cssi/SciSciGPT-SciSciNet huggingface dataset:
A PHASE I STUDY OF CONVECTION-ENHANCED DELIVERY OF LIPOSOMAL-IRINOTECAN USING REAL-TIME IMAGING WITH GADOLINIUM IN PATIENTS WITH RECURRENT HIGH GRADE GLIOMA

BACKGROUND: Chemotherapy for high grade glioma (HGG) is limited by poor activity of available agents and compromised delivery across the blood brain barrier (BBB). Convection enhanced delivery (CED) improves chemotherapy delivery by utilizing fluid convection established as a result of a pressure gradient, obviating the challenges of crossing the BBB while minimizing systemic toxicity. CED of nanoliposomal irinotecan (MM-398) has been optimized in rat, dog, and primate models. A recent study in mice with intracranial glioblastoma xenografts compared routes of delivery for liposomal irinotecan by CED or IV and showed superior anti-tumor activity of CED. A major clinical advance in the use of CED over recent trials is the development of real time CED (RCD), which utilizes MRI to visualize the CED process with the aid of co-convected contrast agents and thus monitor delivery into the brain and to take corrective action for technical complexities. METHODS: With support from an R21 we will conduct the first in human phase I study of CED of liposomal-irinotecan using real-time imaging with gadolinium in patients with recurrent HGG. This is a single center, prospective, 3 + 3 dose escalating, single-arm, phase I trial with a four-level dose escalation, expecting to enroll at least 3 patients in each level and expanding the highest level to 12 patients total. Dose levels are 20 mg, 40 mg, 60 mg, and 80 mg liposomal-irinotecan, given via up to 3 catheters surgically placed in an intra-tumoral (IT) location. Concentration of gadoteridol will be 2 mM for all dose groups; both agents will be combined and co-infused via the same catheters. Subjects in the two lowest dose groups will have tumor volumes of 1-4 cm3, the third dose group will be 2-5 cm3 and the highest dose group will have tumor volume 2-6 cm3. Maximum total volume infused will be 1.0 ml for two lowest dose groups, 1.5 ml for the third dose group, and 2.0 ml for the highest dose group. RESULTS: Interim safety, efficacy, and imaging response results will be presented. Utilizing imaging software, we'll present the correlation of pre-infusion modeling of the drug distribution with post-infusion imaging and determination of the total volume of distribution (Vd) and the Vd to volume infused (Vi) ratio for each infusion. CONCLUSIONS: Image-guided distribution allows for real-time placement and adjustment of cannula for real time CED of MM-398 into the brains of patients with recurrent HGG. SECONDARY CATEGORY: Imaging.
"Your Brain Becomes a Rainbow": Perceptions and Traits of 4th-Graders in a School-Based Mindfulness Intervention.

ABSTRACTAlthough mindfulness, or the self-regulation of attention, has been found beneficial in reducing teacher stress and burnout and in increasing students’ cognitive and emotional regulatory skills, no study has explored students’ attitudes toward meditation practices in depth. This mixed-methods study reports results from a randomized, controlled trial of a 10-week mindfulness intervention in a public school setting with 28 4th-grade students from lower income and ethnic minority backgrounds. Over the course of the intervention, students were asked to respond to writing and drawing prompts about their feelings and attitudes toward mindfulness. At the end of the intervention, the experimental teacher rated students on how often they had practiced mindfulness breathing during class. Qualitative analysis of journal entries yielded personality traits of students who were receptive or resistant to mindfulness training. Practical strategies for identifying and remediating resistant students and for impleme...
Applied Research Perspectives of Alpha-Keto Acids: From Production to Applications

Alpha-keto acids are the deaminated form of amino acids, which have been used in several applications in the medicine, food, and feed industries. In vivo, alpha-keto acids are ketogenic or glucogenic precursors, which regulate protein turnover. Since alpha-keto acids do not have amino groups, substitution of amino acids with their specific alpha-keto acids in the diets helps kidneys and livers to reduce urea accumulation in the body. Additionally, alpha-keto acids are used in animal diets, especially in the poultry industry as a nutrient supplement for environmental and animal growth issues. Moreover, several alpha-keto acids have been reported to be used as flavor enhancers in the food industry. In this review, characteristics, chemical and biological production methods, detection analyses, and the application of various alpha-keto acids are summarized. Furthermore, potential future studies and applications of alpha-keto acids are discussed.
Introduction to Evidence and Innovation in Housing Law and Policy

This introductory chapter to the edited volume "Evidence and Innovation in Housing Law and Policy" emphasizes housing's dual role as a vehicle for building community and as a vehicle for building wealth. The volume examines the impact of housing law and policy on households, neighborhoods, urban landscapes, and financial markets. We briefly introduce each of the thirteen contributions to this interdisciplinary volume, which address topics ranging from the recent financial crisis to discrimination and gentrification. We also include an open access table of contents.
Melnikov analysis for a ship with a general roll-damping model

In the framework of a general roll-damping model, we study the influence of different damping models on the nonlinear roll dynamics of ships through a detailed Melnikov analysis. We introduce the concept of the Melnikov equivalent damping and use phase-plane concepts to obtain simple expressions for what we call the Melnikov damping coefficients. We also study the sensitivity of these coefficients to parameter variations. As an application, we consider the equivalence of the linear-plus-cubic and linear-plus-quadratic damping models, and we derive a condition under which the two models yields the same Melnikov predictions. The free- and forced-oscillation behaviors of the models satisfying this condition are also compared.
Interventions Promoting Colorectal Cancer Screening Among Latino Men: A Systematic Review.

