PERIODIC CONTROLS IN AN OSCILLATING DOMAIN: CONTROLS VIA UNFOLDING AND HOMOGENIZATION

An optimal control problem in a two-dimensional domain with a rapidly oscillating boundary is considered. The main features of this article are on two points, namely, we consider periodic controls in the thin periodic slabs of period epsilon > 0, a small parameter, and height O(1) in the oscillatory part, and the controls are characterized using unfolding operators. We then do a homogenization analysis of the optimal control problems as epsilon -> 0 with L-2 as well as Dirichlet (gradient-type) cost functionals.

First Structural View of a Peptide Interacting with the Nucleotide Binding Domain of Heat Shock Protein 90

The involvement of Hsp90 in progression of diseases like cancer, neurological disorders and several pathogen related conditions is well established. Hsp90, therefore, has emerged as an attractive drug target for many of these diseases. Several small molecule inhibitors of Hsp90, such as geldanamycin derivatives, that display antitumor activity, have been developed and are under clinical trials. However, none of these tested inhibitors or drugs are peptide-based compounds. Here we report the first crystal structure of a peptide bound at the ATP binding site of the N-terminal domain of Hsp90. The peptide makes several specific interactions with the binding site residues, which are comparable to those made by the nucleotide and geldanamycin. A modified peptide was designed based on these interactions. Inhibition of ATPase activity of Hsp90 was observed in the presence of the modified peptide. This study provides an alternative approach and a lead peptide molecule for the rational design of effective inhibitors of Hsp90 function.

Evidence for N-7 guanine methyl transferase activity encoded within the modular domain of RNA-dependent RNA polymerase L of a Morbillivirus

Post-transcriptional modification of viral mRNA is essential for the translation of viral proteins by cellular translation machinery. Due to the cytoplasmic replication of Paramyxoviruses, the viral-encoded RNA-dependent RNA polymerase (RdRP) is thought to possess all activities required for mRNA capping and methylation. In the present work, using partially purified recombinant RNA polymerase complex of rinderpest virus expressed in insect cells, we demonstrate the in vitro methylation of capped mRNA. Further, we show that a recombinant C-terminal fragment (1717-2183 aa) of L protein is capable of methylating capped mRNA, suggesting that the various post-transcriptional activities of the L protein are located in independently folding domains.

Ultrafast Chemical Dynamics in Time Domain Through Fluorescence Spectroscopy

While absorption and emission spectroscopy have always been used to detect and characterize molecules and molecular complexes, the availability of ultrashort laser pulses and associated computer-aided optical detection techniques allowed study of chemical processes directly in the time domain at unprecedented time scales, through appearance and disappearance of fluorescence from participating chemical species. Application of such techniques to chemical dynamics in liquids, where many processes occur with picosecond and femtosecond time scales lead to the discovery of a host of new phenomena that in turn led to the development of many new theories. Experiment and theory together provided new and valuable insight into many fundamental chemical processes, like isomerization dynamics, electron and proton transfer reactions, vibrational energy and phase relaxation, photosynthesis, to name just a few. In this article, we shall review a few of such discoveries in attempt to provide a glimpse of the fascinating research employing fluorescence spectroscopy that changed the field of chemical dynamics forever.

Botulinum neurotoxin type-A enters a non-recycling pool of synaptic vesicles

Neuronal communication relies on synaptic vesicles undergoing regulated exocytosis and recycling for multiple rounds of fusion. Whether all synaptic vesicles have identical protein content has been challenged, suggesting that their recycling ability may differ greatly. Botulinum neurotoxin type-A (BoNT/A) is a highly potent neurotoxin that is internalized in synaptic vesicles at motor nerve terminals and induces flaccid paralysis. Recently, BoNT/A was also shown to undergo retrograde transport, suggesting it might enter a specific pool of synaptic vesicles with a retrograde trafficking fate. Using high-resolution microscopy techniques including electron microscopy and single molecule imaging, we found that the BoNT/A binding domain is internalized within a subset of vesicles that only partially co-localize with cholera toxin B-subunit and have markedly reduced VAMP2 immunoreactivity. Synaptic vesicles loaded with pHrodo-BoNT/A-Hc exhibited a significantly reduced ability to fuse with the plasma membrane in mouse hippocampal nerve terminals when compared with pHrodo-dextran-containing synaptic vesicles and pHrodo-labeled anti-GFP nanobodies bound to VAMP2-pHluorin or vGlut-pHluorin. Similar results were also obtained at the amphibian neuromuscular junction. These results reveal that BoNT/A is internalized in a subpopulation of synaptic vesicles that are not destined to recycle, highlighting the existence of significant molecular and functional heterogeneity between synaptic vesicles.

