Mutant CEBPA directly drives the expression of the targetable tumor-promoting factor CD73 in AML

The key myeloid transcription factor (TF), CEBPA, is frequently mutated in acute myeloid leukemia (AML), but the direct molecular effects of this leukemic driver mutation remain elusive. To investigate mutant AML, we performed microscale, in vivo chromatin immunoprecipitation sequencing and identified a set of aberrantly activated enhancers, exclusively occupied by the leukemia-associated CEBPA-p30 isoform. Comparing gene expression changes in human mutant AML and the corresponding mouse model, we identified , encoding CD73, as a cross-species AML gene with an upstream leukemic enhancer physically and functionally linked to the gene. Increased expression of CD73, mediated by the CEBPA-p30 isoform, sustained leukemic growth via the CD73/A2AR axis. Notably, targeting of this pathway enhanced survival of AML-transplanted mice. Our data thus indicate a first-in-class link between a cancer driver mutation in a TF and a druggable, direct transcriptional target

PIPS: Pathogenicity Island Prediction Software

The adaptability of pathogenic bacteria to hosts is influenced by the genomic plasticity of the bacteria, which can be increased by such mechanisms as horizontal gene transfer. Pathogenicity islands play a major role in this type of gene transfer because they are large, horizontally acquired regions that harbor clusters of virulence genes that mediate the adhesion, colonization, invasion, immune system evasion, and toxigenic properties of the acceptor organism. Currently, pathogenicity islands are mainly identified in silico based on various characteristic features: (1) deviations in codon usage, G+C content or dinucleotide frequency and (2) insertion sequences and/or tRNA genetic flanking regions together with transposase coding genes. Several computational techniques for identifying pathogenicity islands exist. However, most of these techniques are only directed at the detection of horizontally transferred genes and/or the absence of certain genomic regions of the pathogenic bacterium in closely related non-pathogenic species. Here, we present a novel software suite designed for the prediction of pathogenicity islands (pathogenicity island prediction software, or PIPS). In contrast to other existing tools, our approach is capable of utilizing multiple features for pathogenicity island detection in an integrative manner. We show that PIPS provides better accuracy than other available software packages. As an example, we used PIPS to study the veterinary pathogen Corynebacterium pseudotuberculosis, in which we identified seven putative pathogenicity islands

High-Density Transcriptional Initiation Signals Underline Genomic Islands in Bacteria

Genomic islands (GIs), frequently associated with the pathogenicity of bacteria and having a substantial influence on bacterial evolution, are groups of “alien” elements which probably undergo special temporal–spatial regulation in the host genome. Are there particular hallmark transcriptional signals for these “exotic” regions? We here explore the potential transcriptional signals that underline the GIs beyond the conventional views on basic sequence composition, such as codon usage and GC property bias. It showed that there is a significant enrichment of the transcription start positions (TSPs) in the GI regions compared to the whole genome of Salmonella enterica and Escherichia coli. There was up to a four-fold increase for the 70% GIs, implying high-density TSPs profile can potentially differentiate the GI regions. Based on this feature, we developed a new sliding window method GIST, Genomic-island Identification by Signals of Transcription, to identify these regions. Subsequently, we compared the known GI-associated features of the GIs detected by GIST and by the existing method Islandviewer to those of the whole genome. Our method demonstrates high sensitivity in detecting GIs harboring genes with biased GI-like function, preferred subcellular localization, skewed GC property, shorter gene length and biased “non-optimal” codon usage. The special transcriptional signals discovered here may contribute to the coordinate expression regulation of foreign genes. Finally, by using GIST, we detected many interesting GIs in the 2011 German E. coli O104:H4 outbreak strain TY-2482, including the microcin H47 system and gene cluster ycgXEFZ-ymgABC that activates the production of biofilm matrix. The aforesaid findings highlight the power of GIST to predict GIs with distinct intrinsic features to the genome. The heterogeneity of cumulative TSPs profiles may not only be a better identity for “alien” regions, but also provide hints to the special evolutionary course and transcriptional regulation of GI regions

A study of some factors affecting the effectiveness of casing treatment in a contra-rotating axial compressor stage

199-207<span style="font-size:11.0pt;line-height:115%; font-family:" calibri","sans-serif";mso-ascii-theme-font:minor-latin;mso-fareast-font-family:="" "times="" new="" roman";mso-fareast-theme-font:minor-fareast;mso-hansi-theme-font:="" minor-latin;mso-bidi-font-family:"times="" roman";mso-ansi-language:en-us;="" mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">The paper presents the results of an experimental investigation on the effects of some factors on the effectiveness of casing treatment in a contra-rotating axial compressor stage having a hub-tip ratio of 0.667 and tip diameter of 486 mm. Three types of casing treatments, viz., axial slots, axial skewed slots and circumferential grooves, have been examined for different contra-speed ratios and for two settings of axial spacing between contra-rotors, viz., close (1/3rd of blade chord) and large (2 times blade chord). The radial variation of flow structure, and pressure quantities are examined at downstream of contra-rotors for solid as well as treated casing and these traverse results are analyzed to derive the relative total head loss coefficients and total to total blade element efficiency for contra-rotors as well as the contra-stage. The study reveals that the type of casing treatment used, the speed ratio and the axial gap between contra-rotors significantly affects the effectiveness of casing treatment.</span

