Laser Shock Microformingof Thin Metal Sheets with ns Lasers

Continuous and long-pulse lasers have been used for the forming of metal sheets in macroscopic mechanical applications. However, for the manufacturing of micro-electromechanical systems (MEMS), the use of ns laser pulses provides a suitable parameter matching over an important range of sheet components that, preserving the short interaction time scale required for the predominantly mechanical (shock) induction of deformation residual stresses, allows for the successful processing of components in a medium range of miniaturization without appreciable thermal deformation.. In the present paper, the physics of laser shock microforming and the influence of the different experimental parameters on the net bending angle are presented

Laser Shock Microforming of Thin Metal Sheets

Continuous and long-pulse lasers have been used for the forming of metal sheets in macroscopic mechanical applications. However, for the manufacturing of micro-electromechanical systems (MEMS), the applicability of such type of lasers is limited by the long-relaxation-time of the thermal fields responsible for the forming phenomena. As a consequence of such slow relaxation, the final sheet deformation state is attained only after a certain time, what makes the generated internal residual stress fields more dependent on ambient conditions and might make difficult the subsequent assembly process from the point of view of residual stresses due to adjustment. The use of ns laser pulses provides a suitable parameter matching for the laser forming of an important range of sheet components used in MEMS that, preserving the short interaction time scale required for the predominantly mechanic (shock) induction of deformation residual stresses, allows for the successful processing of components in a medium range of miniaturization, particularly important according to its frequent use in such systems. In the present paper, a discussion is presented on the physics of laser shock microforming and the influence of the different effects on the net bending angle. The experimental setup used for the experiments, sample fabrication and experimental results of influence of number of laser pulses on the net bending angle are also presented

Generalizing with perceptrons in case of structured phase- and pattern-spaces

We investigate the influence of different kinds of structure on the learning behaviour of a perceptron performing a classification task defined by a teacher rule. The underlying pattern distribution is permitted to have spatial correlations. The prior distribution for the teacher coupling vectors itself is assumed to be nonuniform. Thus classification tasks of quite different difficulty are included. As learning algorithms we discuss Hebbian learning, Gibbs learning, and Bayesian learning with different priors, using methods from statistics and the replica formalism. We find that the Hebb rule is quite sensitive to the structure of the actual learning problem, failing asymptotically in most cases. Contrarily, the behaviour of the more sophisticated methods of Gibbs and Bayes learning is influenced by the spatial correlations only in an intermediate regime of $\alpha$, where $\alpha$ specifies the size of the training set. Concerning the Bayesian case we show, how enhanced prior knowledge improves the performance.Comment: LaTeX, 32 pages with eps-figs, accepted by J Phys

Somatostatin subtype-2 receptor-targeted metal-based anticancer complexes

Conjugates of a dicarba analogue of octreotide, a potent somatostatin agonist whose receptors are overexpressed on tumor cells, with [PtCl 2(dap)] (dap = 1-(carboxylic acid)-1,2-diaminoethane) (3), [(η 6-bip)Os(4-CO 2-pico)Cl] (bip = biphenyl, pico = picolinate) (4), [(η 6-p-cym)RuCl(dap)] + (p-cym = p-cymene) (5), and [(η 6-p-cym)RuCl(imidazole-CO 2H)(PPh 3)] + (6), were synthesized by using a solid-phase approach. Conjugates 3-5 readily underwent hydrolysis and DNA binding, whereas conjugate 6 was inert to ligand substitution. NMR spectroscopy and molecular dynamics calculations showed that conjugate formation does not perturb the overall peptide structure. Only 6 exhibited antiproliferative activity in human tumor cells (IC 50 = 63 ± 2 μ in MCF-7 cells and IC 50 = 26 ± 3 μ in DU-145 cells) with active participation of somatostatin receptors in cellular uptake. Similar cytotoxic activity was found in a normal cell line (IC 50 = 45 ± 2.6 μ in CHO cells), which can be attributed to a similar level of expression of somatostatin subtype-2 receptor. These studies provide new insights into the effect of receptor-binding peptide conjugation on the activity of metal-based anticancer drugs, and demonstrate the potential of such hybrid compounds to target tumor cells specifically. © 2012 American Chemical Society

RNA Oligomerisation without Added Catalyst from 2 ',3 '-Cyclic Nucleotides by Drying at Air-Water Interfaces

