415 research outputs found
Complete Nondiagonal Reflection Matrices of RSOS/SOS and Hard Hexagon Models
In this paper we compute the most general nondiagonal reflection matrices of
the RSOS/SOS models and hard hexagon model using the boundary Yang-Baxter
equations. We find new one-parameter family of reflection matrices for the RSOS
model in addition to the previous result without any parameter. We also find
three classes of reflection matrices for the SOS model, which has one or two
parameters. For the hard hexagon model which can be mapped to RSOS(5) model by
folding four RSOS heights into two, the solutions can be obtained similarly
with a main difference in the boundary unitarity conditions. Due to this, the
reflection matrices can have two free parameters. We show that these extra
terms can be identified with the `decorated' solutions. We also generalize the
hard hexagon model by `folding' the RSOS heights of the general RSOS(p) model
and show that they satisfy the integrability conditions such as the Yang-
Baxter and boundary Yang-Baxter equations. These models can be solved using the
results for the RSOS models.Comment: 18pages,Late
Development of an assay by liquid chromatography coupled to tandem mass spectrometry for thiopurines drugs in whole blood and application for their Therapeutic Drug Monitoring
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The combined diabetes and renal control trial (C-DIRECT) - a feasibility randomised controlled trial to evaluate outcomes in multi-morbid patients with diabetes and on dialysis using a mixed methods approach
Background: This cluster randomised controlled trial set out to investigate the feasibility and acceptability of the “Combined Diabetes and Renal Control Trial” (C-DIRECT) intervention, a nurse-led intervention based on motivational interviewing and self-management in patients with coexisting end stage renal diseases and diabetes mellitus (DM ESRD). Its efficacy to improve glycaemic control, as well as psychosocial and self-care outcomes were also evaluated as secondary outcomes.
Methods: An assessor-blinded, clustered randomised-controlled trial was conducted with 44 haemodialysis patients with DM ESRD and ≥ 8% glycated haemoglobin (HbA1c), in dialysis centres across Singapore. Patients were randomised according to dialysis shifts. 20 patients were assigned to intervention and 24 were in usual care. The C-DIRECT intervention consisted of three weekly chair-side sessions delivered by diabetes specialist nurses. Data on recruitment, randomisation, and retention, and secondary outcomes such as clinical endpoints, emotional distress, adherence, and self-management skills measures were obtained at baseline and at 12 weeks follow-up. A qualitative evaluation using interviews was conducted at the end of the trial.
Results: Of the 44 recruited at baseline, 42 patients were evaluated at follow-up. One patient died, and one discontinued the study due to deteriorating health. Recruitment, retention, and acceptability rates of C-DIRECT were generally satisfactory HbA1c levels decreased in both groups, but C-DIRECT had more participants with HbA1c < 8% at follow up compared to usual care. Significant improvements in role limitations due to physical health were noted for C-DIRECT whereas levels remained stable in usual care. No statistically significant differences between groups were observed for other clinical markers and other patient-reported outcomes. There were no adverse effects.
