The main objectives of this analysis are to examine the benefits and costs of fuel-saving technologies for new heavy-duty vehicles (HDVs) in India over the next 10 years and, to explore how various scenarios for the deployment of vehicles with these technologies will impact petroleum consumption and carbon dioxide (CO2) emissions over the next three decades. The study team developed simulation models for three representative HDV types—a 40-tonne tractor-trailer, 25-tonne rigid truck, and 16-tonne transit bus—based on top-selling vehicle models in the Indian market. The baseline technology profiles for all three vehicles were developed using India-specific engine data and vehicle specification information from manufacturer literature and input from industry experts. For each of the three vehicles we developed a comprehensive set of seven efficiency technology packages drawing from five major areas: engine, transmission and driveline, tires, aerodynamics, and weight reduction. Our analysis finds that India has substantial opportunity to improve HDV fuel efficiency levels using cost-effective technologies. Results from our simulation modeling of three representative HDV types—a tractor-trailer, rigid truck, and transit bus—reveal that per-vehicle fuel consumption reductions between roughly 20% and 35% are possible with technologies that provide a return on the initial capital investment within 1 to 2 years. Though most of these technologies are currently unavailable in India, experiences in other more advanced markets such as the US and EU suggest that with sufficient incentives and robust regulatory design, significant progress can be made in developing and deploying efficiency technologies that can provide real-world fuel savings for new commercial vehicles in India over the next 10 years. Bringing HDVs in India up to world-class technology levels will yield substantial petroleum and GHG reductions. By 2030, the fuel and CO2 reductions of the scenarios range from 10% to 34%, and at the end of 2050, these reductions grow to 13% and 41%. If we constrain the analysis to select the most efficient technology package that provides the fleets with payback times of 3 years or less, there are annual fleet-wide savings of roughly 11 MTOE of diesel and 34 MMT of CO2 in 2030, and this grows to 31 MTOE and 97 MMT by 2050.

LNK (SH2B3) is an adaptor protein studied extensively in normal and malignant hematopoietic cells. In these cells, it downregulates activated tyrosine kinases at the cell surface resulting in an antiproliferative effect. To date, no studies have examined activities of LNK in solid tumors. In this study, we found by in silico analysis and staining tissue arrays that the levels of LNK expression were elevated in high-grade ovarian cancer. To test the functional importance of this observation, LNK was either overexpressed or silenced in several ovarian cancer cell lines. Remarkably, overexpression of LNK rendered the cells resistant to death induced by either serum starvation or nutrient deprivation, and generated larger tumors using a murine xenograft model. In contrast, silencing of LNK decreased ovarian cancer cell growth in vitro and in vivo. Western blot studies indicated that overexpression of LNK upregulated and extended the transduction of the mitogenic signal, whereas silencing of LNK produced the opposite effects. Furthermore, forced expression of LNK reduced cell size, inhibited cell migration and markedly enhanced cell adhesion. Liquid chromatography-mass spectroscopy identified 14-3-3 as one of the LNK-binding partners. Our results suggest that in contrast to the findings in hematologic malignancies, the adaptor protein LNK acts as a positive signal transduction modulator in ovarian cancers.

Partial tandem duplication of MLL (MLL-PTD) characterizes acute myeloid leukemia (AML) patients often with a poor prognosis. To understand the order of occurrence of MLL-PTD in relation to other major AML mutations and to identify novel mutations that may be present in this unique AML molecular subtype, exome and targeted sequencing was performed on 85 MLL-PTD AML samples using HiSeq-2000. Genes involved in the cohesin complex (STAG2), a splicing factor (U2AF1) and a poorly studied gene, MGA were recurrently mutated, whereas NPM1, one of the most frequently mutated AML gene, was not mutated in MLL-PTD patients. Interestingly, clonality analysis suggests that IDH2/1, DNMT3A, U2AF1 and TET2 mutations are clonal and occur early, and MLL-PTD likely arises after these initial mutations. Conversely, proliferative mutations (FLT3, RAS), typically appear later, are largely subclonal and tend to be unstable. This study provides important insights for understanding the relative importance of different mutations for defining a targeted therapeutic strategy for MLL-PTD AML patients.

Acute promyelocytic leukemia (APL) is a subtype of myeloid leukemia characterized by differentiation block at the promyelocyte stage. Besides the presence of chromosomal rearrangement t(15;17), leading to the formation of PML-RARA (promyelocytic leukemia-retinoic acid receptor alpha) fusion, other genetic alterations have also been implicated in APL. Here, we performed comprehensive mutational analysis of primary and relapse APL to identify somatic alterations, which cooperate with PML-RARA in the pathogenesis of APL. We explored the mutational landscape using whole-exome (n=12) and subsequent targeted sequencing of 398 genes in 153 primary and 69 relapse APL. Both primary and relapse APL harbored an average of eight non-silent somatic mutations per exome. We observed recurrent alterations of FLT3, WT1, NRAS and KRAS in the newly diagnosed APL, whereas mutations in other genes commonly mutated in myeloid leukemia were rarely detected. The molecular signature of APL relapse was characterized by emergence of frequent mutations in PML and RARA genes. Our sequencing data also demonstrates incidence of loss-of-function mutations in previously unidentified genes, ARID1B and ARID1A, both of which encode for key components of the SWI/SNF complex. We show that knockdown of ARID1B in APL cell line, NB4, results in large-scale activation of gene expression and reduced in vitro differentiation potential.