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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 199 records · Page 11

Cerebral perfusion computed tomography deconvolution via structure tensor total variation regularization

Purpose: Cerebral perfusion computed tomography (PCT) imaging as an accurate and fast acute ischemic stroke examination has been widely used in clinic. Meanwhile, a major drawback of PCT imaging is the high radiation dose due to its dynamic scan protocol. The purpose of this work is to develop a robust perfusion deconvolution approach via structure tensor total variation (STV) regularization (PD-STV) for estimating an accurate residue function in PCT imaging with the low-milliampere-seconds (low-mAs) data acquisition. Methods: Besides modeling the spatio-temporal structure information of PCT data, the STV regularization of the present PD-STV approach can utilize the higher order derivatives of the residue function to enhance denoising performance. To minimize the objective function, the authors propose an effective iterative algorithm with a shrinkage/thresholding scheme. A simulation study on a digital brain perfusion phantom and a clinical study on an old infarction patient were conducted to validate and evaluate the performance of the present PD-STV approach. Results: In the digital phantom study, visual inspection and quantitative metrics (i.e., the normalized mean square error, the peak signal-to-noise ratio, and the universal quality index) assessments demonstrated that the PD-STV approach outperformed other existing approaches in terms of the performance of noise-induced artifacts reduction and accurate perfusion hemodynamic maps (PHM) estimation. In the patient data study, the present PD-STV approach could yield accurate PHM estimation with several noticeable gains over other existing approaches in terms of visual inspection and correlation analysis. Conclusions: This study demonstrated the feasibility and efficacy of the present PD-STV approach in utilizing STV regularization to improve the accuracy of residue function estimation of cerebral PCT imaging in the case of low-mAs.

60 APPLIED LIFE SCIENCES↗

SU-D-303-03: Impact of Uncertainty in T1 Measurements On Quantification of Dynamic Contrast Enhanced MRI

Purpose: Quantification of dynamic contrast enhanced (DCE) MRI requires native longitudinal relaxation time (T1) measurement. This study aimed to assess uncertainty in T1 measurements using two different methods. Methods and Materials: Brain MRI scans were performed on a 3T scanner in 9 patients who had low grade/benign tumors and partial brain radiotherapy without chemotherapy at pre-RT, week-3 during RT (wk-3), end-RT, and 1, 6 and 18 months after RT. T1-weighted images were acquired using gradient echo sequences with 1) 2 different flip angles (50 and 150), and 2) 5 variable TRs (100–2000ms). After creating quantitative T1 maps, average T1 was calculated in regions of interest (ROI), which were distant from tumors and received a total of accumulated radiation doses < 5 Gy at wk-3. ROIs included left and right normal Putamen and Thalamus (gray matter: GM), and frontal and parietal white matter (WM). Since there were no significant or even a trend of T1 changes from pre-RT to wk-3 in these ROIs, a relative repeatability coefficient (RC) of T1 as a measure of uncertainty was estimated in each ROI using the data pre-RT and at wk-3. The individual T1 changes at later time points were evaluated compared to the estimated RCs. Results: The 2-flip angle method produced small RCs in GM (9.7–11.7%) but large RCs in WM (12.2–13.6%) compared to the saturation-recovery (SR) method (11.0–17.7% for GM and 7.5–11.2% for WM). More than 81% of individual T1 changes were within T1 uncertainty ranges defined by RCs. Conclusion: Our study suggests that the impact of T1 uncertainty on physiological parameters derived from DCE MRI is not negligible. A short scan with 2 flip angles is able to achieve repeatability of T1 estimates similar to a long scan with 5 different TRs, and is desirable to be integrated in the DCE protocol. Present study was supported by National Institute of Health (NIH) under grant numbers; UO1 CA183848 and RO1 NS064973.

