cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 185: Development of a novel non-diuretic brain-penetrating ethacrynic acid analog and demonstration of its potent efficacy in orthotopic glioblastoma (GBM) models

The incidence of pediatric and adult brain tumors has continued to rise and temozolomide (TMZ) has remained the sole choice for chemotherapy of these cancers. A number of factors including the inefficient drug entry through the BBB, intratumoral heterogeneity, overexpression of MGMT repair protein and bone marrow toxicity due to alkylating regimens have impeded successful therapy of these cancers. There is, therefore, an urgent need to design new, more effective brain-penetrating drugs that can effectively eliminate brain tumors. We are highly interested in exploiting the elevated oxidative stress present in gliomas and have synthesized a hydrophobic, non-diuretic analog of ethacrynic acid (EA) called KSS72 [1-(2,3-dichloro-4-methoxyphenyl)-2-methylenebutan-1-one] by removing the carboxylate side chain. KSS72 was selectively cytotoxic to cancer cells including gliomas. Compared to EA which does not cross the BBB, Pharmacokinetics following intravenous or oral administrations in mice showed its excellent penetrance through the blood brain-barrier, KSS72 accumulating at levels equivalent to TMZ (25% of plasma levels) in the brain In vitro assays measuring protein carbonyl content, GSH content, ROS generation, GSTpi enzyme activity and others showed that KSS72 triggers a redox imbalance by inhibiting GSTpi and by lowering the antioxidant (GSH) and reducing equivalent (NADPH) levels, leading to a significant elevation of ROS levels. We also showed the upregulation of endoplasmic reticulum (ER) stress-responsive proteins, activation of MAPK, autophagy and apoptotic pathways by KSS72 in several cell lines. KSS72-induced autophagy was a post event of redox perturbation that displayed a wide array of characteristic features including double membranous vacuoles with entrapped organelles, acidic vesicular organelles, and increased expression of LC3-II and beclin-1. In view of its excellent brain penetrance and multiple cytocidal events mediated by ROS and autophagy, we tested the antitumor efficacy of KSS72 in human GBM cell lines and intracranial GBM xenografts. SF-188 human GBM cells expressing firefly luciferase were injected into the brain just left of bregma for the development of orthotopic GBM in nude mice. These mice were given 25 mg/kg/day of KSS72 intraperitoneally for 2 weeks. The animals when imaged by IVIS after luciferin injections showed a complete lack of intracranial tumors in all KSS72 administered animals. HE 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 185. doi:10.1158/1538-7445.AM2017-185
The \(L^1\) Theory for Scalar Conservation Laws

The theory of the scalar balance law, in several spatial dimensions, has reached a state of virtual completeness. In the framework of classical solutions, the elementary, yet effective, method of characteristics yields a sharper version of Theorem 5.1.1, determining explicitly the life span of solutions with Lipschitz continuous initial data and thereby demonstrating that in general this life span is finite. Thus one must deal with weak solutions, even when the initial data are very smooth. In regard to weak solutions, the special feature that sets the scalar balance law apart from systems of more than one equation is the size of its family of entropies. It will be shown that the abundance of entropies induces an effective characterization of admissible weak solutions as well as very strong L 1-stability and L ∞-monotonicity properties. Armed with such powerful a priori estimates, one can construct admissible weak solutions in a number of ways. As a sample, construction by the method of vanishing viscosity, the theory of L 1-contraction semigroups, the layering method, a relaxation method and an approach motivated by the kinetic theory will be presented here. The method of vanishing viscosity will also be employed for solving the initial-boundary value problem. When the initial data are functions of locally bounded variation then so are the solutions. Remarkably, however, even solutions that are merely in L ∞ exhibit the same geometric structure as BV functions, with jump discontinuities assembling on “manifolds” of codimension one.
United States v. Havens: Impeachment by Illegally Obtained Evidence

In a series of cases, the U.S. Supreme Court developed an impeachment exception to the exclusionary rule, whereby evidence obtained in violation of either the fourth or fifth amendment was admissible to impeach the direct testimony of a defendant who has taken the witness stand in his or her own defense. In United States v. Havens, decided in 1980, the Supreme Court extended the impeachment exception to the defendant’s cross-examination testimony. Havens raised a number of crucial issues, including the impact of the impeachment exception on the defendant’s right to testify in his or her own defense. Most importantly, the case raised the question whether the exclusionary rule remains a viable means of protecting fourth amendment rights. This article explores the implications of the Havens case on criminal defendants and on the criminal justice system in general. It argues that, on balance, the Supreme Court should move in the direction of a narrowly circumscribed impeachment exception, rather than the open door Havens provides for the introduction of illegally obtained evidence.
Multi-Material Volume Rendering with a Physically-Based Surface Reflection Model

Rendering techniques that increase realism in volume visualization help enhance perception of the 3D features in the volume data. While techniques focusing on high-quality global illumination have been extensively studied, few works handle the interaction of light with materials in the volume. Existing techniques for light-material interaction are limited in their ability to handle high-frequency real-world material data, and the current treatment of volume data poorly supports the correct integration of surface materials. In this paper, we introduce an alternative definition for the transfer function which supports surface-like behavior at the boundaries between volume components and volume-like behavior within. We show that this definition enables multi-material rendering with high-quality, real-world material data. We also show that this approach offers an efficient alternative to pre-integrated rendering through isosurface techniques. We introduce arbitrary spatially-varying materials to achieve better multi-material support for scanned volume data. Finally, we show that it is possible to map an arbitrary set of parameters directly to a material representation for the more intuitive creation of novel materials.
Trait mindfulness predicts the presence but not the magnitude of cortisol responses to acute stress.

