cssi/SciSciGPT-SciSciNet huggingface dataset:
Novel EGFRvIII-CAR transgenic mice for rigorous preclinical studies in syngeneic mice

BackgroundRigorous preclinical studies of chimeric antigen receptor (CAR) immunotherapy will require large quantities of consistent and high-quality CAR-transduced T (CART)-cells that can be used in syngeneic mouse glioblastoma (GBM) models. To this end, we developed a novel transgenic (Tg) mouse strain with a fully murinized CAR targeting epidermal growth factor receptor variant III (EGFRvIII). MethodsWe first established the murinized version of EGFRvIII-CAR and validated its function using a retroviral vector (RV) in C57BL/6J mice bearing syngeneic SB28 GBM expressing EGFRvIII. Next, we created C57BL/6J-background Tg mice carrying the anti-EGFRvIII-CAR downstream of a Lox-Stop-Lox cassette in the Rosa26 locus. We bred these mice with CD4-Cre Tg mice to allow CAR expression on T-cells and evaluated the function of the CART-cells both in vitro and in vivo. In order to inhibit immunosuppressive myeloid cells within SB28 GBM, we also evaluated a combination approach of CART and an anti-EP4 compound (ONO-AE3-208). ResultsBoth RV- and Tg-CART-cells demonstrated specific cytotoxic activities against SB28-EGFRvIII cells. A single intravenous infusion of EGFRvIII-CART-cells prolonged the survival of glioma-bearing mice when preceded by a lymphodepletion regimen with recurrent tumors displaying profound EGFRvIII loss. The addition of ONO-AE3-208 resulted in long-term survival in a fraction of CART-treated mice and those survivors demonstrated delayed growth of subcutaneously re-challenged both EGFRvIII+ and parental EGFRvIII- SB28. ConclusionOur new syngeneic CAR Tg mouse model can serve as a useful tool to address clinically relevant questions and develop future immunotherapeutic strategies. Importance of studyThe majority of preclinical studies evaluating CART therapy for GBM have utilized xenografts implanted into immunocompromised mice. Because the successful development of these strategies will depend on the understanding of critical interactions between therapeutic cells and the endogenous immune environment, it is essential to develop a novel immunocompetent system which allows us to study these interactions in a robust and reproducible manner. To this end, we created a Tg mouse strain in which all T-cells express a murinized EGFRvIII-CAR. T-cells derived from these mice demonstrated consistent CAR expression and EGFRvIII-specific cytotoxicity while traditional transduction with a CAR vector showed batch-to-batch variability. The syngeneic system also gave us the opportunity to evaluate a combination regimen with blockade of myeloid-derived suppressor cells. The Tg-CART mice represent a novel system for robust, and reproducible preclinical investigations.
Worldsheet Path Integral: Complex Coordinates

In the two previous chapters, the amplitudes computed from the worldsheet path integrals have been written covariantly for a generic curved background metric. In this chapter, we start to use complex coordinates and finally take the background metric to be flat. This is the usual starting point for computing amplitudes since it allows to make contact with CFTs and to employ tools from complex analysis. We first recall few facts on 2d complex manifolds before briefly describing how to rewrite the scattering amplitudes in complex coordinates.
Population registration of echo flow in the big brown bat's auditory midbrain.

Echolocating bats navigate through cluttered environments that return cascades of echoes in response to the bat’s broadcasts. We show that local field potentials from the big brown bat’s auditory m...
Optimized Workflow for High Spatial Resolution MALDI Imaging Mass Spectrometry of Fresh-Frozen Bone

Bone and bone marrow are vital to mammalian structure, movement, and immunity. These tissues are also commonly subjected to pathological alterations giving rise to debilitating diseases like rheumatoid arthritis, osteoporosis, osteomyelitis, and cancer. Technologies such as matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) enable the discovery of spatially resolved chemical information in biological tissue samples to help elucidate the complex molecular processes underlying pathology. Traditionally, preparation of native osseous tissue for MALDI IMS has been difficult due to the mineralized composition and heterogenous morphology of the tissue, and compensation for these challenges with decalcification and fixation protocols can remove or delocalize molecular species. Here, sample preparation methods were advanced to enable multimodal MALDI IMS of undecalcified, fresh-frozen murine femurs allowing the distribution of endogenous lipids to be linked to specific tissue structures and cell types. Adhesive-bound bone sections were mounted onto ITO coated glass slides with a microscopy-compatible glue and freeze-dried to minimize artificial bone marrow damage. Subliming matrix does not induce further bone marrow cracks, and recrystallizing the deposited matrix improves lipid signal. High spatial resolution (10 μm) MALDI IMS was leveraged to characterize lipid distributions in fresh-frozen bone, and complementary microscopy modalities aided tissue and cell assignments. For example, various phosphatidylcholines localize to bone marrow, adipose tissue, marrow adipose tissue, and muscle. Furthermore, we discovered that [sphingomyelin(42:1) + H]+ was abundant in megakaryocytes, whereas [sphingomyelin(42:2) + H]+ was diminished in this cell type. These data reflect the vast molecular and cellular heterogeneity indicative of the bone marrow and the soft tissue surrounding the femur. Therefore, this application of multimodal MALDI IMS has the potential to advance bone-related biomedical research by offering deep molecular coverage in a preserved native bone microenvironment.
Dex-NeRF: Using a Neural Radiance Field to Grasp Transparent Objects