60 APPLIED LIFE SCIENCES↗

Space radiation absorbed dose distribution in a human phantom

The radiation risk to astronauts has always been based on measurements using passive thermoluminescent dosimeters (TLDs). The skin dose is converted to dose equivalent using an average radiation quality factor based on model calculations. The radiological risk estimates, however, are based on organ and tissue doses. This paper describes results from the first space flight (STS-91, 51.65 degrees inclination and approximately 380 km altitude) of a fully instrumented Alderson Rando phantom torso (with head) to relate the skin dose to organ doses. Spatial distributions of absorbed dose in 34 1-inch-thick sections measured using TLDs are described. There is about a 30% change in dose as one moves from the front to the back of the phantom body. Small active dosimeters were developed specifically to provide time-resolved measurements of absorbed dose rates and quality factors at five organ locations (brain, thyroid, heart/lung, stomach and colon) inside the phantom. Using these dosimeters, it was possible to separate the trapped-proton and the galactic cosmic radiation components of the doses. A tissue-equivalent proportional counter (TEPC) and a charged-particle directional spectrometer (CPDS) were flown next to the phantom torso to provide data on the incident internal radiation environment. Accurate models of the shielding distributions at the site of the TEPC, the CPDS and a scalable Computerized Anatomical Male (CAM) model of the phantom torso were developed. These measurements provided a comprehensive data set to map the dose distribution inside a human phantom, and to assess the accuracy and validity of radiation transport models throughout the human body. The results show that for the conditions in the International Space Station (ISS) orbit during periods near the solar minimum, the ratio of the blood-forming organ dose rate to the skin absorbed dose rate is about 80%, and the ratio of the dose equivalents is almost one. The results show that the GCR model dose-rate predictions are 20% lower than the observations. Assuming that the trapped-belt models lead to a correct orbit-averaged energy spectrum, the measurements of dose rates inside the phantom cannot be fully understood. Passive measurements using 6Li- and 7Li-based detectors on the astronauts and inside the brain and thyroid of the phantom show the presence of a significant contribution due to thermal neutrons, an area requiring additional study.

STS-91 Shuttle Project↗

Mechanisms of mTORC1 activation by RHEB and inhibition by PRAS40

The mechanistic target of rapamycin complex 1 (mTORC1) controls cell growth and metabolism in response to nutrients, energy levels, and growth factors. It contains the atypical kinase mTOR and the RAPTOR subunit that binds to the Tor signalling sequence (TOS) motif of substrates and regulators. mTORC1 is activated by the small GTPase RHEB (Ras homologue enriched in brain) and inhibited by PRAS40. Here we present the 3.0 ångström cryo-electron microscopy structure of mTORC1 and the 3.4 ångström structure of activated RHEB–mTORC1. RHEB binds to mTOR distally from the kinase active site, yet causes a global conformational change that allosterically realigns active-site residues, accelerating catalysis. Here, cancer-associated hyperactivating mutations map to structural elements that maintain the inactive state, and we provide biochemical evidence that they mimic RHEB relieving auto-inhibition. We also present crystal structures of RAPTOR–TOS motif complexes that define the determinants of TOS recognition, of an mTOR FKBP12–rapamycin-binding (FRB) domain–substrate complex that establishes a second substrate-recruitment mechanism, and of a truncated mTOR–PRAS40 complex that reveals PRAS40 inhibits both substrate-recruitment sites. These findings help explain how mTORC1 selects its substrates, how its kinase activity is controlled, and how it is activated by cancer-associated mutations.

59 BASIC BIOLOGICAL SCIENCES↗

Efficient Distributed Sequence Parallelism for Transformer-Based Image Segmentation

We introduce an efficient distributed sequence parallel approach for training transformer-based deep learning image segmentation models. The neural network models are comprised of a combination of a Vision Transformer encoder with a convolutional decoder to provide image segmentation mappings. The utility of the distributed sequence parallel approach is especially useful in cases where the tokenized embedding representation of image data are too large to fit into standard computing hardware memory. To demonstrate the performance and characteristics of our models trained in sequence parallel fashion compared to standard models, we evaluate our approach using a 3D MRI brain tumor segmentation dataset. We show that training with a sequence parallel approach can match standard sequential model training in terms of convergence. Furthermore, we show that our sequence parallel approach has the capability to support training of models that would not be possible on standard computing resources.

