Study of Theoretical and Observed Capacities of Bored Cast-Insitu Piles in Tuff, Braccia and Weathered Basalt

The termination depth of bored cast in situ piles poses serious problem to the field engineers particularly on weak weathered rock, stiff clays and dense sands. Some sort of decision making tool is available for driven piles in the form of driving formulae. The first part of paper deals with a simple method based on penetration resistance to the advancement of bore and its relation with end bearing and frictional resistance offered by formation. The second and third parts of paper deal with a newly conceived dynamic method for ascertaining the safe load on pile and its comparison with the safe load value derived from penetration resistance actually observed. The dynamic test proposed is simpler, quicker cost effective and shall be an excellent quality assurance tool for the bored cast-in-situ piles

Effect of hydrogen on ground state structures of small silicon clusters

We present results for ground state structures of small Si$_{n}$H (2 \leq \emph{n} \leq 10) clusters using the Car-Parrinello molecular dynamics. In particular, we focus on how the addition of a hydrogen atom affects the ground state geometry, total energy and the first excited electronic level gap of an Si$_{n}$ cluster. We discuss the nature of bonding of hydrogen in these clusters. We find that hydrogen bonds with two silicon atoms only in Si$_{2}$H, Si$_{3}$H and Si$_{5}$H clusters, while in other clusters (i.e. Si$_{4}$H, Si$_{6}$H, Si$_{7}$H, Si$_{8}$H, Si$_{9}$H and Si$_{10}$H) hydrogen is bonded to only one silicon atom. Also in the case of a compact and closed silicon cluster hydrogen bonds to the cluster from outside. We find that the first excited electronic level gap of Si$_{n}$ and Si$_{n}$H fluctuates as a function of size and this may provide a first principles basis for the short-range potential fluctuations in hydrogenated amorphous silicon. Our results show that the addition of a single hydrogen can cause large changes in the electronic structure of a silicon cluster, though the geometry is not much affected. Our calculation of the lowest energy fragmentation products of Si$_{n}$H clusters shows that hydrogen is easily removed from Si$_{n}$H clusters.Comment: one latex file named script.tex including table and figure caption. Six postscript figure files. figure_1a.ps and figure_1b.ps are files representing Fig. 1 in the main tex

Disulfiram/copper selectively eradicates AML leukemia stem cells in vitro and in vivo by simultaneous induction of ROS-JNK and inhibition of NF-κB and Nrf2

© 2017 The Authors. Published by Nature Publishing Group. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1038/cddis.2017.176Acute myeloid leukemia (AML) is a heterogeneous malignancy. Despite the advances in past decades, the clinical outcomes of AML patients remain poor. Leukemia stem cells (LSCs) is the major cause of the recurrence of AML even after aggressive treatment making, promoting development of LSC-targeted agents is an urgent clinical need. Although the antitumor activity of disulfiram (DS), an approved anti-alcoholism drug, has been demonstrated in multiple types of tumors including hematological malignancies such as AML, it remains unknown whether this agent would also be able to target cancer stem cells like LSCs. Here, we report the in vitro and in vivo activity of DS in combination with copper (Cu) against CD34(+)/CD38(+) leukemia stem-like cells sorted from KG1α and Kasumi-1 AML cell lines, as well as primary CD34(+) AML samples. DS plus Cu (DS/Cu) displayed marked inhibition of proliferation, induction of apoptosis, and suppression of colony formation in cultured AML cells while sparing the normal counterparts. DS/Cu also significantly inhibited the growth of human CD34(+)/CD38(+) leukemic cell-derived xenografts in NOD/SCID mice. Mechanistically, DS/Cu-induced cytotoxicity was closely associated with activation of the stress-related ROS-JNK pathway as well as simultaneous inactivation of the pro-survival Nrf2 and nuclear factor-κB pathways. In summary, our findings indicate that DS/Cu selectively targets leukemia stem-like cells both in vitro and in vivo, thus suggesting a promising LSC-targeted activity of this repurposed agent for treatment of relapsed and refractory AML