The ability to grasp and manipulate transparent objects is a major challenge for robots. Existing depth cameras have difficulty detecting, localizing, and inferring the geometry of such objects. We propose using neural radiance fields (NeRF) to detect, localize, and infer the geometry of transparent objects with sufficient accuracy to find and grasp them securely. We leverage NeRF's view-independent learned density, place lights to increase specular reflections, and perform a transparency-aware depth-rendering that we feed into the Dex-Net grasp planner. We show how additional lights create specular reflections that improve the quality of the depth map, and test a setup for a robot workcell equipped with an array of cameras to perform transparent object manipulation. We also create synthetic and real datasets of transparent objects in real-world settings, including singulated objects, cluttered tables, and the top rack of a dishwasher. In each setting we show that NeRF and Dex-Net are able to reliably compute robust grasps on transparent objects, achieving 90% and 100% grasp success rates in physical experiments on an ABB YuMi, on objects where baseline methods fail.
Patterns of Aid to Hazard Victims

Although no amount of aid, financial or otherwise, can completely compensate for all the consequences of a major trauma, the restoration of the status quo ante can be aided considerably by various kinds of help. The sources of help and the extent to which they affect the household’s return to normality are the subjects of this chapter. We consider such diverse sources of aid as insurance payments, gifts, and loans, as well as help in goods or services rendered by relatives, friends, and neighbors.
HCI in the classroom

Human-Computer Interaction is a recognized field in the CS curriculum, as of Computing Curricula 2001. But what is it? Can you teach it without a formal background in the subject? This workshop addresses both questions, through a combination of lecture/demonstrations, group exercises, and discussion of how to fit HCI into an already-crowded CS curriculum. Each participant may request a copy of User-Centered Website Development: A Human-Computer Interaction Approach, by Dan McCracken and Rosalee Wolfe (DePaul University). All will receive a CD containing instructor supplements, including a complete set of PowerPoint slides. NSF support is gratefully acknowledged.
Mechanical and surface coagulation: III. Promotion of mechanical coagulation by addition of destabilizing electrolyte

Abstract By means of synthetic latices as model systems, it was shown that originally very stable colloidal solutions which cannot be coagulated mechanically, by stirring or shaking, can be made subject to mechanical coagulation if one reduces their stability sufficiently. Sensitization was brought about in the systems investigated by adding a sufficient amount of sensitizing electrolyte. The “critical” amount was found to be less than that required for bulk coagulation of measurable rate in the systems at rest. A test of the theoretical equation developed previously for surface coagulation was found to apply in the present instance also, except for deviations in the later stages of coagulation which are explained as the result of stabilizer desorption from the colloid surface. In contradistinction, the Smoluchowski theory of bulk coagulation failed throughout to satisfy the kinetics of the coagulation process.
Temporal and spatial Bean pod mottle virus-induced gene silencing in soybean.

Virus-induced gene silencing (VIGS) is a powerful reverse genetics tool in plant science. In this study, we investigated the temporal and spatial silencing patterns achieved by Bean pod mottle virus (BPMV)-based VIGS in soybean using virus constructs targeting green fluorescence protein (GFP). Silencing GFP enabled an in-depth analysis of silencing in soybean tissues over time in a transgenic line constitutively expressing GFP. We discovered evidence for variable GFP silencing based on insert orientation and targeted region in the coding sequence. A 3' sequence in reverse orientation produced the strongest silencing phenotypes. Furthermore, we documented that BPMV VIGS can achieve widespread silencing in a broad range of tissues, including leaves, stems, flowers and roots. Near-complete silencing was attained in leaves and flowers. Although weaker than in shoots, the observed gene silencing in soybean roots will also allow reverse genetics studies in this tissue. When GFP fluorescence was assayed in cross-sections of stems and leaf petioles, near-complete and uniform silencing was observed in all cell types. Silencing was observed from as early as 2 weeks post-virus inoculation in leaves to 7 weeks post-virus inoculation in flowers, suggesting that this system can induce and maintain silencing for significant durations.
Linearization and PID parameters design for nonlinear systems

Proportional plus integral plus derivative (PID) controller design techniques for nonlinear systems are presented. Lyapunov's linearization theorem is applied to a nonlinear system at an operation point. After the linearized model is obtained, a PID controller can be designed for the linearized model and the controller can then be applied to the original nonlinear counterpart at the operation point. For systems with hard nonlinearities, a multiloop control configuration is utilized to solve the problem associated with the uncontrollability due to the existence of hard nonlinearities. Theoretical background and computer simulation results are shown. >
Abstract T P290: Predictors of Outcome in Patients Presenting with Acute Ischemic Stroke and Mild Stroke Scale Scores