Lyngaas, Isaac↗

Transcriptional Regulation of Enhancers Active in Protodomains of the Developing Cerebral Cortex

Elucidating the genetic control of cerebral cortical (pallial) development is essential for understanding function, evolution, and disorders of the brain. Transcription factors (TFs) that embryonically regulate pallial regionalization are expressed in gradients, raising the question of how discrete domains are generated. Here, we provide evidence that small enhancer elements active in protodomains integrate broad transcriptional information. CreER T2 and GFP expression from 14 different enhancer elements in stable transgenic mice allowed us to define a comprehensive regional fate map of the pallium. We explored transcriptional mechanisms that control the activity of the enhancers using informatics, in vivo occupancy by TFs that regulate cortical patterning ( CoupTFI, Pax6 , and Pbx1 ), and analysis of enhancer activity in Pax6 mutants. Overall, the results provide insights into how broadly expressed patterning TFs regulate the activity of small enhancer elements that drive gene expression in pallial protodomains that fate map to distinct cortical regions.

59 BASIC BIOLOGICAL SCIENCES↗

MicroXRF tomographic visualization of zinc and iron in the zebrafish embryo at the onset of the hatching period

Transition metals such as zinc, copper, and iron play key roles in cellular proliferation, cell differentiation, growth, and development. Over the past decade, advances in synchrotron X-ray fluorescence instrumentation presented new opportunities for the three-dimensional mapping of trace metal distributions within intact specimens. Taking advantage of microXRF tomography, we visualized the 3D distribution of zinc and iron in a zebrafish embryo at the onset of the hatching period. The reconstructed volumetric data revealed distinct differences in the elemental distributions, with zinc predominantly localized to the yolk and yolk extension, and iron to various regions of the brain as well as the myotome extending along the dorsal side of the embryo. The data set complements an earlier tomographic study of an embryo at the pharyngula stage (24 hpf), thus offering new insights into the trace metal distribution at key stages of embryonic development.

59 BASIC BIOLOGICAL SCIENCES↗

A design philosophy for multi-layer neural networks with applications to robot control

A system is proposed which receives input information from many sensors that may have diverse scaling, dimension, and data representations. The proposed system tolerates sensory information with faults. The proposed self-adaptive processing technique has great promise in integrating the techniques of artificial intelligence and neural networks in an attempt to build a more intelligent computing environment. The proposed architecture can provide a detailed decision tree based on the input information, information stored in a long-term memory, and the adapted rule-based knowledge. A mathematical model for analysis will be obtained to validate the cited hypotheses. An extensive software program will be developed to simulate a typical example of pattern recognition problem. It is shown that the proposed model displays attention, expectation, spatio-temporal, and predictory behavior which are specific to the human brain. The anticipated results of this research project are: (1) creation of a new dynamic neural network structure, and (2) applications to and comparison with conventional multi-layer neural network structures. The anticipated benefits from this research are vast. The model can be used in a neuro-computer architecture as a building block which can perform complicated, nonlinear, time-varying mapping from a multitude of input excitory classes to an output or decision environment. It can be used for coordinating different sensory inputs and past experience of a dynamic system and actuating signals. The commercial applications of this project can be the creation of a special-purpose neuro-computer hardware which can be used in spatio-temporal pattern recognitions in such areas as air defense systems, e.g., target tracking, and recognition. Potential robotics-related applications are trajectory planning, inverse dynamics computations, hierarchical control, task-oriented control, and collision avoidance.

Vadiee, Nader↗

Characterization of tissue magnetic susceptibility-induced distortions for MRIgRT