Abstract Background Mindfulness, or the practice of observing present moment experiences with acceptance, is thought to improve health at least partially by limiting hypothalamic-pituitary-adrenal (HPA) axis over-responsiveness during episodes of acute stress. However, models of allostatic load suggest that HPA axis under-responsiveness can also be detrimental to health, and the relationship between mindfulness and cortisol under-responsiveness has yet to be examined. The present study therefore aimed to address this knowledge gap, and to revisit the relationship between mindfulness and acute cortisol response magnitude while excluding (or statistically controlling for) individuals displaying HPA axis under-responsiveness. Methods Participants (124 healthy undergraduate students) were subjected to a stressful speech task, and completed a trait mindfulness questionnaire. Salivary cortisol was collected 0, +15, +25, +40, and +55 min post-stressor onset. Results Greater trait mindfulness was associated with greater odds of displaying a cortisol response relative to none, but was unrelated to the magnitude of cortisol responses among those who displayed an acute response. Conclusions In the present sample, trait mindfulness was associated with cortisol responses, but this was driven by the fact that subjects low in mindfulness were more likely to be non-responders. Contrasting the effects of mindfulness on the presence (i.e., present vs. absent) and the degree (i.e., magnitude) of acute stress responses may therefore be warranted in future research.
Longitudinal analysis of hospital charges following injury in a level 1 pediatric trauma system

Abstract Background The treatment of injured children contributes substantially to the financial burden of a health care system. The purpose of this study was to characterize these charges at a level-1 pediatric trauma center. Methods Financial data for children ( Results 5853 trauma patients were included with average annual charges of $11,128,730. The most common mechanisms of injury were fall (44%), sports (12%), and bike (9%). The median ISS was 6 (IQR 4–10) with a mortality rate of 1.8% and Z-score of 13.04 (p Conclusions The value proposition in health care requires us to define outcomes relative to costs. Injury severity, major injury location, and hospital length of stay are the highest contributors for the financial burden of pediatric traumatic injury, while inpatient readmissions and inpatient rehabilitation drove higher charges in the years following discharge. Type of Study Clinical Research Paper. Level of Evidence II - Cohort Study.
Neighbour tolerance, not suppression, provides competitive advantage to non-native plants

High competitive ability has often been invoked as a key determinant of invasion success and ecological impacts of non-native plants. Yet our understanding of the strategies that non-natives use to gain competitive dominance remains limited. Particularly, it remains unknown whether the two non-mutually exclusive competitive strategies, neighbour suppression and neighbour tolerance, are equally important for the competitive advantage of non-native plants. Here, we analyse data from 192 peer-reviewed studies on pairwise plant competition within a Bayesian multilevel meta-analytic framework and show that non-native plants outperform their native counterparts due to high tolerance of competition, as opposed to strong suppressive ability. Competitive tolerance ability of non-native plants was driven by neighbour's origin and was expressed in response to a heterospecific native but not heterospecific non-native neighbour. In contrast to natives, non-native species were not more suppressed by hetero- vs. conspecific neighbours, which was partially due to higher intensity of intraspecific competition among non-natives. Heterogeneity in the data was primarily associated with methodological differences among studies and not with phylogenetic relatedness among species. Altogether, our synthesis demonstrates that non-native plants are competitively distinct from native plants and challenges the common notion that neighbour suppression is the primary strategy for plant invasion success.
Performability Analysis of TDMA Cellular Systems Based on Composite and Hierarchical Markov Chain Models

Composite Markov chain models are built to study the performability of wireless TDMA system with and without automatic protection switching for the control channel. The models are then decomposed hierarchically. Measures of interest are explicitly given in closed form for the approximate hierarchical models, that are proven to be more robust and less time-consuming without losing accuracy. The presented models are of great interest in wireless network design and operation.
Are predictors of coronary heart disease and lower-extremity arterial disease in type 1 diabetes the same?: A prospective study