Objective: Although NIHSS is a known predictor of outcome in acute ischemic stroke, there are other factors like age, ambulatory status and ability to swallow that may be predictors of outcome, but are not assessed by the traditional NIHSS. The aim of this retrospective review was to identify predictors of outcome in mild ischemic stroke. METHODS: Discharge outcomes from patients who presented to our large academic stroke center with acute ischemic stroke from 2005-2013 were retrospectively reviewed. Of 7189 patients reviewed, 2597 had initial NIHSS <5. At the time of abstract submission data was available for 971 patients. Outcome measures were modified rankin score (MRS) and discharge to home. RESULTS: In this retrospective review, 64% of patients with NIHSS 0-4 were discharged directly home independent of treatment. The mean age of patients discharged to home was 62 and of those not being discharged to home was 70. Of those patients discharged to home, 99% were able to ambulate independently and 98% passed their dysphagia screen. Of patients unable to be discharged directly to home, 6% were not ambulating independently and 17% did not pass their dysphagia screen. Univariate analysis of variance revealed a significant effect of dysphagia screen (p 0.05). CONCLUSIONS: In patients with mild stroke scale scores defined as NIHSS 0-4, several factors including age, ambulatory status, and ability to swallow may be independent predictors of functional outcome. These data support the development of a modified grading system for assessing functional outcome in mild stroke that considers these factors. ![][1] [1]: /embed/graphic-1.gif
Intrusion Detection for CPS Real-Time Controllers

Security in CPS-based real-time embedded systems controlling the power grid has been an afterthought, but it is becoming a critical issue as CPS systems are networked and inter-dependent. This work presents a set of mechanisms for timebased intrusion detection, i.e., the execution of unauthorized instructions in realtime CPS environments. The novelty is the utilization of information obtained by static timing analysis for intrusion detection. Real-time CPS systems are unique in that timing bounds on code sections are readily available since they are required for schedulability analysis.We demonstrate how micro-timings can be exploited for multiple granularity levels of application code to track execution progress. Through bounds checking of these micro-timings, we develop techniques to detect intrusions (1) in a self-checking manner by the application and (2) through the operating system scheduler, which are novel contributions to the real-time/embedded systems domain to the best of our knowledge.
Marital Satisfaction and Maternal Emotional Expressiveness: Links with Children's Sibling Relationships

Associations between marital quality, maternal emotional expressiveness and children's sibling relationships were examined in a sample of 64 seven-year-olds and their mothers. Mothers reported on the quality of their marital relationships, and children rated the quality of their sibling relationships. Mothers and children provided data on maternal emotional expressiveness. Results indicated that marital dissatisfaction was associated with hostile and rivalrous sibling relationships and with maternal negative emotional expressiveness. Mothers' negative emotional expressiveness was correlated with hostile and rivalrous sibling relationships, and maternal positive emotional expressiveness was associated with affectionate sibling relationships. Maternal emotional expressiveness mediated the links between the marital relationship and sibling hostility and rivalry.
Retrieval practice and spacing effects in young and older adults: An examination of the benefits of desirable difficulty

In the present study, we examined how the function relating continued retrieval practice (e.g., one, three, or five tests) and long-term memory retention is modulated by desirable difficulty (R. A. Bjork, 1994). Of particular interest was how retrieval difficulty differed across young and older adults and across manipulations of lag (Exp. 1) and spacing (Exp. 2). To extend on previous studies, the acquisition phase response latency was used as a proxy for retrieval difficulty, and our analysis of final-test performance was conditionalized on acquisition phase retrieval success, to more directly examine the influence of desirable difficulty on retention. The results from Experiment 1 revealed that continued testing in the short-lag condition led to consistent increases in retention, whereas continued testing in the long-lag condition led to increasingly smaller benefits in retention for both age groups. The results from Experiment 2 revealed that repeated spaced testing enhanced retention relative to taking one spaced test, for both age groups; however, repeated massed testing only enhanced retention over taking one test for young adults. Across both experiments, the response latency results were overall consistent with an influence of desirable difficulty on retention. The discussion focuses on the role of desirable difficulty during encoding in producing the benefits of lag, spacing, and testing.
The Effect of the Combined Volume on the Efficiency of Gibbs Ensemble Simulations

Abstract Simulation in the Gibbs ensemble, introduced [1,2] and recently reviewed [3] by Panagiotopoulos, combines simulation techniques in the canonical, isobaric and grand-canonical ensembles (all at constant temperature). It has been immediately recognized that the method will face similar limitations at liquid densities as the grand-canonical ensemble simulations, the difficulty of inserting a new molecule into the liquid phase [4]. Accordingly, the cavity biased inserting, originally developed in the grand-canonical ensemble [5,6] was shown to improve the simulation efficiency [7] and improvements in the insertion success rate were also obtained with an orientational biasing technique [8].
A cephalometric evaluation of edentulous Rhesus monkeys (Macaca mulatta): a long-term study.

