Optimal sensor placement in linear arrays : part I - AoA based localization

In this paper, we examine the optimal linear separation requirements for AoA sensors, in order to achieve the best performance in estimating the position of a target subjected to noisy measurements. Cramer-Rao inequality and the corresponding Fisher information matrix are used to analyze the sensor-target geometry, in order to characterize localization performance with respect to the linear spacial distribution of sensors.

Apical localization of zinc transporter ZnT4 in human airway epithelial cells and its loss in a murine model of allergic airway inflammation

The apical cytoplasm of airway epithelium (AE) contains abundant labile zinc (Zn) ions that are involved in the protection of AE from oxidants and inhaled noxious substances. A major question is how dietary Zn traffics to this compartment. In rat airways, in vivo selenite autometallographic (Se-AMG)-electron microscopy revealed labile Zn-selenium nanocrystals in structures resembling secretory vesicles in the apical cytoplasm. This observation was consistent with the starry-sky Zinquin fluorescence staining of labile Zn ions confined to the same region. The vesicular Zn transporter ZnT4 was likewise prominent in both the apical and basal parts of the epithelium both in rodent and human AE, although the apical pools were more obvious. Expression of ZnT4 mRNA was unaffected by changes in the extracellular Zn concentration. However, levels increased 3-fold during growth of cells in air liquid interface cultures and decreased sharply in the presence of retinoic acid. When comparing nasal versus bronchial human AE cells, there were significant positive correlations between levels of ZnT4 from the same subject, suggesting that nasal brushings may allow monitoring of airway Zn transporter expression. Finally, there were marked losses of both basally-located ZnT4 protein and labile Zn in the bronchial epithelium of mice with allergic airway inflammation. This study is the first to describe co-localization of zinc vesicles with the specific zinc transporter ZnT4 in airway epithelium and loss of ZnT4 protein in inflamed airways. Direct evidence that ZnT4 regulates Zn levels in the epithelium still needs to be provided. We speculate that ZnT4 is an important regulator of zinc ion accumulation in secretory apical vesicles and that the loss of labile Zn and ZnT4 in airway inflammation contributes to AE vulnerability in diseases such as asthma.

Efficient algorithms for subwindow search in object detection and localization

Recently, a simple yet powerful branch-and-bound method called Efficient Subwindow Search (ESS) was developed to speed up sliding window search in object detection. A major drawback of ESS is that its computational complexity varies widely from O(n²) to O(n⁴) for n × n matrices. Our experimental experience shows that the ESS's performance is highly related to the optimal confidence levels which indicate the probability of the object's presence. In particular, when the object is not in the image, the optimal subwindow scores low and ESS may take a large amount of iterations to converge to the optimal solution and so perform very slow. Addressing this problem, we present two significantly faster methods based on the linear-time Kadane's Algorithm for 1D maximum subarray search. The first algorithm is a novel, computationally superior branchand- bound method where the worst case complexity is reduced to O(n³). Experiments on the PASCAL VOC 2006 data set demonstrate that this method is significantly and consistently faster (approximately 30 times faster on average) than the original ESS. Our second algorithm is an approximate algorithm based on alternating search, whose computational complexity is typically O(n²). Experiments shows that (on average) it is 30 times faster again than our first algorithm, or 900 times faster than ESS. It is thus wellsuited for real time object detection.

Biosynthesis, localization, and macromolecular arrangement of the plasmodium falciparum translocon of exported proteins (PTEX)

To survive within its host erythrocyte, Plasmodium falciparum must export hundreds of proteins across both its parasite plasma membrane and surrounding parasitophorous vacuole membrane, most of which are likely to use a protein complex known as PTEX (Plasmodium translocon of exported proteins). PTEX is a putative protein trafficking machinery responsible for the export of hundreds of proteins across the parasitophorous vacuole membrane and into the human host cell. Five proteins are known to comprise the PTEX complex, and in this study, three of the major stoichiometric components are investigated including HSP101 (a AAA+ ATPase), a protein of no known function termed PTEX150, and the apparent membrane component EXP2. We show that these proteins are synthesized in the preceding schizont stage (PTEX150 and HSP101) or even earlier in the life cycle (EXP2), and before invasion these components reside within the dense granules of invasive merozoites. From these apical organelles, the protein complex is released into the host cell where it resides with little turnover in the parasitophorous vacuole membrane for most of the remainder of the following cell cycle. At this membrane, PTEX is arranged in a stable macromolecular complex of >1230 kDa that includes an ∼600-kDa apparently homo-oligomeric complex of EXP2 that can be separated from the remainder of the PTEX complex using non-ionic detergents. Two different biochemical methods undertaken here suggest that PTEX components associate as EXP2-PTEX150-HSP101, with EXP2 associating with the vacuolar membrane. Collectively, these data support the hypothesis that EXP2 oligomerizes and potentially forms the putative membrane-spanning pore to which the remainder of the PTEX complex is attached.