For the emergence of life, the abiotic synthesis of RNA from its monomers is a central step. We found that in alkaline, drying conditions in bulk and at heated air-water interfaces, 2 ',3 '-cyclic nucleotides oligomerised without additional catalyst, forming up to 10-mers within a day. The oligomerisation proceeded at a pH range of 7-12, at temperatures between 40-80 degrees C and was marginally enhanced by K+ ions. Among the canonical ribonucleotides, cGMP oligomerised most efficiently. Quantification was performed using HPLC coupled to ESI-TOF by fitting the isotope distribution to the mass spectra. Our study suggests a oligomerisation mechanism where cGMP aids the incorporation of the relatively unreactive nucleotides C, A and U. The 2 ',3 '-cyclic ribonucleotides are byproducts of prebiotic phosphorylation, nucleotide syntheses and RNA hydrolysis, indicating direct recycling pathways. The simple reaction condition offers a plausible entry point for RNA to the evolution of life on early Earth

Genetic Identification of a Network of Factors that Functionally Interact with the Nucleosome Remodeling ATPase ISWI

Nucleosome remodeling and covalent modifications of histones play fundamental roles in chromatin structure and function. However, much remains to be learned about how the action of ATP-dependent chromatin remodeling factors and histone-modifying enzymes is coordinated to modulate chromatin organization and transcription. The evolutionarily conserved ATP-dependent chromatin-remodeling factor ISWI plays essential roles in chromosome organization, DNA replication, and transcription regulation. To gain insight into regulation and mechanism of action of ISWI, we conducted an unbiased genetic screen to identify factors with which it interacts in vivo. We found that ISWI interacts with a network of factors that escaped detection in previous biochemical analyses, including the Sin3A gene. The Sin3A protein and the histone deacetylase Rpd3 are part of a conserved histone deacetylase complex involved in transcriptional repression. ISWI and the Sin3A/Rpd3 complex co-localize at specific chromosome domains. Loss of ISWI activity causes a reduction in the binding of the Sin3A/Rpd3 complex to chromatin. Biochemical analysis showed that the ISWI physically interacts with the histone deacetylase activity of the Sin3A/Rpd3 complex. Consistent with these findings, the acetylation of histone H4 is altered when ISWI activity is perturbed in vivo. These findings suggest that ISWI associates with the Sin3A/Rpd3 complex to support its function in vivo

Essential Role of Chromatin Remodeling Protein Bptf in Early Mouse Embryos and Embryonic Stem Cells

We have characterized the biological functions of the chromatin remodeling protein Bptf (Bromodomain PHD-finger Transcription Factor), the largest subunit of NURF (Nucleosome Remodeling Factor) in a mammal. Bptf mutants manifest growth defects at the post-implantation stage and are reabsorbed by E8.5. Histological analyses of lineage markers show that Bptf−/− embryos implant but fail to establish a functional distal visceral endoderm. Microarray analysis at early stages of differentiation has identified Bptf-dependent gene targets including homeobox transcriptions factors and genes essential for the development of ectoderm, mesoderm, and both definitive and visceral endoderm. Differentiation of Bptf−/− embryonic stem cell lines into embryoid bodies revealed its requirement for development of mesoderm, endoderm, and ectoderm tissue lineages, and uncovered many genes whose activation or repression are Bptf-dependent. We also provide functional and physical links between the Bptf-containing NURF complex and the Smad transcription factors. These results suggest that Bptf may co-regulate some gene targets of this pathway, which is essential for establishment of the visceral endoderm. We conclude that Bptf likely regulates genes and signaling pathways essential for the development of key tissues of the early mouse embryo

The spotted gar genome illuminates vertebrate evolution and facilitates human-teleost comparisons

To connect human biology to fish biomedical models, we sequenced the genome of spotted gar (Lepisosteus oculatus), whose lineage diverged from teleosts before teleost genome duplication (TGD). The slowly evolving gar genome has conserved in content and size many entire chromosomes from bony vertebrate ancestors. Gar bridges teleosts to tetrapods by illuminating the evolution of immunity, mineralization and development (mediated, for example, by Hox, ParaHox and microRNA genes). Numerous conserved noncoding elements (CNEs; often cis regulatory) undetectable in direct human-teleost comparisons become apparent using gar: functional studies uncovered conserved roles for such cryptic CNEs, facilitating annotation of sequences identified in human genome-wide association studies. Transcriptomic analyses showed that the sums of expression domains and expression levels for duplicated teleost genes often approximate the patterns and levels of expression for gar genes, consistent with subfunctionalization. The gar genome provides a resource for understanding evolution after genome duplication, the origin of vertebrate genomes and the function of human regulatory sequences