Minimal set of generators for the derivation module of certain monomial curves

Let K be a field of characteristic zero and let m(0),..., m(e-1) be a sequence of positive integers. Let C be an algebroid monomial curve in the affine e-space A(K)(e) defined parametrically by X-0 = T-m0,..., Xe-1 = Tme-1 and let A be the coordinate ring of C. In this paper, we assume that some e - 1 terms of m(0),..., m(e-1) form an arithmetic sequence and construct a minimal set of generators for the derivation module Der(K)(A) of A and write an explicit formula for mu (Der(K)(A)).

Fuzzy logic intelligent system for gas turbine module and system fault isolation

A fuzzy logic intelligent system is developed for gas-turbine fault isolation. The gas path measurements used for fault isolation are exhaust gas temperature, low and high rotor speed, and fuel flow. These four measurements are also called the cockpit parameters and are typically found in almost all older and newer jet engines. The fuzzy logic system uses rules developed from a model of performance influence coefficients to isolate engine faults while accounting for uncertainty in gas path measurements. It automates the reasoning process of an experienced powerplant engineer. Tests with simulated data show that the fuzzy system isolates faults with an accuracy of 89% with only the four cockpit measurements. However, if additional pressure and temperature probes between the compressors and before the burner, which are often found in newer jet engines, are considered, the fault isolation accuracy rises to as high as 98%. In addition, the additional sensors are useful in keeping the fault isolation system robust as quality of the measured data deteriorates.

Insulin Growth Factor-2 Binding Protein 3 (IGF2BP3) Is a Glioblastoma-specific Marker That Activates Phosphatidylinositol 3-Kinase/Mitogen-activated Protein Kinase (PI3K/MAPK) Pathways by Modulating IGF-2

Glioblastoma is the most common and malignant form of primary astrocytoma. Upon investigation of the insulin-like growth factor (IGF) pathway, we found the IGF2BP3/IMP3 transcript and protein to be up-regulated in GBMs but not in lower grade astrocytomas (p<0.0001). IMP3 is an RNA binding protein known to bind to the 5'-untranslated region of IGF-2 mRNA, thereby activating its translation. Overexpression-and knockdown-based studies establish a role for IMP3 in promoting proliferation, anchorage-independent growth, invasion, and chemoresistance. IMP3 overexpressing B16F10 cells also showed increased tumor growth, angiogenesis, and metastasis, resulting in poor survival in a mouse model. Additionally, the infiltrating front, perivascular, and subpial regions in a majority of the GBMs stained positive for IMP3. Furthermore, two different murine glioma models were used to substantiate the above findings. In agreement with the translation activation functions of IMP3, we also found increased IGF-2 protein in the GBM tumor samples without a corresponding increase in its transcript levels. Also, in vitro IMP3 overexpression/knockdown modulated the IGF-2 protein levels without altering its transcript levels. Additionally, IGF-2 neutralization and supplementation studies established that the proproliferative effects of IMP3 were indeed mediated through IGF-2. Concordantly, PI3K and MAPK, the downstream effectors of IGF-2, are activated by IMP3 and are found to be essential for IMP3-induced cell proliferation. Thus, we have identified IMP3 as a GBM-specific proproliferative and proinvasive marker acting through IGF-2 resulting in the activation of oncogenic PI3K and MAPK pathways.

ESAT-6 induced COX-2 expression involves coordinated interplay between PI3K and MAPK signaling

Macrophages, as sentinels of robust host immunity, are key regulators of innate immune responses against invading mycobacteria; however, pathogenic mycobacteria survive in the infected host by subverting host innate immunity. Infection dependent expression of early secreted antigenic target protein 6 (ESAT-6) by Mycobacterium tuberculosis is strongly correlated with subversion of innate immune responses against invading mycobacteria. As a part of multifaceted immunity to mycobacterial infection, induced expression of cyclooxygenase-2 (COX-2) may act as an important influencing factor towards effective host immunity. In the current investigation, we demonstrate that ESAT-6 triggers COX-2 expression both in vitro and in vivo in a TLR2 dependent manner. Signaling perturbation data suggest that signaling dynamics of PI3K and p38 and JNK1/2 MAPK assume critical importance in ESAT-6 triggered expression of COX-2 in macrophages. Interestingly, ESAT-6 triggered PI3K-MAPK signaling axis holds the capacity to regulate coordinated activation of NF-kappa B and AP-1. Overall, current investigation provides mechanistic insights into ESAT-6 induced COX-2 expression and unravels TLR2 mediated interplay of PI3K and MAPK signaling axis as a rate-determining step during intricate host immune responses. These findings would serve as a paradigm to understand pathogenesis of mycobacterial infection and clearly pave a way towards development of novel therapeutics. (C) 2011 Elsevier Ltd. All rights reserved.