Introduction Colorectal cancer, the second leading cause of cancer death in the United States, is also among the most preventable cancers. However, Latino men are less likely than non-Latino men to engage in preventive screening. Compared with 60% of non-Latino white men and women, only 42% of Latino men are up to date with colorectal cancer screening guidelines, which may result in diagnosis at advanced disease stages and increased deaths. We evaluated the literature on colorectal cancer screening interventions among Latino men to characterize intervention components effective in increasing colorectal cancer screening. Methods Two independent reviewers searched MEDLINE, CINAHL, and PsycINFO to identify articles on intervention studies that promote colorectal cancer screening among Latino men. Inclusion criteria were randomized controlled or comparative effectiveness trials, an outcome of any colorectal cancer screening test, published in English, US-based, results published from January 2004 through December 2016, Latino or Spanish-speaking male participants, and a minimum of one patient-level component. Two other reviewers independently assessed article quality and conducted data abstraction. Results Forty-four studies met the inclusion criteria; only 7 studies with 20% or more Latinos and 39% or more men were included in the final analyses. The most common intervention strategies included one-on-one interactions with a patient navigator and reducing structural barriers (eg, providing fecal occult blood tests). Interventions using small media produced mixed results. Conclusion Although intervention studies focused on colorectal cancer screening among men of racial/ethnic minorities are scarce, our findings highlight promising strategies that were effective at increasing colorectal cancer screening among Latino men. Additional research in the area of Latino men's health is needed, especially to further develop and test theoretically grounded interventions that promote colorectal cancer screening with larger samples of men and across diverse geographic areas in the United States.
Synthesis of Platinum-nickel Nanowires and Optimization for Oxygen Reduction Performance

Platinum-nickel (Pt-Ni) nanowires were developed as fuel cell electrocatalysts, and were optimized for the performance and durability in the oxygen reduction reaction. Spontaneous galvanic displacement was used to deposit Pt layers onto Ni nanowire substrates. The synthesis approach produced catalysts with high specific activities and high Pt surface areas. Hydrogen annealing improved Pt and Ni mixing and specific activity. Acid leaching was used to preferentially remove Ni near the nanowire surface, and oxygen annealing was used to stabilize near-surface Ni, improving durability and minimizing Ni dissolution. These protocols detail the optimization of each post-synthesis processing step, including hydrogen annealing to 250 °C, exposure to 0.1 M nitric acid, and oxygen annealing to 175 °C. Through these steps, Pt-Ni nanowires produced increased activities more than an order of magnitude than Pt nanoparticles, while offering significant durability improvements. The presented protocols are based on Pt-Ni systems in the development of fuel cell catalysts. These techniques have also been used for a variety of metal combinations, and can be applied to develop catalysts for a number of electrochemical processes.
The Finite-Dimensional Commutation Condition

In Chapter 1, we indicated that in order to obtain a useful commutation theory connecting operators A and B with their resolvents, semigroup-exponentials, and operational images, it is desirable to impose a finite-dimensionality condition upon their iterated commutators [A,B] = AB - BA, [A, [A,B]], etc. (Here A and B are endomorphisms of a dense domain D in a Banach or locally convex space E.) Below in Section 2A we distinguish several technically different ways in which this condition enters into the development. Section 2B presents examples of differential operators which satisfy the condition.
Measurements of oxygen flux from arterioles imply high permeability of perfused tissue to oxygen.

A mathematical model developed for the analysis of oxygen flux from an arteriole surrounded by perfused tissue was used to analyze experimental data in the resting hamster cheek pouch retractor muscle. The flux predicted by the model, with the commonly accepted values of tissue permeability to oxygen (the Krogh diffusion coefficient), was an order of magnitude smaller than the average value of experimentally observed oxygen flux. The values of permeability required by the model to equate the predicted and observed oxygen flux are one to two orders of magnitude higher than the accepted values. Also, the values of the oxygen tension gradient in the arteriolar wall predicted by Fick’s law are an order of magnitude greater than the measured values reported in the literature. Since the accepted values of permeability are based on experiments with unperfused tissue and the values predicted by the model are for blood-perfused tissue, we conjecture that tissue permeability is a function of the perfusion conditions. Hence, there is a need for re-examination of the distribution of resistance to oxygen transport along the pathway between red blood cells and mitochondria. Theoretical estimates based on accepted values of tissue permeability to oxygen show resistances to oxygen transport inside and outside the capillaries to be of similar magnitude. However, if the tissue component of the resistance is significantly reduced because of greater permeability, the intracapillary resistance becomes dominant and is responsible for most of the drop in the oxygen tension between the red blood cells and the tissue.
Development of intestinal mucosal barrier function to antigens and bacterial toxins.

