The putative nucleic acid helicase Sen1p is required for formation and stability of termini and for maximal rates of synthesis and levels of accumulation of small nucleolar RNAs in Saccharomyces cerevisiae

Sen1p from Saccharomyces cerevisiae is a nucleic acid helicase related to DEAD box RNA helicases and type I DNA helicases. The temperature-sensitive sen1-1 mutation located in the helicase motif alters the accumulation of pre-tRNAs, pre-rRNAs, and some small nuclear RNAs. In this report, we show that cells carrying sen1-1 exhibit altered accumulation of several small nucleolar RNAs (snoRNAs) immediately upon temperature shift. Using Northern blotting, RNase H cleavage, primer extension, and base compositional analysis, we detected three forms of the snoRNA snR13 in wild-type cells: an abundant TMG-capped 124-nucleotide (nt) mature form (snR13F) and two less abundant RNAs, including a heterogeneous population of approximately 1,400-nt 3'-extended forms (snR13R) and a 108-nt 5'-truncated form (snR13T) that is missing 16 nt at the 5' end. A subpopulation of snR13R contains the same 5' truncation. Newly synthesized snR13R RNA accumulates with time at the expense of snR13F following temperature shift of sen1-1 cells, suggesting a possible precursor-product relationship. snR13R and snR13T both increase in abundance at the restrictive temperature, indicating that Sen1p stabilizes the 5' end and promotes maturation of the 3' end. snR13F contains canonical C and D boxes common to many snoRNAs. The 5' end of snR13T and the 3' end of snR13F reside within C2U4 sequences that immediately flank the C and D boxes. A mutation in the 5' C2U4 repeat causes underaccumulation of snR13F, whereas mutations in the 3' C2U4 repeat cause the accumulation of two novel RNAs that migrate in the 500-nt range. At the restrictive temperature, double mutants carrying sen1-1 and mutations in the 3' C2U4 repeat show reduced accumulation of the novel RNAs and increased accumulation of snR13R RNA, indicating that Sen1p and the 3' C2U4 sequence act in a common pathway to facilitate 3' end formation. Based on these findings, we propose that Sen1p and the C2U4 repeats that flank the C and D boxes promote maturation of the 3' terminus and stability of the 5' terminus and are required for maximal rates of synthesis and levels of accumulation of mature snR13F.     

Robust congestion control in cognitive radio network using dynamic event‐triggered sliding mode

The ever‐increasing service demand from wireless users under restricted bandwidth necessitates the development of suitable congestion control scheme for throughput maximization. A robust congestion controller design has been addressed in this work to sustain necessary Quality of Service in Cognitive Radio Network. The goal is to reduce packet loss while ensuring optimum utilization of available resources. Sliding mode controller proclaimed for its disturbance rejection capabilities and robustness has been used to design the proposed controller. Using the benefits of sliding mode control, dynamic event‐triggering strategies have been combined for better utilization in resource‐constrained environments. Control execution requires minimal updates while guaranteeing the desired closed‐loop system behavior. The controller efficacy has been validated in simulations.     

Divergent Synthesis and Evaluation of the in vitro Cytotoxicity Profiles of 3,4-Ethylenedioxythiophenyl-2-propen-1-one Analogues

A new series of 3,4-ethylenedioxythiophene (EDOT)-appended propenones were prepared by condensation reaction and their in vitro cytotoxicity effects were evaluated against five human cancer cell lines. Preliminary structure–activity relationships of EDOT-incorporated 2-propenone derivatives were also established. The EDOT-appended enones demonstrated significant cytotoxicity against human cancer cell lines. The most active analogue, (E)-3-(2,3-dihydrothieno[3,4-b][1,4]dioxin-5-yl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one ( 3 p , GI₅₀=110 nm ), severely inhibited the clonogenic potential of cancer cells, and induced cell-cycle arrest in the G2/M phase and caused an accumulation of HCT116 colon cancer cells with >4 N DNA content. Also, 3 p exhibited weak inhibition of the enzymatic activity of human topoisomerase I. Molecular docking studies indicated preferential binding of the compounds to the ATP-binding pocket of the human checkpoint 2 kinase (Chk2) catalytic domain, thus, identifying a novel diaryl 2-propenone chemotype for the development of potent inhibitors of Chk2.     

A voting-based technique for word spotting in handwritten document images

Multimedia Tools and Applications - Word spotting in handwritten document images is a field of immense interest due to its widespread applications. Recognition-free and recognition-based approaches...     

Multiphase Assembly of Small Molecule Microcrystalline Peptide Hydrogel Allows Immunomodulatory Combination Therapy for Long‐Term Heart Transplant Survival

Combination therapies that target multiple pathways involved in immune rejection of transplants hold promise for patients in need of restorative surgery. Herein, a noninteracting multiphase molecular assembly approach is developed to crystallize tofacitinib, a potent JAK1/3 inhibitor, within a shear‐thinning self‐assembled fibrillar peptide hydrogel network. The resulting microcrystalline tofacitinib hydrogel (MTH) can be syringe‐injected directly to the grafting site during surgery to locally deliver the small molecule. The rate of drug delivered from MTH is largely controlled by the dissolution of the encapsulated microcrystals. A single application of MTH, in combination with systemically delivered CTLA4‐Ig, a co‐stimulation inhibitor, affords significant graft survival in mice receiving heterotopic heart transplants. Locoregional studies indicate that the local delivery of tofacitinib at the graft site enabled by MTH is required for the observed enhanced graft survival.     

Designing balanced wrapper chains in 3D SoC under constrained TSVs

Innovations in Systems and Software Engineering - Three-dimensional integrated circuit (3D-IC) has emerged as a savior of failing Moore’s law, where reduced length of interconnects is...     

Can deep learning solve a preschool image understanding problem?

Neural Computing and Applications - Automatic assessment of learning is a process where the computer system automatically generates test items and evaluates the responses. Image is one of the major...