Structure and Dynamics of Mono- vs. Doubly Lipidated Rab5 in Membranes

The Rab5 small GTPase is a regulator of endosomal trafficking and vesicle fusion. It possesses two adjacent cysteine residues for post-translational geranylgeranylation at its C-terminus for the protein to associate with the early endosome membrane. We compare the effect of mono-lipidification of only one cysteine residue with the doubly modified, fully functional Rab protein in both guanosine diphosphate (GDP)- and guanosine triphosphate (GTP)-bound states and in different membranes (one, three, and six-component membranes). Molecular simulations show that the mono-geranylgeranylated protein is less strongly associated with the membranes and diffuses faster than the doubly lipidated protein. The geranylgeranyl anchor membrane insertion depth is smaller and the protein–membrane distance distribution is broad and uncharacteristic for the membrane composition. The mono-geranylgeranylated protein reveals an unspecific association with the membrane and an orientation at the membrane that does not allow a nucleotide-specific recruitment of further effector proteins. This work shows that double-lipidification is critical for Rab5 to perform its physiological function and mono-geranylgeranylation renders it membrane-associated but non-functional

Aluminium-oxide wires for superconducting high kinetic inductance circuits

We investigate thin films of conducting aluminium-oxide, also known as granular aluminium, as a material for superconducting high quality, high kinetic inductance circuits. The films are deposited by an optimised reactive DC magnetron sputter process and characterised using microwave measurement techniques at milli-Kelvin temperatures. We show that, by precise control of the reactive sputter conditions, a high room temperature sheet resistance and therefore high kinetic inductance at low temperatures can be obtained. For a coplanar waveguide resonator with 1.5\,k$\Omega$ sheet resistance and a kinetic inductance fraction close to unity, we measure a quality factor in the order of 700\,000 at 20\,mK. Furthermore, we observe a sheet resistance reduction by gentle heat treatment in air. This behaviour is exploited to study the kinetic inductance change using the microwave response of a coplanar wave guide resonator. We find the correlation between the kinetic inductance and the sheet resistance to be in good agreement with theoretical expectations.Comment: 16 pages, 7 figure

Leptin receptor action and mechanisms of leptin resistance

The adipose tissue-derived hormone leptin regulates energy balance and neuroendocrine function. Resistance to the appetite-suppressing effects of leptin is associated with common forms of obesity. Here, we review the mechanisms by which leptin activates intracellular signals and the roles that these signals play in leptin action in vivo. Furthermore, we discuss potential mechanisms of leptin resistance, specifically focusing on data regarding the neuroanatomical locus of leptin resistance and potential mechanisms by which expression of the suppressor of cytokine signaling-3 may impair leptin action.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42888/1/18_2004_Article_4432.pd

Investigation of superstorm Sandy 2012 in a multi-disciplinary approach

At the end of October 2012, Hurricane Sandy moved from the Caribbean Sea into the Atlantic Ocean and entered the United States not far from New York. Along its track, Sandy caused more than 200 fatalities and severe losses in Jamaica, The Bahamas, Haiti, Cuba, and the US. This paper demonstrates the capability and potential for near-real-time analysis of catastrophes. It is shown that the impact of Sandy was driven by the superposition of different extremes (high wind speeds, storm surge, heavy precipitation) and by cascading effects. In particular the interaction between Sandy and an extra-tropical weather system created a huge storm that affected large areas in the US. It is examined how Sandy compares to historic hurricane events, both from a hydro-meteorological and impact perspective. The distribution of losses to different sectors of the economy is calculated with simple input-output models as well as government estimates. Direct economic losses are estimated about USD 4.2 billion in the Caribbean and between USD 78 and 97 billion in the US. Indirect economic losses from power outages is estimated in the order of USD 16.3 billion. Modelling sector-specific dependencies quantifies total business interruption losses between USD 10.8 and 15.5 billion. Thus, seven years after the record impact of Hurricane Katrina in 2005, Hurricane Sandy is the second costliest hurricane in the history of the United States

Investigation of superstorm Sandy 2012 in a multi-disciplinary approach

At the end of October 2012, Hurricane Sandy moved from the Caribbean Sea into the Atlantic Ocean and entered the United States not far from New York. Along its track, Sandy caused more than 200 fatalities and severe losses in Jamaica, The Bahamas, Haiti, Cuba, and the US. This paper demonstrates the capability and potential for near-real-time analysis of catastrophes. It is shown that the impact of Sandy was driven by the superposition of different extremes (high wind speeds, storm surge, heavy precipitation) and by cascading effects. In particular the interaction between Sandy and an extra-tropical weather system created a huge storm that affected large areas in the US. It is examined how Sandy compares to historic hurricane events, both from a hydro-meteorological and impact perspective. The distribution of losses to different sectors of the economy is calculated with simple input-output models as well as government estimates. Direct economic losses are estimated about USD 4.2 billion in the Caribbean and between USD 78 and 97 billion in the US. Indirect economic losses from power outages is estimated in the order of USD 16.3 billion. Modelling sector-specific dependencies quantifies total business interruption losses between USD 10.8 and 15.5 billion. Thus, seven years after the record impact of Hurricane Katrina in 2005, Hurricane Sandy is the second costliest hurricane in the history of the United States

Leptin Receptor Signaling and Action in the Central Nervous System

The increasing incidence of obesity in developed nations represents an ever‐growing challenge to health care by promoting diabetes and other diseases. The discovery of the hormone, leptin, a decade ago has facilitated the acquisition of new knowledge regarding the regulation of energy balance. A great deal remains to be discovered regarding the molecular and anatomic actions of leptin, however. Here, we discuss the mechanisms by which leptin activates intracellular signals, the roles that these signals play in leptin action in vivo, and sites of leptin action in vivo. Using “reporter” mice, in which LRb‐expressing (long form of the leptin receptor) neurons express the histological marker, β‐galactosidase, coupled with the detection of LRb‐mediated signal transducer and activator of transcription 3 signaling events, we identified LRb expression in neuronal populations both within and outside the hypothalamus. Understanding the regulation and physiological function of these myriad sites of central leptin action will be a crucial next step in the quest to understand mechanisms of leptin action and energy balance.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93692/1/oby.2006.310.pd

A spatial-temporal vulnerability assessment to support the building of community resilience against power outage impacts

Power outages are among the most serious Critical Infrastructure (CI) disruptions and require effective disaster management with collaboration of affected CI providers and disaster management authorities. To support building community resilience, we introduce a vulnerability assessment which allows an enhanced spatial-temporal understanding of initial power outage impacts. Using the assessment enables planers to better identify which and when CIs become vulnerable and how important they are in comparison to other CIs before the overall crisis situation escalates and unmanageable cascading effects occur. The assessment addresses the initial phase of a power outage and corresponding early measures of local risk and crisis management organizations according to the German disaster management system. The assessment is an indicator-based approach which is extended to consider time-depending effects through time-referenced demand and the depletion of Coping Capacity Resources (CCR). The estimation of the relevance of CIs regarding the provision of vital services and products is addressed by a modified Delphi method. In addition, an expert survey was conducted to shed light on the evaluation of coping resources. In this paper, we describe the components of the assessment and propose different aggregation approaches which each enhances the understanding of spatial-temporal impacts of a power outage, and, hence, increases the forecasting capability for disaster management authorities. For demonstration purposes, the assessment is implemented for the case of the city of Mannheim, Germany.Thomas Münzberg, Marcus Wiens, Frank Schultman