Endoplasmic Reticulum Stress-Mediated Activation of p38 MAPK, Caspase-2 and Caspase-8 Leads to Abrin-Induced Apoptosis

Abrin from Abrus precatorius plant is a potent protein synthesis inhibitor and induces apoptosis in cells. However, the relationship between inhibition of protein synthesis and apoptosis is not well understood. Inhibition of protein synthesis by abrin can lead to accumulation of unfolded protein in the endoplasmic reticulum causing ER stress. The observation of phosphorylation of eukaryotic initiation factor 2 alpha and upregulation of CHOP (CAAT/enhancer binding protein (C/EBP) homologous protein), important players involved in ER stress signaling by abrin, suggested activation of ER stress in the cells. ER stress is also known to induce apoptosis via stress kinases such as p38 MAPK and JNK. Activation of both the pathways was observed upon abrin treatment and found to be upstream of the activation of caspases. Moreover, abrin-induced apoptosis was found to be dependent on p38 MAPK but not JNK. We also observed that abrin induced the activation of caspase-2 and caspase-8 and triggered Bid cleavage leading to mitochondrial membrane potential loss and thus connecting the signaling events from ER stress to mitochondrial death machinery.

Cell (module) temperature regulated performance of a building integrated photovoltaic system in tropical conditions

The performance of a building integrated photovoltaic system (BIPV) has to be commendable, not only on the electrical front but also on the thermal comfort front, thereby fulfilling the true responsibility of an energy providing shelter. Given the low thermal mass of BIPV systems, unintended and undesired outcomes of harnessing solar energy - such as heat gain into the building, especially in tropical regions - have to be adequately addressed. Cell (module) temperature is one critical factor that affects both the electrical and the thermal performance of such installations. The current paper discusses the impact of cell (module) temperature on both the electrical efficiency and thermal comfort by investigating the holistic performance of one such system (5.25 kW(p)) installed at the Centre for Sustainable Technologies in the Indian Institute of Science, Bangalore. Some recommendations (passive techniques) for improving the performance and making BIPV structures thermally comfortable have been listed out. (C) 2014 Elsevier Ltd. All rights reserved.

Exploring the Crystal Structure Landscape with a Heterosynthon Module: Fluorobenzoic Acid:1,2-Bis(4-pyridyl)ethylene 2:1 Cocrystals

The crystal structure landscape of the 2:1 benzoic acid:dipyridylethylene cocrystal (BA:DPE-I) is explored experimentally with fluoro-substituted benzoic acids and extended with studies employing the Cambridge Structural Database (CSD). The interpretation of the cocrystal landscape is facilitated by considering the kinetically favored and robust acidpyridine heterosynthon as a modular unit. Information based on high-throughput crystallography shows that polymorphs and pseudopolymorphs may belong to the same landscape but arise from different crystallization pathways because of complex and different kinetic features, and secondary synthon preferences. Using the CSD as a guide, the coformer was changed from 1,2-bis(4-pyridyl)ethylene (DPE-I) to 1,2-bis(4-pyridyl)ethane (DPE-II) and this provides an extended interpretation of the BA:DPE-I cocrystal landscape, also highlighting the complexity of the kineticthermodynamic dichotomy during the molecule-to-crystal progression.

Unconjugated Bilirubin exerts Pro-Apoptotic Effect on Platelets via p38-MAPK activation

Thrombocytopenia is one of the most frequently observed secondary complications in many pathological conditions including liver diseases, where hyperbilirubinemia is very common. The present study sought to find the cause of thrombocytopenia in unconjugated hyperbilirubinemic conditions. Unconjugated bilirubin (UCB), an end-product of heme catabolism, is known to have pro-oxidative and cytotoxic effects at high serum concentration. We investigated the molecular mechanism underlying the pro-apoptotic effect of UCB on human platelets in vitro, and followed it up with studies in phenylhydrazine-induced hyperbilirubinemic rat model and hyperbilirubinemic human subjects. UCB is indeed found to significantly induce platelet apoptotic events including elevated endogenous reactive oxygen species generation, mitochondrial membrane depolarization, increased intracellular calcium levels, cardiolipin peroxidation and phosphatidylserine externalization (p < 0.001) as evident by FACS analysis. The immunoblots show the elevated levels of cytosolic cytochrome c and caspase activation in UCB-treated platelets. Further, UCB is found to induce mitochondrial ROS generation leading to p38 activation, followed by downstream activation of p53, ultimately resulting in altered expression of Bcl-2 and Bax proteins as evident from immunoblotting. All these parameters conclude that elevated unconjugated bilirubin causes thrombocytopenia by stimulating platelet apoptosis via mitochondrial ROS-induced p38 and p53 activation.