During the past several years our laboratory has attempted to define factors that contribute to the mucosal barrier of the intestine against the uptake of pathologic quantities of antigens and microbial organisms and their enterotoxins. It has become apparent from these studies that numerous components contribute to the collective exclusion of these noxious substances within the gut. Table 1 lists the components of the mucosal barrier as we currently envision it. It consists of numerous luminal factors such as gastric acid and peptic enzymes to minimize bacterial/ antigen penetration into the small intestine, and proteolytic pancreatic enzyme activity to decrease the protein antigen load to the mucosal surface. In addition to luminal factors, the mucosal surface, including the mucus layer, appears to be an important deterrent to the colonization of bacteria and to the attachment and uptake of foreign antigens. Finally, the unique secretory IgA antibody system is of major immunologic importance to the exclusion of antigens from the luminal surface (1,2).
What Is an Affinograph

An affinograph is a dynamic graph image of family relationships accumulated through descent, civil unions, informal unions, marriage, procreation, and adoption. An affinograph gives a more precise meaning to families referred to as broken, nuclear, reconstituted, blended, single-parent, and others. Affinographs transfer descriptive narratives of family relations into images that help generate working hypotheses for clinical interventions, teaching, and research. Five assumptions underlie affinograph images: One, affinal relations vary from ephemeral to life long. Two, each adult may remain eligible to start a new relationship regardless of the current marital status. Three, families can be formed with or without marriage. Four, relationship commitment is gender neutral. And five, a person may have more than two parents.
A Perception-Based Fuzzy Route Planing Algorithm for Autonomous Unmanned Ground Vehicles

Path planning plays an integral role in mission planning for ground vehicle operations in urban areas. Determining the optimum path through an urban area is a well-understood problem for traditiona...
A Scalable and Low Power DCNN for Multimodal Data Classification

This paper presents SensorNet which is a scalable and low power embedded Deep Convolutional Neural Network (DCNN), designed to classify multimodal time series signals. Time series signals generated by different sensor modalities with different sampling rates are first converted to images (2-D signals) and then DCNN is utilized to automatically learn shared features in the images and perform the classification. SensorNet is scalable with respect to different types of multi-channel time series data, and does not require expert knowledge for extracting features for each sensor data. Additionally, it can achieve very high detection accuracy for different case studies, and has a very efficient architecture which makes it suitable to be employed at IoT and wearable devices. A custom low power hardware architecture is also designed for the efficient deployment of SensorNet at embedded real-time systems. SensorNet performance is evaluated using three different case studies including Physical Activity Monitoring, stand-alone Tongue Drive System (sdTDS) and Stress Detection and it achieves an average detection accuracy of 98%, 96.2% and 94% for each case study, respectively. We implement SensorNet using our custom hardware architecture on Xilinx FPGA (Artix-7) which on average consumes 0.3 mJ energy per classification while meeting all applications time requirements. To further reduce the power consumption, SensorNet is implemented using ASIC at the post layout level in 65-nm CMOS technology which consumes approximately 8$\times$ lower power compared to the FPGA.
P-006 Magnetic resonance venogram 3-dimensional live guidance during venous sinus stenting treatment: safety and efficacy

Objective Venous Sinus Stenting (VSS) is emerging as a promising treatment for Idiopathic Intracranial Hypertension. VSS procedures face certain procedural challenges, including navigation without road-map and the potential risk of occluding large cortical veins (i.e. vein of Labbe) due to the stent. Our group sought to minimize the risks of VSS procedures with new imaging modalities that allow for safer navigation and optimal placement of the stents. The purpose of this study was to evaluate the benefits of a new bi-plane live 3D guidance technique using pre-operative Magnetic Resonance Venogram (MRV) datasets instead of conventional 2D technique. Methods We performed an IRB approved retrospective evaluation of 80 consecutive patients treated for VSS between Jan-2015 and Feb-2018 (57 with conventional 2D roadmapping only, 23 with additional MRV bi-plane 3D guidance after the software was made available at our institution). The following procedural data where compared between the conventional guidance and the MRV 3D guidance groups: delayed flow in large cortical veins post-stenting, dose area product (DAP), cumulated air kerma (CAK), and fluoroscopy time. Two experienced neuro-interventionalists, not involved in the treatments, reviewed images from the last 10 MRV 3D guided procedures. At first they reviewed conventional 2D images only and then they reviewed the MRV 3D guided images, and successively assessed their consensus confidence level using a 3-points scale from low to high confidence on the following parameters: venous sinus anatomy, location of large cortical veins, length of venous sinus stenosis and landing zones and length of stent-construct. Results MRV bi-plane 3D guidance was successful in all cases but one, where registration failed. In the MRV guided group, there was significantly less occurrence of delayed flow in the large cortical veins versus the conventional group (1 vs 8, p When comparing conventional images and MRV guided images from the same procedures, there was increased operator confidence regarding the location of the major cortical veins, the length of venous sinus stenosis and the landing zones and the length of stent-construct (1.9 vs 2.9, p=0.002). Conclusion By better visualization of the large cortical veins and ability to make more accurate measurements in regards to the venous sinus stenosis, MRV bi-plane 3D guidance can improve safety of VSS procedures without any increase in radiation or procedural time. Disclosures T. Link: None. B. Rapoport: None. G. Avignon: 5; C; General Electric. P. Ozbek: 5; C; General Electric. A. Patsalides: None.
Escaping the Robot’s Loop? Power and Purpose, Myth and History in Westworld’s Manufactured Frontier

