Super-Resolved Enhancement of a Single Image and Its Application in Cardiac MRI

Super-resolved image enhancement is of great importance in medical imaging. Conventional methods often require multiple low resolution (LR) images from different views of the same object or learning from large amount of training datasets to achieve success. However, in real clinical environments, these prerequisites are rarely fulfilled. In this paper, we present a self-learning based method to perform superresolution (SR) from a single LR input. The mappings between the given LR image and its downsampled versions are modeled using support vector regression on features extracted from sparse coded dictionaries, coupled with dual-tree complex wavelet transform based denoising. We demonstrate the efficacy of our method in application of cardiac MRI enhancement. Both quantitative and qualitative results show that our SR method is able to preserve fine textural details that can be corrupted by noise, and therefore can maintain crucial diagnostic information

Strong and Tunable Nonlinear Optomechanical Coupling in a Low-Loss System

A major goal in optomechanics is to observe and control quantum behavior in a system consisting of a mechanical resonator coupled to an optical cavity. Work towards this goal has focused on increasing the strength of the coupling between the mechanical and optical degrees of freedom; however, the form of this coupling is crucial in determining which phenomena can be observed in such a system. Here we demonstrate that avoided crossings in the spectrum of an optical cavity containing a flexible dielectric membrane allow us to realize several different forms of the optomechanical coupling. These include cavity detunings that are (to lowest order) linear, quadratic, or quartic in the membrane's displacement, and a cavity finesse that is linear in (or independent of) the membrane's displacement. All these couplings are realized in a single device with extremely low optical loss and can be tuned over a wide range in situ; in particular, we find that the quadratic coupling can be increased three orders of magnitude beyond previous devices. As a result of these advances, the device presented here should be capable of demonstrating the quantization of the membrane's mechanical energy.Comment: 12 pages, 4 figures, 1 tabl

Structure and mechanism of human DNA polymerase η

The variant form of the human syndrome xeroderma pigmentosum (XPV) is caused by a deficiency in DNA polymerase eta (Pol eta), a DNA polymerase that enables replication through ultraviolet-induced pyrimidine dimers. Here we report high-resolution crystal structures of human Pol eta at four consecutive steps during DNA synthesis through cis-syn cyclobutane thymine dimers. Pol eta acts like a 'molecular splint' to stabilize damaged DNA in a normal B-form conformation. An enlarged active site accommodates the thymine dimer with excellent stereochemistry for two-metal ion catalysis. Two residues conserved among Pol eta orthologues form specific hydrogen bonds with the lesion and the incoming nucleotide to assist translesion synthesis. On the basis of the structures, eight Pol eta missense mutations causing XPV can be rationalized as undermining the molecular splint or perturbing the active-site alignment. The structures also provide an insight into the role of Pol eta in replicating through D loop and DNA fragile sites

Factorization and resummation of s-channel single top quark production

In this paper we study the factorization and resummation of s-channel single top quark production in the Standard Model at both the Tevatron and the LHC. We show that the production cross section in the threshold limit can be factorized into a convolution of hard function, soft function and jet function via soft-collinear-effective-theory (SCET), and resummation can be performed using renormalization group equation in the momentum space resummation formalism. We find that in general, the resummation effects enhance the Next-to-Leading-Order (NLO) cross sections by about $3$ at both the Tevatron and the LHC, and significantly reduce the factorization scale dependence of the total cross section at the Tevatron, while at the LHC we find that the factorization scale dependence has not been improved, compared with the NLO results.Comment: 29 pages, 7 figures; version published in JHE

Piperidinols that show anti-tubercular activity as inhibitors of arylamine N-acetyltransferase: an essential enzyme for mycobacterial survival inside macrophages

