Germanium:gallium photoconductors for far infrared heterodyne detection

Highly compensated Ge:Ga photoconductors have been fabricated and evaluated for high bandwidth heterodyne detection. Bandwidths up to 60 MHz have been obtained with corresponding current responsivity of 0.01 A/W

Supersymmetric reduced models with a symmetry based on Filippov algebra

Generalizations of the reduced model of super Yang-Mills theory obtained by replacing the Lie algebra structure to Filippov $n$-algebra structures are studied. Conditions for the reduced model actions to be supersymmetric are examined. These models are related with what we call \{cal N}_{min}=2 super $p$-brane actions.Comment: v3: In the previous versions we overlooked that Eq.(3.9) holds more generally, and missed some supersymmetric actions. Those are now included and modifications including a slight change in the title were made accordingly. 1+18 page

Visualisation and graph-theoretic analysis of a large-scale protein structural interactome

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.Abstract Background Large-scale protein interaction maps provide a new, global perspective with which to analyse protein function. PSIMAP, the Protein Structural Interactome Map, is a database of all the structurally observed interactions between superfamilies of protein domains with known three-dimensional structure in the PDB. PSIMAP incorporates both functional and evolutionary information into a single network. Results We present a global analysis of PSIMAP using several distinct network measures relating to centrality, interactivity, fault-tolerance, and taxonomic diversity. We found the following results: Centrality: we show that the center and barycenter of PSIMAP do not coincide, and that the superfamilies forming the barycenter relate to very general functions, while those constituting the center relate to enzymatic activity. Interactivity: we identify the P-loop and immunoglobulin superfamilies as the most highly interactive. We successfully use connectivity and cluster index, which characterise the connectivity of a superfamily's neighbourhood, to discover superfamilies of complex I and II. This is particularly significant as the structure of complex I is not yet solved. Taxonomic diversity: we found that highly interactive superfamilies are in general taxonomically very diverse and are thus amongst the oldest. Fault-tolerance: we found that the network is very robust as for the majority of superfamilies removal from the network will not break up the network. Conclusions Overall, we can single out the P-loop containing nucleotide triphosphate hydrolases superfamily as it is the most highly connected and has the highest taxonomic diversity. In addition, this superfamily has the highest interaction rank, is the barycenter of the network (it has the shortest average path to every other superfamily in the network), and is an articulation vertex, whose removal will disconnect the network. More generally, we conclude that the graph-theoretic and taxonomic analysis of PSIMAP is an important step towards the understanding of protein function and could be an important tool for tracing the evolution of life at the molecular level.Published versio

Fluctuation-Induced Interactions between Rods on a Membrane

We consider the interaction between two rods embedded in a fluctuating surface. The modification of fluctuations by the rods leads to an attractive long-range interaction between them. We consider fluctuations governed by either surface tension (films) or bending rigidity (membranes). In both cases the interaction falls off with the separation of the rods as $1/R^4$. The orientational part of the interaction is proportional to $\cos^2\left[ \theta_1+\theta_2 \right]$ in the former case, and to $\cos^2\left[ 2\left(\theta_1+\theta_2\right) \right]$ in the latter, where $\theta_1$ and $\theta_2$ are angles between the rods and the line joining them. These interactions are somewhat reminiscent of dipolar forces and will tend to align collections of such rods into chains.Comment: REVTEX, 14 pages, with 2 Postscript figure

Mechanism of Action of Risuteganib for Retinal Diseases through Protection of Retinal Pigment Epithelium (RPE) and Enhancement of Mitochondrial Functions

Purpose : Risuteganib is a novel synthetic peptide that has advanced through Phase II clinical trials, showing promising efficacy in retinal diseases, including dry age-related macular degeneration (AMD) and diabetic macular edema (DME). This study is to explore the mechanism of action (MOA) of risuteganib by uncovering its functional target(s) and the associated cell layer. Methods : Fluorescent staining of mouse and rat retinal cryo-sections was performed with risuteganib-dye conjugates and compared with control peptide. Protective effects against oxidative stress was studied in ARPE-19 cell line challenged with tert-Butyl Hydroperoxide (tBHP) using WST-1 assay and Caspase 3/7 apoptosis assay. Mitochondrial bioenergetics were measured using Seahorse XF cell mito stress test. Results : Peptide-dye staining of animal retinal tissue indicated preferential localization of risuteganib in the RPE layer. 24hr risuteganib pretreatment significantly rescued ARPE-19 cells from tBHP-induced oxidative stress in WST-1 assay (p<0.05) and Caspase 3/7 apoptosis assay (p<0.01). Seahorse bioenergetics measurement of ARPE-19 cells showed that risuteganib dose-dependently enhanced mitochondrial basal, maximal and ATP-related respirations of RPE cells. Conclusions : Oxidative stress is one of the hallmarks of retinal diseases AMD and DME, and is associated with impaired RPE function. The observations of preferential binding to RPE layers in retina and the protection of mitochondrial function in RPE cells against oxidative stress in vitro, suggest that the clinically observed therapeutic effect of risuteganib in dry AMD and DME may be associated with supporting RPE cells and maintaining mitochondrial stability and function. Such a novel MOA of risuteganib could lead to new strategies for treatment of retinal diseases