Contextualising Westworld in the long history of robots in American culture, this paper explores how the show’s focus on narrative loops reflects a larger interest in the power of history to raise the consciousness of disempowered peoples. As a twenty-first-century TV show about robots, Westworld is burdened by the plots and tropes that have dominated over two centuries of stories about robots and automata, including the 1973 film of the same name. Like its robotic “hosts,” however, the show is trying to break out of the conventional narrative loop of mechanical rebellion that has become engrained in popular culture. It does so, the paper argues, by substituting a cathartic and supportive narrative of resistance that focuses, contrary to almost all other robot stories, on the bodies and minds of white women and men and women of colour. The show, the paper suggests, is about the consciousness-raising power of history.
Can Metabolic Pathways Be Therapeutic Targets in Rheumatoid Arthritis

The metabolic rewiring of tumor cells and immune cells has been viewed as a promising source of novel drug targets. Many of the molecular pathways implicated in rheumatoid arthritis (RA) directly modify synovium metabolism and transform the resident cells, such as the fibroblast-like synoviocytes (FLS), and the synovial tissue macrophages (STM), toward an overproduction of enzymes, which degrade cartilage and bone, and cytokines, which promote immune cell infiltration. Recent studies have shown metabolic changes in stromal and immune cells from RA patients. Metabolic disruption in the synovium provide the opportunity to use in vivo metabolism-based imaging techniques for patient stratification and to monitor treatment response. In addition, these metabolic changes may be therapeutically targetable. Thus, resetting metabolism of the synovial membrane offers additional opportunities for disease modulation and restoration of homeostasis in RA. In fact, rheumatologists already use the antimetabolite methotrexate, a chemotherapy agent, for the treatment of patients with inflammatory arthritis. Metabolic targets that do not compromise systemic homeostasis or corresponding metabolic functions in normal cells could increase the drug armamentarium in rheumatic diseases for combination therapy independent of systemic immunosuppression. This article summarizes what is known about metabolism in synovial tissue cells and highlights chemotherapies that target metabolism as potential future therapeutic strategies for RA.
Do gender and age affect willingness to ride in driverless vehicles: If so, then why?

Abstract Background In the past few years, there have been great strides in the development of technology for driverless vehicles. However, research into consumer perceptions of this technology has lagged behind the technology itself. A few reports have indicated that age and gender might have effects on consumers’ willingness to ride in driverless vehicles; however, to date, none of these studies has sufficiently explained why these effects occur. The current study seeks to address this gap with a causal mediation model using various scales and emotional responses as potential mediators. Methods In three studies, participants were presented with two hypothetical scenarios about riding in a driverless ambulance or car. They responded to five previously validated scales and provided six emotional responses to the scenarios. These 11 potential mediators were tested in order to develop a causal model. Results The data was mixed with regards to the effect of Age on willingness to ride in driverless vehicles. There was a strong effect of Gender across all three studies, with females being less willing to ride compared to their male counterparts. This effect is explained largely by fear. The cause of fear is largely explained by participants’ perceptions on the complexity and value of driverless vehicles, as well as the “fun factor” involved. Conclusions When reporting what type of person is willing, or not willing, to ride in a driverless vehicle, it is also important to note why they respond in this manner.
Burnout Levels and Mood States Among Athletic Training Students in Professional Master's Programs

Context Professional master's athletic training students are at high risk for changes in mood state and an increase in burnout levels during an academic semester due to stressors including academic...
No evidence for preservation of somatostatin-containing neurons after intrastriatal injections of quinolinic acid

>BEAL ET AL. REPLY—Davies and Roberts contend that quinolinic acid striatal lesions do not spare somatostatin (NADPH-diaphorase) neurons. We have attempted to resolve the discrepancy by carefully re-examining our own material. There is one major methodological difference between the two reports. Davies and Roberts examined regions containing the lesion cores in which there is almost total neuronal loss and marked gliosis as depicted in their Fig. 1 and the data given in Fig. 2a. They found no selective sparing of neurons within this region and our own findings are in agreement with that result. Since we believe that sparing of somatostatin neurons is relative and not absolute, we make our counts in regions posterior to the lesion, where there is a depletion of total Nissl-stained neurons in the range of 50%. Within this region we find significant increases in NADPH-diaphorase neurons relative to acetylcholinesterase neurons. We have further examined this issue by counting numbers of NADPH-diaphorase neurons relative to the total number of Nissl-stained neurons. NADPH-diaphorase neurons are significantly increased as a percentage of the total neuronal population in this area. These results are consistent with the findings of Choi and colleagues who showed that quinolinic acid results in relative, but not absolute, sparing of NADPH-diaphorase neurons in cortical cell cultures (Science 234, 73-76; 1986).
Immunobiology of Transplantation