Abstract In the Type 1 diabetes population, coronary heart disease (CHD) and lower-extremity arterial disease (LEAD) are the two common macrovascular complications leading to early mortality and morbidity. However, it is not clear if these two complications share the same risk factors. The Pittsburgh Epidemiology of Diabetes Complications (EDC) Study prospectively examined and compared the risk factors for LEAD and CHD (including CHD morbidity and mortality). EDC subjects (332 men and 325 women), all diagnosed at Children’s Hospital of Pittsburgh between 1950 and 1980, were first examined at baseline (1986–1988), and then biennially, for diabetes complications and their risk factors. Data used in the current analysis were from the first 6 years of follow-up, 98% provided at least some follow-up data for these analyses. CHD was defined as the presence of angina (diagnosed by the EDC examining physician) or a history of confirmed myocardial infarction or CHD death. An ankle-to-arm ratio of less than 0.9 at rest was considered to be evidence of LEAD. Among 635 subjects without CHD at baseline, 57 developed CHD (1.69/100 person-years), and among 579 without LEAD at baseline, 70 developed LEAD (2.31/100 person-years). CHD incidence rate was slightly higher in males, while LEAD incidence rate was slightly higher in females. Compared to non-incident cases, subjects who developed either complication were older, had a longer diabetes duration, higher LDL and total cholesterol, and were more likely to be hypertensive. In multivariate analyses, hypertension, low HDL cholesterol level, high white cell count, depression, and nephropathy were the independent risk factors for CHD (including morbidity and mortality). For LEAD, higher HbA1 level, higher LDL cholesterol level and smoking were the important contributing factors. In conclusion, the risk factor patterns differ between the two vascular complications. Glycemic control does not predict CHD overall but does predict LEAD, while hypertension and inflammatory markers are more closely related to CHD than to LEAD.
Assessing the Performance and Validity of Diagnostic Tests and Screening Programs

Although surgery is primarily a therapeutic intervention, surgeons also play a pivotal role in the initial evaluation and diagnosis of surgical disease. Indeed, recent scientific and technologic advances (nte.g., molecular markers of disease) have considerably expanded the catalog of diagnostic tests available to contemporary surgeons. At the same time, many established (and widespread) screening programs (nte.g., mammography, colonoscopy, prostate-specific antigen [PSA]) are designed to detect conditions that are treated primarily with surgical interventions. Moreover, given the substantial morbidity that may accompany surgical intervention, it is imperative that surgeons critically assess the value of a diagnostic test before using its results as the basis for intervention.
Bidirectional glutathione transport by cultured human retinal pigment epithelial cells

PURPOSE: To characterize glutathione (GSH) transport by cultured human retinal pigment epithelial (HRPE) cells. METHODS: Cultured HRPE cells were pretreated with acivicin for GSH efflux and with buthionine sulfoximine for GSH uptake to prevent the breakdown and resynthesis of GSH. Efflux was measured by the linear rate of accumulation of GSH in the supernatant; uptake was measured using [35S] GSH plus varying concentrations of GSH. Molecular forms were verified by high-performance liquid chromatography. HRPE cell mRNA was probed for the presence of the two recently cloned rat sinusoidal and canalicular GSH transporters, (RsGshT and RcGshT), by Northern blot analysis. RESULTS: Glutathione efflux was temperature dependent (undetectable at 4 degrees C), and its averaged 23 +/- 3.3 pmol/10(6) cells/minute or 10% of the total GSH effluxed per hour (total cell GSH = 13.6 +/- 1.5 nmol/10(6) cells). Efflux was not influenced by dithiothreitol or sulfobromophthalein-reduced GSH adduct, agents known to affect liver sinusoidal GSH transport. Glutathione uptake was linear up to 45 minutes and was temperature dependent. The difference between 37 degrees C and 4 degrees C uptake values represented true uptake. Glutathione uptake (2 microCi/ml + 1 mM mass) was Na independent and was inhibited significantly by phenol-3,6-dibromphthalein disulfonate. The kinetics of GSH uptake was assessed by measuring uptake with 35S-GSH and 0.05 to 40 mM extracellular GSH for 30 minutes. Uptake was saturable with Vmax = 18.7 +/- 1.7 nmol/10(6) cells/30 minutes, Km = 12.1 +/- 1.9 mM, n (binding site) = 1. On Northern blot analysis, HRPE cells express mRNA for RcGshT but not for RsGshT. CONCLUSIONS: The similarities in functional characteristics of GSH transport and the presence of RcGshT-like mRNA suggest GSH transport in HRPE cells is mediated by a RcGshT homolog. Although the transporter can operate bidirectionally, it is expected to be a net efflux pump under normal physiologic conditions because the intracellular GSH concentration is much higher.
Percutaneous lumbar discectomy and decompression

The decrease in the popularity of chemonucleolysis has created a surge of interest in mechanical nuclear decompression and discectomy. Our interest and experience in this unique approach, which permits access to the intervertebral disc without the necessity of violating the spinal canal, dates back to 1973 [3]. Originally, we were utilizing a cannula with the external diameter of 3 mm; however, our subsequent experimental work led us to use a larger diameter sheath to provide an adequate annular opening and permit better access to the intervertebral disc. The intraoperative pressure measurement of a herniated lumbar disc prior to and following the annular fenestration suggests that an adequate fenestration of the annulus, to allow the continuous decompression of the disc, is desirable [2]. A small window in the annulus is easily blocked by blood clots and nuclear debris.
Embryonal Stem (ES) Cell-Derived Macrophages : A Cellular System that Facilitates the Genetic Dissection of Macrophage Function.