Abstract 1. The rate, location, and magnitude of residual bone resorption, and morphologic changes in the gonial region, the ramus, and the condyle of the mandible were monitored cephalometrically for a period of 234 weeks in four adult Rhesus monkeys (Macaca mulatta) following complete extraction of the dentition. 2. Bone resorption in the residual ridges of the maxillae and mandible was most apparent in the first year following extraction. However, it continued at a reduced rate throughout the entire period studied. 3. The residual ridges of both the maxillae and mandible in their anterior-most regions underwent bone resorption during the first 2 years of the study, following which both areas became depositional. It was suggested that this reversal in alveolar bony remodeling may have been a result of behavioral-functionalfactors related to altered perioral muscle function. 4. The magnitude of residual bone resorption in the mandible was found to be between 4% (just mesial to the canine) and 45% (just mesial to the first molar) and greater in the mandible than in the maxillae. 5. Within the arch, variability in the amount of residual bone resorption was found. For the maxillae, the posterior, middle, and anterior regions, respectively, underwent increasingly greater amounts of resorption. Within the mandible, the posterior and anterior regions lost approximately equal amounts of alveolar bone, while the middle portion of the mandibular residual ridge underwent significantly greater resorption. 6. It was hypothesized that the increase in residual bone resorption in the middle region of the mandible is probably due to relatively greater compressive forces transmitted through that region during mastication. 7. Alterations in the morphology of the gonial region and the mandibular condyle during the experimental period were not pronounced and did not differ from values obtained in normally growing control animals. 8. The mandibular ramus, however, underwent relatively greater resorption along its anterior border than deposition along its posterior border, resulting in a narrower ramus. It was suggested that this was probably due to a reduction in the functional activity of the temporal and masseter muscles.
A Is for Apple: Mnemonic Symbols Hinder the Interpretation of Algebraic Expressions

Abstract This study examined how literal symbols affect students' understanding of algebraic expressions. Middle school students (N = 322) were randomly assigned to 1 of 3 conditions in which they were asked to interpret an expression (e.g., 4c + 3b) in a story problem. Each literal symbol represented the price of an item. In the c-and-b condition, the symbols used were the 1st letters of the items (e.g., price of a cake in dollars = c; price of a brownie in dollars = b). In the other 2 conditions, c and b were replaced with nonmnemonic English letters (x and y) or Greek letters (? and ?). Incorrect interpretations of the expression were most common among students in the c-and-b condition. Moreover, students in this condition were more likely than students in the other conditions to misinterpret the symbols as labels for objects (e.g., c stands for cake). An analysis of participating students' textbooks revealed that mnemonic symbols were used correctly and were not uncommon. Results suggest that the use of mnemonic symbols may hinder students' interpretation of algebraic expressions.
Components of cooperative learning: Effects of collaborative skills and academic group contingencies on achievement and mainstreaming

Abstract The effects of four conditions were investigated: (a) opportunity to interact with classmates, (b) positive goal interdependence, (c) positive goal interdependence with a collaborative-skills group contingency, and (d) positive goal interdependence with both collaborative-skills and academic group contingencies. The dependent variables were achievement, cross-handicap relationships, and voluntary use of collaborative skills. Two subject populations were studied: (a) 83 eighthgrade nonhandicapped students and (b) four socially isolated and withdrawn students (2 eighth grade and 2 eleventh grade). The results indicate that positive goal interdependence with both collaborative-skills and academic group contingencies promoted the most positive relationships with nonhandicapped classmates, most frequent engagement in cooperative skills, and the highest achievement.
Appearance of the Moss-Harlow Effect with Stimuli Equated for Novelty.

Abstract An experiment tested for the Moss-Harlow Effect in 3- and 5-year-olds with stimulus novelty equated. Experimental groups familiarized themselves with each pair of test objects by sorting them, then received a P or N information trial and test trials. The Effect was found after the equation for novelty. Age did not interact with type of information trial. The Effect appears better interpreted in terms of an exploratory tendency than of stimulus novelty.
Electronic Requirements for Oxygen Atom Transfer from Alkyl Hydroperoxides. Model Studies on Multisubstrate Flavin-Containing Monooxygenases

Density functional calculations at the B3LYP/6-31+G(d,p) level are used to study the mechanism of 4a-hydroperoxyflavin oxidation of a series of heteroatom nucleophiles. The oxidation of xenobiotics...
Effect of Nanoclay Content on Void Morphology in Resin Transfer Molded Composites

Effects of nanoclay content on morphology and spatial distribution of voids in resin transfer molded nanoclay/E-glass/epoxy composite disks are investigated. Closite25A nanoclay loads of 2, 5, and 10 wt% are mixed by sonication with a low-viscosity epoxy resin prior to filling the mold cavity containing 13.6% E-glass preform by volume. A disk without nanoclay is also molded. Once the molded composites are cured, voids on radial composite samples are evaluated via microscopic image analysis. The addition of nanoclay is found to result in a significant increase in the apparent viscosity of the clay-epoxy mixture, thus increasing the molding pressure. Void occurrence is observed to increase considerably with increasing nanoclay content, from 2.1% in the composite without nanoclay to 5.1 and 8.3% in the composites molded with 5 and 10 wt% nanoclay, respectively. However, the composite with 2 wt% nanoclay yields the lowest void content of 0.7%. Voids are observed to be, in average, smaller after the addition of nanoclay at all nanoclay concentrations. Presence of nanoclay in the impregnating resin induces at least 60% reduction in voids located inside fiber tows, which are trapped by the fluid front motion during impregnation. Irregularly shaped voids are also observed to decrease with increasing nanoclay content. A nonuniform void content and morphology is observed radially, which seems to be affected by the flow kinematics as well as possible breakdown and filtration of clay clusters.
A Columbine Study: Giving Voice, Hearing Meaning