The immune system is a highly complex and integrated array of cells and molecules capable of providing protection from a hostile environment where pathogens abound. Immune function is critical in the setting of both autologous and allogeneic hematopoietic cell transplantation (HCT). The major cellular populations and mechanisms of action pertinent to the setting of HCT will be discussed. Due to the enormity of the topic great detail cannot be provided, but is available from a number of other sources.
Promises, Deceit and White-Collar Criminality Within the Theranos Scandal

Theranos rose to prominence by selling a dream that a company could make blood testing less painful and more effective. The company strove to bring new technology to the laboratory industry that wo...
Return of the Golden Calf: Economy, Idolatry, and Secularization since Gaudium et spes

Pope Francis consistently addresses economic issues with the concept of idolatry, but Gaudium et spes treats the economy as an autonomous, secular realm amenable to technocratic solutions guided by...
An RNAi screen in C. elegans for genes that play a role in secretion and cleavage of VAPB MSP domain

VAPB (VPR-1 in C. elegans) is a type-II ER transmembrane protein whose N-terminal Major Sperm Protein domain (MSPd) is cleaved and secreted. Mutations in the MSPd of human VAPB cause impaired secretion and are associated with Amyotrophic Lateral Sclerosis (ALS). In C. elegans, the secreted MSPd signals non-cell-autonomously to regulate striated muscle mitochondrial morphology and gonad development. As VAPB/VPR-1 does not have a signal peptide and its MSPd extends into the cytosol, it is unclear how the protein is proteolytically cleaved and secreted. To identify genes that are involved in VPR-1 cleavage and unconventional secretion, we performed an RNA interference (RNAi) screen in C. elegans. Worms null for vpr-1 are sterile and have striated muscle mitochondrial abnormalities. These defects can be rescued by vpr-1 expression in the neurons, germline, or intestine, implying that these three tissues share a common machinery to cleave and secrete the MSPd. Examination of shared gene expression in these tissues revealed a list of 422 genes, which we targeted with RNAi. vpr-1 null worms expressing vpr-1 from intestine were used in the screen, and the brood size of these worms after RNAi knockdown was scored. Disruption of factors involved in VPR-1 MSPd processing and/or secretion should revert fertility phenotypes in these worms. We identified many genes that induce compromised fertility when knocked down in these but not wild type worms, including a V-SNARE, several proteasome components, stress response molecules, and mitochondrial genes. Our screen thus identified many potential players involved in MSPd processing and/or secretion. SummaryThe MSP domain (MSPd) of a type-II ER transmembrane protein called VAPB is cleaved and secreted to function as a non-cell-autonomous signal. The topology of VAPB positions MSPd in the cytosol. It is thus unclear how MSPd is cleaved from VAPB and released extracellularly. Using C. elegans, we screened 422 genes by RNAi to identify potential candidates regulating MSPd cleaving and secretion. We identified the Golgi v-SNARE YKT-6 and several components of the 20S and 19S proteasome that may mediate MSPd trafficking and cleaving, respectively. These results have promising implications in advancing our understanding of MSPd signaling.
Disparities in cancer prevalence, incidence, and mortality for incarcerated and formerly incarcerated patients: A scoping review.

Background Racial and ethnic minority status, structural racism, low educational attainment, and poverty are consistently associated with cancer disparities and with higher rates of incarceration. The objective of this scoping review is to conduct a qualitative synthesis of the literature on cancer prevalence, incidence, mortality, and disparities in these outcomes for incarcerated and formerly incarcerated patients, as this literature is fragmented and heterogenous. Methods This scoping review included Bureau of Justice Statistics reports and searched PubMed in May 2021 for all English language studies published between 1990 and 30 April 2021, that reported on cancer prevalence, incidence, or mortality for incarcerated or formerly incarcerated individuals in the United States. Results Twenty studies were selected. Data on cancer prevalence and incidence were scarce but suggested that incarcerated and formerly incarcerated patients have a similar overall risk of cancer diagnosis as the general population, but elevated risk of certain cancers such as cervical, lung, colorectal, and hepatocellular carcinoma for which effective prevention and screening interventions exist. Cancer mortality data in state and local jails as well as prisons were robust and suggests that both incarcerated and formerly incarcerated patients have higher cancer mortality than the general population. Conclusions Incarcerated and formerly incarcerated patients likely have a higher risk of dying from cancer than the general population, but important gaps in our knowledge about the extent and drivers of disparities for this population remain. Additional research is needed to guide interventions to reduce cancer disparities for patients experiencing incarceration.
Effects of Two Systems of Weight Training on Circulorespiratory Endurance and Related Physiological Factors

Abstract Three groups, two experimental and one control, consisting of 20 college freshmen in each group, were tested doing moderate and all-out exercise on a bicycle ergometer. Selected physiological responses and the circulorespiratory endurance times were measured. An eight-week training period followed during which the experimental groups participated in weight-training programs and the control subjects in archery or bait casting. After training, the tests were again administered. Though there was an indication of improved circulorespiratory responses by the weight-training groups following training, statistical treatment of the data revealed no significant differences among the three groups in their responses to exercise.
Inhibition of lymphocyte-mediated cytolysis by 2-fluoroadenosine--evidence for two discrete mechanisms of drug action.