Purpose: MR image geometric integrity is one of the building blocks of MRI-guided radiotherapy. In particular, tissue magnetic susceptibility-induced effects are patient-dependent and their behavior is difficult to assess and predict. In this study, the authors investigated in detail the characteristics of susceptibility ({chi}) distortions in the context of MRIgRT, including the case of two common MR-linac system configurations. Methods: The magnetic field distortions were numerically simulated for several imaging parameters and anatomical sites, i.e., brain, lung, pelvis (with air pockets), and prostate. The simulation process consisted of (a) segmentation of patient CT data into susceptibility relevant anatomical volumes (i.e., soft-tissue, bone and air/lung), (b) conversion of CT data into susceptibility masks by assigning bulk {chi} values to the structures defined at (a), (c) numerical computations of the local magnetic fields by using a finite difference algorithm, and (d) generation of the geometric distortion maps from the magnetic field distributions. For each patient anatomy, the distortions were quantified at the interfaces of anatomical structures with significantly different {chi} values. The analysis was performed for two specific orientations of the external main magnetic field (B{sub 0}) characteristic to the MR-linac systems, specifically along the z-axis for a bore MR scanner and in the (x,y)-plane for a biplanner magnet. The magnetic field local perturbations were reported in ppm. The metrics used to quantify the geometric distortions were the maximum, mean, and range of distortions. The numerical simulation algorithm was validated using phantom data measurements. Results: Susceptibility-induced distortions were determined for both quadratic and patient specific geometries. The numerical simulations showed a good agreement with the experimental data. The measurements were acquired at 1.5 and 3 T and with an encoding gradient varying between 3 and 20 mT/m by using an annular phantom mimicking the water-air and water-oil {chi} interfaces. For quadratic geometries, the magnitude of field distortion increased rapidly with the size of the inhomogeneity up to about 10 mm and then tended to plateau. This trend became more evident for materials with a larger {Delta}{chi} relative to water. The simulations showed only a slight increase in the maximum distortion values when the B{sub 0} orientation was varied with regard to the shape of the {chi} inhomogeneity. In the case of patient anatomy, the largest distortion values arose at the air-soft-tissue interface. Considering the two MR-linac system configurations and comparing the field distortion values corresponding to all organ structures, the distortions tended to be larger for the biplanar magnet. The authors provide a reference table with ppm values which can be used to easily evaluate the geometric distortions for patient data as a function of B{sub 0} and the strength of the encoding gradient. Conclusions: The susceptibility distortions were quantified as a function of multiple parameters such as the {chi} inhomogeneity size and shape, the magnitude of B{sub 0} and the readout gradient, and the orientation of B{sub 0} with respect to the sample geometry. The analysis was performed for several anatomical sites and corresponding to two B{sub 0} orientations as featured by MR-linac systems.

60 APPLIED LIFE SCIENCES↗

Brain Tumor Therapy-Induced Changes in Normal-Appearing Brainstem Measured With Longitudinal Diffusion Tensor Imaging

Purpose: To characterize therapy-induced changes in normal-appearing brainstems of childhood brain tumor patients by serial diffusion tensor imaging (DTI). Methods and Materials: We analyzed 109 DTI studies from 20 brain tumor patients, aged 4 to 23 years, with normal-appearing brainstems included in the treatment fields. Those with medulloblastomas, supratentorial primitive neuroectodermal tumors, and atypical teratoid rhabdoid tumors (n = 10) received postoperative craniospinal irradiation (23.4-39.6 Gy) and a cumulative dose of 55.8 Gy to the primary site, followed by four cycles of high-dose chemotherapy. Patients with high-grade gliomas (n = 10) received erlotinib during and after irradiation (54-59.4 Gy). Parametric maps of fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were computed and spatially registered to three-dimensional radiation dose data. Volumes of interest included corticospinal tracts, medial lemnisci, and the pons. Serving as an age-related benchmark for comparison, 37 DTI studies from 20 healthy volunteers, aged 6 to 25 years, were included in the analysis. Results: The median DTI follow-up time was 3.5 years (range, 1.6-5.0 years). The median mean dose to the pons was 56 Gy (range, 7-59 Gy). Three patterns were seen in longitudinal FA and apparent diffusion coefficient changes: (1) a stable or normal developing time trend, (2) initial deviation from normal with subsequent recovery, and (3) progressive deviation without evidence of complete recovery. The maximal decline in FA often occurred 1.5 to 3.5 years after the start of radiation therapy. A full recovery time trend could be observed within 4 years. Patients with incomplete recovery often had a larger decline in FA within the first year. Radiation dose alone did not predict long-term recovery patterns. Conclusions: Variations existed among individual patients after therapy in longitudinal evolution of brainstem white matter injury and recovery. Early response in brainstem anisotropy may serve as an indicator of the recovery time trend over 5 years after radiation therapy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Neurovascular effects of simulated space radiation

