Release dynamics of nanodiamonds created by laser-driven shock-compression of polyethylene terephthalate.

Laser-driven dynamic compression experiments of plastic materials have found surprisingly fast formation of nanodiamonds (ND) via X-ray probing. This mechanism is relevant for planetary models, but could also open efficient synthesis routes for tailored NDs. We investigate the release mechanics of compressed NDs by molecular dynamics simulation of the isotropic expansion of finite size diamond from different P-T states.

Direct observation of strong momentum-dependent electron-phonon coupling in a metal.

Phonon scattering in metals is one of the most fundamental processes in materials science. However, understanding such processes has remained challenging and requires detailed information on interactions between phonons and electrons. We use an ultrafast electron diffuse scattering technique to resolve the nonequilibrium phonon dynamics in femtosecond-laser-excited tungsten in both time and momentum.

A hidden Markov model for continuous longitudinal data with missing responses and dropout.

We propose a hidden Markov model for multivariate continuous longitudinal responses with covariates that accounts for three different types of missing pattern: (I) partially missing outcomes at a given time occasion, (II) completely missing outcomes at a given time occasion (intermittent pattern), and (III) dropout before the end of the period of observation (monotone pattern). The missing-at-random (MAR) assumption is formulated to deal with the first two types of missingness, while to account for the informative dropout, we rely on an extra absorbing state. Estimation of the model parameters is based on the maximum likelihood method that is implemented by an expectation-maximization (EM) algorithm relying on suitable recursions.

Novel fabrication tools for dynamic compression targets with engineered voids using photolithography methods.

Mesoscale imperfections, such as pores and voids, can strongly modify the properties and the mechanical response of materials under extreme conditions. Tracking the material response and microstructure evolution during void collapse is crucial for understanding its performance. In particular, imperfections in the ablator materials, such as voids, can limit the efficiency of the fusion reaction and ultimately hinder ignition.

Multi-frame, ultrafast, x-ray microscope for imaging shockwave dynamics.

Inertial confinement fusion (ICF) holds increasing promise as a potential source of abundant, clean energy, but has been impeded by defects such as micro-voids in the ablator layer of the fuel capsules. It is critical to understand how these micro-voids interact with the laser-driven shock waves that compress the fuel pellet. At the Matter in Extreme Conditions (MEC) instrument at the Linac Coherent Light Source (LCLS), we utilized an x-ray pulse train with ns separation, an x-ray microscope, and an ultrafast x-ray imaging (UXI) detector to image shock wave interactions with micro-voids.

Atomistic deformation mechanism of silicon under laser-driven shock compression.

Silicon (Si) is one of the most abundant elements on Earth, and it is the most widely used semiconductor. Despite extensive study, some properties of Si, such as its behaviour under dynamic compression, remain elusive. A detailed understanding of Si deformation is crucial for various fields, ranging from planetary science to materials design.

Diamond formation kinetics in shock-compressed C─H─O samples recorded by small-angle x-ray scattering and x-ray diffraction.

Extreme conditions inside ice giants such as Uranus and Neptune can result in peculiar chemistry and structural transitions, e.g., the precipitation of diamonds or superionic water, as so far experimentally observed only for pure C─H and HO systems, respectively.

The Hedgehog-GLI Pathway Regulates MEK5-ERK5 Expression and Activation in Melanoma Cells.

Malignant melanoma is the deadliest skin cancer, with a poor prognosis in advanced stages. We recently showed that the extracellular signal-regulated kinase 5 (ERK5), encoded by the gene, plays a pivotal role in melanoma by regulating cell functions necessary for tumour development, such as proliferation. Hedgehog-GLI signalling is constitutively active in melanoma and is required for proliferation.

Loss-of-Function Mutations in TRAF7 and KLF4 Cooperatively Activate RAS-Like GTPase Signaling and Promote Meningioma Development.

Meningiomas are the most common benign brain tumors. Mutations of the E3 ubiquitin ligase TRAF7 occur in 25% of meningiomas and commonly cooccur with mutations in KLF4, yet the functional link between TRAF7 and KLF4 mutations remains unclear. By generating an meningioma model derived from primary meningeal cells, we elucidated the cooperative interactions that promote meningioma development.

The Noonan Syndrome Gene Controls Cardiovascular Function by Regulating Vesicular Trafficking.

Rationale: Noonan syndrome (NS) is one of the most frequent genetic disorders. Bleeding problems are among the most common, yet poorly defined complications associated with NS. A lack of consensus on the management of bleeding complications in patients with NS indicates an urgent need for new therapeutic approaches.

Nature of Hexagonal Silicon Forming via High-Pressure Synthesis: Nanostructured Hexagonal 4H Polytype.

Hexagonal Si allotropes are expected to enhance light absorption in the visible range as compared to common cubic Si with diamond structure. Therefore, synthesis of these materials is crucial for the development of Si-based optoelectronics. In this work, we combine in situ high-pressure high-temperature synthesis and vacuum heating to obtain hexagonal Si.

ERK5 is activated by oncogenic BRAF and promotes melanoma growth.

Malignant melanoma is among the most aggressive cancers and its incidence is increasing worldwide. Targeted therapies and immunotherapy have improved the survival of patients with metastatic melanoma in the last few years; however, available treatments are still unsatisfactory. While the role of the BRAF-MEK1/2-ERK1/2 pathway in melanoma is well established, the involvement of mitogen-activated protein kinases MEK5-ERK5 remains poorly explored.

Transition from silicene monolayer to thin Si films on Ag(111): comparison between experimental data and Monte Carlo simulation.