Abstract 2-Fluoroadenosine (F-Ado) is a potent, irreversible inhibitor of lymphocyte-mediated cytolysis (LMC) in vitro: the irreversibility of this inhibition has been attributed to the metabolism of F-Ado to 2-fluoroadenosine t′-triphosphate (F-ATP) and 2-fluoroadenosine 3′, 5′-monophosphate (F-cAMP) within the cytotoxic lymphocytes [T. P. Zimmerman, J. L. Rideout, G. Wolberg, G.S. Duncan and G. B. Elion, J. biol. Chem.251, 6757 (1976)]. The present study was undertaken to define better the biochemical events intrinsic to the inhibition of LMC by F-Ado. Several purine ribonucleosides, which are themselves non-inhibitory towar LMC, have been found to inhibit the metabolism of F-Ado to F-ATP and F-cAMP by the cytotoxic lymphocytes. The reduction in F-cAMP formation caused by these ribonucleosides was counterbalanced by their augmentation of the elevation of lymphocytic cyclic AMP (cAMP) caused by F-Ado. While interference with the metabolism of F-Ado had little or no effect on the immediate inhibitory activity of F-Ado toward LMC, prevention of the cellular formation of F-ATP and F-cAMP did allow most of the inhibitory activity of F-Ado to be reversed after washing the lymphocytes free of exogenous F-Ado. The relative efficacy of these ribonucleosides in allowing reversibility of the inhibitory activity of F-Ado toward LMC followed the same order as did their efficacy in preventing the metabolism of F-Ado by the cytotoxic lymphocytes: 8-aza-adenosine > inosine > guanosine. Cytotoxic lymphocytes which had been preloaded with nucleotides of F-Ado (via prior incubation with F-Ado and subsequent washout of residual extracellular drug) exhibited increased inhibition of their cytolytic activity upon subsequent incubation with an inhibitor (Ro 20-1724) of cAMP phosphodiesterase. Under these latter experimental conditions, Ro 20-1724 caused a 2- to 3-fold elevation of F-cAMP in the cytotoxic lymphocytes but did not raise cAMP above control levels. These results suggest that F-Ado can inhibit LMC by either of two distinct mechanisms: (1) an extracellular mechanism, wherein F-Ado binds reversibly to an adenosine receptor present on the plasma membrane of the cytotoxic lymphocytes and reversibly activates a functionally associated adenylate cyclase, thereby causing an elevation of cellular cAMP; and (2) an intracellular mechanism, wherein F-Ado is metabolized irreversibly (during the 1- to 2-hr experimental period) by the cytotoxic lymphocytes to F-cAMP which, by reason of its ability to activate cAMP-dependent protein kinase, mimics the effect of elevated cellular levels of cAMP.
Active Transport of Choline by a Marine Pseudomonad

A marine pseudomonad, BAL-31, accumulates the phospholipid nitrogen base, choline, although no detectable amount of choline is incorporated into polar lipids. Metabolic inhibitors such as cyanide and azide block the uptake process as does starving for oxygen by using nitrogen gas. Only very close structural analogues show any inhibition of transport, indicating that the uptake process has great structural specificity. The export of choline out of the cells is also an energy-dependent process and is markedly reduced during oxygen depletion. The constitutive level of choline transport is increased by approximately a factor of three after a brief induction period. Two other gram-negative bacteria also accumulate choline, whereas a gram-positive bacterium, Bacillus subtilis, and a yeast, Saccharomyces cerevisiae, fail to show any detectable accumulation.
The Two-Dimensional Potential Equation

In this chapter we wish to discuss some aspects of the potential equation $$ {{u}_{{xx}}} + {{u}_{{yy}}} = 0, \left( {x,y} \right) \in R,$$ (1) $$u = g\left( {x,y} \right), \left( {x,y} \right) \in \Gamma$$ (2) where Γ is the boundary of the region R in figure 1.
DBrev: Dreaming of a Database Revolution

The database community has provided excellent frameworks for ecient querying and online transaction or analytical processing. The main assumption underlying most of these frameworks is that there is no uncertainty regarding the stored data. However, in recent years, many important applications have emerged that need to manage noisy, corrupted, or incomplete data. This includes, e.g., anonymized data, data derived from sensor systems, or data from information extraction and integration systems. For such applications the assumption of logical consistency may not be valid and needs to be revised. In particular, techniques like probabilistic modelling and statistical inference may be necessary to be able to draw meaningful conclusions from the underlying data. This paper presents DBrev, a hypothetical, intelligent database system for managing large quantities of data that involves uncertainty. We explain the main features of DBrev based on the scenario of information extraction and integration. We point out research challenges that need to be tackled and discuss a new set of assumptions that future database management frameworks need to build on.
EHR-based Visualization Tool: Adoption Rates, Satisfaction, and Patient Outcomes