A major health risk for human deep space exploration is central nervous system (CNS) damage by ionizing radiation. Simulated galactic cosmic rays or their components, especially high-linear energy transfer particles such as 56Fe ions, have been shown to cause CNS damage, neuroinflammation and cognitive dysfunction in rodent models, but their effects on human CNS remain to be investigated. CNS damage from any insult, including ionizing radiation, is partially mediated by the blood-brain barrier (BBB), which regulates interactions between CNS and the rest of the body. Astrocytes are major cellular regulators of BBB permeability and also modulate neuroinflammation and neurodegeneration. However, BBB and astrocyte functions in regulating CNS responses to space radiation remain little investigated, especially in human organ analogs. Therefore, we developed and utilized a high-throughput 3D human neurovascular organ-on-a-chip model, seeded with induced pluripotent stem cell-derived cells. The effects of time course, ionizing radiation dose and dose rate were mapped by exposing the model to either acute, high dose rate radiation with simulated galactic cosmic rays or 600 MeV/n 56Fe particles, or protracted, low dose rate gamma radiation using a 57Co sealed source setup. We investigated BBB permeability, oxidative stress, cellular damage and secreted factors over the time period between 24 hours – 2 weeks after 0.1 – 0.8 Gy irradiation. We observed that ionizing radiation exposure increased BBB permeability, caused oxidative stress, damaged endothelial cells and altered expression of inflammatory cytokines with a subset of outcomes dependent on ionizing radiation dose rate. Furthermore, our results indicated that astrocyte functions were primarily deleterious at early time points and protective later after irradiation, resembling CNS responses to injury in vivo. Our findings in organ models were complemented by studies on true spaceflight using mouse spatial and single cell multi-omics, which similarly indicated spaceflight-mediated changes in astrocyte functions. In summary, our study evaluates the regulation of neurovascular responses to simulated space radiation, suggesting astrocytes as targets for countermeasures to mitigate CNS damage in deep space exploration.

Radiation↗

TU-CD-304-05: 4Ï€ Non-Coplanar Radiotherapy: From Mathematical Modeling to Clinical Implementation

Purpose: To develop and clinically implement 4π radiotherapy, an inverse optimization platform that maximally utilizes non-coplanar intensity modulated radiotherapy (IMRT) beams to significantly improve critical organ sparing. Methods: A 3D scanner was used to digitize the human and phantom subject surfaces, which were positioned in the computer assisted design (CAD) model of a TrueBeam machine to create a virtual geometrical model, based on which, the feasible beam space was calculated for different tumor locations. Beamlets were computed for all feasible beams using convolution/superposition. A column generation algorithm was employed to optimize patient specific beam orientations and fluence maps. Optimal routing through all selected beams were calculated by a level set method. The resultant plans were converted to XML files and delivered to phantoms in the TrueBeam developer mode. Finally, 4π plans were recomputed in Eclipse and manually delivered to recurrent GBM patients. Results: Compared to IMRT utilizing manually selected beams and volumetric modulated arc therapy plans, markedly improved dosimetry was observed using 4π for the brain, head and neck, liver, lung, and prostate patients. The improvements were due to significantly improved conformality and reduced high dose spillage to organs mediolateral to the PTV. The virtual geometrical model was experimentally validated. Safety margins with 99.9% confidence in collision avoidance were included to the model based model accuracy estimates determined via 300 physical machine to phantom distance measurements. Automated delivery in the developer mode was completed in 10 minutes and collision free. Manual 4 π treatment on the GBM cases resulted in significant brainstem sparing and took 35–45 minutes including multiple images, which showed submillimeter cranial intrafractional motion. Conclusion: The mathematical modeling utilized in 4π is accurate to create and guide highly complex non-coplanar IMRT treatments that consistently and significantly outperform human-operator-created plans. Deliverability of such plans is clinically demonstrated. This work is funded by Varian Medical Systems and the NSF Graduate Research Fellowship DGE-1144087.