The monocyte/macrophage (Mo) contributes to atherosclerotic lesion initiation and progression through a variety of interactions with cells of the artery wall that depend on the elucidation of a host of cytokines and growth factors by cells residing in the intima. The number and complexity of these interactions make it difficult to determine which cellular functions are contributing to the progression of atherosclerosis and which might be exploited to interrupt that progression. Studies of macrophage functions in atherosclerosis have been hindered by the limitations of available macrophage cell lines and primary cultures, including poor transfectability and the transformed state of imMortal cell lines. Recent studies have demonstrated that pluripotential mouse embryonic stem cells can be differentiated down specific hematopoietic lineages in vitro, including lines that give rise to macrophages (1). This technique provides a genetically tractable cellular system for studying myeloid cell function. Macrophages arising from this differentiation system demonstrate cell surface presentation of classic macrophage markers and macrophage functions including phagocytosis and responses to inflammatory stimuli. There are several important advantages inherent in using embryonic stem (ES) cell derived macrophages as a cell culture system for studying Mo function. As the cells are not transformed, and the progenitor cells arising from ES cells are capable of reconstituting the entire hematopoietic compartment of a mouse, they represent a cell culture system that appears to retain the physiologic regulation on growth and differentiation that is absent from transformed myelomonocytic cell lines.
Evaluation of Slum Upgrading Programs: A Literature Review

In the last decades the developing world experienced a rapid urbanization of the population. Cities were not prepared to meet the needs of the fast and unplanned growing population and in many cities slums emerged. There have been various types of interventions to deal with the slums problem worldwide: from relocation of slum dwellers to integral interventions, consisting of both infrastructure works and social services targeted to poor neighborhoods. This paper analyses the methods that have been used in a number of upgrading programs and detects the gaps in the literature. To make exposition clear, the programs are divided according to their main outcomes of interest: housing, neighborhood and individual. For each group of outcomes an extensive review of the literature is presented. Also methodological issues regarding implementation and identification strategies for the effects of the interventions are assessed. Finally, the document details some relevant indicators for evaluating slum upgrading programs and suggests avenues for future research.
Hypogammaglobulinemia and Its Implications in Patients Treated with Daratumumab: A Single Institution Experience

Introduction: Daratumumab is an IgG Kappa monoclonal antibody (mAB) to CD38, a surface glycoprotein expressed on plasma cells. It was approved in 2015 as monotherapy for Multiple Myeloma (MM) patients who failed three prior lines of therapy. Its approval was then expanded to second line and most recently first line. As such, patients are now getting earlier and longer exposure to this mAB. Disease response to daratumumab is monitored by demonstrating a fall in paraprotein levels. It is becoming widely appreciated that hypogammaglobulinemia (HGGE) ie. (IgG Methods: We conducted a retrospective chart review of all patients treated with daratumumab as single agent or in combination (November 2015-June 2019), who had documented baseline and post therapy quantitative IgG levels. Demographics, subtype of plasma cell disease, bone marrow cytogenetics/FISH, serial IgG levels, incidence of significant infections and need for IVIG therapy were collected as part of this exploratory data analysis. Results: Among 145 eligible patients, 53% were male, 37% Hispanic, 19% Black/African American and 72% were age Conclusion: Our study identifies a high incidence of meaningful HGGE in patients on daratumumab. In the non-IgG subtype, the relationship is straightforward, as any drop in IgG reflects a drop in polyclonal immunoglobulins and impaired humoral immunity. In contrast, in the IgG subtype, a fall in IgG levels has two components; a fall in the monoclonal protein (indicative of favorable disease response) as well as a fall in polyclonal IgG. There was a lower incidence of pre and post treatment HGGE in the IgG cohort compared to the non-IgG cohort( ie.IgA, IgD, Free Kappa and Free Lambda). In contrast the incidence of infection in both cohorts were very similar. This suggests that polyclonal HGGE in IgG subtype plasma cell disorders may be largely undetected and undertreated, due to apparently normal IgG levels caused by pathologic production of monoclonal IgG. When we attempt to subtract the monoclonal element (m-spike in the serum protein electrophoresis) from the total IgG, the magnitude of hypogammaglobulinemia in the IgG cohort approximates that of the non-IgG group. Given that daratumumab adds a small amount to the measured m-spike, further techniques to quantify true polyclonal IgG levels in the IgG cohort are needed. The incidence and depth of HGGE associated with daratumumab has not been previously well quantified. Our study demonstrates that the incidence of HGGE doubled after therapy with daratumumab (30.3% vs 61.4%). This data will sensitize physicians and possibly lead to generation of guidelines for closer monitoring of IgG, use of IVIG and other precautions in patients on daratumumab. In our own institution, we anticipate the detection of HGGE and use of IVIG in these patients to increase substantially. Download : Download high-res image (568KB) Download : Download full-size image Disclosures Hoffman: Celgene: Speakers Bureau.
Conservative numerical methods for nonlinear oscillators

I show that it is straightforward to derive numerical methods that conserve the energy of nonlinear oscillators. The derivation is first done for a single particle and then extended to multiple particle systems. Examples considered include the pendulum, the Henon-Heiles model, and the Fermi-Pasta-Ulam problem. Numerical experiments are shown and comparisons are made with nonconservative methods.
Discovery of high-entropy ceramics via machine learning