Background: Electronic health records (EHRs) have the potential to enhance patient-provider communication and improve patient outcomes. However, in order to impact patient care, clinical decision support (CDS) and communication tools targeting such needs must be integrated into clinical workflow and be flexible with regard to the changing health care landscape. Design: The Stroke Prevention in Healthcare Delivery Environments (SPHERE) team developed and implemented the SPHERE tool, an EHR-based CDS visualization, to enhance patient-provider communication around cardiovascular health (CVH) within an outpatient primary care setting of a large academic medical center. Implementation: We describe our successful CDS alert implementation strategy and report adoption rates. We also present results of a provider satisfaction survey showing that the SPHERE tool delivers appropriate content in a timely manner. Patient outcomes following implementation of the tool indicate one-year improvements in some CVH metrics, such as body mass index and diabetes. Discussion: Clinical decision-making and practices change rapidly and in parallel to simultaneous changes in the health care landscape and EHR usage. Based on these observations and our preliminary results, we have found that an integrated, extensible, and workflow-aware CDS tool is critical to enhancing patient-provider communications and influencing patient outcomes.
Capacity Cost Allocation in the Provision of Urban Public Services: The Case of Gas Distribution

This paper analyzes the pattern of price discrimination and cross-subsidization that result from traditional gas distribution cost allocation procedures. A gas distribution capital cost function is developed, using the Box-Cox transformation and estimation procedure applied to a cross-section of 65 communities, and is used to assess the deviations between distribution marginal costs and actual cost allocations. The major conclusions are that current pricing practices produce an aggregate net subsidy to all combined customer classes, that both intra- and inter-class cross-subsidizations are occurring, with the commercial and small industrial markets as the major losers, and that the smaller communities tend to subsidize the larger ones. These results support a move away from current, company-level pricing practices towards locally differentiated pricing.
The Transformations T, CP and CPT in the Presence of Vacuum Degeneracy

On etudie les effets de la degenerescence du vide sur des concepts relies aux transformations impropres CP et T. On considere deux types de degenerescence
Characterization of the binding properties and physiological action of divalinal-angiotensin IV, a putative AT4 receptor antagonist

Abstract Divalinal-Ang IV [Vψ(CH 2 -NH 2 )YVψ(CH 2 -NH 2 )HPF] is being employed increasingly as a specific AT 4 antagonist. This use, which necessitates a comprehensive physiological and pharmacological evaluation of Divalinal-Ang IV's functional and receptor binding characteristics in order to ensure its efficacy and specificity, was the stimulus for this study using bovine adrenal membranes. [ 125 I]Ang IV and [ 125 I]Divalinal-Ang IV were shown to bind with high affinity to a similar number of binding sites, suggesting that both bound the same receptor. This notion was verified by competition curves using [ 125 I]Ang IV and [ 125 I]Divalinal-Ang IV that indicated identical rank order affinities for several angiotensin-related peptides and 100% cross-displacement by Ang IV and Divalinal-Ang IV. Furthermore, an autoradiographic comparison of [ 125 I]Ang IV and [ 125 I]Divalinal-Ang IV in 20 μm sections of bovine adrenals revealed near identical binding distributions characterized by heavy binding in the glomerulosa layer and the medulla. Physiological studies in which test compounds were injected into the internal carotid of the rat and cerebral blood flow (CBF) was measured by laser Doppler flowmetry indicated that pretreatment with Divalinal-Ang IV, but not DuP 753 or PD123177, blocked the increased flow observed with Ang IV infusion. Conversely, DuP 753, but not Divalinal-Ang IV or PD123177, inhibited the decrease in flow witnessed with Ang II. Metabolic stability studies utilizing rat kidney homogenates as a peptidase source, demonstrated that the structural changes present in Divalinal-Ang IV greatly increased its resistance to metabolism as compared to Ang IV. Together, these studies show that Divalinal-Ang IV is a stable, efficacious and specific inhibitor of AT 4 receptors.
Chemotherapy with cytochalasin congeners in vitro and in vivo against murine models

Background Despite inherent differences between the cytoskeletal networks of malignant and normal cells, and the clinical antineoplastic activity of microtubule-directed agents, there has yet to be a microfilament-directed agent approved for clinical use. One of the most studied microfilament-directed agents has been cytochalasin B, a mycogenic toxin known to disrupt the formation of actin polymers. Therefore, this study sought to expand on our previous work with the microfilament-directed agent, along with other less studied cytochalasin congeners. Materials and Methods We determined whether cytochalasin B exerted significant cytotoxic effects in vitro on adherent M109 lung carcinoma and B16BL6 and B16F10 murine melanomas, or on suspension P388/ADR murine leukemia cells. We also examined whether cytochalasin B, its reduced congener 21, 22-dihydrocytochalasin B (DiHCB), or cytochalasin D could synergize with doxorubicin (ADR) against ADR-resistant P388/ADR leukemia cells, and produce significant cytotoxicity in vitro. For in vivo characterization, cytochalasins B and D were administered intraperitoneally (i.p.) to Balb/c mice challenged with drug sensitive P388-S or multidrug resistant P388/ADR leukemias. Results Cytochalasin B demonstrated higher cytotoxicity against adherent lung carcinoma and melanoma cells than against suspension P388/ADR leukemia cells, as assessed by comparative effects on cell growth, and IC50 and IC80 values. Isobolographic analysis indicated that both cytochalasin B and DiHCB demonstrate considerable drug synergy with ADR against ADR-resistant P388/ADR leukemia, while cytochalasin D exhibits only additivity with ADR against the same cell line. In vivo, cytochalasins B and D substantially increased the life expectancy of mice challenged with P388/S and P388/ADR leukemias, and in some cases, produced long-term survival. Conclusion Taken together, it appears that cytochalasins have unique antineoplastic activity that could potentiate a novel class of chemotherapeutic agents.
Relation of baseline plasma ADMA levels to cardiovascular morbidity and mortality at two years in men with diabetes mellitus referred for coronary angiography.