60 APPLIED LIFE SCIENCES↗

Nonlocal atlas-guided multi-channel forest learning for human brain labeling

Purpose: It is important for many quantitative brain studies to label meaningful anatomical regions in MR brain images. However, due to high complexity of brain structures and ambiguous boundaries between different anatomical regions, the anatomical labeling of MR brain images is still quite a challenging task. In many existing label fusion methods, appearance information is widely used. However, since local anatomy in the human brain is often complex, the appearance information alone is limited in characterizing each image point, especially for identifying the same anatomical structure across different subjects. Recent progress in computer vision suggests that the context features can be very useful in identifying an object from a complex scene. In light of this, the authors propose a novel learning-based label fusion method by using both low-level appearance features (computed from the target image) and high-level context features (computed from warped atlases or tentative labeling maps of the target image). Methods: In particular, the authors employ a multi-channel random forest to learn the nonlinear relationship between these hybrid features and target labels (i.e., corresponding to certain anatomical structures). Specifically, at each of the iterations, the random forest will output tentative labeling maps of the target image, from which the authors compute spatial label context features and then use in combination with original appearance features of the target image to refine the labeling. Moreover, to accommodate the high inter-subject variations, the authors further extend their learning-based label fusion to a multi-atlas scenario, i.e., they train a random forest for each atlas and then obtain the final labeling result according to the consensus of results from all atlases. Results: The authors have comprehensively evaluated their method on both public LONI-LBPA40 and IXI datasets. To quantitatively evaluate the labeling accuracy, the authors use the dice similarity coefficient to measure the overlap degree. Their method achieves average overlaps of 82.56% on 54 regions of interest (ROIs) and 79.78% on 80 ROIs, respectively, which significantly outperform the baseline method (random forests), with the average overlaps of 72.48% on 54 ROIs and 72.09% on 80 ROIs, respectively. Conclusions: The proposed methods have achieved the highest labeling accuracy, compared to several state-of-the-art methods in the literature.

61 RADIATION PROTECTION AND DOSIMETRY↗

Chronic infusion of lisinopril into hypothalamic paraventricular nucleus modulates cytokines and attenuates oxidative stress in rostral ventrolateral medulla in hypertension

The hypothalamic paraventricular nucleus (PVN) and rostral ventrolateral medulla (RVLM) play a critical role in the generation and maintenance of sympathetic nerve activity. The renin–angiotensin system (RAS) in the brain is involved in the pathogenesis of hypertension. This study was designed to determine whether inhibition of the angiotensin-converting enzyme (ACE) in the PVN modulates cytokines and attenuates oxidative stress (ROS) in the RVLM, and decreases the blood pressure and sympathetic activity in renovascular hypertensive rats. Renovascular hypertension was induced in male Sprague–Dawley rats by the two-kidney one-clip (2K1C) method. Renovascular hypertensive rats received bilateral PVN infusion with ACE inhibitor lisinopril (LSP, 10 μg/h) or vehicle via osmotic minipump for 4 weeks. Mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA), and plasma proinflammatory cytokines (PICs) were significantly increased in renovascular hypertensive rats. The renovascular hypertensive rats also had higher levels of ACE in the PVN, and lower level of interleukin-10 (IL-10) in the RVLM. In addition, the levels of PICs, the chemokine MCP-1, the subunit of NAD(P)H oxidase (gp91{sup phox}) and ROS in the RVLM were increased in hypertensive rats. PVN treatment with LSP attenuated those changes occurring in renovascular hypertensive rats. Our findings suggest that the beneficial effects of ACE inhibition in the PVN in renovascular hypertension are partly due to modulation cytokines and attenuation oxidative stress in the RVLM. - Highlights: • Chronic ACE inhibition in PVN on renovascular hypertension was investigated. • 2K1C resulted in sympathoexcitation, increased plasma PICs and hypertension. • 2K1C rats had higher levels of cytokines and reactive oxygen species (ROS) in RVLM. • Chronic inhibiting PVN ACE attenuates cytokines and ROS in RVLM in hypertension.

60 APPLIED LIFE SCIENCES↗

Neuroanatomical and cognitive correlates of visual hallucinations in Parkinson’s disease and dementia with Lewy bodies: Voxel-based morphometry and neuropsychological meta-analysis

Visual hallucinations (VH) are common in Parkinson's disease and dementia with Lewy bodies, two forms of Lewy body disease (LBD), but the neural substrates and mechanisms involved are still unclear. We conducted meta-analyses of voxel-based morphometry (VBM) and neuropsychological studies investigating the neuroanatomical and cognitive correlates of VH in LBD. For VBM (12 studies), we used Seed-based d Mapping with Permutation of Subject Images (SDM-PSI), including statistical parametric maps for 50% of the studies. For neuropsychology (35 studies), we used MetaNSUE to consider non-statistically significant unreported effects. VH were associated with smaller grey matter volume in occipital, frontal, occipitotemporal, and parietal areas (peak Hedges' g -0.34 to -0.49). In patients with Parkinson's disease without dementia, VH were associated with lower verbal immediate memory performance (Hedges' g -0.52). Both results survived correction for multiple comparisons. Here, abnormalities in these brain regions might reflect dysfunctions in brain networks sustaining visuoperceptive, attention, and executive abilities, with the latter also being at the basis of poor immediate memory performance.

