Synthesis, crystal structures, hydrogen bonding graph-sets and theoretical studies of nickel (+II) co-ordinations with pyridine-2,6-dicarboxamide oxime

The pyridine-2,6-dicarboxamide oxime, C7H9N5O2, was Synthesis and  characterises with 1H NMR and FTIR spectroscopy . The reaction of this ligand with nickel (II) perchlorate yielded green crystals of formula  [Ni(C<sub>7</sub>H<sub>9</sub>N<sub>5</sub>O<sub>2</sub>)<sub>2</sub>]<sup>2+</sup>,2[ClO<sub>4</sub>]-, which crystallized in the monoclinic space group C2/c with a = 14.915(2), b = 0.895(2), c = 8.205(1) Å, β = 114.69(1), and Z = 4. The complex consists of discrete cations (+II) and one perchlorate anion, the  cations existing in a slightly distorted octahedral  complex with bonding through the heterocyclic and oxime nitrogen atoms. The structure is held together through N-H…O, O-H…O and C-H...O hydrogen bonds occurring  between the coordinated oxime  molecules and the perchlorate counter-ion. Computational investigations of nickel(II) complex are done by using M062X method with 6-31+G(d)(LANL2DZ) basis set in vacuo.Keywords: Oxime complexe; Crystal structure; Hydrogen-bonding graph-set; DFT; M062X method; 6-31+G(d)(LANL2DZ) basis

Synthesis, quantum chemical computations and x-ray crystallographic studies of a new complex based of manganese (+II)

The ligand oxime, C7H9N5O2, was Synthesis and characterises with different characterization methods such as 1H NMR and FTIR spectroscopy. The complexation of this ligand with manganese (II) perchlorate yielded pink crystals of formula [Mn (C7H9N5O2)2]2+, 2[ClO4]-, which crystallized in the monoclinic space group P21/n with a = 12.824(3), b=13.799(2), c=15.441(4)Å, β = 100.17(2), and Z = 4. The complex consists of cations (+II) and two perchlorate anions, the cations part existing in a slightly distorted octahedral complex. Computational investigations of manganese (II) complex are done by using the DFTmethod with B3LYP functional in conjunction with the 6-31G(d,p) and lanl2dz basis sets in the gas phase imposing the C1 and C2v symmetries.Keywords: Manganese complex; Crystal structure; DFT method; B3LYP functional; 6-31G(d,p) and (LANL2DZ) basi

A Neural Circuit Arbitrates between Persistence and Withdrawal in Hungry Drosophila

In pursuit of food, hungry animals mobilize significant energy resources and overcome exhaustion and fear. How need and motivation control the decision to continue or change behavior is not understood. Using a single fly treadmill, we show that hungry flies persistently track a food odor and increase their effort over repeated trials in the absence of reward suggesting that need dominates negative experience. We further show that odor tracking is regulated by two mushroom body output neurons (MBONs) connecting the MB to the lateral horn. These MBONs, together with dopaminergic neurons and Dop1R2 signaling, control behavioral persistence. Conversely, an octopaminergic neuron, VPM4, which directly innervates one of the MBONs, acts as a brake on odor tracking by connecting feeding and olfaction. Together, our data suggest a function for the MB in internal state-dependent expression of behavior that can be suppressed by external inputs conveying a competing behavioral drive

Sequential Prediction over Hierarchical Structures

We study sequential compound decision problems in the context of sequential prediction of real valued sequences. In particular, we consider finite state (FS) predictors that are constructed based on a hierarchical structure, such as the order preserving patterns of the sequence history. We define hierarchical equivalence classes by tying certain models at a hierarchy level in a recursive manner in order to mitigate undertraining problems. These equivalence classes defined on a hierarchical structure are then used to construct a super exponential number of sequential FS predictors based on their combinations and permutations. We then introduce truly sequential algorithms with computational complexity only linear in the pattern length that 1) asymptotically achieve the performance of the best FS predictor or the best linear combination of all the FS predictors in an individual sequence manner without any stochastic assumptions over any data length n under a wide range of loss functions; 2) achieve the mean square error of the best linear combination of all FS filters or predictors in the steady-state for certain nonstationary models. We illustrate the superior convergence and tracking capabilities of our algorithm with respect to several state-of-the-art methods in the literature through simulations over synthetic and real benchmark data. © 1991-2012 IEEE

Salt inducible kinases as novel Notch interactors in the developing Drosophila retina

Developmental processes require strict regulation of proliferation, differentiation and patterning for the generation of final organ size. Aberrations in these fundamental events are critically important in tumorigenesis and cancer progression. Salt inducible kinases (Siks) are evolutionarily conserved genes involved in diverse biological processes, including salt sensing, metabolism, muscle, cartilage and bone formation, but their role in development remains largely unknown. Recent findings implicate Siks in mitotic control, and in both tumor suppression and progression. Using a tumor model in the Drosophila eye, we show that perturbation of Sik function exacerbates tumor-like tissue overgrowth and metastasis. Furthermore, we show that both Drosophila Sik genes, Sik2 and Sik3, function in eye development processes. We propose that an important target of Siks may be the Notch signaling pathway, as we demonstrate genetic interaction between Siks and Notch pathway members. Finally, we investigate Sik expression in the developing retina and show that Sik2 is expressed in all photoreceptors, basal to cell junctions, while Sik3 appears to be expressed specifically in R3/R4 cells in the developing eye. Combined, our data suggest that Sik genes are important for eye tissue specification and growth, and that their dysregulation may contribute to tumor formation