Abstract Background Patients with diabetes mellitus (DM) have been shown to have higher levels of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of endothelial nitric oxide (NO) synthase. Higher plasma levels of ADMA have been implicated in the pathogenesis of endothelial dysfunction and atherosclerosis by lowering NO levels. High baseline plasma levels of ADMA in patients with DM have been shown to predict diabetes related complications. However, there are limited data on the prognostic significance of baseline ADMA levels in patients with established DM. Methods The present study investigated the long-term prognostic significance of baseline plasma ADMA levels in a well-characterized cohort of 170 high-risk diabetic men with known or suspected coronary artery disease who were referred for coronary angiography. All patients were followed prospectively for the development of vascular outcomes, including all-cause mortality. Results After controlling for a variety of baseline variables (including established biomarkers such as hs-CRP and fibrinogen), plasma ADMA levels (analyzed as the upper tertile of baseline values compared with the lower two tertiles) were a strong and independent predictor of all-cause mortality (HR 2.63, 95% CI 1.13–6.11, p =0.0247) when using a Cox proportional hazards model. In addition, baseline ADMA values were also an independent predictor of the composite outcome of all-cause mortality or MI (fatal or non-fatal) (HR 2.44, 95% CI 1.26–4.72, p =0.0079), as well as the composite outcome of all-cause mortality, MI (fatal or nonfatal), or stroke (HR 2.00, 95% CI 1.10–3.62, p =0.0232). Conclusion These data demonstrate that elevated baseline levels of ADMA are a strong and independent predictor of cardiovascular outcomes (including all-cause mortality) in patients with DM.
NMR studies of p-dioxene oriented in two lyotropic mesophases

Abstract Proton magnetic resonance spectra of p -dioxene oriented in two different lyotropic mesophases as well as natural abundance 13 CH satellite and carbon-13 spectra of dioxene have been obtained and analyzed. Orientational parameters and the out-of-plane twist angle were determined from the liquid crystalline spectra. The twist angle was compared with a value determined from extended Huckel calculations.
Alkali-negative-ion – molecule collisions

Absolute total cross sections for electron detachment and charge transfer (including dissociative charge transfer) have been measured for collisions of ${\mathrm{Na}}^{\mathrm{\ensuremath{-}}}$ and ${\mathrm{K}}^{\mathrm{\ensuremath{-}}}$ with ${\mathrm{H}}_{2}$, ${\mathrm{D}}_{2}$, ${\mathrm{N}}_{2}$, ${\mathrm{O}}_{2}$, CO, ${\mathrm{CO}}_{2}$, and ${\mathrm{CH}}_{4}$ targets. The collision energies of this investigation range from the energetic thresholds for detachment up to 300 eV (in the laboratory frame). In this energy range, electron detachment is observed to be the dominant process for all of the targets except ${\mathrm{O}}_{2}$. For several of these systems, a simple optical model can be used to reproduce the observed values of the cross sections for detachment. In the case of the ${\mathrm{CO}}_{2}$ target, some of the detached electrons appear to be due to charge transfer to metastable ${\mathrm{CO}}_{2}$${\mathrm{}}^{\mathrm{\ensuremath{-}}}$. Significant isotope effects are observed for the ${\mathrm{H}}_{2}$ and ${\mathrm{D}}_{2}$ targets.
NASA's advanced multimission operations system: a case study in software architecture evolution

Virtually all software systems of significant size and longevity eventually undergo changes to their basic architectural structure. Such changes may be prompted by new feature requests, new quality attribute requirements, changing technology, or other reasons. Whatever the cause, software architecture evolution is commonplace in real-world software projects. However, research in this area has suffered from problems of validation; previous work has tended to make heavy use of toy examples and hypothetical scenarios and has not been well supported by real-world examples. To help address this problem, this paper presents a case study of an ongoing effort at the Jet Propulsion Laboratory to rearchitect the Advanced Multimission Operations System used to operate NASA's deep-space and astrophysics missions. Based on examination of project documents and interviews with project personnel, I describe the goals and approach of this evolution effort, then demonstrate how approaches and formal methods from previous research in architecture evolution may be applied to this evolution while using languages and tools already in place at the Jet Propulsion Laboratory.