60 APPLIED LIFE SCIENCES↗

Molecular cloning, genomic organization, chromosome mapping, tissues expression pattern and identification of a novel splicing variant of porcine CIDEb gene

Cell death-inducing DNA fragmentation factor-α-like effector b (CIDEb) is a member of the CIDE family of apoptosis-inducing factors, CIDEa and CIDEc have been reported to be Lipid droplets (LDs)-associated proteins that promote atypical LD fusion in adipocytes, and responsible for liver steatosis under fasting and obese conditions, whereas CIDEb promotes lipid storage under normal diet conditions [1], and promotes the formation of triacylglyceride-enriched VLDL particles in hepatocytes [2]. Here, we report the gene cloning, chromosome mapping, tissue distribution, genetic expression analysis, and identification of a novel splicing variant of the porcine CIDEb gene. Sequence analysis shows that the open reading frame of the normal porcine CIDEb isoform covers 660bp and encodes a 219-amino acid polypeptide, whereas its alternative splicing variant encodes a 142-amino acid polypeptide truncated at the fourth exon and comprised of the CIDE-N domain and part of the CIDE-C domain. The deduced amino acid sequence of normal porcine CIDEb shows an 85.8% similarity to the human protein and 80.0% to the mouse protein. The CIDEb genomic sequence spans approximately 6KB comprised of five exons and four introns. Radiation hybrid mapping demonstrated that porcine CIDEb is located at chromosome 7q21 and at a distance of 57cR from the most significantly linked marker, S0334, regions that are syntenic with the corresponding region in the human genome. Tissue expression analysis indicated that normal CIDEb mRNA is ubiquitously expressed in many porcine tissues. It was highly expressed in white adipose tissue and was observed at relatively high levels in the liver, lung, small intestine, lymphatic tissue and brain. The normal version of CIDEb was the predominant form in all tested tissues, whereas the splicing variant was expressed at low levels in all examined tissues except the lymphatic tissue. Furthermore, genetic expression analysis indicated that CIDEb mRNA levels were significantly higher in the white adipose tissue of lean pigs than their obese counterparts, in contrast to porcine CIDEa and CIDEc [3]. We therefore speculate that CIDEb may play a contrary role to the other CIDEs. The basic molecular information we provide here will be useful for further investigations of the physiological function of the gene, which will be helpful in better understanding the role of the CIDE family in lipid metabolism in pig models.

60 APPLIED LIFE SCIENCES↗

MO-G-304-04: Generating Well-Dispersed Representations of the Pareto Front for Multi-Criteria Optimization in Radiation Treatment Planning

Purpose: To present a novel multi-criteria optimization (MCO) solution approach that generates well-dispersed representation of the Pareto front for radiation treatment planning. Methods: Different algorithms have been proposed and implemented in commercial planning software to generate MCO plans for external-beam radiation therapy. These algorithms consider convex optimization problems. We propose a grid-based algorithm to generate well-dispersed treatment plans over Pareto front. Our method is able to handle nonconvexity in the problem to deal with dose-volume objectives/constraints, biological objectives, such as equivalent uniform dose (EUD), tumor control probability (TCP), normal tissue complication probability (NTCP), etc. In addition, our algorithm is able to provide single MCO plan when clinicians are targeting narrow bounds of objectives for patients. In this situation, usually none of the generated plans were within the bounds and a solution is difficult to identify via manual navigation. We use the subproblem formulation utilized in the grid-based algorithm to obtain a plan within the specified bounds. The subproblem aims to generate a solution that maps into the rectangle defined by the bounds. If such a solution does not exist, it generates the solution closest to the rectangle. We tested our method with 10 locally advanced head and neck cancer cases. Results: 8 objectives were used including 3 different objectives for primary target volume, high-risk and low-risk target volumes, and 5 objectives for each of the organs-at-risk (OARs) (two parotids, spinal cord, brain stem and oral cavity). Given tight bounds, uniform dose was achieved for all targets while as much as 26% improvement was achieved in OAR sparing comparing to clinical plans without MCO and previously proposed MCO method. Conclusion: Our method is able to obtain well-dispersed treatment plans to attain better approximation for convex and nonconvex Pareto fronts. Single treatment plan can be achieved when given bounds on the objectives.

60 APPLIED LIFE SCIENCES↗