Biochemical Characterization of Nonamer Binding Domain of RAG1 Reveals its Thymine Preference with Respect to Length and Position

RAG complex consisting of RAG1 and RAG2 is a site-specific endonuclease responsible for the generation of antigen receptor diversity. It cleaves recombination signal sequence (RSS), comprising of conserved heptamer and nonamer. Nonamer binding domain (NBD) of RAG1 plays a central role in the recognition of RSS. To investigate the DNA binding properties of the domain, NBD of murine RAG1 was cloned, expressed and purified. Electrophoretic mobility shift assays showed that NBD binds with high affinity to nonamer in the context of 12/23 RSS or heteroduplex DNA. NBD binding was specific to thymines when single stranded DNA containing poly A, C, G or T were used. Biolayer interferometry studies showed that poly T binding to NBD was robust and comparable to that of 12RSS. More than 23 nt was essential for NBD binding at homothymidine stretches. On a double-stranded DNA, NBD could bind to A:T stretches, but not G:C or random sequences. Although NBD is indispensable for sequence specific activity of RAGs, external supplementation of purified nonamer binding domain to NBD deleted cRAG1/cRAG2 did not restore its activity, suggesting that the overall domain architecture of RAG1 is important. Therefore, we define the sequence requirements of NBD binding to DNA.

A survey on compressed domain video analysis techniques

Image and video analysis requires rich features that can characterize various aspects of visual information. These rich features are typically extracted from the pixel values of the images and videos, which require huge amount of computation and seldom useful for real-time analysis. On the contrary, the compressed domain analysis offers relevant information pertaining to the visual content in the form of transform coefficients, motion vectors, quantization steps, coded block patterns with minimal computational burden. The quantum of work done in compressed domain is relatively much less compared to pixel domain. This paper aims to survey various video analysis efforts published during the last decade across the spectrum of video compression standards. In this survey, we have included only the analysis part, excluding the processing aspect of compressed domain. This analysis spans through various computer vision applications such as moving object segmentation, human action recognition, indexing, retrieval, face detection, video classification and object tracking in compressed videos.

EXACT INTERNAL CONTROLLABILITY FOR THE WAVE EQUATION IN A DOMAIN WITH OSCILLATING BOUNDARY WITH NEUMANN BOUNDARY CONDITION

In this paper, we study the exact controllability of a second order linear evolution equation in a domain with highly oscillating boundary with homogeneous Neumann boundary condition on the oscillating part of boundary. Our aim is to obtain the exact controllability for the homogenized equation. The limit problem with Neumann condition on the oscillating boundary is different and hence we need to study the exact controllability of this new type of problem. In the process of homogenization, we also study the asymptotic analysis of evolution equation in two setups, namely solution by standard weak formulation and solution by transposition method.

Differential dynamics of the serotonin(1A) receptor in membrane bilayers of varying cholesterol content revealed by all atom molecular dynamics simulation

The serotonin(1A) receptor belongs to the superfamily of G protein-coupled receptors (GPCRs) and is a potential drug target in neuropsychiatric disorders. The receptor has been shown to require membrane cholesterol for its organization, dynamics and function. Although recent work suggests a close interaction of cholesterol with the receptor, the structural integrity of the serotonin(1A) receptor in the presence of cholesterol has not been explored. In this work, we have carried out all atom molecular dynamics simulations, totaling to 3s, to analyze the effect of cholesterol on the structure and dynamics of the serotonin(1A) receptor. Our results show that the presence of physiologically relevant concentration of membrane cholesterol alters conformational dynamics of the serotonin(1A) receptor and, on an average lowers conformational fluctuations. Our results show that, in general, transmembrane helix VII is most affected by the absence of membrane cholesterol. These results are in overall agreement with experimental data showing enhancement of GPCR stability in the presence of membrane cholesterol. Our results constitute a molecular level understanding of GPCR-cholesterol interaction, and represent an important step in our overall understanding of GPCR function in health and disease.

A coupled discriminative dictionary and transformation learning approach with applications to cross domain matching

Cross domain and cross-modal matching has many applications in the field of computer vision and pattern recognition. A few examples are heterogeneous face recognition, cross view action recognition, etc. This is a very challenging task since the data in two domains can differ significantly. In this work, we propose a coupled dictionary and transformation learning approach that models the relationship between the data in both domains. The approach learns a pair of transformation matrices that map the data in the two domains in such a manner that they share common sparse representations with respect to their own dictionaries in the transformed space. The dictionaries for the two domains are learnt in a coupled manner with an additional discriminative term to ensure improved recognition performance. The dictionaries and the transformation matrices are jointly updated in an iterative manner. The applicability of the proposed approach is illustrated by evaluating its performance on different challenging tasks: face recognition across pose, illumination and resolution, heterogeneous face recognition and cross view action recognition. Extensive experiments on five datasets namely, CMU-PIE, Multi-PIE, ChokePoint, HFB and IXMAS datasets and comparisons with several state-of-the-art approaches show the effectiveness of the proposed approach. (C) 2015 Elsevier B.V. All rights reserved.

