Technologies for 3D Heterogeneous Integration

3D-Integration is a promising technology towards higher interconnect densities and shorter wiring lengths between multiple chip stacks, thus achieving a very high performance level combined with low power consumption. This technology also offers the possibility to build up systems with high complexity just by combining devices of different technologies. For ultra thin silicon is the base of this integration technology, the fundamental processing steps will be described, as well as appropriate handling concepts. Three main concepts for 3D integration have been developed at IZM. The approach with the greatest flexibility called Inter Chip Via - Solid Liquid Interdiffusion (ICV-SLID) is introduced. This is a chip-to-wafer stacking technology which combines the advantages of the Inter Chip Via (ICV) process and the solid-liquid-interdiffusion technique (SLID) of copper and tin. The fully modular ICV-SLID concept allows the formation of multiple device stacks. A test chip was designed and the total process sequence of the ICV-SLID technology for the realization of a three-layer chip-to-wafer stack was demonstrated. The proposed wafer-level 3D integration concept has the potential for low cost fabrication of multi-layer high-performance 3D-SoCs and is well suited as a replacement for embedded technologies based on monolithic integration. To address yield issues a wafer-level chip-scale handling is presented as well, to select known-good dies and work on them with wafer-level process sequences before joining them to integrated stacks.Comment: Submitted on behalf of EDA Publishing Association (http://irevues.inist.fr/handle/2042/16838

Mass transport perspective on an accelerated exclusion process: Analysis of augmented current and unit-velocity phases

In an accelerated exclusion process (AEP), each particle can "hop" to its adjacent site if empty as well as "kick" the frontmost particle when joining a cluster of size $\ell \leq \ell_\text{max}$. With various choices of the interaction range, $\ell_\text{max}$, we find that the steady state of AEP can be found in a homogeneous phase with augmented currents (AC) or a segregated phase with holes moving at unit velocity (UV). Here we present a detailed study on the emergence of the novel phases, from two perspectives: the AEP and a mass transport process (MTP). In the latter picture, the system in the UV phase is composed of a condensate in coexistence with a fluid, while the transition from AC to UV can be regarded as condensation. Using Monte Carlo simulations, exact results for special cases, and analytic methods in a mean field approach (within the MTP), we focus on steady state currents and cluster sizes. Excellent agreement between data and theory is found, providing an insightful picture for understanding this model system.Comment: 13 pages, 8 figure

Transport by molecular motors in the presence of static defects

The transport by molecular motors along cytoskeletal filaments is studied theoretically in the presence of static defects. The movements of single motors are described as biased random walks along the filament as well as binding to and unbinding from the filament. Three basic types of defects are distinguished, which differ from normal filament sites only in one of the motors' transition probabilities. Both stepping defects with a reduced probability for forward steps and unbinding defects with an increased probability for motor unbinding strongly reduce the velocities and the run lengths of the motors with increasing defect density. For transport by single motors, binding defects with a reduced probability for motor binding have a relatively small effect on the transport properties. For cargo transport by motors teams, binding defects also change the effective unbinding rate of the cargo particles and are expected to have a stronger effect.Comment: 20 pages, latex, 7 figures, 1 tabl

3D System Integration for high density Interconnects

3D-Integration is a promising technology towards higher interconnect densities and shorter wiring lengths between multiple chip stacks, thus achieving a very high performance level combined with low power consumption. This technology also offers the possibility to build up systems with high complexity by combining devices of different technologies. The fundamental processing steps will be described, as well as appropriate handling concepts and first electrical results of realized 3D-integrated stacks

Deterministic and stochastic descriptions of gene expression dynamics

A key goal of systems biology is the predictive mathematical description of gene regulatory circuits. Different approaches are used such as deterministic and stochastic models, models that describe cell growth and division explicitly or implicitly etc. Here we consider simple systems of unregulated (constitutive) gene expression and compare different mathematical descriptions systematically to obtain insight into the errors that are introduced by various common approximations such as describing cell growth and division by an effective protein degradation term. In particular, we show that the population average of protein content of a cell exhibits a subtle dependence on the dynamics of growth and division, the specific model for volume growth and the age structure of the population. Nevertheless, the error made by models with implicit cell growth and division is quite small. Furthermore, we compare various models that are partially stochastic to investigate the impact of different sources of (intrinsic) noise. This comparison indicates that different sources of noise (protein synthesis, partitioning in cell division) contribute comparable amounts of noise if protein synthesis is not or only weakly bursty. If protein synthesis is very bursty, the burstiness is the dominant noise source, independent of other details of the model. Finally, we discuss two sources of extrinsic noise: cell-to-cell variations in protein content due to cells being at different stages in the division cycles, which we show to be small (for the protein concentration and, surprisingly, also for the protein copy number per cell) and fluctuations in the growth rate, which can have a significant impact.Comment: 23 pages, 5 figures; Journal of Statistical physics (2012

Molecular Spiders with Memory

Synthetic bio-molecular spiders with "legs" made of single-stranded segments of DNA can move on a surface which is also covered by single-stranded segments of DNA complementary to the leg DNA. In experimental realizations, when a leg detaches from a segment of the surface for the first time it alters that segment, and legs subsequently bound to these altered segments more weakly. Inspired by these experiments we investigate spiders moving along a one-dimensional substrate, whose legs leave newly visited sites at a slower rate than revisited sites. For a random walk (one-leg spider) the slowdown does not effect the long time behavior. For a bipedal spider, however, the slowdown generates an effective bias towards unvisited sites, and the spider behaves similarly to the excited walk. Surprisingly, the slowing down of the spider at new sites increases the diffusion coefficient and accelerates the growth of the number of visited sites.Comment: 10 pages, 3 figure

TRPM8 is required for survival and radioresistance of glioblastoma cells

TRPM8 is a Ca$^{2+}$-permeable nonselective cation channel belonging to the melastatin sub-group of the transient receptor potential (TRP) family. TRPM8 is aberrantly overexpressed in a variety of tumor entities including glioblastoma multiforme where it reportedly contributes to tumor invasion. The present study aimed to disclose further functions of TRPM8 in glioma biology in particular upon cell injury by ionizing radiation. To this end, TCGA data base was queried to expose the TRPM8 mRNA abundance in human glioblastoma specimens and immunoblotting was performed to analyze the TRPM8 protein abundance in primary cultures of human glioblastoma. Moreover, human glioblastoma cell lines were irradiated with 6 MV photons and TRPM8 channels were targeted pharmacologically or by RNA interference. TRPM8 abundance, Ca$^{2+}$ signaling and resulting K$^{+}$ channel activity, chemotaxis, cell migration, clonogenic survival, DNA repair, apoptotic cell death, and cell cycle control were determined by qRT-PCR, fura-2 Ca$^{2+}$ imaging, patch-clamp recording, transfilter migration assay, wound healing assay, colony formation assay, immunohistology, flow cytometry, and immunoblotting. As a result, human glioblastoma upregulates TRPM8 channels to variable extent. TRPM8 inhibition or knockdown slowed down cell migration and chemotaxis, attenuated DNA repair and clonogenic survival, triggered apoptotic cell death, impaired cell cycle and radiosensitized glioblastoma cells. Mechanistically, ionizing radiation activated and upregulated TRPM8-mediated Ca$^{2+}$ signaling that interfered with cell cycle control probably via CaMKII, cdc25C and cdc2. Combined, our data suggest that TRPM8 channels contribute to spreading, survival and radioresistance of human glioblastoma and, therefore, might represent a promising target in future anti-glioblastoma therapy