Although high-entropy materials are attracting considerable interest due to a combination of useful properties and promising applications, predicting their formation remains a hindrance for rational discovery of new systems. Experimental approaches are based on physical intuition and/or expensive trial and error strategies. Most computational methods rely on the availability of sufficient experimental data and computational power. Machine learning (ML) applied to materials science can accelerate development and reduce costs. In this study, we propose an ML method, leveraging thermodynamic and compositional attributes of a given material for predicting the synthesizability (i.e., entropy-forming ability) of disordered metal carbides. The relative importance of the thermodynamic and compositional features for the predictions are then explored. The approach’s suitability is demonstrated by comparing values calculated with density functional theory to ML predictions. Finally, the model is employed to predict the entropy-forming ability of 70 new compositions; several predictions are validated by additional density functional theory calculations and experimental synthesis, corroborating the effectiveness in exploring vast compositional spaces in a high-throughput manner. Importantly, seven compositions are selected specifically, because they contain all three of the Group VI elements (Cr, Mo, and W), which do not form room temperature-stable rock-salt monocarbides. Incorporating the Group VI elements into the rock-salt structure provides further opportunity for tuning the electronic structure and potentially material performance.
A disproportionate burden: strict voter identification laws and minority turnout

Critics of the recent proliferation of strict photo identification laws claim these laws impose a disproportionate burden on racial minorities. Yet, empirical studies of the impact of these laws on...
Using gas dynamic models to improve exhaust system design for large-bore, two-stroke engines:

It is vital to have accurate predictions of the gas exchange behavior of an engine in order to reliably study engine performance and emissions using engine simulation models. There are a multitude ...
Time and voltage domain load models for appliance-level grid edge simulation and control

Abstract Developments in simulation and distributed control of distributed energy resources require increasingly granular characterization and modeling of load behavior. Previous work has demonstrated the viability of voltage-based power control of residential appliances to enable load flexibility without service interruption. However, conventional static and dynamic load models fail to capture the coupled voltage and state dynamics relevant for this type of control. We develop a new class of dynamic load models for residential appliances. The input-output dynamics are learned by varying input voltage, which is enabled by custom hardware capable of controlling single-phase AC voltage and collecting high-resolution measurements. We estimate model parameters using nonlinear least squares regression and particle swarm optimization. The RMSE of power predictions is significantly reduced for loads with coupled time and voltage dynamics relative to traditional models. Using these models for voltage-based power control can help improve the ability of DERs to provide grid services.
Effects of Metering Precision and Terminal Controllability on Runway Throughput

In order to efficiently use available runway capacity while avoiding undue congestion within terminal airspace, systems of flow control and en route metering have been implemented. Recent work in a...
Abnormalities of the Lung Surfactant System in Acute Lung Injury

Since initially reported, the adult respiratory distress syndrome (ARDS) has become a well recognized pulmonary complication that may develop as a result of numerous conditions. These include: fractures and head trauma; hypovolemic shock; disseminated intravascular coagulation; thermal injury; sepsis; oxygen toxicity; hyper-transfusion; inhalation and aspiration of toxins and irritants; pulmonary infections; cardiac surgery with cardiopulmonary bypass; complicated abdominal surgery; drug overdose; pancreatitis; and AIDS. Aspiration and sepsis remain the most common predisposing factors (Fowler et al. 1985). Connors et al. estimated that ARDS affects 150000 hospitalized patients yearly in the United States (1981). Mortality has remained in excess of 50% despite advances in sophisticated therapeutic maneuvers and cardiopulmonary support (Fowler et al. 1983).
Dog Therapy with Cancer Treatment

Therapy dog visits can improve physical and psychosocial factors in ­cancer patients. Both pediatric and adult cancer patients can benefit from complementary therapy dog visits. Cancer patients and the parents of children being treated for cancer usually consider therapy dog interventions to be treatment. Therapy dog benefits have been reported in patients undergoing diagnostic testing and during inpatient cancer care, chemotherapy, and end-of-life care.
Macromolecular Synthesis in Newly Transformed Cells of Bacillus subtilis

The capacity of newly transformed cells of Bacillus subtilis to synthesize deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and protein has been determined by following the kinetics of suicide after their exposure to tritiated precursors of each of these macromolecules. Competent cells, whether transformed or not, are heterogeneous with respect to DNA synthesis. About 40 to 50% are latent in DNA synthesis. This latency may persist for 2.5 to 3 hr since transformants are resistant to thymineless death for this period after DNA addition. The remainder of the transformants synthesize DNA at one-half the rate of the cells of the total population. Synthesis of stable RNA does not occur at an appreciable rate in newly transformed cells. Newly transformed cells, however, do synthesize protein extensively, as demonstrated by the lethality of incorporated tritiated amino acids. Either chloramphenicol or actinomycin D treatment during the time of exposure to the tritiated amino acid prevented the suicide of transformants.
Hot wire measurements of freestream and shock layer disturbances.