Latent M. tuberculosis infection presents one of the major obstacles in the global eradication of tuberculosis (TB). Cholesterol plays a critical role in the persistence of M. tuberculosis within the macrophage during latent infection. Catabolism of cholesterol contributes to the pool of propionyl-CoA, a precursor that is incorporated into cell-wall lipids. Arylamine N-acetyltransferase (NAT) is encoded within a gene cluster that is involved in the cholesterol sterol-ring degradation and is essential for intracellular survival. The ability of the NAT from M. tuberculosis (TBNAT) to utilise propionyl-CoA links it to the cholesterol-catabolism pathway. Deleting the nat gene or inhibiting the NAT enzyme prevents intracellular survival and results in depletion of cell-wall lipids. TBNAT has been investigated as a potential target for TB therapies. From a previous high-throughput screen, 3-benzoyl-4-phenyl-1-methylpiperidinol was identified as a selective inhibitor of prokaryotic NAT that exhibited antimycobacterial activity. The compound resulted in time-dependent irreversible inhibition of the NAT activity when tested against NAT from M. marinum (MMNAT). To further evaluate the antimycobacterial activity and the NAT inhibition of this compound, four piperidinol analogues were tested. All five compounds exert potent antimycobacterial activity against M. tuberculosis with MIC values of 2.3-16.9 µM. Treatment of the MMNAT enzyme with this set of inhibitors resulted in an irreversible time-dependent inhibition of NAT activity. Here we investigate the mechanism of NAT inhibition by studying protein-ligand interactions using mass spectrometry in combination with enzyme analysis and structure determination. We propose a covalent mechanism of NAT inhibition that involves the formation of a reactive intermediate and selective cysteine residue modification. These piperidinols present a unique class of antimycobacterial compounds that have a novel mode of action different from known anti-tubercular drugs

Adipocyte mitochondrial genes and the forkhead factor FOXC2 are decreased in type 2 diabetes patients and normalized in response to rosiglitazone

<p>Abstract</p> <p>Background</p> <p>FOXC2 has lately been implicated in diabetes and obesity as well as mitochondrial function and biogenesis and also as a regulator of mtTFA/Tfam. In this study, the expression of FOXC2 and selected genes involved in mitochondrial function and biogenesis in healthy subjects and in a matched cohort with type 2 diabetes patients before and after treatment with rosiglitazone was determined. Quantitative real time PCR was used to analyze both RNA and DNA from biopsies from subcutaneous adipose tissue.</p> <p>Methods</p> <p>Blood samples and subcutaneous abdominal fat biopsies were collected from 12 T2D patients, of which 11 concluded the study, pre-treatment and 90 days after initiation of rosiglitazone treatment, and from 19 healthy control subjects on the first and only visit from healthy subjects. Clinical parameters were measured on the blood samples. RNA and DNA were prepared from the fat biopsies and gene expression was measured with real time PCR.</p> <p>Results</p> <p>The expression level of genes in the mitochondrial respiratory complexes I - IV were significantly downregulated in the diabetic patients and restored in response to rosiglitazone treatment. Rosiglitazone treatment also increased the relative number of mitochondria in diabetic patients compared with controls. Furthermore, the transcription factors FOXC2 and mtTFA/Tfam displayed a response pattern identical to the mitochondrial genes.</p> <p>Conclusions</p> <p>FOXC2, mtTFA/Tfam and subunits of the respiratory complexes I - IV show equivalent regulation in gene expression levels in response to TZD treatment. This, together with the knowledge that FOXC2 has a regulatory function of mtTFA/Tfam and mitochondrial biogenesis, suggests that FOXC2 has a possible functional role in the TZD activated mitochondrial response.</p

Structural Characterization of Minor Ampullate Spidroin Domains and Their Distinct Roles in Fibroin Solubility and Fiber Formation

10.1371/journal.pone.0056142PLoS ONE82

Potential antimutagenic activity of berberine, a constituent of Mahonia aquifolium