On a quiet spring morning, the 20th of April 1999, Columbine High School emerged from relative anonymity as a typical suburban high school and became internationally recognized as a symbol of school violence and tragic loss. As a parent whose child was in the school at the time of the attack, I struggled to make sense of the tragedy. I decided to conduct research into the experience as a way to learn lessons that might help others exposed to community-wide trauma in the future. Through modified oral history interviews of other Columbine parents in combination with other qualitative research strategies, I collected and studied stories of the events of that day and the years following. An unexpected by-product emerged from the study, for it seemed that I was not only learning about crisis response and trauma care but also offering a means for parents to gain comfort in reflecting on their own experience. This paper describes the distinct approach that I employed to create a gateway to understanding this experience. It does not explicate the findings of the Columbine study but instead explores the potential for positive outcomes for those who, by giving voice to their stories, can connect to a deeper appreciation for their own experience.
Multi-criteria group consensus under linear cost opinion elasticity

Consensus is a pivotal concept in group decision making. Many times, such a consensus is achieved by the experts shifting their opinion towards a point of mutual consent. Such a shift in many cases is the result of laborious negotiations, which escalates the cost of reaching the consensus. Moreover, many times the group decision is multi-criteria oriented in which the experts need to agree on each criterion separately. This paper describes three problems where experts of unequal importance and with a linear cost of changing their opinion (opinion elasticity) consider a single and a multi-criteria decision consensus. These problems achieve a minimum cost consensus without a budget limit. It turns out that the optimal consensus point is at the median opinion for rectilinear cost function and at the weighted average opinion for squared geometric distance calculations. Linear-time algorithms are presented for all cost consensus problems with no budget limits. Proofs, computational complexity and examples are provided for these algorithms.
Effect of ferromagnetism in α-Fe on the form of Au-Fe phase boundaries

Abstract The effect of ferromagnetic interaction in bcc α-Fe on the form of the Au-Fe phase diagram is investigated in this work. An earlier phase diagram modeling indicated that the experimental and calculated (Au)/[(Au) + (α-Fe)] solvus boundaries disagreed significantly. It was speculated that a slow segregation process into (Au) and (α-Fe) caused the disagreement. Present calculation shows that the experimental data correspond to the (Au)/[(Au) + (γ-Fe)] metastable boundary. Therefore, the crystal structure of the initial precipitate in (Au) on cooling may be fcc, the same as that of the matrix.
Should all patients with chronic kidney disease receive an EPO-type drug?

Many patients either do not receive these drugs or have low hemoglobin levels despite treatment. Thus, there are opportunities for better management.
DOCUMENT DETECTION SUMMARY OF RESULTS

This section presents a summary of the TIPSTER results, including some comparative system performance and some conclusions about the success of the detection half of the TIPSTER phase I project. For more details on the individual experiments, please see the system overviews.
Background factors and success in college physics

The author has cast a new light on some old myths concerning predictors of success in college physics.
On Scientific Workflow Scheduling in Clouds under Budget Constraint

Next-generation e-Science features large-scale, compute-intensive workflows of many computing modules that are typically executed in a distributed manner. With the recent emergence of cloud computing and the rapid deployment of cloud infrastructures, an increasing number of scientific workflows have been shifted or are in active transition to cloud environments. As cloud computing makes computing a utility, scientists across different application domains are facing the same challenge of reducing financial cost in addition to meeting the traditional goal of performance optimization. We construct analytical models to quantify the network performance of scientific workflows using cloud-based computing resources, and formulate a task scheduling problem to minimize the workflow end-to-end delay under a user-specified financial constraint. We rigorously prove that the proposed problem is not only NP-complete but also non-approximable. We design a heuristic solution to this problem, and illustrate its performance superiority over existing methods through extensive simulations and real-life workflow experiments based on proof-of-concept implementation and deployment in a local cloud test bed.
Progressive resistive exercise in weaning high quadriplegics from the ventilator

Acutely high level quadriplegics may experience neuromuscular respiratory insufficiency secondary to loss of use of intercostal and abdominal muscles as well as partial involvement of the phrenic nerve. Frequently, these patients will require mechanical ventilation in the initial stages of their treatment. These patients may present difficulty with weaning off the ventilator. In addition, poor respiratory reserve increases the risk of episodic decompensation. We have instituted a progressive resistive exercise protocol (PRE) analogous to PRE commonly used in training skeletal muscle, to wean patients off the ventilator. This involves determining the patient's endurance to the development of fatigue while off the ventilator. Patients are re-evaluated weekly until they are weaned from the ventilator. Three case studies are reported in which this protocol was used. In addition to our standard respiratory therapy and physical therapy protocols, values for vital capacity and maximum inspiratory force at admission and post-weaning were recorded. After completion of the programme, none of the patients required re-intubation or subsequent mechanical ventilation. This method of diaphragm training may be useful in weaning high level quadriplegics from the ventilator.
Evaluation of dosimetric margins in prostate IMRT treatment plans.

