene have a parabolic energy spectrum but are chiral and exhibit Berry’s phase 2pi affecting their quantum dynamics. The Landau quantization of these fermions results in plateaus in Hall conductivity at standard integer positions but the last (zero-level) plateau is missing. The zero-level anomaly is accompanied by metallic conductivity in the limit of low concentrations and high magnetic fields, in stark contrast to the conventional, insulating behavior in this regime. The revealed chiral fermions have no known analogues and present an intriguing case for quantum-mechanical studies
The Effective Fragment Molecular Orbital Method for Fragments Connected by Covalent Bonds
We extend the effective fragment molecular orbital method (EFMO) into
treating fragments connected by covalent bonds. The accuracy of EFMO is
compared to FMO and conventional ab initio electronic structure methods for
polypeptides including proteins. Errors in energy for RHF and MP2 are within 2
kcal/mol for neutral polypeptides and 6 kcal/mol for charged polypeptides
similar to FMO but obtained two to five times faster. For proteins, the errors
are also within a few kcal/mol of the FMO results. We developed both the RHF
and MP2 gradient for EFMO. Compared to ab initio, the EFMO optimized structures
had an RMSD of 0.40 and 0.44 {\AA} for RHF and MP2, respectively.Comment: Revised manuscrip
Precision Gauge Unification from Extra Yukawa Couplings
We investigate the impact of extra vector-like GUT multiplets on the
predicted value of the strong coupling. We find in particular that Yukawa
couplings between such extra multiplets and the MSSM Higgs doublets can resolve
the familiar two-loop discrepancy between the SUSY GUT prediction and the
measured value of alpha_3. Our analysis highlights the advantages of the
holomorphic scheme, where the perturbative running of gauge couplings is
saturated at one loop and further corrections are conveniently described in
terms of wavefunction renormalization factors. If the gauge couplings as well
as the extra Yukawas are of O(1) at the unification scale, the relevant
two-loop correction can be obtained analytically. However, the effect persists
also in the weakly-coupled domain, where possible non-perturbative corrections
at the GUT scale are under better control.Comment: 26 pages, LaTeX. v6: Important early reference adde
Radiative Electroweak Symmetry Breaking in a Little Higgs Model
We present a new Little Higgs model, motivated by the deconstruction of a
five-dimensional gauge-Higgs model. The approximate global symmetry is
, breaking to , with a gauged subgroup of
, breaking to . Radiative corrections produce an additional small vacuum misalignment,
breaking the electroweak symmetry down to . Novel features of this
model are: the only un-eaten pseudo-Goldstone boson in the effective theory is
the Higgs boson; the model contains a custodial symmetry, which ensures that
at tree-level; and the potential for the Higgs boson is generated
entirely through one-loop radiative corrections. A small negative mass-squared
in the Higgs potential is obtained by a cancellation between the contribution
of two heavy partners of the top quark, which is readily achieved over much of
the parameter space. We can then obtain both a vacuum expectation value of
GeV and a light Higgs boson mass, which is strongly correlated with the
masses of the two heavy top quark partners. For a scale of the global symmetry
breaking of TeV and using a single cutoff for the fermion loops, the
Higgs boson mass satisfies 120 GeV GeV over much of
the range of parameter space. For raised to 10 TeV, these values increase
by about 40 GeV. Effects at the ultraviolet cutoff scale may also raise the
predicted values of the Higgs boson mass, but the model still favors
GeV.Comment: 32 pages, 10 figures, JHEP style. Version accepted for publication in
JHEP. Includes additional discussion of sensitivity to UV effects and
fine-tuning, revised Fig. 9, added appendix and additional references
Scintigraphic assessment of bone status at one year following hip resurfacing : comparison of two surgical approaches using SPECT-CT scan
Objectives: To study the vascularity and bone metabolism of the femoral head/neck following hip resurfacing arthroplasty, and to use these results to compare the posterior and the trochanteric-flip approaches.
Methods: In our previous work, we reported changes to intra-operative blood flow during hip resurfacing arthroplasty comparing two surgical approaches. In this study, we report the vascularity and the metabolic bone function in the proximal femur in these same patients at one year after the surgery. Vascularity and bone function was assessed using scintigraphic techniques. Of the 13 patients who agreed to take part, eight had their arthroplasty through a posterior approach and five through a trochanteric-flip approach.
Results: One year after surgery, we found no difference in the vascularity (vascular phase) and metabolic bone function (delayed phase) at the junction of the femoral head/neck between the two groups of patients. Higher radiopharmaceutical uptake was found in the region of the greater trochanter in the trochanteric-flip group, related to the healing osteotomy.
Conclusions: Our findings using scintigraphic techniques suggest that the greater intra-operative reduction in blood flow to the junction of the femoral head/neck, which is seen with the posterior approach compared with trochanteric flip, does not result in any difference in vascularity or metabolic bone function one year after surgery
Review of multi-scale electromagnetic modeling
This paper reviews various methods to solve multiscale problems ranging from low-frequency methods to very high-frequency methods. ©2010 IEEE.published_or_final_versionThe 2010 International Conference on Electromagnetics in Advanced Applications (ICEAA), Sydney, N.S.W., 20-24 September 2010. In Proceedings of ICEAA'10, 2010, p. 641-64
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