Conclusions: The trial demonstrated satisfactory feasibility. A brief intervention delivered on bedside as part of routine dialysis care showed some benefits in glycaemic control and on QOL domain compared with usual care, although no effect was observed in other secondary outcomes. Further research is needed to design and assess interventions to promote diabetes self-management in socially vulnerable patients
Tree-level FCNC in the B system: from CP asymmetries to rare decays
Tree-level Flavor-Changing Neutral Currents (FCNC) are characteristic of
models with extra vector-like quarks. These new couplings can strongly modify
the B^0 CP asymmetries without conflicting with low--energy constraints. In the
light of a low CP asymmetry in B --> J/\psi K_{S}, we discuss the implications
of these contributions. We find that even these low values can be easily
accommodated in these models. Furthermore, we show that the new data from B
factories tend to favor an O(20) enhancement of the b --> d l \bar{l}
transition over the SM expectation.Comment: 5 pages, 4 figures. Accepted version in PRD. Updated analysis with
the new results from BaBar and BELLE. Figures enlarged, small typos
corrected. Conclusions essentially unchange
Constraints on the Mass and Mixing of the 4th Generation Quark From Direct CP Violation and Rare K Decays
We investigate the for in a
sequential fourth generation model. By giving the basic formulae for
in this model, we analyze the numerical results
which are dependent of and imaginary part of the fourth CKM
factor, (or and the
fourth generation CKM matrix phase ). We find that, unlike the SM, when
taking the central values of all parameters for ,
the values of can easily fit to the current
experimental data for all values of hadronic matrix elements estimated from
various approaches. Also, we show that the experimental values of
and rare K decays can provide a strong constraint
on both mass and mixing of the fourth generation quark. When taking the values
of hadronic matrix elements from the lattice or 1/N expansion calculations, a
large region of the up-type quark mass is excluded.Comment: 18 pages, 4 eps figure
Structural analysis of MDM2 RING separates degradation from regulation of p53 transcription activity
MDM2–MDMX complexes bind the p53 tumor-suppressor protein, inhibiting p53's transcriptional activity and targeting p53 for proteasomal degradation. Inhibitors that disrupt binding between p53 and MDM2 efficiently activate a p53 response, but their use in the treatment of cancers that retain wild-type p53 may be limited by on-target toxicities due to p53 activation in normal tissue. Guided by a novel crystal structure of the MDM2–MDMX–E2(UbcH5B)–ubiquitin complex, we designed MDM2 mutants that prevent E2–ubiquitin binding without altering the RING-domain structure. These mutants lack MDM2's E3 activity but retain the ability to limit p53′s transcriptional activity and allow cell proliferation. Cells expressing these mutants respond more quickly to cellular stress than cells expressing wild-type MDM2, but basal p53 control is maintained. Targeting the MDM2 E3-ligase activity could therefore widen the therapeutic window of p53 activation in tumors
3D printed kidney phantoms for an LED-based photoacoustic and ultrasound imaging system
Photoacoustic imaging is a powerful and increasingly popular technique for tissue diagnostics. Suitable tissue- equivalent phantoms are in high demand for validating photoacoustic imaging methods and for clinical training. In this work, we describe a method of directly 3D printing a photoacoustic tissue-equivalent phantom of a kidney based on Gel Wax, which is a mix of polymer and mineral oil. A kidney phantom that is compatible with photoacoustic scanning will enable clinicians to evaluate a portable LED-based photoacoustic and ultrasound imaging system as a means of locating tumors and other abnormalities. This represents a significant step towards clinical translation of the compact system. Training using realistic phantoms reduces the risks associated with clinical procedures. Complications during procedures can arise due to the specific structure of the kidney under investigation. Thus the ability to create a 3D printed phantom based on detailed anatomical images of a specific patient enables clinicians to train on a phantom with exactly the same structure as the kidney to be treated. Recently we developed a novel 3D printer based on gel wax. The device combines native gel wax with glass microspheres and titanium dioxide (TiO 2 ) particles to obtain a medium with tissue-like optical and acoustic properties. 3D models created using this printer can be given a range of values of optical absorption reduced scattering coefficients. The ability to 3D patient-specific phantoms at low cost has the potential to revolutionize the production and use of tissue-equivalent phantoms in future, and can be applied to a wide range of organs and imaging modalities
Progress report no. 4