Meso-phase Pitches from the Residue of Oil Refinery

876-882The meso-phase pitches were prepared after heating bitumen (residue of oil refinery) at 370-500°C for preparation of different types of industrial products such as, carbon fibres, high density graphite, needle coke and many other value added products. The variety of pitches are prepared by polymerization and condensation reactions during heat treatment , depending upon several factors like, rate of heating, duration of heat treatment, atmosphere, rate of flowing gas, pressure and type of vessel. Rheological behaviour indicates that polymerization takes place at higher temperature. The kinetic parameters such as, order of reaction (n) and activation energy (Ea) were calculated from thermograms and the value was found to be about 34 k cal/<span style="font-size:12.0pt;mso-bidi-font-size:8.0pt;font-family:Arial; mso-bidi-font-style:italic" lang="EN-US">mol. Some pitches like, binder pitches, impregnating pitches of very high industrial importance are obtained from meso-phase pitches with due selection of different properties. </span

Development of bitumen emulsion based cold mix technology for construction of roads under different climatic conditions of India

729-743T<span style="color:#111111; mso-bidi-language:HI">o deve<span style="color:black; mso-bidi-language:HI">lop <span style="color:#111111;mso-bidi-language: HI">enviro<span style="color:black; mso-bidi-language:HI">nm<span style="color:#111111;mso-bidi-language: HI">ent <span style="color:black; mso-bidi-language:HI">and <span style="color:#111111;mso-bidi-language: HI">ceo-<span style="color:black; mso-bidi-language:HI">friendl<span style="color:#111111;mso-bidi-language: HI">y cold mix <span style="color:black; mso-bidi-language:HI">t<span style="color:#111111;mso-bidi-language: HI">echno<span style="color:black; mso-bidi-language:HI">log<span style="color:#111111;mso-bidi-language: HI">y, field trials we<span style="color:black; mso-bidi-language:HI">r<span style="color:#111111;mso-bidi-language: HI">e conducted using bitumen <span style="color:#111111; mso-bidi-language:HI">emulsio<span style="color:black; mso-bidi-language:HI">n <span style="color:#111111;mso-bidi-language: HI">on Jammu-Srinagar Highway NH-1A near Patnitop (J&amp;K) under snow bound arc a, <span style="color:black; mso-bidi-language:HI">Jow<span style="color:#111111;mso-bidi-language: HI">ai-Badarpur Roa<span style="color:black; mso-bidi-language:HI">d NH-44 n<span style="color:#111111;mso-bidi-language: HI">ear Silc<span style="color:black; mso-bidi-language:HI">har (Assam) un<span style="color:black; mso-bidi-language:HI">der h<span style="color:#111111;mso-bidi-language: HI">eavy <span style="color:black; mso-bidi-language:HI">rain<span style="color:#111111;mso-bidi-language: HI">fall and H-S Road near Han<span style="color:#111111; mso-bidi-language:HI">umanga<span style="color:black; mso-bidi-language:HI">rh <span style="color:#111111;mso-bidi-language: HI">(Rajas<span style="color:black; mso-bidi-language:HI">th<span style="color:#111111;mso-bidi-language: HI">an) <span style="color:black; mso-bidi-language:HI">under de<span style="color:#111111;mso-bidi-language: HI">sert c<span style="color:black; mso-bidi-language:HI">lim<span style="color:#111111;mso-bidi-language: HI">ate. <span style="color:black; mso-bidi-language:HI">Spec<span style="color:#111111;mso-bidi-language: HI">ific<span style="color:black; mso-bidi-language:HI">ati<span style="color:#111111;mso-bidi-language: HI">ons <span style="color:black; mso-bidi-language:HI">ad<span style="color:#111111;mso-bidi-language: HI">opted we<span style="color:black; mso-bidi-language:HI">re 25 m<span style="color:#111111;mso-bidi-language: HI">m semi de<span style="color:black; mso-bidi-language:HI">n<span style="color:#2D2D2D;mso-bidi-language: HI">se bitumin<span style="color:#111111; mso-bidi-language:HI">ous <span style="color:black;mso-bidi-language: HI">concr<span style="color:#111111; mso-bidi-language:HI">ete (<span style="color:black;mso-bidi-language: HI">SDBC) and 20 <span style="color:#111111; mso-bidi-language:HI">mm premi<span style="color:#111111; mso-bidi-language:HI">x carpet (<span style="color:black; mso-bidi-language:HI">PMC<span style="color:#2D2D2D;mso-bidi-language: HI">) fo<span style="color:black; mso-bidi-language:HI">r la<span style="color:#111111;mso-bidi-language: HI">ying <span style="color:black; mso-bidi-language:HI">t<span style="color:#111111;mso-bidi-language: HI">est sections wi<span style="color: black;mso-bidi-language:HI">th b<span style="color:#111111;mso-bidi-language: HI">itume<span style="color:black; mso-bidi-language:HI">n e<span style="color:black; mso-bidi-language:HI">mul<span style="color:#111111;mso-bidi-language: HI">sion a<span style="color:black; mso-bidi-language:HI">nd c<span style="color:#111111;mso-bidi-language: HI">ontrol s<span style="color:black; mso-bidi-language:HI">ecti<span style="color:#111111;mso-bidi-language: HI">on with pav<span style="color:black; mso-bidi-language:HI">ing bitum<span style="color:#111111;mso-bidi-language: HI">en 80/100. L<span style="color:#111111; mso-bidi-language:HI">aborato<span style="color:black; mso-bidi-language:HI">ry <span style="color:#111111;mso-bidi-language: HI">mix des<span style="color:black; mso-bidi-language:HI">ign f<span style="color:#111111;mso-bidi-language: HI">or SDBC w<span style="color:black; mso-bidi-language:HI">ith <span style="color:#111111;mso-bidi-language: HI">bitumen emulsion w<span style="color:black; mso-bidi-language:HI">a<span style="color:#111111;mso-bidi-language: HI">s develo<span style="color:black; mso-bidi-language:HI">ped u<span style="color:#111111;mso-bidi-language: HI">sing Marshall me<span style="color:black; mso-bidi-language:HI">thod. Marshall s<span style="color:black; mso-bidi-language:HI">pecimens or cold mi<span style="color:#111111; mso-bidi-language:HI">x were prepared, cured at 40°<span style="color:black; mso-bidi-language:HI">C fo<span style="color:#111111;mso-bidi-language: HI">r 3 day<span style="color:black; mso-bidi-language:HI">s and test<span style="color:#111111;mso-bidi-language: HI">ed at 25<span style="color:#2D2D2D; mso-bidi-language:HI">°C for <span style="color:#111111; mso-bidi-language:HI">sta<span style="color:black; mso-bidi-language:HI">bility and flow value. Post construction performance evaluation has been carried out at 6-month intervals for 5-6 years. SDBC and PMC with bitumen emulsion performed better or comparable with that of conventional paving grade bitumen. Due to low viscosity, bitumen emulsion penetrated into cracks and helped in sealing them during tack coating, which resulted into retardation of reflective cracks on overlays. Performance of SDBC with bitumen emulsion was also found comparable with that of paving grade bitumen. </span

