Note on New KLT relations

In this short note, we present two results about KLT relations discussed in recent several papers. Our first result is the re-derivation of Mason-Skinner MHV amplitude by applying the S_{n-3} permutation symmetric KLT relations directly to MHV amplitude. Our second result is the equivalence proof of the newly discovered S_{n-2} permutation symmetric KLT relations and the well-known S_{n-3} permutation symmetric KLT relations. Although both formulas have been shown to be correct by BCFW recursion relations, our result is the first direct check using the regularized definition of the new formula.Comment: 15 Pages; v2: minor correction

Thermomechanical couplings in shape memory alloy materials

In this work we address several theoretical and computational issues which are related to the thermomechanical modeling of shape memory alloy materials. More specifically, in this paper we revisit a non-isothermal version of the theory of large deformation generalized plasticity which is suitable for describing the multiple and complex mechanisms occurring in these materials during phase transformations. We also discuss the computational implementation of a generalized plasticity based constitutive model and we demonstrate the ability of the theory in simulating the basic patterns of the experimentally observed behavior by a set of representative numerical examples

Polymeric Micelles in Anticancer Therapy: Targeting, Imaging and Triggered Release

Micelles are colloidal particles with a size around 5–100 nm which are currently under investigation as carriers for hydrophobic drugs in anticancer therapy. Currently, five micellar formulations for anticancer therapy are under clinical evaluation, of which Genexol-PM has been FDA approved for use in patients with breast cancer. Micelle-based drug delivery, however, can be improved in different ways. Targeting ligands can be attached to the micelles which specifically recognize and bind to receptors overexpressed in tumor cells, and chelation or incorporation of imaging moieties enables tracking micelles in vivo for biodistribution studies. Moreover, pH-, thermo-, ultrasound-, or light-sensitive block copolymers allow for controlled micelle dissociation and triggered drug release. The combination of these approaches will further improve specificity and efficacy of micelle-based drug delivery and brings the development of a ‘magic bullet’ a major step forward

Preparation and Evaluation of Poly(Ethylene Glycol)–Poly(Lactide) Micelles as Nanocarriers for Oral Delivery of Cyclosporine A

A series of monomethoxy poly(ethylene glycol)–poly(lactide) (mPEG–PLA) diblock copolymers were designed according to polymer–drug compatibility and synthesized, and mPEG–PLA micelle was fabricated and used as a nanocarrier for solubilization and oral delivery of Cyclosporine A (CyA). CyA was efficiently encapsulated into the micelles with nanoscaled diameter ranged from 60 to 96 nm with a narrow size distribution. The favorable stabilities of CyA-loaded polymeric micelles were observed in simulated gastric and intestinal fluids. The in vitro drug release investigation demonstrated that drug release was retarded by polymeric micelles. The enhanced intestinal absorption of CyA-loaded polymeric micelles, which was comparable to the commercial formulation of CyA (Sandimmun Neoral®), was found. These suggested that polymeric micelles might be an effective nanocarrier for solubilization of poorly soluble CyA and further improving oral absorption of the drug

Steroid Hormone Control of Cell Death and Cell Survival: Molecular Insights Using RNAi

The insect steroid hormone ecdysone triggers programmed cell death of obsolete larval tissues during metamorphosis and provides a model system for understanding steroid hormone control of cell death and cell survival. Previous genome-wide expression studies of Drosophila larval salivary glands resulted in the identification of many genes associated with ecdysone-induced cell death and cell survival, but functional verification was lacking. In this study, we test functionally 460 of these genes using RNA interference in ecdysone-treated Drosophila l(2)mbn cells. Cell viability, cell morphology, cell proliferation, and apoptosis assays confirmed the effects of known genes and additionally resulted in the identification of six new pro-death related genes, including sorting nexin-like gene SH3PX1 and Sox box protein Sox14, and 18 new pro-survival genes. Identified genes were further characterized to determine their ecdysone dependency and potential function in cell death regulation. We found that the pro-survival function of five genes (Ras85D, Cp1, CG13784, CG32016, and CG33087), was dependent on ecdysone signaling. The TUNEL assay revealed an additional two genes (Kap-α3 and Smr) with an ecdysone-dependent cell survival function that was associated with reduced cell death. In vitro, Sox14 RNAi reduced the percentage of TUNEL-positive l(2)mbn cells (p<0.05) following ecdysone treatment, and Sox14 overexpression was sufficient to induce apoptosis. In vivo analyses of Sox14-RNAi animals revealed multiple phenotypes characteristic of aberrant or reduced ecdysone signaling, including defects in larval midgut and salivary gland destruction. These studies identify Sox14 as a positive regulator of ecdysone-mediated cell death and provide new insights into the molecular mechanisms underlying the ecdysone signaling network governing cell death and cell survival

Reputation and identity conflict in management consulting

This is the author accepted manuscript. The final version is available from SAGE Publications via the DOI in this record.Based on a case study of a large consulting firm, this paper makes two contributions to the literature on reputation and identity by examining how an organization responds when its identity is substantially misaligned with the experience and perceptions of external stakeholders that form the basis of reputational judgments. First, rather than triggering some form of identity adaptation, it outlines how other forms of identity can come into play to remediate this gap, buffering the organization’s identity from change. This shift to other individual identities is facilitated by a low organizational identity context even when the identity of the firm is coherent and strong. The second contribution concerns the conceptualization of consulting and other professional service firms. We explain how reputation and identity interact in the context of the distinctive organizational features of these firms. Notably, their loosely coupled structure and the central importance of expert knowledge claims enable individual consultants both to reinforce and supplement corporate reputation via individual identity work