Statement of responsibility on title-page reads: editors: M.J. Driscoll, D.D. Lanning, I. Kaplan, A.T. Supple ; contributors: A. Alvim, G.J. Brown, J.K. Chan, T.P. Choong, M.J. Driscoll, G. A. Ducat, I.A. Forbes, M.V. Gregory, S.Y. Ho, C.M. Hove, O. K. Kadiroglu, R.J. Kennerley, D.D. Lanning, J.L. Lazewatsky, L. Lederman, A.S. Leveckis, V.A. Miethe, P. A. Scheinert, A.M. Thompson, N.E. Todreas, C.P. Tzanos, and P.J. WoodIncludes bibliographical referencesProgress report; June 30, 1973U.S. Atomic Energy Commission contract: AT(11-1)225
The use of cystatin C to inhibit epithelial–mesenchymal transition and morphological transformation stimulated by transforming growth factor-β
INTRODUCTION: Transforming growth factor-β (TGF-β) is a potent suppressor of mammary epithelial cell (MEC) proliferation and is thus an inhibitor of mammary tumor formation. Malignant MECs typically evolve resistance to TGF-β-mediated growth arrest, enhancing their proliferation, invasion, and metastasis when stimulated by TGF-β. Recent findings suggest that therapeutics designed to antagonize TGF-β signaling may alleviate breast cancer progression, thereby improving the prognosis and treatment of breast cancer patients. We identified the cysteine protease inhibitor cystatin C (CystC) as a novel TGF-β type II receptor antagonist that inhibits TGF-β binding and signaling in normal and cancer cells. We hypothesized that the oncogenic activities of TGF-β, particularly its stimulation of mammary epithelial–mesenchymal transition (EMT), can be prevented by CystC. METHOD: Retroviral infection was used to constitutively express CystC or a CystC mutant impaired in its ability to inhibit cathepsin protease activity (namely Δ14CystC) in murine NMuMG MECs and in normal rat kidney (NRK) fibroblasts. The effect of recombinant CystC administration or CystC expression on TGF-β stimulation of NMuMG cell EMT in vitro was determined with immunofluorescence to monitor rearrangements of actin cytoskeletal architecture and E-cadherin expression. Soft-agar growth assays were performed to determine the effectiveness of CystC in preventing TGF-β stimulation of morphological transformation and anchorage-independent growth in NRK fibroblasts. Matrigel invasion assays were performed to determine the ability of CystC to inhibit NMuMG and NRK motility stimulated by TGF-β. RESULTS: CystC and Δ14CystC both inhibited NMuMG cell EMT and invasion stimulated by TGF-β by preventing actin cytoskeletal rearrangements and E-cadherin downregulation. Moreover, both CystC molecules completely antagonized TGF-β-mediated morphological transformation and anchorage-independent growth of NRK cells, and inhibited their invasion through synthetic basement membranes. Both CystC and Δ14CystC also inhibited TGF-β signaling in two tumorigenic human breast cancer cell lines. CONCLUSION: Our findings show that TGF-β stimulation of initiating metastatic events, including decreased cell polarization, reduced cell–cell contact, and elevated cell invasion and migration, are prevented by CystC treatment. Our findings also suggest that the future development of CystC or its peptide mimetics hold the potential to improve the therapeutic response of human breast cancers regulated by TGF-β
MiR-107 and MiR-185 Can Induce Cell Cycle Arrest in Human Non Small Cell Lung Cancer Cell Lines
BACKGROUND: MicroRNAs (miRNAs) are short single stranded noncoding RNAs that suppress gene expression through either translational repression or degradation of target mRNAs. The annealing between messenger RNAs and 5' seed region of miRNAs is believed to be essential for the specific suppression of target gene expression. One miRNA can have several hundred different targets in a cell. Rapidly accumulating evidence suggests that many miRNAs are involved in cell cycle regulation and consequentially play critical roles in carcinogenesis. METHODOLOGY/PRINCIPAL FINDINGS: Introduction of synthetic miR-107 or miR-185 suppressed growth of the human non-small cell lung cancer cell lines. Flow cytometry analysis revealed these miRNAs induce a G1 cell cycle arrest in H1299 cells and the suppression of cell cycle progression is stronger than that by Let-7 miRNA. By the gene expression analyses with oligonucleotide microarrays, we find hundreds of genes are affected by transfection of these miRNAs. Using miRNA-target prediction analyses and the array data, we listed up a set of likely targets of miR-107 and miR-185 for G1 cell cycle arrest and validate a subset of them using real-time RT-PCR and immunoblotting for CDK6. CONCLUSIONS/SIGNIFICANCE: We identified new cell cycle regulating miRNAs, miR-107 and miR-185, localized in frequently altered chromosomal regions in human lung cancers. Especially for miR-107, a large number of down-regulated genes are annotated with the gene ontology term 'cell cycle'. Our results suggest that these miRNAs may contribute to regulate cell cycle in human malignant tumors
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