MPTP activates ASK1-p38 MAPK signaling pathway through TNF-dependent Trx1 oxidation in parkinsonism mouse model

Activation of apoptosis signal regulating kinase 1 (ASK1)-p38 MAPK death signaling cascade is irn plicated in the death of dopaminergic neurons in substantia nigra in Parkinson's disease (PD). We investigated upstream activators of ASK1 using an MPTP mouse model of parkinsonism and assessed the temporal cascade of death signaling in ventral midbrain (VMB) and striatum (ST). MPTP selectively activated ASK1 and downstream 1)38 MAPK in a time dependent manner in VMB alone. This occurred through selective protein thiol oxidation of the redox-sensitive thiol disulfide oxidoreductase, thiorcdoxin (Trxl), resulting in release of its inhibitory association with ASK1, while glutathione-S-transferase ji 1 (GSTM1) remained in reduced form in association with ASK1. Levels of tumor necrosis factor (TNF), a known activator of ASK1, increased early after MPTP in VMB. Protein ovariation netvvork analysis (PCNA) using protein states as nodes revealed TNF to be an important node regulating the ASK1 signaling cascade. In confirmation, blocking MPTP-mecliated TNF signaling through intrathecal administration of TNFneutralizing antibody prevented Trxl oxidation and downstream ASK1-p38 MAPK activation. Averting an early increase in TNF, which leads to protein thiol oxidation resulting in activation of ASK1-p38 signaling, may be critical for neuroprotection in PD. Importantly, network analysis can help in understanding the cause/effect relationship within protein networks in complex disease states. (C) 2015 Published by Elsevier Inc.

High temperature direct double side cooled inverter module for hybrid electric vehicle application

In this paper a novel approach to the design and fabrication of a high temperature inverter module for hybrid electrical vehicles is presented. Firstly, SiC power electronic devices are considered in place of the conventional Si devices. Use of SiC raises the maximum practical operating junction temperature to well over 200°C, giving much greater thermal headroom between the chips and the coolant. In the first fabrication, a SiC Schottky barrier diode (SBD) replaces the Si pin diode and is paired with a Si-IGBT. Secondly, double-sided cooling is employed, in which the semiconductor chips are sandwiched between two substrate tiles. The tiles provide electrical connections to the top and the bottom of the chips, thus replacing the conventional wire bonded interconnect. Each tile assembly supports two IGBTs and two SBDs in a half-bridge configuration. Both sides of the assembly are cooled directly using a high-performance liquid impingement system. Specific features of the design ensure that thermo-mechanical stresses are controlled so as to achieve long thermal cycling life. A prototype 10 kW inverter module is described incorporating three half-bridge sandwich assemblies, gate drives, dc-link capacitance and two heat-exchangers. This achieves a volumetric power density of 30W/cm3.

User’s Guide to For2R: A Module of Fortran 95 Output Routines Compatible with the R Statistics Language

For2R is a collection of Fortran routines for saving complex data structures into a file that can be read in the R statistics environment with a single command.1 For2R provides both the means to transfer data structures significantly more complex than simple tables, and an archive mechanism to store data for future reference. We developed this software because we write and run computationally intensive numerical models in Fortran, C++, and AD Model Builder. We then analyse results with R. We desired to automate data transfer to speed diagnostics during working-group meetings. We thus developed the For2R interface to write an R data object (of type list) to a plain-text file. The master list can contain any number of matrices, values, dataframes, vectors or lists, all of which can be read into R with a single call to the dget function. This allows easy transfer of structured data from compiled models to R. Having the capacity to transfer model data, metadata, and results has sharply reduced the time spent on diagnostics, and at the same time, our diagnostic capabilities have improved tremendously. The simplicity of this interface and the capabilities of R have enabled us to automate graph and table creation for formal reports. Finally, the persistent storage in files makes it easier to treat model results in analyses or meta-analyses devised months—or even years—later. We offer For2R to others in the hope that they will find it useful. (PDF contains 31 pages)