Validation of the porous-medium approach to model interlayer-cooled 3D-chip stacks

Interlayer cooling is the only heat removal concept which scales with the number of active tiers in a vertically integrated chip stack. In this work, we numerically and experimentally characterize the performance of a three tier chip stack with a footprint of 1cm2. The implementation of 100μm pitch area array interconnect compatible heat transfer structures results in a maximal junction temperature increase of 54.7K at 1bar pressure drop with water as coolant for 250W/cm2 hot-spot and 50W/cm2 background heat flux. The total power removed was 390W which corresponds to a 3.9kW/cm3 volumetric heat flow. An efficient multi-scale modeling approach is proposed to predict the temperature response in the complete chip stack. The experimental validation confirmed an accuracy of +/- 10%. Detailed sub-domain modeling with parameter extraction is the base for the system level porous-media calculations with thermal field-coupling between solid – fluid and solid – solid interfaces. Furthermore, the strength and weakness of microchannel and pin fin heat transfer geometries in 2-port and 4-port fluid architectures is identified. Microchannels efficiently mitigate hot spots by distributing the dissipated heat to multiple cavities due to their low porosity. Pin fins with improved permeability and convective heat dissipation are advantageous at small power map contrast and aligned hot spots on the different tiers. Large stacks of 4cm2 can be cooled sufficiently by the 4-port fluid delivery architecture. The flow rate is improved four times compared to the 2-port fluid manifold. The non-uniformity of the flow in case of the 4-port demands a more careful floor- planning with hot spots placed in the chip stack corners. This is especially true in case of communicating heat transfer geometries such as pin fin structures with zero fluid velocity in the stack center. This large velocity contrast can be reduced by the implementation of non- communicating microchannels

Identifying allosteric fluctuation transitions between different protein conformational states as applied to Cyclin Dependent Kinase 2

BACKGROUND: The mechanisms underlying protein function and associated conformational change are dominated by a series of local entropy fluctuations affecting the global structure yet are mediated by only a few key residues. Transitional Dynamic Analysis (TDA) is a new method to detect these changes in local protein flexibility between different conformations arising from, for example, ligand binding. Additionally, Positional Impact Vertex for Entropy Transfer (PIVET) uses TDA to identify important residue contact changes that have a large impact on global fluctuation. We demonstrate the utility of these methods for Cyclin-dependent kinase 2 (CDK2), a system with crystal structures of this protein in multiple functionally relevant conformations and experimental data revealing the importance of local fluctuation changes for protein function. RESULTS: TDA and PIVET successfully identified select residues that are responsible for conformation specific regional fluctuation in the activation cycle of Cyclin Dependent Kinase 2 (CDK2). The detected local changes in protein flexibility have been experimentally confirmed to be essential for the regulation and function of the kinase. The methodologies also highlighted possible errors in previous molecular dynamic simulations that need to be resolved in order to understand this key player in cell cycle regulation. Finally, the use of entropy compensation as a possible allosteric mechanism for protein function is reported for CDK2. CONCLUSION: The methodologies embodied in TDA and PIVET provide a quick approach to identify local fluctuation change important for protein function and residue contacts that contributes to these changes. Further, these approaches can be used to check for possible errors in protein dynamic simulations and have the potential to facilitate a better understanding of the contribution of entropy to protein allostery and function

7th Drug hypersensitivity meeting: part two

No abstract availabl

Gypsum Karst Landscape in the Sivas Basin

The Tertiary Sivas Basin, Central Anatolia, includes one of the most outstanding gypsum karst terrains in the world, covering an area of 2140 km2. This gypsum karst significantly contributes to enrich the diversity of karst landscapes in Turkey and constitutes an excellent natural laboratory for understanding their evolution because it develops and degrades much faster than carbonate karst landscapes. The ENE–WSW trending Sivas gypsum karst terrain is 280 km long and 55 km wide. The karst landscapes are mainly developed on Oligocene gypsum deposits. Sivas gypsum karst terrain has a wide variety of well-developed karst features such as karren, different types of dolines (solution, collapse and suffosion), blind valleys, karst springs, swallow holes (ponors), karstified paleo-valleys, caves, unroofed caves, natural bridges, gorges, uvalas and poljes. Solution dolines, which riddle a large part of the area, are the most common landform. The Kızılırmak River and its tributaries drain the Sivas Basin. Therefore, Quaternary evolution of the Kızılırmak River has played an important role in the long-term evolution of the karst landscape in the basin. Karst development in some parts of the basin has also been affected by halokinetic structures