Fructose-1,6-bisphosphate and aldolase mediate glucose sensing by AMPK

葡萄糖是生物中最基本、最主要的营养物质，它不仅是机体能量的主要来源，也是生物质合成的主要原料。因此，葡萄糖的水平对于生物体是极其重要的。然而，在生活中，体内葡萄糖水平的波动是十分常见的，这是因为我们不可能每时每刻都在摄入葡萄糖：睡一大觉、剧烈运动几个小时或者太忙了没时间吃饭，都会引起葡萄糖水平的显著下降。这时，机体能够触发一套有效的过程应对这类“不利情况”，其中最为关键的就是激活“代谢的核心调节”——AMPK。在葡萄糖水平下降时，被激活的AMPK能够迅速启动脂肪、蛋白质的分解代谢，关闭它们的合成代谢，从而起到维持机体的能量和物质代谢的平衡，弥补机体因葡萄糖不足引起的胁迫压力。那么，机体如何感受葡萄糖水平下降，并“传递”给AMPK使其激活呢？林圣彩教授课题组的这项研究正是发现了生理状态下机体感受葡萄糖水平的机制。通过研究他们发现，无论在不含葡萄糖的细胞培养条件下，还是在饥饿的低血糖的动物体内，都不能观测到AMP水平的上升，这充分说明了机体有一套尚不为人知的、独立于AMP的感应葡萄糖水平的机制。在进一步的研究中他们揭示了这一完整过程：葡萄糖水平下降将引起的葡萄糖代谢中间物——果糖1,6-二磷酸（fructose-1,6-bisphosphate）水平的下降，该过程进一步地被糖酵解通路上的代谢酶——醛缩酶（aldolase）感应，因为醛缩酶正是将含有6个碳原子的果糖1,6-二磷酸裂解成三碳糖的酶，一旦醛缩酶“吃不到”由葡萄糖衍生的果糖1,6-二磷酸，它便“翻脸”，传递给也正是林圣彩教授课题组先前发现的溶酶体途径进而激活AMPK。该过程完全不涉及AMP水平，即能量水平的变化，是一条全新的、完全建立在实际的生理情况上的通路。林圣彩教授进一步地把葡萄糖水平总结为一种“状态信号”，以区别于传统的“能量信号”。据悉，该葡萄糖感知通路的发现对开发用于治疗肥胖症，乃至延长寿命的药物具有深远的意义。【Abstract】The major energy source for most cells is glucose, from which ATP is generated via glycolysis and/or oxidative metabolism. Glucose deprivation activates AMP-activated protein kinase (AMPK)1, but it is unclear whether this activation occurs solely via changes in AMP or ADP, the classical activators of AMPK2, 3, 4, 5. Here, we describe an AMP/ADP-independent mechanism that triggers AMPK activation by sensing the absence of fructose-1,6-bisphosphate (FBP), with AMPK being progressively activated as extracellular glucose and intracellular FBP decrease. When unoccupied by FBP, aldolases promote the formation of a lysosomal complex containing at least v-ATPase, ragulator, axin, liver kinase B1 (LKB1) and AMPK, which has previously been shown to be required for AMPK activation6, 7. Knockdown of aldolases activates AMPK even in cells with abundant glucose, whereas the catalysis-defective D34S aldolase mutant, which still binds FBP, blocks AMPK activation. Cell-free reconstitution assays show that addition of FBP disrupts the association of axin and LKB1 with v-ATPase and ragulator. Importantly, in some cell types AMP/ATP and ADP/ATP ratios remain unchanged during acute glucose starvation, and intact AMP-binding sites on AMPK are not required for AMPK activation. These results establish that aldolase, as well as being a glycolytic enzyme, is a sensor of glucose availability that regulates AMPK.D.G.H. was supported by an Investigator Award from the Wellcome Trust (097726) and a Programme Grant from Cancer Research UK (C37030/A15101). S.-C.L. was supported by grants from the National Key Research and Development Project of China (2016YFA0502001) and the National Natural Science Foundation of China (#31430094, #31690101, #31571214, #31601152 and #J1310027)

Macrophage-Specific Chemokines Induced via Innate Immunity by Amino Acid Copolymers and Their Role in EAE

The random amino acid copolymer poly(Y,E,A,K)n (Copaxone®) is widely used in multiple sclerosis treatment and a second generation copolymer poly(Y,F,A,K)n with enhanced efficacy in experimental autoimmune encephalomyelitis in mice has been described. A major mechanism through which copolymers function to ameliorate disease is the generation of immunosuppressive IL-10-secreting regulatory T cells entering the CNS. In addition, the antigen presenting cell to which these copolymers bind through MHC Class II proteins may have an important role. Here, both CCL22 (a Th2 cell chemoattractant) in large amounts and CXCL13 in much smaller amounts are shown to be secreted after administration of YFAK to mice and to a smaller extent by YEAK parallel to their serum concentrations. Moreover, bone marrow-derived macrophages secrete CCL22 in vitro in response to YFAK and to higher concentrations of YEAK. Strikingly, these chemokines are also secreted into serum of MHC Class II −/− mice, indicating that an innate immune receptor on these cells also has an important role. Thus, both the innate and the adaptive immune systems are involved in the mechanism of EAE amelioration by YFAK. The enhanced ability of YFAK to stimulate the innate immune system may account for its enhanced efficacy in EAE treatment