This work introduces a new concept—the dosimetric margin distribution (DMD)—and uses it to explain the sensitivity of a group of prostate IMRT treatment plans to patient setup errors. Prior work simulated the effect of setup errors on 27 prostate IMRT treatment plans and found the plans could tolerate larger setup errors than predicted by the van Herk margin formula. The conjectured reason for this disagreement was a breakdown in van Herk's assumption that the planned dose distribution conforms perfectly to target structures. To resolve the disagreement, this work employed the same 27 plans to evaluate the actual margin distributions that exist between: (i) the clinical target volume (CTV) and planning target volume (PTV) and (ii) the CTV and PTV minimum dose isodose surface. These distributions were evaluated for both prostate and nodal targets. Distribution (ii) is the DMD. The dosimetric margin in a given direction determines the probability that the CTV will be underdosed due to setup errors in that direction. Averaging over 4π sr gives the overall probability of CTV coverage. Minimum doses for prostate and nodal PTVs were obtained from dose volume histograms. Corresponding isodose surfaces were created and converted to regions of interest (ROIs). CTV, PTV, and isodose ROIs were saved as mesh files and then imported into a computational geometry application which calculated distances between meshes (i.e., margins) in 614 discrete directions covering 4π sr in 10 deg increments. Measured prostate CTV-to-PTV margins were close to the nominal value of 0.5 cm specified in the treatment planning protocol. However, depending on direction, prostate dosimetric margins ranged from 0.5 to 3 cm, reflecting the imperfect conformance of the planned dose distribution to the prostate PTV. For the nodal CTV, the nominal CTV-to-PTV margin employed in treatment planning was again 0.5 cm. However, due to the planning protocol, the nodal PTV follows the surface of the nodal CTV in several places, ensuring that there is no room for rigid body motion of the nodal CTV inside the nodal PTV. Measured nodal CTV-to-PTV margins were therefore zero, while nodal dosimetric margins ranged from 0.2 to 2.8 cm. Prostate and nodal target coverage were found to be well correlated with the measured DMDs, thereby resolving the apparent disagreement with our prior results. The principal conclusion is that target coverage in the presence of setup errors should be evaluated using the DMD, rather than the CTV-to-PTV margin distribution. The DMD is a useful planning metric, which generalizes the ICRU conformity index. DMDs could vary with number of beams, beam arrangements, TPS, and treatment site.
Persistence of ivermectin in plasma and faeces following treatment of cows with ivermectin sustained-release, pour-on or injectable formulations

Sixteen young dairy cows were randomly allocated to 4 groups of 4 animals each: Group 1 cows were each given a single Ivomec SR Bolus; Group 2 cows were treated with the Ivomec Pour-on formulation; Group 3 cows were injected with the Ivomec Subcutaneous Injection; Group 4 cows were untreated controls. Blood and faecal samples were collected from all cows on the day before treatment and on days 1, 2, 3, 7, 14, 21, 28, 35, 42 and 49 after treatment for HPLC determination of plasma and faecal ivermectin concentrations. Group 1 (SR Bolus) cows had mean (+/- S.D.) plasma ivermectin concentrations ranging from 5.6 +/- 1.8 micrograms l-1 (p.p.b.) at 14 days to 11.0 +/- 4.7 micrograms l-1 at 49 days. Faecal ivermectin concentrations were little changed from 4.0 +/- 2.0 micrograms g-1 (p.p.m.) dry wt (dry weight) [0.5 +/- 0.2 microgram g-1 wet wt (wet weight)] at 14 days to 3.0 +/- 2.0 micrograms g-1 dry wt (0.5 +/- 0.4 microgram g-1 wet wt) at 49 days. Group 2 (Pour-on) cows showed a rapid rise in plasma concentrations to 32.9 +/- 15.7 micrograms l-1 2 days after treatment, followed by a gradual decline to 1.3 +/- 0.07 micrograms l-1 at 28 days. Faecal ivermectin concentrations rose sharply to 18.5 +/- 7.4 micrograms g-1 dry wt (2.8 +/- 1.2 micrograms g-1 wet wt) 2 days after treatment, then fell to 0.04 +/- 0.004 microgram g-1 dry wt (0.006 +/- 0.0004 microgram g-1 wet wt) at 28 days. Group 3 (Injection) cows also showed a rapid rise to an early plasma peak of 46.1 +/- 22.7 micrograms l-1 3 days after treatment, followed by a gradual decline to 1.3 micrograms l-1 at 35 days. Faecal ivermectin concentrations rose to 1.2 +/- 0.34 micrograms g-1 dry wt (0.2 +/- 0.05 microgram g-1 wet wt) at 3 days, declining to 0.08 +/- 0.0001 microgram g-1 dry wt (0.01 +/- 0.0008 microgram g-1 wet wt) at 28 days. No ivermectin was detected in the plasma or faeces of Group 4 (Control) cows. Concentrations of ivermectin potentially toxic to dung-breeding or dung-feeding invertebrates were excreted for the duration of the study in dung of cows treated with the SR Bolus and for 28 days in the dung of cows treated with the Pour-on or injectable formulations.
Simultaneous study on energy consumption and emission generation for an ethylene plant under different start-up strategies