Scanning tunneling microscopy (STM), Auger electron spectroscopy (AES) and low energy electron diffraction have been used to follow the growth of Si films on Ag(111) at various temperatures. Using a simple growth model, we have simulated the distribution of film thickness as a function of coverage during evaporation, for the different temperatures. In the temperature regime where multilayer silicene has been claimed to form (470-500 K), a good agreement is found with AES intensity variations and STM measurements within a Ag surfactant mediated growth, whereas a model with multilayer silicene growth fails to reproduce the AES measurements.

A joint model for longitudinal and survival data based on an AR(1) latent process.

A critical problem in repeated measurement studies is the occurrence of nonignorable missing observations. A common approach to deal with this problem is joint modeling the longitudinal and survival processes for each individual on the basis of a random effect that is usually assumed to be time constant. We relax this hypothesis by introducing time-varying subject-specific random effects that follow a first-order autoregressive process, AR(1).

Luciferase Reporter Assays to Study Transcriptional Activity of Hedgehog Signaling in Normal and Cancer Cells.

The measurement of the transcriptional activity of the HH signaling pathway is widely used as an indication of pathway activation. Luciferase reporter assays are powerful tools to measure the specific ability of a transcription factor to bind to its consensus sequence and to activate transcription of target genes. Here, we describe a protocol to measure the transcriptional activity of the HH pathway in normal and cancer cells.

Cooperative integration between HEDGEHOG-GLI signalling and other oncogenic pathways: implications for cancer therapy.

The HEDGEHOG-GLI (HH-GLI) signalling is a key pathway critical in embryonic development, stem cell biology and tissue homeostasis. In recent years, aberrant activation of HH-GLI signalling has been linked to several types of cancer, including those of the skin, brain, lungs, prostate, gastrointestinal tract and blood. HH-GLI signalling is initiated by binding of HH ligands to the transmembrane receptor PATCHED and is mediated by transcriptional effectors that belong to the GLI family, whose activity is finely tuned by a number of molecular interactions and post-translation modifications.

Surgical management of pancreatic neuroendocrine neoplasms.

Pancreatic neuroendocrine neoplasms are relatively rare entities, representing approximately 1% to 2% of all pancreatic tumors. Owing to their rarity as well as their relatively indolent natural history, treatment approaches are not yet standardized. A formal pancreatic resection is usually mandatory for large and localized sporadic pancreatic tumors or in the presence of symptoms.

A new constant memory recursion for hidden Markov models.

We develop the recursion for hidden Markov (HM) models proposed by Bartolucci and Besag (2002), and we show how it may be used to implement an estimation algorithm for these models that requires an amount of memory not depending on the length of the observed series of data. This recursion allows us to obtain the conditional distribution of the latent state at every occasion, given the previous state and the observed data. With respect to the estimation algorithm based on the well-known Baum-Welch recursions, which requires an amount of memory that increases with the sample size, the proposed algorithm also has the advantage of not requiring dummy renormalizations to avoid numerical problems.

Culture and isolation of melanoma-initiating cells.

Melanoma is the most aggressive skin cancer. This unit illustrates protocols for culture and isolation of human melanoma cancer stem cells/tumor-initiating cells (CSC/TIC). We describe two complementary methods to enrich for melanoma CSC/TIC.

The involvement of a Nanog, Klf4 and c-Myc transcriptional circuitry in the intertwining between neoplastic progression and reprogramming.

One undisputed milestone of traditional oncology is neoplastic progression, which consists of a progressive selection of dedifferentiated cells driven by a chance sequence of genetic mutations. Recently it has been demonstrated that the overexpression of well-defined transcription factors reprograms somatic cells to the pluripotent stem status. The demonstration raises crucial questions as to whether and to what extent this reprogramming contributes to tumorigenesis, and whether the epigenetic changes involved in it are reversible.

Hedgehog-GLI signaling drives self-renewal and tumorigenicity of human melanoma-initiating cells.

The question of whether cancer stem/tumor-initiating cells (CSC/TIC) exist in human melanomas has arisen in the last few years. Here, we have used nonadherent spheres and the aldehyde dehydrogenase (ALDH) enzymatic activity to enrich for CSC/TIC in a collection of human melanomas obtained from a broad spectrum of sites and stages. We find that melanomaspheres display extensive in vitro self-renewal ability and sustain tumor growth in vivo, generating human melanoma xenografts that recapitulate the phenotypic composition of the parental tumor.

Melanoma antigen-11 inhibits the hypoxia-inducible factor prolyl hydroxylase 2 and activates hypoxic response.

Activation of hypoxia-inducible factors (HIF), responsible for tumor angiogenesis and glycolytic switch, is regulated by reduced oxygen availability. Normally, HIF-alpha proteins are maintained at low levels, controlled by site-specific hydroxylation carried out by HIF prolyl hydroxylases (PHD) and subsequent proteasomal degradation via the von Hippel-Lindau ubiquitin ligase. Using a yeast two-hybrid screen, we identified an interaction between melanoma antigen-11 (MAGE-11) cancer-testis antigen and the major HIF-alpha hydroxylating enzyme PHD2.

p66Shc/Notch-3 interplay controls self-renewal and hypoxia survival in human stem/progenitor cells of the mammary gland expanded in vitro as mammospheres.

The comprehension of the basic biology of stem cells is expected to provide a useful insight into the pathogenesis of cancer. In particular, there is evidence that hypoxia promotes stem cell renewal in vitro as well as in vivo. It therefore seems reasonable that stem cell survival and hypoxia response are strictly connected at molecular level.