Development of methodology for emergency repair of airfield pavements

49-53Emergency repair of airfields have to be carried out at utmost priority. New development in weapon technology with deep strike and increased demands in aircraft operations make existing crater repair procedures inadequate. Field trials were conducted for crater repair at Hindon and Jaisalmer Air Base. The filling of central crater and deep adjacent area is recommended by the use of recycled pavement aggregates of different sizes in layers

Use of waste plastics and copper slag for low cost bituminous roads

938-944Study presents use of waste plastics and copper slag (CS) in hot bituminous mixes to enhance pavement performance, protect environment and provide low cost roads. Waste plastic modified bitumen (WPMB) has been prepared by adding mixed plastic waste (5%) in shredded form with suitable cross-linking agent in 80/100 bitumen and blended for 1 h at 160°C. Physical properties of WPMB are found within specified limits (IS: 15462-2004). Delhi quartzite aggregate (size, 20 mm, 10 mm), stone dust and lime along with varying concentrations of CS as aggregate filler is taken for preparation of Marshall specimens (60/70 paving bitumen, 80/100 paving bitumen and WPMB). Optimum binder content is achieved at 5.2% (by wt of mix). Marshall specimens are also prepared with composition of CS (10, 15 and 20%) replacing stone dust; CS (15%) has been found best

Photo-catalysed synthesis, characterization and thermal behaviour of the adducts of 8-hydroxyquinoline with the photoproducts of octacyanomolybdate(IV) and -tungstate(IV) with 1,2,3-benzotriazole and triethylenetetramine

423-427The 8-hydroxyquinoline adducts and complexes of molybdenum(IV) and tungsten(IV) of the type K2[Mo(CN)(OH)(O2)(C6H5N3)(C9H7ON)]·2C9H7ON·H2O [I], K2[W(O2)(O)(C9H7ON)3] [II] and K3[W(CN)2(O2)(OH)(C9H7ON)·2C9H7ON·2H2O [III) have been synthesised starting from the octacyanomolybdate(IV) or -tungstate(IV) by exposure to UV light in the ligand field band in the presence of 1,2,3-benzotriazole or triethylenetetramine. The IR spectra of the complexes I and III show a strong band of nC=Nstretching in the range 2100-2150 cm-1. The oxine group n(C-O)in the complexes I, II and III is represented by a strong peak in the range 1100-1140 cm- 1. The lower region of the IR spectra shows M=O stretching while the higher range the n(N- H) and n(OH) modes. The thermal decomposition of the complexes starts from 160°C with the removal of uncoordinated water and continues up to 800°C.Oxine and cyano groups are removed stage by stage. The final products from the thermal treatment are oxides of the type K2O· MO3 (where M=Mo, W). The kinetic parameters, viz., order of reaction (n) and activation energy (Ea) have been determined using TG curves