Preliminary results of hypersonic helium tunnel investigations of whether disturbance measurements in the freestream alone are adequate to describe the model boundary-layer input disturbances, or whether the model shock wave changes the freestream disturbances before they reach the model boundary layer. It was found that the spectra in the freestream are typical of the wide band turbulence as it exists for sound radiated from a turbulent boundary layer. In the shock layer some redistribution of the spectra seems to occur, especially at the highest stagnation pressure, but the more interesting feature is the gradual development of a discrete component, around 70 kHz in the spectra. This feature is believed to be associated with boundary-layer transition.
Immunofluorescence radioautography: Simultaneous visualization of DNA replication and supramolecular antigens in individual cells☆

Abstract A procedure is described which permits the simultaneous light microscopic examination of the distribution of a cellular antigen by immunofluorescence and the radioautographic determination of whether the same cell is in S phase. Cells are viewed simultaneously with epifluorescence illumination to visualize antigens and transmitted darkfield illumination to determine DNA replication. Alternatively, the same cell can be viewed first in epifluorescence and subsequently in brightfield or phase contrast to visualize radioautographic grains. The method is illustrated with antibodies to tubulin, myosin and cytochrome oxidase. Comparison of the radioautographic and immunofluorescence images demonstrates that the arrangement of cytoskeletal structure is maintained throughout interphase and is not altered during DNA replication. Immunofluorescence radioautography should be useful in any system where a comparison in individual cells between replication and the appearance, distribution or rearrangement of specific antigens is desired.
Behavioral Thermoregulation in the Cold

The sections in this article are: 1 The Concept of Thermoneutrality 1.1 The Thermoneutral Zone 1.2 The Thermal Comfort Zone 2 Forced Movements 3 What Affects the Thermal Comfort Zone? 3.1 The Concept of Setpoint 3.2 Hypoxia 3.3 Fever 3.4 Circadian Rhythms 4 Examples of Behavioral Thermoregulation 4.1 Constructing a Microenvironment 4.2 Social Aggregation 4.3 Postural Changes 4.4 Preening 4.5 Alterations in Food Intake 5 Parental Thermoregulation for Offspring 6 Summary
Design of a donor-driven data collection strategy for operational improvement of blood donation process

BACKGROUND: Prior studies have noted that donor retention may be negatively impacted by the total time it takes to complete the blood donation process. STUDY DESIGN AND METHODS: To gain a comprehensive understanding of the blood donation process and examine opportunities for operational improvements, an educational partnership established between a blood bank and a university designed and implemented a donor-driven data collection strategy. RESULTS: A large amount of real-time, comprehensive, donor-reported data was collected as donors navigated the process, which has enabled a thorough analysis of the process and its potential improvements. CONCLUSION: In this paper, we describe the design and implementation efforts, examine the challenges in operationalizing a donor-driven data collection approach, and present insights and recommendations for its application in similar settings.
Goosecoid promotes head organizer activity by direct repression of Xwnt8 in Spemann's organizer.

Formation of the vertebrate body plan is controlled by discrete head and trunk organizers that establish the anteroposterior pattern of the body axis. The Goosecoid (Gsc) homeodomain protein is expressed in all vertebrate organizers and has been implicated in the activity of Spemann’s organizer in Xenopus. The role of Gsc in organizer function was examined by fusing defined transcriptional regulatory domains to the Gsc homeodomain. Like native Gsc, ventral injection of an Engrailed repressor fusion (Eng-Gsc) induced a partial axis, while a VP16 activator fusion (VP16-Gsc) did not, indicating that Gsc functions as a transcriptional repressor in axis induction. Dorsal injection of VP16-Gsc resulted in loss of head structures anterior to the hindbrain, while axial structures were unaffected, suggesting a requirement for Gsc function in head formation. The anterior truncation caused by VP16-Gsc was fully rescued by Frzb, a secreted Wnt inhibitor, indicating that activation of ectopic Wnt signaling was responsible, at least in part, for the anterior defects. Supporting this idea, Xwnt8 expression was activated by VP16-Gsc in animal explants and the dorsal marginal zone, and repressed by Gsc in Activin-treated animal explants and the ventral marginal zone. Furthermore, expression of Gsc throughout the marginal zone inhibited trunk formation, identical to the effects of Frzb and other Xwnt8 inhibitors. A region of the Xwnt8 promoter containing four consensus homeodomain-binding sites was identified and this region mediated repression by Gsc and activation by VP16-Gsc, consistent with direct transcriptional regulation of Xwnt8 by Gsc. Therefore, Gsc promotes head organizer activity by direct repression of Xwnt8 in Spemann’s organizer and this activity is essential for anterior development.
Shear wave model of southern Africa from regional Rayleigh wave tomography with 2‐D sensitivity kernels

