A hierarchical approach to model parameter optimization for developmental systems.

In the context of Systems Biology, computer simulations of gene regulatory networks provide a powerful tool to validate hypotheses and to explore possible system behaviors. Nevertheless, modeling a system poses some challenges of its own: especially the step of model calibration is often difficult due to insufficient data. For example when considering developmental systems, mostly qualitative data describing the developmental trajectory is available while common calibration techniques rely on high-resolution quantitative data. Focusing on the calibration of differential equation models for developmental systems, this study investigates different approaches to utilize the available data to overcome these difficulties. More specifically, the fact that developmental processes are hierarchically organized is exploited to increase convergence rates of the calibration process as well as to save computation time. Using a gene regulatory network model for stem cell homeostasis in Arabidopsis thaliana the performance of the different investigated approaches is evaluated, documenting considerable gains provided by the proposed hierarchical approach.

A convex optimization framework for global tractography

In this article we present a novel approach for diffusion MRI global tractography. Our formulation models the signal in each voxel as a linear combination of fiber-tract basis func- tions, which consist of a comprehensive set of plausible fiber tracts that are locally compatible with the measured MR signal. This large dictionary of candidate fibers is directly estimated from the data and, subsequently, efficient convex optimization techniques are used for recovering the smallest subset globally best fitting the measured signal. Experimen- tal results conducted on a realistic phantom demonstrate that our approach significantly reduces the computational cost of global tractography while still attaining a reconstruction quality at least as good as the state-of-the-art global methods.

Dose optimization approach to fast X-ray microtomography of the lung alveoli.

A basic prerequisite for in vivo X-ray imaging of the lung is the exact determination of radiation dose. Achieving resolutions of the order of micrometres may become particularly challenging owing to increased dose, which in the worst case can be lethal for the imaged animal model. A framework for linking image quality to radiation dose in order to optimize experimental parameters with respect to dose reduction is presented. The approach may find application for current and future in vivo studies to facilitate proper experiment planning and radiation risk assessment on the one hand and exploit imaging capabilities on the other.

Limits on the validity of infinite length assumptions for modelling shallow landslides

The infinite slope method is widely used as the geotechnical component of geomorphic and landscape evolution models. Its assumption that shallow landslides are infinitely long (in a downslope direction) is usually considered valid for natural landslides on the basis that they are generally long relative to their depth. However, this is rarely justified, because the critical length/depth (L/H) ratio below which edge effects become important is unknown. We establish this critical L/H ratio by benchmarking infinite slope stability predictions against finite element predictions for a set of synthetic two-dimensional slopes, assuming that the difference between the predictions is due to error in the infinite slope method. We test the infinite slope method for six different L/H ratios to find the critical ratio at which its predictions fall within 5% of those from the finite element method. We repeat these tests for 5000 synthetic slopes with a range of failure plane depths, pore water pressures, friction angles, soil cohesions, soil unit weights and slope angles characteristic of natural slopes. We find that: (1) infinite slope stability predictions are consistently too conservative for small L/H ratios; (2) the predictions always converge to within 5% of the finite element benchmarks by a L/H ratio of 25 (i.e. the infinite slope assumption is reasonable for landslides 25 times longer than they are deep); but (3) they can converge at much lower ratios depending on slope properties, particularly for low cohesion soils. The implication for catchment scale stability models is that the infinite length assumption is reasonable if their grid resolution is coarse (e.g. >25?m). However, it may also be valid even at much finer grid resolutions (e.g. 1?m), because spatial organization in the predicted pore water pressure field reduces the probability of short landslides and minimizes the risk that predicted landslides will have L/H ratios less than 25. Copyright (c) 2012 John Wiley & Sons, Ltd.

Development, optimization, and validation of novel anti-TEM1/CD248 affinity agent for optical imaging in cancer.