Altered intracellular localization and valosin-containing protein (p97 VCP) interaction underlie ATP7A-related distal motor neuropathy

ATP7A is a P-type ATPase that regulates cellular copper homeostasis by activity at the trans-Golgi network (TGN) and plasma membrane (PM), with the location normally governed by intracellular copper concentration. Defects in ATP7A lead to Menkes disease or its milder variant, occipital horn syndrome or to a newly discovered condition, ATP7A-related distal motor neuropathy (DMN), for which the precise pathophysiology has been obscure. We investigated two ATP7A motor neuropathy mutations (T994I, P1386S) previously associated with abnormal intracellular trafficking. In the patients' fibroblasts, total internal reflection fluorescence microscopy indicated a shift in steady-state equilibrium of ATP7AT994I and ATP7AP1386S, with exaggerated PM localization. Transfection of Hek293T cells and NSC-34 motor neurons with the mutant alleles tagged with the Venus fluorescent protein also revealed excess PM localization. Endocytic retrieval of the mutant alleles from the PM to the TGN was impaired. Immunoprecipitation assays revealed an abnormal interaction between ATP7AT994I and p97/VCP, an ubiquitin-selective chaperone which is mutated in two autosomal dominant forms of motor neuron disease: amyotrophic lateral sclerosis and inclusion body myopathy with early-onset Paget disease and fronto-temporal dementia. Small-interfering RNA (SiRNA) knockdown of p97/VCP corrected ATP7AT994I mislocalization. Flow cytometry documented that non-permeabilized ATP7AP1386S fibroblasts bound a carboxyl-terminal ATP7A antibody, consistent with relocation of the ATP7A di-leucine endocytic retrieval signal to the extracellular surface and partially destabilized insertion of the eighth transmembrane helix. Our findings illuminate the mechanisms underlying ATP7A-related DMN and establish a link between p97/VCP and genetically distinct forms of motor neuron degeneration.

Localization with ghost elimination of emitters via time-delay-of-arrival measurements

This paper investigates the theoretical requirements for unique localization of multiple emitters using time delay of arrival(TDoA) subjected to the data-association problem. Specifically, an examination is carried out to find the necessary fundamental requirements to solve the so-called ghost node problem pertaining to sensor arrays.

Multiple emitter localization using range only measurements considering geometrical constraints

This paper proposes a constrained optimization approach to improve the accuracy of a Time-of-Arrival (ToA) based multiple target localization system. Instead of using an overdetermined measurement system, this paper uses local distance measurements between the targets/emitters as the geometric constraint.Computer simulations are used to evaluate the performance of the geometrically constrained optimization method.

Optimal sensor placement in range based localization for linear arrays

This paper investigates the linear separation requirements for range sensors in order to achieve the optimal performance in estimating the position of a target from multiple and typically noisy sensor measurements. We analyze the sensor-target geometry in terms of the Cramer-Rao inequality and the corresponding Fisher information matrix, in order to characterize localization performance with respect to the linear special distribution.

Localization with ghost elimination of emitters via time-of-arrival measurements

This paper looks at the theoretical conditions underpinning unique localization of synchronized multiple emitters using Time-of-Arrival measurements subjected to the data-association problem. The necessary fundamental requirements to solve the so-called ghost node problem associated with sensor arrays are examined. We derive a measurement bound for ideal situations and the underlying concepts are illustrated via simulations.

Localization of copper and copper transporters in the human brain

Disturbances in brain copper result in rare and severe neurological disorders and may play a role in the pathogenesis and progression of multiple neurodegenerative diseases. Our current understanding of mammalian brain copper transport is based on model systems outside the central nervous system and no data are available regarding copper transport systems in the human brain. To address this deficit, we quantified regional copper concentrations and examined the distribution and cellular localization of the copper transport proteins Copper transporter 1, Atox1, ATP7A, and ATP7B in multiple regions of the human brain using inductively coupled plasma-mass spectrometry, Western blot and immunohistochemistry. We identified significant relationships between copper transporter levels and brain copper concentrations, supporting a role for these proteins in copper transport in the human brain. Interestingly, the substantia nigra contained twice as much copper than that in other brain regions, suggesting an important role for copper in this brain region. Furthermore, ATP7A levels were significantly greater in the cerebellum, compared with other brain regions, supporting an important role for ATP7A in cerebellar neuronal health. This study provides novel data regarding copper regulation in the human brain, critical to understand the mechanisms by which brain copper levels can be altered, leading to neurological disease.