SUMMARY Rayleigh-wave phase velocities are computed at the period range of 20–167 s in southern Africa from a two-plane-wave (TPW) tomography method using 2-D, Born approximation sensitivity kernels. These phase velocities are compared with the results of the TPW method using Gaussian sensitivity functions and the correlation between the two methods is good up to 100 s. The correlation coefficient becomes less than 0.5 at periods greater than 111 s, indicating significant finite-frequency effects at long periods. The correlation of phase velocity between adjacent frequencies increases with period for inversions using the 2-D sensitivity kernels, while such a systematic trend is not observed for inversions using Gaussian sensitivity functions. In addition, low phase velocity anomalies at long periods (111–167 s) are better and more consistently imaged from inversions using 2-D sensitivity kernels. To account for finite-frequency effects and improve resolution, the 2-D sensitivity kernels are therefore recommended in regional TPW tomography. A 3-D shear wave model is developed from the phase velocities obtained in southern Africa. The new model confirms the existence of a fast mantle lid underlain by a low-velocity zone revealed in a previous model constrained from the TPW method using Gaussian sensitivity functions. One new feature in this model is the vertical alignment of a shallow low-velocity anomaly with a deep high-velocity anomaly at the western Bushveld province. The alignment provides new evidence to support the interpretation of the slow anomaly as the result of high iron content from the Bushveld intrusion and the fast as a more depleted residual mantle. A low-velocity channel at the depths of 220–310 km from the Namaqua–Natal Belt to the northwest of the Kaapvaal Craton is also imaged. It suggests that the hot asthenosphere beneath the mobile belt can migrate into the craton area through a weak channel and produce thermal disturbance at the base of the craton. Further more, low-velocity anomalies from 100 to 140 km in the 3-D model agree well with the localities of kimberlites erupted at 65–104 Ma in the Kaapvaal Craton. This observation supports that kimberlites are generated in the lithosphere by thermal disturbance and provides additional evidence for the depth extent of mantle xenoliths.
Evaluation of Vacutainer Plus Low Lead Tubes for Blood Lead and Erythrocyte Protoporphyrin Testing

Lead poisoning is an important preventable environmental health problem. Blood lead concentrations as low as 100 μg/L (0.48 μmol/L) in whole blood have been shown to affect children’s neuropsychologic or cognitive performance adversely (1)(2)(3). In view of this, in 1991 the Centers for Disease Control and Prevention (CDC) lowered the concentration of lead in blood considered safe from 250 to 100 μg/L (from 1.21 to 0.48 μmol/L) (4). This lowered threshold has been reaffirmed by the CDC in their 1997 document on screening children for lead exposure (5). Before 1991, erythrocyte protoporphyrin (EP) was the standard test for screening children for lead poisoning; however, it was subsequently found to be an insensitive predictor of blood lead concentrations above the lower threshold (6). However, serial EP measurements, paired with matching blood lead measurements, are still useful in managing children with lead poisoning. In the absence of additional exposure of the child to lead, the EP concentration will continue to decrease at a faster rate than is reflected by the blood lead concentration as lead reequilibrates among blood, soft tissue, and bone stores. Another recommendation in the 1991 CDC statement was to screen all children 6 months to 6 years of age for lead poisoning, using a direct blood lead measurement. Venous blood is preferred for blood lead measurement because capillary measurements may be falsely increased by skin contamination with lead. The issue …
Tracking individual secretory vesicles during exocytosis reveals an ordered and regulated process

Post-Golgi secretory vesicle trafficking is a coordinated process, with transport and regulatory mechanisms to ensure appropriate exocytosis. While the contributions of many individual regulatory proteins to this process are well studied, the timing and dependencies of events have not been defined. Here we track individual secretory vesicles and associated proteins in vivo during tethering and fusion in budding yeast. Secretory vesicles tether to the plasma membrane very reproducibly for ∼18 s, which is extended in cells defective for membrane fusion and significantly lengthened and more variable when GTP hydrolysis of the exocytic Rab is delayed. Further, the myosin-V Myo2p regulates the tethering time in a mechanism unrelated to its interaction with exocyst component Sec15p. Two-color imaging of tethered vesicles with Myo2p, the GEF Sec2p, and several exocyst components allowed us to document a timeline for yeast exocytosis in which Myo2p leaves 4 s before fusion, whereas Sec2p and all the components of the exocyst disperse coincident with fusion.
A flexible resampling mechanism for parallel particle filters

This paper presents an efficient flexible resampling architecture for parallel particle filtering. The architecture incorporates distributed, delayed resampling mechanisms for fast resampling processing. The architecture consists up to four resampling units and 16 processing elements. Their interconnection can be dynamically reconfigured. The architecture is designed and evaluated for bearing tracking example. The architecture is designed for 0.25 /spl mu/m CMOS technology.
Branching ratio for S(33PJ) and S(31D2) atom production in the photodissociation of CS2 at 193 nm

Abstract Resonance-enhanced photoionization has been used to follow S(3P2) in the photodissociation of CS2 at 193 nm. The contributions from initial photodissociation and from S(1D) relaxation have been resolved and give a (15±5)% yield of S(1D). The possibility of secondary production of S(3Pj) by CS photodissociation with a second 193 nm photon is discussed. Although this might raise the S(1D) yield to (26±8)%, production of S(3PJ) is still the dominant photodissociation channel.
Smooth indentation of a transversely isotropic cantilever beam

Abstract The response of a transversely isotropic beam of finite length to a frictionless cylindrical and flat indenter is studied. Solutions are obtained through a global-local technique, which accounts for the local behavior near the indenter, as well as the global beam behavior. The method of analysis superposes an infinite elastic layer solution derived through the use of integral transforms with a beam theory solution. Local indenter stresses, as well as displacements and rotations, are computed for each case and plotted for various ratios of contact width to beam length and for various positions of the indenters. To study the effects of anisotropy, each problem is solved using two materials: one nearly isotropic, the other highly anisotropic. Results are compared to those of an earlier isotropic study, and to Hertz theory and beam theory solutions.
TOTAL REACTION AND ELASTIC SCATTERING CROSS SECTIONS FOR 22.8-Mev PROTONS ON URANIUM ISOTOPES