Abstract Chemical plant start-ups are very critical dynamic operations, which normally consume huge amount of energy and also generate large quantities of off-spec products for flaring, causing significant and intensive air emissions. Many studies have been individually conducted on energy savings or emission reductions under plant normal conditions. However, quantitative studies on simultaneous energy consumption and emission generation for chemical plant start-ups are still lacking. In this study, plant-wide dynamic simulations are employed to investigate energy consumption and emission generation for an ethylene plant under different start-up strategies. Dynamic modeling and simulations for two start-up designs associated with three start-up operating procedures are performed. Based on plant-wide dynamic simulations, dynamic profiles of energy consumption and emission generation during the plant start-up are obtained and analyzed. Details of energy accounting on cooling and heating duties of key distillation towers, auxiliary heat exchanger duties, and power consumption for compressor system are provided for each start-up case. Through comprehensive analysis, the most desirable start-up solution is identified. This virtual study not only characterizes the emission generation during the plant start-up, supporting flare minimization activities that benefits environmental sustainability, but also enhances critical research on energy and raw material savings during the plant start-up that will benefit the industrial sustainability.
The catalytic nature of science: Implications for scientific problem solving in the 21st century

Abstract This paper discusses key elements of scientific problem solving from a cognitive perspective in an effort to help scientists and engineers understand and manage their problem solving efforts more effectively. Toward this end, the Adaption–Innovation (A–I) theory of Kirton is reviewed and placed into the context of science in order to highlight its potential contributions and possible limitations. In particular, A–I theory is used to help explain different preferences for managing scientific structure, the need for a diversity of cognitive styles in scientific work, and the relationship between scientific progress and the paradox of structure. Directions for future research in this area and comments on the special implications of A–I theory for senior scientists and other technical problem solving leaders are also discussed.
Comparison of two‐electron densities reconstructed from one‐electron density matrices

We consider approximate reconstruction of spinless and spin-resolved two-electron charge densities, intracule densities, and extracule densities utilizing only the one-electron reduced density matrix. Using large basis set, configuration interaction density matrices for the ground state of Be, we compare the two-electron densities obtained using several proposed reconstruction functionals ("natural orbital functionals") for the two-electron density and density matrix. We also analyze the intracule and extracule densities obtained from these reconstructions. Several of the proposed natural orbital functionals are found to produce unphysical negative values for the pair density when two parallel-spin electrons approach one another. Ancillary results from this study include new, simplified formulas for the intracule and extracule densities, and a mathematical justification for an approximate relation between atomic intracule and extracule densities that has previously been reported on the basis of extensive Hartree-Fock calculations. © 2002 Wiley Periodicals, Inc. Int J Quantum Chem 90: 355-369, 2002
Mdm2 is a novel activator of ApoCIII promoter which is antagonized by p53 and SHP inhibition

We examined the effect of Mdm2 on regulation of the ApoCIII promoter and its cross-talk with p53 and nuclear receptor SHP. Overexpression of Mdm2 markedly enhanced ApoCIII promoter activity by HNF4α. A direct association of Mdm2 protein with the HNF4α protein was observed by co-immunoprecipitation. Ectopic expression of p53 decreased HNF4α activation of the ApoCIII promoter and antagonized the effect of Mdm2. Co-expression of SHP further strengthened p53 inhibition and abolished Mdm2 activation of the ApoCIII promoter. Mdm2 inhibited p53-mediated enrichment of HNF4α to the ApoCIII promoter while simultaneously reducing p53 binding and increasing recruitment of SHP to the ApoCIII promoter. The results from this study implicate a potentially important function of Mdm2 in regulation of lipoprotein metabolism.
Persistent propensities: Portrait of a familiar controversy

Susan Mills and John Beatty's propensity interpretation of ‘fitness’ encountered very different philosophical criticisms by Alexander Rosenberg and Kenneth Waters. These criticisms and the rejoinders to them are both predictable and important. They are predictable as raisingkinds of issues typically associated with disposition concepts (this is established through a systematic review of the problems generated by Carnap's dispositional interpretation of all scientific terms). They are important as referring the resolution of these issues to the development of evolutionary biology. This historical approach to the propensity interpretation of ‘fitness’ draws attention to the precarious relation between philosophical clarification of scientific concepts and any given state of the empirical arts.
Treating brain tumors with PDE4 inhibitors

Speculation regarding dysregulation of cAMP metabolism in oncogenesis has existed since the discovery of cAMP more than 50years ago. Recent data confirm the relevance of disordered cAMP metabolism to the genesis of multiple cancers and suggest that the mechanism might involve altered expression and activity of phosphodiesterases (PDEs). These discoveries coincide with the rapid development and clinical evaluation of PDE inhibitors for non-cancer indications. Thus, the time is ripe to evaluate PDE inhibitors as cancer chemotherapeutics. Here we highlight recent evidence that abnormal regulation of cAMP levels might be a determinant of brain tumorigenesis and that altered PDE expression is one the mechanisms of its dysregulation. Recent preclinical and clinical experience with inhibitors of PDE4 indicates that this might be a promising approach to brain tumor therapy.
Predictors of Emotional Problems in Children With Diabetes Mellitus

