Inkjet Printing of Viscous Monodisperse Microdroplets by Laser-Induced Flow Focusing

The on-demand generation of viscous microdroplets to print functional or biological materials remains challenging using conventional inkjet-printing methods, mainly due to aggregation and clogging issues. In an effort to overcome these limitations, we implement a jetting method to print viscous microdroplets by laser-induced shockwaves. We experimentally investigate the dependence of the jetting regimes and the droplet size on the laser-pulse energy and on the inks' physical properties. The range of printable liquids with our device is significantly extended compared to conventional inkjet printers's performances. In addition, the laser-induced flow-focusing phenomenon allows us to controllably generate viscous microdroplets up to 210 mPa s with a diameter smaller than the nozzle from which they originated (200 mu m). Inks containing proteins are printed without altering their functional properties, thus demonstrating that this jetting technique is potentially suitable for bioprinting

Ground and excited state communication within a ruthenium containing benzimidazole metallopolymer

Emission spectroscopy and electrochemistry has been used to probe the electronic communication between adjacent metal centres and the conjugated backbone within a family of imidazole based metallopolymer, [Ru(bpy)2(PPyBBIM)n]2+, in the ground and excited states, bpy is 2,2’-bipyridyl, PPyBBIM is poly[2-(2-pyridyl)-bibenzimidazole] and n = 3, 10 or 20. Electronic communication in the excited state is not efficient and upon optical excitation dual emission is observed, i.e., both the polymer backbone and the metal centres emit. Coupling the ruthenium moiety to the imidazole backbone results in a red shift of approximately 50 nm in the emission spectrum. Luminescent lifetimes of up to 120 ns were also recorded. Cyclic voltammetry was also utilized to illustrate the distance dependence of the electron hopping rates between adjacent metal centres with ground state communication reduced by up to an order of magnitude compared to previously reported results when the metal to backbone ratio was not altered. DCT and De values of up to 3.96 x 10-10 and 5.32 x 10-10 cm2S-1 were observed with corresponding conductivity values of up to 2.34 x 10-8 Scm-1

Mixmaster universe in Horava-Lifshitz gravity

We consider spatially homogeneous (but generally non-isotropic) cosmologies in the recently proposed Horava-Lifshitz gravity and compare them to those of general relativity using Hamiltonian methods. In all cases, the problem is described by an effective point particle moving in a potential well with exponentially steep walls. Focusing on the closed-space cosmological model (Bianchi type IX), the mixmaster dynamics is now completely dominated by the quadratic Cotton tensor potential term for very small volume of the universe. Unlike general relativity, where the evolution towards the initial singularity always exhibits chaotic behavior with alternating Kasner epochs, the anisotropic universe in Horava-Lifshitz gravity (with parameter lambda > 1/3) is described by a particle moving in a frozen potential well with fixed (but arbitrary) energy E. Alternating Kasner epochs still provide a good description of the early universe for very large E, but the evolution appears to be non-ergodic. For very small E there are harmonic oscillations around the fully isotropic model. The question of chaos remains open for intermediate energy levels.Comment: 1+35 pages, 4 figure

The antigen presenting potential of Vγ9Vδ2 T-cells during Plasmodium falciparum blood-stage infection.

During Plasmodium falciparum infections, erythrocyte-stage parasites inhibit dendritic cell maturation and function; compromising development of effective anti-malarial adaptive immunity. Human Vγ9Vδ2 T-cells can act in vitro as APCs and induce αβ T-cell activation. However, the relevance of this activity in pathophysiological contexts in vivo has remained elusive. Since Vγ9Vδ2 T-cells are activated during the early immune response against P.falciparum infection, we investigated whether they could contribute to the instruction of adaptive immune responses toward malaria parasites. In P.falciparum-infected patients,Vγ9Vδ2 T-cells presented an increased surface expression of APC-associated markers HLA-DR and CD86. In response to infected red blood cells in vitro, Vγ9Vδ2 T-cells readily up-regulated surface expression of HLA-DR, HLA-ABC, CD40, CD80, CD83 and CD86, induced naive αβ T-cell responses, and cross-presented soluble prototypical protein to antigen-specific CD8+ T-cells. Our findings indicate that P. falciparum parasites induce genuine APC properties in Vγ9Vδ2 T-cells and qualify this subset as an alternative professional APC in malaria patients, which could be harnessed for therapeutic interventions and vaccine design

Purine twisted-intercalating nucleic acids: a new class of anti-gene molecules resistant to potassium-induced aggregation

Sequence-specific targeting of genomic DNA by triplex-forming oligonucleotides (TFOs) is a promising strategy to modulate in vivo gene expression. Triplex formation involving G-rich oligonucleotides as third strand is, however, strongly inhibited by potassium-induced TFO self-association into G-quartet structures. We report here that G-rich TFOs with bulge insertions of (R)-1-O-[4-(1-pyrenylethynyl)-phenylmethyl] glycerol (called twisted intercalating nucleic acids, TINA) show a much lower tendency to aggregate in potassium than wild-type analogues do. We designed purine-motif TINA–TFOs for binding to a regulatory polypurine-polypyrimidine (pur/pyr) motif present in the promoter of the KRAS proto-oncogene. The binding of TINA–TFOs to the KRAS target has been analysed by electrophoresis mobility shift assays and DNase I footprinting experiments. We discovered that in the presence of potassium the wild-type TFOs did not bind to the KRAS target, differently from the TINA analogues, whose binding was observed up to 140 mM KCl. The designed TINA–TFOs were found to abrogate the formation of a DNA–protein complex at the pur/pyr site and to down-regulate the transcription of CAT driven by the murine KRAS promoter. Molecular modelling of the DNA/TINA–TFO triplexes are also reported. This study provides a new and promising approach to create TFOs to target in vivo the genome