BACKGROUND: As part of a study aimed at developing new pharmaceutical products from natural resources, the purpose of this research was twofold: (1) to fractionate crude extracts from the bark of Mahonia aquifolium and (2) to evaluate the strength of the antimutagenic activity of the separate components against one of the common direct-acting chemical mutagens. METHODS: The antimutagenic potency was evaluated against acridine orange (AO) by using Euglena gracilis as an eukaryotic test model, based on the ability of the test compound/fraction to prevent the mutagen-induced damage of chloroplast DNA. RESULTS: It was found that the antimutagenicity of the crude Mahonia extract resides in both bis-benzylisoquinoline (BBI) and protoberberine alkaloid fractions but only the protoberberine derivatives, jatrorrhizine and berberine, showed significant concentration-dependent inhibitory effect against the AO-induced chloroplast mutagenesis of E. gracilis. Especially berberine elicited, at a very low dose, remarkable suppression of the AO-induced mutagenicity, its antimutagenic potency being almost three orders of magnitude higher when compared to its close analogue, jatrorrhizine. Possible mechanisms of the antimutagenic action are discussed in terms of recent literature data. While the potent antimutagenic activity of the protoberberines most likely results from the inhibition of DNA topoisomerase I, the actual mechanism(s) for the BBI alkaloids is hard to be identified. CONCLUSIONS: Taken together, the results indicate that berberine possesses promising antimutagenic/anticarcinogenic potential that is worth to be investigated further

Non-Conjugated Small Molecule FRET for Differentiating Monomers from Higher Molecular Weight Amyloid Beta Species

Background: Systematic differentiation of amyloid (Aβ) species could be important for diagnosis of Alzheimer's disease (AD). In spite of significant progress, controversies remain regarding which species are the primary contributors to the AD pathology, and which species could be used as the best biomarkers for its diagnosis. These controversies are partially caused by the lack of reliable methods to differentiate the complicated subtypes of Aβ species. Particularly, differentiation of Aβ monomers from toxic higher molecular weight species (HrMW) would be beneficial for drug screening, diagnosis, and molecular mechanism studies. However, fast and cheap methods for these specific aims are still lacking. Principal Findings: We demonstrated the feasibility of a non-conjugated FRET (Förster resonance energy transfer) technique that utilized amyloid beta (Aβ) species as intrinsic platforms for the FRET pair assembly. Mixing two structurally similar curcumin derivatives that served as the small molecule FRET pair with Aβ40 aggregates resulted in a FRET signal, while no signal was detected when using Aβ40 monomer solution. Lastly, this FRET technique enabled us to quantify the concentrations of Aβ monomers and high molecular weight species in solution. Significance: We believe that this FRET technique could potentially be used as a tool for screening for inhibitors of Aβ aggregation. We also suggest that this concept could be generalized to other misfolded proteins/peptides implicated in various pathologies including amyloid in diabetes, prion in bovine spongiform encephalopathy, tau protein in AD, and α-synuclein in Parkinson disease.National Institute on Aging (K25AG036760

Conformational changes during human P2X7 receptor activation examined by structural modelling and cysteine-based cross-linking studies

The P2X7 receptor (P2X7R) is important in mediating a range of physiological functions and pathologies associated with tissue damage and inflammation and represents an attractive therapeutic target. However, in terms of their structure-function relationships, the mammalian P2X7Rs remain poorly characterised compared to some of their other P2XR counterparts. In this study, combining cysteine-based cross-linking and whole-cell patch-clamp recording, we examined six pairs of residues (A44/I331, D48/I331, I58/F311, S60/L320, I75/P177 and K81/V304) located in different parts of the extracellular and transmembrane domains of the human P2X7R. These residues are predicted to undergo substantial movement during the transition of the receptor ion channel from the closed to the open state, predictions which are made based on structural homology models generated from the crystal structures of the zebrafish P2X4R. Our results provide evidence that among the six pairs of cysteine mutants, D48C/I133C and K81C/V304C formed disulphide bonds that impaired the channel gating to support the notion that such conformational changes, particularly those in the outer ends of the transmembrane domains, are critical for human P2X7R activation