Synthetic & Structural Studies on the Polymeric Complexes of Terephthaloyl-bis-(N-phenylhydroxamic Acid) (TPHA) & Sebacyl-bis(N-phenylhydroxamic Acid) (SPHA) with Co(II), Ni(II), Cu(II) & Zn(II)

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Classification of fibroglandular tissue distribution in the breast based on radiotherapy planning CT

Accurate segmentation of breast tissues is required for a number of applications such as model based deformable registration in breast radiotherapy. The accuracy of breast tissue segmentation is affected by the spatial distribution (or pattern) of fibroglandular tissue (FT). The goal of this study was to develop and evaluate texture features, determined from planning computed tomography (CT) data, to classify the spatial distribution of FT in the breas

Effective repair of articular cartilage using human pluripotent stem cell-derived tissue

In an effort to develop an effective source of clinically relevant cells and tissues for cartilage repair a directed differentiation method was used to generate articular chondrocytes and cartilage tissues from human embryonic stem cells (hESCs). It has previously been demonstrated that chondrocytes derived from hESCs retain a stable cartilage-forming phenotype following subcutaneous implantation in mice. In this report, the potential of hESC-derived articular-like cartilage to repair osteochondral defects created in the rat trochlea was evaluated. Articular cartilage-like tissues were generated from hESCs and implanted into the defects. After 6 and 12 weeks, the defects were evaluated histologically and immunohistochemically, and the quality of repair was assessed using a modified ICRS II scoring system. Following 6 and 12 weeks after implantation, hESC-derived cartilage tissues maintained their proteoglycan and type II collagen-rich matrix and scored significantly higher than control defects, which had been filled with fibrin glue alone. Implants were found to be well integrated with native host tissue at the basal and lateral surfaces, although implanted human cells and host cells remained regionally separated. A subset of implants underwent a process of remodeling similar to endochondral ossification, suggesting the potential for a single cartilaginous implant to promote the generation of new subchondral bone in addition to repair of the articular cartilage. The ability to create cartilage tissues with integrative and reparative properties from an unlimited and robust cell source represents a significant advance for cartilage repair that can be further developed in large animal models before clinicalsetting application

Turbulence Fluctuations and New Universal Realizability Conditions in Modelling

General turbulent mean statistics are shown to be characterized by a variational principle. The variational functionals, or ``effective actions'', have experimental consequences for turbulence fluctuations and are subject to realizability conditions of positivity and convexity. An efficient Rayleigh-Ritz algorithm is available to calculate approximate effective actions within PDF closures. Examples are given for Navier-Stokes and for a 3-mode system of Lorenz. The new realizability conditions succeed at detecting {\em a priori} the poor predictions of PDF closures even when the classical 2nd-order moment realizability conditions are satisfied.Comment: 4 pages, LaTeX (Version 2.09), 3 figures, Postscript, Submitted to Phys. Rev. Let

Structural analysis of cross α-helical nanotubes provides insight into the designability of filamentous peptide nanomaterials

The exquisite structure-function correlations observed in filamentous protein assemblies provide a paradigm for the design of synthetic peptide-based nanomaterials. However, the plasticity of quaternary structure in sequence-space and the lability of helical symmetry present significant challenges to the de novo design and structural analysis of such filaments. Here, we describe a rational approach to design self-assembling peptide nanotubes based on controlling lateral interactions between protofilaments having an unusual cross-α supramolecular architecture. Near-atomic resolution cryo-EM structural analysis of seven designed nanotubes provides insight into the designability of interfaces within these synthetic peptide assemblies and identifies a non-native structural interaction based on a pair of arginine residues. This arginine clasp motif can robustly mediate cohesive interactions between protofilaments within the cross-α nanotubes. The structure of the resultant assemblies can be controlled through the sequence and length of the peptide subunits, which generates synthetic peptide filaments of similar dimensions to flagella and pili

Fluctuations in the Irreversible Decay of Turbulent Energy

A fluctuation law of the energy in freely-decaying, homogeneous and isotropic turbulence is derived within standard closure hypotheses for 3D incompressible flow. In particular, a fluctuation-dissipation relation is derived which relates the strength of a stochastic backscatter term in the energy decay equation to the mean of the energy dissipation rate. The theory is based on the so-called ``effective action'' of the energy history and illustrates a Rayleigh-Ritz method recently developed to evaluate the effective action approximately within probability density-function (PDF) closures. These effective actions generalize the Onsager-Machlup action of nonequilibrium statistical mechanics to turbulent flow. They yield detailed, concrete predictions for fluctuations, such as multi-time correlation functions of arbitrary order, which cannot be obtained by direct PDF methods. They also characterize the mean histories by a variational principle.Comment: 26 pages, Latex Version 2.09, plus seceq.sty, a stylefile for sequential numbering of equations by section. This version includes new discussion of the physical interpretation of the formal Rayleigh-Ritz approximation. The title is also change

BRAF inhibition is associated with increased clonality in tumor-infiltrating lymphocytes

There have been significant advances with regard to BRAF-targeted therapies against metastatic melanoma. However, the majority of patients receiving BRAF inhibitors (BRAFi) manifest disease progression within a year. We have recently shown that melanoma patients treated with BRAFi exhibit an increase in melanoma-associated antigens and in CD8+ tumor-infiltrating lymphocytes in response to therapy. To characterize such a T-cell infiltrate, we analyzed the complementarity-determining region 3 (CDR3) of rearranged T-cell receptor (TCR) β chain-coding genes in tumor biopsies obtained before the initiation of BRAFi and 10–14 d later. We observed an increase in the clonality of tumor-infiltrating lymphocytes in 7 of 8 patients receiving BRAFi, with a statistically significant 21% aggregate increase in clonality. Over 80% of individual T-cell clones detected after initiation of BRAFi treatment were new clones. Interestingly, the comparison of tumor infiltrates with clinical responses revealed that patients who had a high proportion of pre-existing dominant clones after the administration of BRAFi responded better to therapy than patients who had a low proportion of such pre-existing dominant clones following BRAFi. These data suggest that although the inhibition of BRAF in melanoma patients results in tumor infiltration by new lymphocytes, the response to treatment appears to be related to the presence of a pre-existing population of tumor-infiltrating T-cell clones

Certain subclasses of multivalent functions defined by new multiplier transformations

In the present paper the new multiplier transformations \mathrm{{\mathcal{J}% }}_{p}^{\delta }(\lambda ,\mu ,l) (\delta ,l\geq 0,\;\lambda \geq \mu \geq 0;\;p\in \mathrm{% }%\mathbb{N} )} of multivalent functions is defined. Making use of the operator $\mathrm{{\mathcal{J}}}_{p}^{\delta }(\lambda ,\mu ,l),$ two new subclasses $\mathcal{P}_{\lambda ,\mu ,l}^{\delta }(A,B;\sigma ,p)$ and $\widetilde{\mathcal{P}}_{\lambda ,\mu ,l}^{\delta }(A,B;\sigma ,p)$\textbf{\ }of multivalent analytic functions are introduced and investigated in the open unit disk. Some interesting relations and characteristics such as inclusion relationships, neighborhoods, partial sums, some applications of fractional calculus and quasi-convolution properties of functions belonging to each of these subclasses $\mathcal{P}_{\lambda ,\mu ,l}^{\delta }(A,B;\sigma ,p)$ and $\widetilde{\mathcal{P}}_{\lambda ,\mu ,l}^{\delta }(A,B;\sigma ,p)$ are investigated. Relevant connections of the definitions and results presented in this paper with those obtained in several earlier works on the subject are also pointed out