Into the Labyrinth: Tales of Organizational Nomadism

Labyrinths and mazes have constituted significant spaces for tales of transformation, from prehistoric designs through the myth of the Minotaur and the pilgrimage design in Chartres cathedral to contemporary novels and pictorial representations. Labyrinths and labyrinthine designs can also commonly be found in present-day organizations. This text, based on an ethnographic study as well as on an analysis of academic discourse, explores their significance as symbol and as physical structure. Drawing upon the notion of transitional space, it presents labyrinths as an indelible part of human experience, an archetype, and a sensemaking tool for understanding and explaining organizational complexity. The unavoidable presence of labyrinthine structures is presented as a counterpoise to the reductionist tendency towards simplification, streamlining and staying on-message, allowing or demanding space for reflection, doubt and uncertainty

Neuropeptide S-Mediated Facilitation of Synaptic Transmission Enforces Subthreshold Theta Oscillations within the Lateral Amygdala

The neuropeptide S (NPS) receptor system modulates neuronal circuit activity in the amygdala in conjunction with fear, anxiety and the expression and extinction of previously acquired fear memories. Using in vitro brain slice preparations of transgenic GAD67-GFP (Δneo) mice, we investigated the effects of NPS on neural activity in the lateral amygdala as a key region for the formation and extinction of fear memories. We are able to demonstrate that NPS augments excitatory glutamatergic synaptic input onto both projection neurons and interneurons of the lateral amygdala, resulting in enhanced spike activity of both types of cells. These effects were at least in part mediated by presynaptic mechanisms. In turn, inhibition of projection neurons by local interneurons was augmented by NPS, and subthreshold oscillations were strengthened, leading to their shift into the theta frequency range. These data suggest that the multifaceted effects of NPS on amygdaloid circuitry may shape behavior-related network activity patterns in the amygdala and reflect the peptide's potent activity in various forms of affective behavior and emotional memory

Molecular Evolution of the Neuropeptide S Receptor

The neuropeptide S receptor (NPSR) is a recently deorphanized member of the G protein-coupled receptor (GPCR) superfamily and is activated by the neuropeptide S (NPS). NPSR and NPS are widely expressed in central nervous system and are known to have crucial roles in asthma pathogenesis, locomotor activity, wakefulness, anxiety and food intake. The NPS-NPSR system was previously thought to have first evolved in the tetrapods. Here we examine the origin and the molecular evolution of the NPSR using in-silico comparative analyses and document the molecular basis of divergence of the NPSR from its closest vertebrate paralogs. In this study, NPSR-like sequences have been identified in a hemichordate and a cephalochordate, suggesting an earlier emergence of a NPSR-like sequence in the metazoan lineage. Phylogenetic analyses revealed that the NPSR is most closely related to the invertebrate cardioacceleratory peptide receptor (CCAPR) and the group of vasopressin-like receptors. Gene structure features were congruent with the phylogenetic clustering and supported the orthology of NPSR to the invertebrate NPSR-like and CCAPR. A site-specific analysis between the vertebrate NPSR and the well studied paralogous vasopressin-like receptor subtypes revealed several putative amino acid sites that may account for the observed functional divergence between them. The data can facilitate experimental studies aiming at deciphering the common features as well as those related to ligand binding and signal transduction processes specific to the NPSR

Diastereoselective Synthesis of C60/Steroid Conjugates

The design and synthesis of fullerene–steroid hybrids by using Prato’s protocol has afforded new fullerene derivatives endowed with epiandrosterone, an important naturally occurring steroid hormone. Since the formation of the pyrrolidine ring resulting from the 1,3-dipolar cyloaddition reaction takes place with generation of a new stereogenic center on the C2 of the five-membered ring, the reaction proceeds with formation of a diastereomeric mixture [compounds 6 and 7 in 70:30 ratio, 8 and 9 in 26:74 ratio (HPLC)] in which the formation of the major diasteroisomers 6 and 9 is consistent with an electrophilic attack of [60]fullerene on the Re face of the azomethine ylide directed by the steroidic unit. The chiroptical properties of these conjugates reveal typical Cotton effects in CD spectra that have been used to assign the absolute configuration of the new fulleropyrrolidines. The electrochemical study of the new compounds reveals the presence of four quasi-reversible reduction waves which are cathodically shifted in comparison with the parent C60, thus ascertaining the proposed structures.Financial support by the Ministerio de Ciencia e Innovación (MINECO) of Spain (CTQ2011-24652, CTQ2011-27253, PIB2010JP-00196, and CSD2007-00010 projects) and CAM (Madrisolar-2) is acknowledged; A.R. thanks UCM for financial support; M.S. is indebted to Programa del Grupo Santander 2012