The total reaction cross sections for 22.8-Mev protons on uranium isotopes were determined by measuring cross sections for ($p$, fission), ($p, {p}^{\ensuremath{'}}$), ($p, d$), ($p, t$), and ($p, \ensuremath{\alpha}$). These data are combined with previously measured ($p, \mathrm{xn}$) cross sections to give total reaction cross sections of 1.43\ifmmode\pm\else\textpm\fi{}0.10, 1.44\ifmmode\pm\else\textpm\fi{}0.10, and 1.39\ifmmode\pm\else\textpm\fi{}0.10 barns for 22.8-Mev protons on ${\mathrm{U}}^{233}$, ${\mathrm{U}}^{235}$, and ${\mathrm{U}}^{238}$, respectively. Angular distributions of ($p, {p}^{\ensuremath{'}}$), ($p, d$), ($p, t$), ($p, \ensuremath{\alpha}$), and proton elastic scattering cross sections are shown for ${\mathrm{U}}^{235}$ and ${\mathrm{U}}^{238}$.
996-12 Overexpression of Sarcoplasmic Reticulum Calcium ATPase in Neonatal Cardiomyocytes Using a Recombinant Adenovirus

Cardiac Sarcoplasmic Reticulum Calcium ATPase (SERCA2) is a membrane pump that plays a major role in regulating calcium levels in cardiac myocytes. Recent data have documented a decrease in SERCA2 levels in human heart failure. In order to further study the importance of SERCA2 levels in cardiac cellular physiology we constructed a recombinant replication deficient adenovirus encoding SERCA2 driven by an SV40 enhanced TK promoter (14CTK). After documenting the presence of the SERCA2 gene by southern analysis of viral DNA. neonatal rat cardiomyocytes were infected with either the SERCA2 encoding adenovirus or an adenovirus encoding beta-galactosidase. Cells were harvested for RNA preparation at 48 hours and for protein at 72 hours post infection. Northern blot analysis using a full length probe specific for rat SERCA2 revealed a several fold induction of SERCA2 mRNA levels compared to cells infected with the beta-galactosidase encoding virus. Western blot analysis with a polyclonal SERCA2 antibody revealed an approximate 2.5 fold induction of SERCA2 protein. These data demonstrate that SERCA2 can be overexpressed in cardiac myocytes using this adenoviral vector based approach. Functional studies of infected cardiomyocytes are currently underway.
Decision-Making of the Multinational Executive: A Research Paradigm:

Studies of executive decision-making have traditionally relied upon introspective description and interpretation. Yet psychologists have developed an evolving sophistication in what has been termed “paramorphic mapping” of the judgmental process. This research domain provides a rich framework within which empirical investigations of executive judgment can be meaningfully explored. This part, Part I of a two-part series, looks at several methodological and theoretical considerations applicable to multinational executive decision-making studies; Part II, to appear in a subsequent issue of this journal, provides evidence gathered in a field application of one particular model discussed, namely, the Brunswik Lens model, in support of its potential in executive decision-making investigations.
Regional profiles of steady-state levels of cyclic nucleotides, cyclic AMP phosphodiesterase, and guanylate cyclase activities during late stages of unilateral ischemia in gerbil forebrain.

The present study was an extension of earlier work regarding the role of cyclic nucleotides and related enzymes during cerebral ischemia in the gerbil. Following unilateral carotid occlusion, levels of cyclicAMP and cyclicGMP were measured in four rapidly inactivated brain regions at 3, 6, and 24 hr after permanent occlusion and at 2hr of occlusion plus 1 hr of reflow. An analysis of variance indicated significant minor fluctuations in the steady-state levels of the two cyclic nucleotides within the frontal cortex, the hippocampus, the striatum, and especially the olfactory tubercle with respect to occlusion time (3 and 24 hr) but not when comparing control vs ischemic hemispheres (except at 3hr). Changes occurred only in animals developing neurological symptoms of ischemia. At 24 hr postocclusion the specific activity of the lowKm form of cyclicAMP phosphodiesterase was elevated especially on the ischemie side when determined in homogenates of the four brain regions. Alternatively, the high-Km form of the enzyme in the presence or absence of Ca+-calmodulin was unchanged. Guanylate cyclase activity in tissue homogenates was not influenced by the conditions of ischemia until 24 hr had elapsed, an event likewise unique to symptomatic gerbils. The sensitivity of the enzyme to hematin-catalase was decreased in the ischemic hemispheres of the hippocampus, striatum, and olfactory tubercle. In addition, further activation of the hematin-catalase response by NaN3 was depressed in the ischemic side of the hippocampus and striatum. Taken together these and previous studies indicate that fluctuations in the steady-state levels of cyclic nucleotides that occur rather prominently during acute and to a lesser degree during prolonged ischemia are not correlated with associated changes in enzymes responsible for their synthesis and/or degradation.