A coupled discriminative dictionary and transformation learning approach with applications to cross domain matching

Cross domain and cross-modal matching has many applications in the field of computer vision and pattern recognition. A few examples are heterogeneous face recognition, cross view action recognition, etc. This is a very challenging task since the data in two domains can differ significantly. In this work, we propose a coupled dictionary and transformation learning approach that models the relationship between the data in both domains. The approach learns a pair of transformation matrices that map the data in the two domains in such a manner that they share common sparse representations with respect to their own dictionaries in the transformed space. The dictionaries for the two domains are learnt in a coupled manner with an additional discriminative term to ensure improved recognition performance. The dictionaries and the transformation matrices are jointly updated in an iterative manner. The applicability of the proposed approach is illustrated by evaluating its performance on different challenging tasks: face recognition across pose, illumination and resolution, heterogeneous face recognition and cross view action recognition. Extensive experiments on five datasets namely, CMU-PIE, Multi-PIE, ChokePoint, HFB and IXMAS datasets and comparisons with several state-of-the-art approaches show the effectiveness of the proposed approach. (C) 2015 Elsevier B.V. All rights reserved.

Intracellular delivery of antibodies by chimeric Sesbania mosaic virus (SeMV) virus like particles

The therapeutic potential of antibodies has not been fully exploited as they fail to cross cell membrane. In this article, we have tested the possibility of using plant virus based nanoparticles for intracellular delivery of antibodies. For this purpose, Sesbania mosaic virus coat protein (CP) was genetically engineered with the B domain of Staphylococcus aureus protein A (SpA) at the beta H-beta I loop, to generate SeMV loop B (SLB), which self-assembled to virus like particles (VLPs) with 43 times higher affinity towards antibodies. CP and SLB could internalize into various types of mammalian cells and SLB could efficiently deliver three different monoclonal antibodies-D6F10 (targeting abrin), anti-a-tubulin (targeting intracellular tubulin) and Herclon (against HER2 receptor) inside the cells. Such a mode of delivery was much more effective than antibodies alone treatment. These results highlight the potential of SLB as a universal nanocarrier for intracellular delivery of antibodies.

Anomalous reduction in domain wall displacement at the morphotropic phase boundary of the piezoelectric alloy system PbTiO3-BiScO3

A comparative study of field-induced domain switching and lattice strain was carried out by in situ electric-field-dependent high-energy synchrotron x-ray diffraction on a morphotropic phase boundary (MPB) and a near-MPB rhombohedral/pseudomonoclinic composition of a high-performance piezoelectric alloy (1-x) PbTiO3-(x)BiScO3. It is demonstrated that the MPB composition showing large d(33) similar to 425 pC/N exhibits significantly reduced propensity of field-induced domain switching as compared to the non-MPB rhombohedral composition (d(33) similar to 260 pC/N). These experimental observations contradict the basic premise of the martensitic-theory-based explanation which emphasizes on enhanced domain wall motion as the primary factor for the anomalous piezoelectric response in MPB piezoelectrics. Our results favor field-induced structural transformation to be the primary mechanism contributing to the large piezoresponse of the critical MPB composition of this system.

Time-Instant Sampling Based Encoding of Time-Varying Acoustic Spectrum

The inner ear has been shown to characterize an acoustic stimuli by transducing fluid motion in the inner ear to mechanical bending of stereocilia on the inner hair cells (IHCs). The excitation motion/energy transferred to an IHC is dependent on the frequency spectrum of the acoustic stimuli, and the spatial location of the IHC along the length of the basilar membrane (BM). Subsequently, the afferent auditory nerve fiber (ANF) bundle samples the encoded waveform in the IHCs by synapsing with them. In this work we focus on sampling of information by afferent ANFs from the IHCs, and show computationally that sampling at specific time instants is sufficient for decoding of time-varying acoustic spectrum embedded in the acoustic stimuli. The approach is based on sampling the signal at its zero-crossings and higher-order derivative zero-crossings. We show results of the approach on time-varying acoustic spectrum estimation from cricket call signal recording. The framework gives a time-domain and non-spatial processing perspective to auditory signal processing. The approach works on the full band signal, and is devoid of modeling any bandpass filtering mimicking the BM action. Instead, we motivate the approach from the perspective of event-triggered sampling by afferent ANFs on the stimuli encoded in the IHCs. Though the approach gives acoustic spectrum estimation but it is shallow on its complete understanding for plausible bio-mechanical replication with current mammalian auditory mechanics insights.

CROWD FLOW SEGMENTATION IN COMPRESSED DOMAIN USING CRF

Crowd flow segmentation is an important step in many video surveillance tasks. In this work, we propose an algorithm for segmenting flows in H.264 compressed videos in a completely unsupervised manner. Our algorithm works on motion vectors which can be obtained by partially decoding the compressed video without extracting any additional features. Our approach is based on modelling the motion vector field as a Conditional Random Field (CRF) and obtaining oriented motion segments by finding the optimal labelling which minimises the global energy of CRF. These oriented motion segments are recursively merged based on gradient across their boundaries to obtain the final flow segments. This work in compressed domain can be easily extended to pixel domain by substituting motion vectors with motion based features like optical flow. The proposed algorithm is experimentally evaluated on a standard crowd flow dataset and its superior performance in both accuracy and computational time are demonstrated through quantitative results.