Dynamic configuration of the CMS Data Acquisition cluster

The CMS Data Acquisition cluster, which runs around 10000 applications, is configured dynamically at run time. XML configuration documents determine what applications are executed on each node and over what networks these applications communicate. Through this mechanism the DAQ System may be adapted to the required performance, partitioned in order to perform (test-) runs in parallel, or re-structured in case of hardware faults. This paper presents the CMS DAQ Configurator tool, which is used to generate comprehensive configurations of the CMS DAQ system based on a high-level description given by the user. Using a database of configuration templates and a database containing a detailed model of hardware modules, data and control links, nodes and the network topology, the tool automatically determines which applications are needed, on which nodes they should run, and over which networks the event traffic will flow. The tool computes application parameters and generates the XML configuration documents as well as the configuration of the run-control system. The performance of the tool and operational experience during CMS commissioning and the first LHC runs are discussed

Atonal homolog 1 Is a Tumor Suppressor Gene

Colon cancer accounts for more than 10% of all cancer deaths annually. Our genetic evidence from Drosophila and previous in vitro studies of mammalian Atonal homolog 1 (Atoh1, also called Math1 or Hath1) suggest an anti-oncogenic function for the Atonal group of proneural basic helix-loop-helix transcription factors. We asked whether mouse Atoh1 and human ATOH1 act as tumor suppressor genes in vivo. Genetic knockouts in mouse and molecular analyses in the mouse and in human cancer cell lines support a tumor suppressor function for ATOH1. ATOH1 antagonizes tumor formation and growth by regulating proliferation and apoptosis, likely via activation of the Jun N-terminal kinase signaling pathway. Furthermore, colorectal cancer and Merkel cell carcinoma patients show genetic and epigenetic ATOH1 loss-of-function mutations. Our data indicate that ATOH1 may be an early target for oncogenic mutations in tissues where it instructs cellular differentiation

Methylation of NR3C1 is related to maternal PTSD, parenting stress and maternal medial prefrontal cortical activity in response to child separation among mothers with histories of violence exposure.

Prior research has shown that mothers with Interpersonal violence-related posttraumatic stress disorder (IPV-PTSD) report greater difficulty in parenting their toddlers. Relative to their frequent early exposure to violence and maltreatment, these mothers display dysregulation of their hypothalamic pituitary adrenal axis (HPA-axis), characterized by hypocortisolism. Considering methylation of the promoter region of the glucocorticoid receptor gene NR3C1 as a marker for HPA-axis functioning, with less methylation likely being associated with less circulating cortisol, the present study tested the hypothesis that the degree of methylation of this gene would be negatively correlated with maternal IPV-PTSD severity and parenting stress, and positively correlated with medial prefrontal cortical (mPFC) activity in response to video-stimuli of stressful versus non-stressful mother-child interactions. Following a mental health assessment, 45 mothers and their children (ages 12-42 months) participated in a behavioral protocol involving free-play and laboratory stressors such as mother-child separation. Maternal DNA was extracted from saliva. Interactive behavior was rated on the CARE-Index. During subsequent fMRI scanning, mothers were shown films of free-play and separation drawn from this protocol. Maternal PTSD severity and parenting stress were negatively correlated with the mean percentage of methylation of NR3C1. Maternal mPFC activity in response to video-stimuli of mother-child separation versus play correlated positively to NR3C1 methylation, and negatively to maternal IPV-PTSD and parenting stress. Among interactive behavior variables, child cooperativeness in play was positively correlated with NR3C1 methylation. Thus, the present study is the first published report to our knowledge, suggesting convergence of behavioral, epigenetic, and neuroimaging data that form a psychobiological signature of parenting-risk in the context of early life stress and PTSD

The triple helix: 50 years later, the outcome

Triplex-forming oligonucleotides constitute an interesting DNA sequence-specific tool that can be used to target cleaving or cross-linking agents, transcription factors or nucleases to a chosen site on the DNA. They are not only used as biotechnological tools but also to induce modifications on DNA with the aim to control gene expression, such as by site-directed mutagenesis or DNA recombination. Here, we report the state of art of the triplex-based anti-gene strategy 50 years after the discovery of such a structure, and we show the importance of the actual applications and the main challenges that we still have ahead of us

Neutrophil cell surface receptors and their intracellular signal transduction pathways

AbstractNeutrophils play a critical role in the host defense against bacterial and fungal infections, but their inappropriate activation also contributes to tissue damage during autoimmune and inflammatory diseases. Neutrophils express a large number of cell surface receptors for the recognition of pathogen invasion and the inflammatory environment. Those include G-protein-coupled chemokine and chemoattractant receptors, Fc-receptors, adhesion receptors such as selectins/selectin ligands and integrins, various cytokine receptors, as well as innate immune receptors such as Toll-like receptors and C-type lectins. The various cell surface receptors trigger very diverse signal transduction pathways including activation of heterotrimeric and monomeric G-proteins, receptor-induced and store-operated Ca2+ signals, protein and lipid kinases, adapter proteins and cytoskeletal rearrangement. Here we provide an overview of the receptors involved in neutrophil activation and the intracellular signal transduction processes they trigger. This knowledge is crucial for understanding how neutrophils participate in antimicrobial host defense and inflammatory tissue damage and may also point to possible future targets of the pharmacological therapy of neutrophil-mediated autoimmune or inflammatory diseases