Multiple studies have documented elevated rates of emotional problems such as depression, anxiety, and eating disorders among youth with diabetes mellitus (DM); however, no known study has investigated factors associated with these psychological difficulties. The extent to which presence of emotional problems was predicted by health insurance coverage, parent involvement in care, symptom severity, family economic impact, and adolescence was investigated in a sample of 779 children with DM. Results showed that adolescent status, symptom severity, and financial problems resulting from DM care were significant risk factors associated with the presence of an emotional problem within this sample of children with diabetes. Implications for clinical practice and future research are discussed.
Correlation of bladder dysfunction and lumbosacral somatosensory evoked potential S‐wave abnormality in spinal‐cord‐injured patients

Thirty-six patients with stable cervical and high thoracic spinal cord injury underwent urodynamic evaluation and lumbosacral somatosensory evoked potential testing. All these patients had a preserved peripheral sensory neuron (normal R-wave). Fifteen of the 36 patients had either an abnormal or absent lumbosacral postsynaptic posterior horn potential (S-wave). Correlation of the S-wave abnormality and urodynamic evaluation in these patients showed a high incidence of abnormal detrusor contractility (87%). This supports an underlying neurogenic dysfunction for the abnormal detrusor behavior in spinal-cordinjured patients.
Expression of cone transducin, Gz alpha, and other G-protein alpha-subunit messenger ribonucleic acids in pancreatic islets

The G-proteins are a family of heterotrimeric guanine nucleotide-binding proteins that play important roles in signal transduction and whose expression is regulated in a tissue-specific manner. Here we have surveyed the expression of G-protein alpha-subunits in mouse pancreatic islets. Degenerate oligonucleotide primers corresponding to conserved primary sequences in known G alpha-subunits were used in a reverse transcriptase-polymerase chain reaction, and the amplified complementary DNA (cDNA) fragments were subcloned and sequenced. Over 100 clones were analyzed, from which we determined that islet cells express at least seven G alpha-subunits: G8 alpha, Gi1 alpha or Gi3 alpha, Gi2 alpha, G11 alpha, G14 alpha, Gz alpha, and Gt2 alpha (cone transducin). In particular, the identification of Gz alpha and Gt2 alpha was of interest in that previous studies had indicated that the expression of Gz alpha was restricted mainly to the brain, retina, and adrenal gland, whereas Gt2 alpha was expressed predominantly ...
Correlated Single-Molecule Spectroscopy and Patch-Clamp Studies of Voltage Gated Ion Channel Activation Dynamics in Living Cells

We have studied the NMDA receptor dynamics in HEK cells and colicin ion channel in lipid bilayer, using our newly developed combining real-time single-molecule FRET imaging with single-channel electric current recording. We were able to probe single ion-channel open-close activation and associated protein conformational changes simultaneously, and thus providing a molecular-level understanding of the dynamics and mechanism of ion-channel activations. The kinetic behavior of ion channel proteins is regulated by subtle conformational changes that are often difficult to characterize by conventional ensemble-averaged static structure analysis and by interpretations of ion-channel electrophysiological measurements. Subtle structural dynamics of ion channels play an important role in regulating channel function and selectivity. Using our unique approaches, we have identified the conformational regulated NMDA ion-channel activities and the associated conformational change dynamics. We were able to probe fluctuating polypeptide-domain diffusional motions of single-molecule colicin channels across a lipid bilayer. A new solvation-desolvation model for voltage-gated ion-channel dynamics has been developed based on our experimental results.
Fluorescence studies on the conformational changes of nucleosome core particles

This paper begins with a review of our measurements of core particle transitions using the steady state intrinsic tyrosine fluorescence. The transitions described here include the opening of the particle at very low ionic strength, a pH-induced transition at physiological ionic strengths near neutral pH, and the high salt dissociation. The second section of the paper describes measurements of the rotational diffusion of the core particle using fluorescence anisotropy decays of ethidium intercalated into the DNA. We find that the low salt transition consists of two main stages as the ionic strength is lowered. Just below 1 mM, rearrangements in the protein core give rise to a drop in the steady state anisotropy. This first change is not accompanied by a measurable change in the rotational correlation time. Below ~0.2 mM an irreversible change sets in, and the average correlation time jumps to a much higher value. We believe that this structure is highly elongated. The pH-induced change does not give rise to a change in the rotational correlation time. At very high ionic strengths above 0.6 M, where the protein begins to dissociate from the DNA, the average rotational correlation time also increases to much higher values. There is no indication of disruption of the core particle below this ionic strength.
Privacy, poverty, and old age

“Privacidad” es definida aqui, como la ocupacion por un individuo o una familia nuclear de una unidad de vivienda separada, la cual no es compartida con otros parientes o no-parientes. Estadisticamente, privacidad es reflejada en la proporcion de personas de una dada edad, quienes son jefes o esposas de jefes de un hogar.