10 research outputs found

    Constrained Flow Shop Scheduling with n-Jobs, 3-Machines, Processing Time Associated with Probability involving Transportation Time, Breakdown Interval and Weightage of Jobs

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    This paper is an attempt to find simple heuristic algorithm for n jobs, 3 machines flow shop scheduling problem in which processing times are associated with probabilities involving transportation time and break down interval. Further jobs are attached with weights to indicate their relative importance. A simple heuristic approach to find optimal or near optimal sequence minimizing the total elapsed time whenever mean weighted production flow time is taken into consideration. The proposed method is very easy to understand and, also provide an important tool for the decision makers. A computer programme followed by a numerical illustration is also given to clarify the algorithm. Keywords: Flow shop scheduling, Processing time, Transportation time, Breakdown interval, Weights of job, Optimal sequenc

    The synthesis and X-Ray structure analysis of an unusual bent anthraquinone based coronand

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    The phase transfer catalyzed cyclisation of 1,8-dihydroxyanthraquinone with bis(2-bromoethyl) ether provides an unusual bent anthraquinone based coronand

    Synthetic ionophores. Part 18: Ag<SUP>+</SUP> selective trithiabenzena-and dithiabenzenapyridinacyclophanes

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    The phase transfer catalysed nucleophilic displacement of 1,3-bis(bromomethyl)benzene, 2-methoxy-5- methyl-1,3-bis(bromomethyl)benzene (2) and 1,4-bis(bromomethyl)benzene with 2-mercaptoethanol gives the respective diols 3, 4 and 12 (80-85%), which undergo intermolecular cyclodehydrochlorination with thiodiglycolyl dichloride and pyridine-2,6-dicarbonyl dichloride?HCl to provide m-phenylene (7-10) and p-phenylene (13-14) based crownophanes. The single crystal X-ray structures of crownophanes 8 and 13 and their NMR studies show that the m-phenylene and p-phenylene rings remain in plane and perpendicular to the macrocyclic ring both in solution and solid phases. These crownophanes offer three soft coordinating sites (3 &#215; S or 2 &#215; S and 1 N) conducive to complexation with Ag+ and the steric restrictions imposed by m- and p-phenylene rings restrict 2 :1 (L :M) sandwich complexation required for complexation with the borderline soft Pb2+ cation. The crownophanes 7 and 9 extract Ag+ 172 and 602 times, respectively, more than Pb2+

    Phenylalanine-Rich Peptides Potently Bind ESAT6, a Virulence Determinant of Mycobacterium tuberculosis, and Concurrently Affect the Pathogen's Growth

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    BACKGROUND:The secretory proteins of Mycobacterium tuberculosis (M. tuberculosis) have been known to be involved in the virulence, pathogenesis as well as proliferation of the pathogen. Among this set, many proteins have been hypothesized to play a critical role at the genesis of the onset of infection, the primary site of which is invariably the human lung. METHODOLOGY/PRINCIPAL FINDINGS:During our efforts to isolate potential binding partners of key secretory proteins of M. tuberculosis from a human lung protein library, we isolated peptides that strongly bound the virulence determinant protein Esat6. All peptides were less than fifty amino acids in length and the binding was confirmed by in vivo as well as in vitro studies. Curiously, we found all three binders to be unusually rich in phenylalanine, with one of the three peptides a short fragment of the human cytochrome c oxidase-3 (Cox-3). The most accessible of the three binders, named Hcl1, was shown also to bind to the Mycobacterium smegmatis (M. smegmatis) Esat6 homologue. Expression of hcl1 in M. tuberculosis H37Rv led to considerable reduction in growth. Microarray analysis showed that Hcl1 affects a host of key cellular pathways in M. tuberculosis. In a macrophage infection model, the sets expressing hcl1 were shown to clear off M. tuberculosis in much greater numbers than those infected macrophages wherein the M. tuberculosis was not expressing the peptide. Transmission electron microscopy studies of hcl1 expressing M. tuberculosis showed prominent expulsion of cellular material into the matrix, hinting at cell wall damage. CONCLUSIONS/SIGNIFICANCE:While the debilitating effects of Hcl1 on M. tuberculosis are unrelated and not because of the peptide's binding to Esat6-as the latter is not an essential protein of M. tuberculosis-nonetheless, further studies with this peptide, as well as a closer inspection of the microarray data may shed important light on the suitability of such small phenylalanine-rich peptides as potential drug-like molecules against this pathogen

    Nonchylous idiopathic pleural effusion in the newborn

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    Congenital isolated pleural effusion is a rare cause of respiratory distress in neonates. It is usually chylous. Herein, we report a rare case of nonchylous congenital idiopathic pleural effusion

    Nonchylous idiopathic pleural effusion in the newborn

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    Congenital isolated pleural effusion is a rare cause of respiratory distress in neonates. It is usually chylous. Herein, we report a rare case of nonchylous congenital idiopathic pleural effusion

    Crystal structure of a calix[4]crown ether-ester and molecular recognition of alkyl- and arylalkylamines