Calcified amorphous tumor of the heart in an adult female: a case report

<p>Abstract</p> <p>Introduction</p> <p>Cardiac calcified amorphous tumor is a rare, non-neoplastic intra-cavity cardiac mass composed of calcium deposits in a background of amorphous degenerating fibrinous material. Only a few cases of this rare lesion have been reported in the available literature. Clinico-pathological differentiation of this lesion from calcified atrial myxoma, calcified thrombi or other cardiac neoplasms is extremely difficult; hence pathologic examination is the mainstay of diagnosis. To the best of our knowledge this entity has not been reported in the Indian literature.</p> <p>Case presentation</p> <p>A 40-year-old woman of Indian origin presented with progressive dyspnea, fatigue and cough. She was diagnosed as having a calcified right atrial mass. The mass was excised. Histologic examination revealed the mass to be composed of amorphous eosinophilic fibrin with dense calcification. No myxomatous tissue was seen and a final diagnosis of calcified amorphous tumor of the heart was rendered.</p> <p>Conclusions</p> <p>Calcified amorphous tumor is a rare cardiac lesion with an excellent outcome following complete surgical removal. Since clinico-radiologic differentiation from other cardiac masses is not possible in most cases, histopathological examination is the only modality for diagnosis. Hence, histopathologists should be aware of this rare entity in the differential diagnoses of cardiac mass.</p

Representing spray zone with cross flow as a well-mixed compartment in a high shear granulator

The spray zone is an important region to control nucleation of granules in a high shear granulator. In this study, a spray zone with cross flow is quantified as a well-mixed compartment in a high shear granulator. Granulation kinetics is quantitatively derived at both particle-scale and spray zone-scale. Two spatial decay rates, DGSDR (droplet-granule spatial decay rate) ζDG and DPSDR (droplet-primary particle spatial decay rate) ζDP, which are functions of volume fraction and diameter of particulate species within the powder bed, are defined to simplify the deduction. It is concluded that in cross flow, explicit analytical results show that the droplet concentration is subject to exponential decay with depth which produces a numerically infinite depth of spray zone in a real penetration process. In a well-mixed spray zone, the depth of the spray zone is 4/(ζDG + ζDP) and π2/3(ζDG + ζDP) in cuboid and cylinder shape, respectively. The first-order droplet-based collision rates of, nucleation rate B0 and rewetting rate RW0 are uncorrelated with the flow pattern and shape of the spray zone. The second-order droplet-based collision rate, nucleated granule-granule collision rate RGG, is correlated with the mixing pattern. Finally, a real formulation case of a high shear granulation process is used to estimate the size of the spray zone. The results show that the spray zone is a thin layer at the powder bed surface. We present, for the first time, the spray zone as a well-mixed compartment. The granulation kinetics of a well-mixed spray zone could be integrated into a Population Balance Model (PBM), particularly to aid development of a distributed model for product quality prediction

Genome-Wide Expression Analysis of a Spinal Muscular Atrophy Model: Towards Discovery of New Drug Targets

Spinal Muscular Atrophy is a recessive genetic disease and affects lower motor neurones and muscle tissue. A single gene is disrupted in SMA: SMN1 activity is abolished but a second copy of the gene (SMN2) provides limited activity. While the SMN protein has been shown to function in the assembly of RNA-protein complexes, it is unclear how the overall reduction in SMN activity specifically results in the neuromuscular phenotypes. Similar to humans, reduced smn activity in the fly causes earliest phenotypes in neuromuscular tissues. To uncover the effects of reduced SMN activity, we have studied gene expression in control and diseased fly tissues using whole genome micro-arrays. A number of gene expression changes are recovered and independently validated. Identified genes show trends in their predicted function: several are consistent with the function of SMN, in addition some uncover novel pathways. This and subsequent genetic analysis in the fly indicates some of the identified genes could be taken for further studies as potential drug targets for SMA and other neuromuscular disorders

Loss of Nrf2 abrogates the protective effect of Keap1 down regulation in a preclinical model of cutaneous squamous cell carcinoma

Cutaneous squamous cell carcinomas (cSCC) are the most common and highly mutated human malignancies, challenging identification of driver mutations and targeted therapies. Transcription factor NF-E2 p45-related factor 2 (Nrf2) orchestrates a cytoprotective inducible program, which counteracts the damaging effects of solar UV radiation, the main etiological factor in cSCC development. Downregulation of Kelch-like ECH-associated protein 1 (Keap1), a Cullin-3/Rbx1 ubiquitin ligase substrate adaptor protein, which mediates the ubiquitination and proteasomal degradation of Nrf2, has a strong protective effect in a preclinical model of cSCC. However, in addition to Nrf2, Keap1 affects ubiquitination of other proteins in the carcinogenesis process, including proteins involved in inflammation and DNA damage repair. Here, we generated Keap1(flox/flox) SKH-1 hairless mice in which Nrf2 is disrupted (Keap1(flox/flox)/Nrf2(−/−)) and subjected them chronically to solar-simulated UV radiation. We found that the incidence, multiplicity and burden of cSCC that form in Keap1(flox/flox)/Nrf2(−/−) mice are much greater than in their Keap1(flox/flox)/Nrf2(+/+) counterparts, establishing Nrf2 activation as the protection mediator. Our findings further imply that inhibition of Nrf2 globally, a strategy proposed for cancer treatment, is unlikely to be beneficial