Tumor Endothelial Marker-1 (TEM1/CD248) is a tumor vascular marker with high therapeutic and diagnostic potentials. Immuno-imaging with TEM1-specific antibodies can help to detect cancerous lesions, monitor tumor responses, and select patients that are most likely to benefit from TEM1-targeted therapies. In particular, near infrared(NIR) optical imaging with biomarker-specific antibodies can provide real-time, tomographic information without exposing the subjects to radioactivity. To maximize the theranostic potential of TEM1, we developed a panel of all human, multivalent Fc-fusion proteins based on a previously identified single chain antibody (scFv78) that recognizes both human and mouse TEM1. By characterizing avidity, stability, and pharmacokinectics, we identified one fusion protein, 78Fc, with desirable characteristics for immuno-imaging applications. The biodistribution of radiolabeled 78Fc showed that this antibody had minimal binding to normal organs, which have low expression of TEM1. Next, we developed a 78Fc-based tracer and tested its performance in different TEM1-expressing mouse models. The NIR imaging and tomography results suggest that the 78Fc-NIR tracer performs well in distinguishing mouse- or human-TEM1 expressing tumor grafts from normal organs and control grafts in vivo. From these results we conclude that further development and optimization of 78Fc as a TEM1-targeted imaging agent for use in clinical settings is warranted.

Optimisation des doses en tomographie computérisée pédiatrique [Patient dose optimization in pediatric computerized tomography]

The development of CT applications might become a public health problem if no effort is made on the justification and the optimisation of the examinations. This paper presents some hints to assure that the risk-benefit compromise remains in favour of the patient, especially when one deals with the examinations of young patients. In this context a particular attention has to be made on the justification of the examination. When performing the acquisition one needs to optimise the extension of the volume investigated together with the number of acquisition sequences used. Finally, the use of automatic exposure systems, now available on all the units, and the use of the Diagnostic Reference Levels (DRL) should allow help radiologists to control the exposure of their patients.

Single-metal deposition: optimization of this fingermark enhancement technique

Following the introduction of single-metal deposition (SMD), a simplified fingermark detection technique based on multimetal deposition, optimization studies were conducted. The different parameters of the original formula were tested and the results were evaluated based on the contrast and overall aspect of the enhanced fingermarks. The new formula for SMD was found based on the most optimized parameters. Interestingly, it was found that important variations from the base parameters did not significantly affect the outcome of the enhancement, thus demonstrating that SMD is a very robust technique. Finally, a comparison of the optimized SMD with multi-metal deposition (MMD) was carried out on different surfaces. It was demonstrated that SMD produces comparable results to MMD, thus validating the technique.

Beyond intracranial pressure: optimization of cerebral blood flow, oxygen, and substrate delivery after traumatic brain injury.

Monitoring and management of intracranial pressure (ICP) and cerebral perfusion pressure (CPP) is a standard of care after traumatic brain injury (TBI). However, the pathophysiology of so-called secondary brain injury, i.e., the cascade of potentially deleterious events that occur in the early phase following initial cerebral insult-after TBI, is complex, involving a subtle interplay between cerebral blood flow (CBF), oxygen delivery and utilization, and supply of main cerebral energy substrates (glucose) to the injured brain. Regulation of this interplay depends on the type of injury and may vary individually and over time. In this setting, patient management can be a challenging task, where standard ICP/CPP monitoring may become insufficient to prevent secondary brain injury. Growing clinical evidence demonstrates that so-called multimodal brain monitoring, including brain tissue oxygen (PbtO2), cerebral microdialysis and transcranial Doppler among others, might help to optimize CBF and the delivery of oxygen/energy substrate at the bedside, thereby improving the management of secondary brain injury. Looking beyond ICP and CPP, and applying a multimodal therapeutic approach for the optimization of CBF, oxygen delivery, and brain energy supply may eventually improve overall care of patients with head injury. This review summarizes some of the important pathophysiological determinants of secondary cerebral damage after TBI and discusses novel approaches to optimize CBF and provide adequate oxygen and energy supply to the injured brain using multimodal brain monitoring.

Breeding system and genetic variance in the monogamous, semi-social shrew, Crocidura russula

The population-genetic consequences of monogamy and male philopatry (a rare breeding system in mammals) were investigated using microsatellite markers in the semisocial and anthropophilic shrew Crocidura russula. A hierarchical sampling design over a 16-km geographical transect revealed a large genetic diversity (h = 0.813) with significant differentiation among subpopulations (F-ST = 5-6%), which suggests an exchange of 4.4 migrants per generation. Demic effective-size estimates were very high, due both to this limited gene inflow and to the inner structure of subpopulations. These were made of 13-20 smaller units (breeding groups), comprising an estimate of four breeding pairs each. Members of the same breeding groups displayed significant coancestries (F-LS = 9-10%), which was essentially due to strong male kinship: syntopic males were on average related at the half-sib level. Female dispersal among breeding groups was not complete (similar to 39%), and insufficient to prevent inbreeding. From our results, the breeding strategy of C. russula seems less efficient than classical mammalian systems (polygyny and male dispersal) in disentangling coancestry from inbreeding, but more so in retaining genetic variance.