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    The crystal and molecular structure of3 has been determined by X-ray analysis. Thecrystal data are: triclinic, space group P'1,a = 12.999(2),b = 14.114(3),c = 16.132(3) Å,α = 91.62(2),β = 97.71(1),γ = 91.38(2)°,V = 2930.6(9) Å<sup>3</sup>,Z = 2,Dm = 1.046 g cm<sup>-3</sup>.Rotational disorder has been seen in the t-butyl groups whichwere refined isotropically. Least-squares refinementbased on F<sup>2</sup>, using 4827 observedreflections with I > 2σ(I) and 18 restraints,led to R = 0.123. The calix is found in a coneconformation. The crown ether part of the molecule isnot in a fully extended conformation but has foldsin the chain. The calix[4]crown ether-ester exhibitsmolecular recognition properties toward alkylamines

    An early cortical progenitor-specific mechanism regulates thalamocortical innervation

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    The cortical subplate is critical in regulating the entry of thalamocortical sensory afferents into the cortex. These afferents reach the subplate at embryonic day (E)15.5 in the mouse, but "wait" for several days, entering the cortical plate postnatally. We report that when transcription factor LHX2 is lost in E11.5 cortical progenitors, which give rise to subplate neurons, thalamocortical afferents display premature, exuberant ingrowth into the E15.5 cortex. Embryonic mutant subplate neurons are correctly positioned below the cortical plate, but they display an altered transcriptome and immature electrophysiological properties during the waiting period. The sensory thalamus in these cortex-specific Lhx2 mutants displays atrophy and by postnatal day (P) 7, sensory innervation to the cortex is nearly eliminated leading to a loss of the somatosensory barrels. Strikingly, these phenotypes do not manifest if LHX2 is lost in postmitotic subplate neurons, and the transcriptomic dysregulation in the subplate resulting from postmitotic loss of LHX2 is vastly distinct from that seen when LHX2 is lost in progenitors. These results demonstrate a mechanism operating in subplate progenitors that has profound consequences on the growth of thalamocortical axons into the cortex. SIGNIFICANCE STATEMENT Thalamocortical nerves carry sensory information from the periphery to the cortex. When they first grow into the embryonic cortex, they "wait" at the subplate, a structure critical for the guidance and eventual connectivity of thalamic axons with their cortical targets. How the properties of subplate neurons are regulated is unclear. We report that transcription factor LHX2 is required in the progenitor "mother" cells of the cortical primordium when they are producing their "daughter" subplate neurons, in order for the thalamocortical pathway to wait at the subplate. Without LHX2 function in subplate progenitors, thalamocortical axons grow past the subplate, entering the cortical plate prematurely. This is followed by their eventual attrition and, consequently, a profound loss of sensory innervation of the mature cortex.</p

    Division of Labor between the Chromodomains of HP1 and Suv39 Methylase Enables Coordination of Heterochromatin Spread

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    In Schizosaccharomyces pombe, heterochromatin spread, which is marked by histone H3 lysine 9 methylation (H3K9me), requires the chromodomains (CD) of the H3K9 methylase Suv39/Clr4 and the HP1/Swi6 protein. It is unclear how the actions of these two H3K9 methylation recognizing CDs are coordinated. We find that the intrinsic preference of Suv39/Clr4 is to generate dimethylated H3K9 product. Recognition of pre-existing H3K9me marks by the CD of Suv39/Clr4 stimulates overall catalysis, enabling accumulation of small amounts of trimethylated product in vivo. Coincidentally, the Suv39/Clr4 CD, unlike the HP1/Swi6 CD, has been shown to prefer the trimethyl state over dimethyl. We show that this preference enables efficient heterochromatin spread in vivo by reducing competition with HP1 proteins for the more prevalent dimethyl state. Our results reveal a strategy by which writers and readers of a chromatin mark exploit different methylation states on the same residue to facilitate collaboration and avoid competition

    \u3ci\u3eDrosophila\u3c/i\u3e Muller F Elements Maintain a Distinct Set of Genomic Properties Over 40 Million Years of Evolution

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    The Muller F element (4.2 Mb, ~80 protein-coding genes) is an unusual autosome of Drosophila melanogaster; it is mostly heterochromatic with a low recombination rate. To investigate how these properties impact the evolution of repeats and genes, we manually improved the sequence and annotated the genes on the D. erecta, D. mojavensis, and D. grimshawi F elements and euchromatic domains from the Muller D element. We find that F elements have greater transposon density (25–50%) than euchromatic reference regions (3–11%). Among the F elements, D. grimshawi has the lowest transposon density (particularly DINE-1: 2% vs. 11–27%). F element genes have larger coding spans, more coding exons, larger introns, and lower codon bias. Comparison of the Effective Number of Codons with the Codon Adaptation Index shows that, in contrast to the other species, codon bias in D. grimshawi F element genes can be attributed primarily to selection instead of mutational biases, suggesting that density and types of transposons affect the degree of local heterochromatin formation. F element genes have lower estimated DNA melting temperatures than D element genes, potentially facilitating transcription through heterochromatin. Most F element genes (~90%) have remained on that element, but the F element has smaller syntenic blocks than genome averages (3.4–3.6 vs. 8.4–8.8 genes per block), indicating greater rates of inversion despite lower rates of recombination. Overall, the F element has maintained characteristics that are distinct from other autosomes in the Drosophila lineage, illuminating the constraints imposed by a heterochromatic milieu
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