Mechanism of Action of Risuteganib for Retinal Diseases through Protection of Retinal Pigment Epithelium (RPE) and Enhancement of Mitochondrial Functions

Purpose : Risuteganib is a novel synthetic peptide that has advanced through Phase II clinical trials, showing promising efficacy in retinal diseases, including dry age-related macular degeneration (AMD) and diabetic macular edema (DME). This study is to explore the mechanism of action (MOA) of risuteganib by uncovering its functional target(s) and the associated cell layer. Methods : Fluorescent staining of mouse and rat retinal cryo-sections was performed with risuteganib-dye conjugates and compared with control peptide. Protective effects against oxidative stress was studied in ARPE-19 cell line challenged with tert-Butyl Hydroperoxide (tBHP) using WST-1 assay and Caspase 3/7 apoptosis assay. Mitochondrial bioenergetics were measured using Seahorse XF cell mito stress test. Results : Peptide-dye staining of animal retinal tissue indicated preferential localization of risuteganib in the RPE layer. 24hr risuteganib pretreatment significantly rescued ARPE-19 cells from tBHP-induced oxidative stress in WST-1 assay (p<0.05) and Caspase 3/7 apoptosis assay (p<0.01). Seahorse bioenergetics measurement of ARPE-19 cells showed that risuteganib dose-dependently enhanced mitochondrial basal, maximal and ATP-related respirations of RPE cells. Conclusions : Oxidative stress is one of the hallmarks of retinal diseases AMD and DME, and is associated with impaired RPE function. The observations of preferential binding to RPE layers in retina and the protection of mitochondrial function in RPE cells against oxidative stress in vitro, suggest that the clinically observed therapeutic effect of risuteganib in dry AMD and DME may be associated with supporting RPE cells and maintaining mitochondrial stability and function. Such a novel MOA of risuteganib could lead to new strategies for treatment of retinal diseases

A Unique Modification of the Eukaryotic Initiation Factor 5A Shows the Presence of the Complete Hypusine Pathway in Leishmania donovani

Deoxyhypusine hydroxylase (DOHH) catalyzes the final step in the post-translational synthesis of an unusual amino acid hypusine (N€-(4-amino-2-hydroxybutyl) lysine), which is present on only one cellular protein, eukaryotic initiation factor 5A (eIF5A). We present here the molecular and structural basis of the function of DOHH from the protozoan parasite, Leishmania donovani, which causes visceral leishmaniasis. The L. donovani DOHH gene is 981 bp and encodes a putative polypeptide of 326 amino acids. DOHH is a HEAT-repeat protein with eight tandem repeats of α-helical pairs. Four conserved histidine-glutamate sequences have been identified that may act as metal coordination sites. A ∼42 kDa recombinant protein with a His-tag was obtained by heterologous expression of DOHH in Escherichia coli. Purified recombinant DOHH effectively catalyzed the hydroxylation of the intermediate, eIF5A-deoxyhypusine (eIF5A-Dhp), in vitro. L. donovani DOHH (LdDOHH) showed ∼40.6% sequence identity with its human homolog. The alignment of L. donovani DOHH with the human homolog shows that there are two significant insertions in the former, corresponding to the alignment positions 159-162 (four amino acid residues) and 174-183 (ten amino acid residues) which are present in the variable loop connecting the N- and C-terminal halves of the protein, the latter being present near the substrate binding site. Deletion of the ten-amino-acid-long insertion decreased LdDOHH activity to 14% of the wild type recombinant LdDOHH. Metal chelators like ciclopirox olamine (CPX) and mimosine significantly inhibited the growth of L. donovani and DOHH activity in vitro. These inhibitors were more effective against the parasite enzyme than the human enzyme. This report, for the first time, confirms the presence of a complete hypusine pathway in a kinetoplastid unlike eubacteria and archaea. The structural differences between the L. donovani DOHH and the human homolog may be exploited for structure based design of selective inhibitors against the parasite