Proton T1 relaxation times of metabolites in human occipital white and gray matter at 7 T.

Proton T1 relaxation times of metabolites in the human brain have not previously been published at 7 T. In this study, T1 values of CH3 and CH2 group of N-acetylaspartate and total creatine as well as nine other brain metabolites were measured in occipital white matter and gray matter at 7 T using an inversion-recovery technique combined with a newly implemented semi-adiabatic spin-echo full-intensity acquired localized spectroscopy sequence (echo time = 12 ms). The mean T1 values of metabolites in occipital white matter and gray matter ranged from 0.9 to 2.2 s. Among them, the T1 of glutathione, scyllo-inositol, taurine, phosphorylethanolamine, and N-acetylaspartylglutamate were determined for the first time in the human brain. Significant differences in T1 between white matter and gray matter were found for water (-28%), total choline (-14%), N-acetylaspartylglutamate (-29%), N-acetylaspartate (+4%), and glutamate (+8%). An increasing trend in T1 was observed when compared with previously reported values of N-acetylaspartate (CH3 ), total creatine (CH3 ), and total choline at 3 T. However, for N-acetylaspartate (CH3 ), total creatine, and total choline, no substantial differences compared to previously reported values at 9.4 T were discernible. The T1 values reported here will be useful for the quantification of metabolites and signal-to-noise optimization in human brain at 7 T. Magn Reson Med 69:931-936, 2013. © 2012 Wiley Periodicals, Inc.

Structure-function characterization and optimization of a plant-derived antibacterial peptide.

Crushed seeds of the Moringa oleifera tree have been used traditionally as natural flocculants to clarify drinking water. We previously showed that one of the seed peptides mediates both the sedimentation of suspended particles such as bacterial cells and a direct bactericidal activity, raising the possibility that the two activities might be related. In this study, the conformational modeling of the peptide was coupled to a functional analysis of synthetic derivatives. This indicated that partly overlapping structural determinants mediate the sedimentation and antibacterial activities. Sedimentation requires a positively charged, glutamine-rich portion of the peptide that aggregates bacterial cells. The bactericidal activity was localized to a sequence prone to form a helix-loop-helix structural motif. Amino acid substitution showed that the bactericidal activity requires hydrophobic proline residues within the protruding loop. Vital dye staining indicated that treatment with peptides containing this motif results in bacterial membrane damage. Assembly of multiple copies of this structural motif into a branched peptide enhanced antibacterial activity, since low concentrations effectively kill bacteria such as Pseudomonas aeruginosa and Streptococcus pyogenes without displaying a toxic effect on human red blood cells. This study thus identifies a synthetic peptide with potent antibacterial activity against specific human pathogens. It also suggests partly distinct molecular mechanisms for each activity. Sedimentation may result from coupled flocculation and coagulation effects, while the bactericidal activity would require bacterial membrane destabilization by a hydrophobic loop.

Diet and breeding success of long-eared owls in a semi-arid environment

Only a few studies, and mostly in temperate climates in Europe, have examined the breeding and diet of long-eared owls (Asia otus) compared to studies of cavity-breeding owls, possibly because of the difficulties in reaching the nests of the former. Here we studied a population of long-eared owls, monitoring the diet of breeding owls and that of owls at a communal roost, every two to three months during 2006 -2009, in a semi-arid region in Israel. It was found that the studied owls produced more young than in most countries in Europe. Diet was not associated with breeding parameters of the owls, whereas laying date was negatively correlated with both clutch size and number of nestlings. We found that more social voles (Microtus socialis) and fewer birds and house mice (Mus musculus) made up the diet at nests than that of adults at the roosts. The diet and breeding of long-eared owls in Israel differ from that in Europe, with birds and mice comprising an important part of the diet, in addition to voles.

An Efficient Segmentation Method for Ultrasound Images based on a Semi-supervised Approach and Patch-based Features

Segmenting ultrasound images is a challenging problemwhere standard unsupervised segmentation methods such asthe well-known Chan-Vese method fail. We propose in thispaper an efficient segmentation method for this class ofimages. Our proposed algorithm is based on asemi-supervised approach (user labels) and the use ofimage patches as data features. We also consider thePearson distance between patches, which has been shown tobe robust w.r.t speckle noise present in ultrasoundimages. Our results on phantom and clinical data show avery high similarity agreement with the ground truthprovided by a medical expert.