cssi/SciSciGPT-SciSciNet huggingface dataset:
International Protection of the Rights of the Individual Against Oppression by His Own State

After separate presentations of the general systems of international law as developed by Grotius and Vattel, it is necessary to compare the two authors in the specific field of this investigation. How would Grotius or Vattel solve certain problems which, according to the present exigencies of international life, involve the individual as such? While one could deal with a variety of problems, this comparison will be limited to one particular field, to the possibility of international protection of the rights of the individual against oppression by his own state.
An Improved API and User Experience for the Mortar Testbed

The lack of access to real-world building data has long been a significant barrier to the development and evaluation of robust applications and analyses that operate on the built environment. The Mortar platform is an open testbed for portable building analytics containing timeseries data for over 100 buildings as well as rich semantic descriptions of the assets and data sources in buildings. Access to Mortar's data is performed through an API which enforces a staged application architecture intended to simplify the development and deployment of analytics applications across a large number of buildings. In practice, users felt overly constrained by the structure enforced by the API and needed a mechanism for discovering the data available in the testbed. In this demonstration, we present (1) an improved, declarative, API for Mortar that decouples application structure from data access, and (2) an interactive query builder interface that assists users in data discovery and in authoring Brick models.
Christian Landlords: Sinners Need Not Apply

As practicing Christians, Kevin Thomas and Joyce Baker refuse to rent their residential properties in Anchorage, Alaska, to unmarried couples. Their refusal is based on the belief that facilitating extramarital sex is sinful. This tenet of their Christian faith, however, places them in direct conflict with state and city laws that prohibit discrimination on the basis of marital status.
MANOVA: A Procedure Whose Time Has Passed?:

Multivariate analysis of variance (MANOVA) is a statistical procedure commonly used in fields such as education and psychology. However, MANOVA’s popularity may actually be for the wrong reasons. T...
Experimental acidification increases susceptibility of Mercenaria mercenaria to infection by Vibrio species.

Abstract Ocean acidification alters seawater carbonate chemistry, which can have detrimental impacts for calcifying organisms such as bivalves. This study investigated the physiological cost of resilience to acidification in Mercenaria mercenaria, with a focus on overall immune performance following exposure to Vibrio spp. Larval and juvenile clams reared in seawater with high pCO2 (~1200 ppm) displayed an enhanced susceptibility to bacterial pathogens. Higher susceptibility to infection in clams grown under acidified conditions was derived from a lower immunity to infection more so than an increase in growth of bacteria under high pCO2. A reciprocal transplant of juvenile clams demonstrated the highest mortality amongst animals transplanted from low pCO2/high pH to high pCO2/low pH conditions and then exposed to bacterial pathogens. Collectively, these results suggest that increased pCO2 will result in immunocompromised larvae and juveniles, which could have complex and pernicious effects on hard clam populations.
Hilar lymphadenopathy, a novel finding in the setting of coronavirus disease (COVID-19): a case report.

As the outbreak of coronavirus disease 2019 (COVID-19) has progressed, computed tomography has emerged as an integral part of the diagnosis alongside reverse transcriptase–polymerase chain reaction assays. Frequently encountered imaging findings include peripheral airspace consolidations; bilateral ground-glass opacities; and, less commonly, cavitation. Hilar lymphadenopathy is a rarely reported finding in the setting of COVID-19. A 73-year-old Caucasian woman presented to our hospital with fever and fatigue. She had a maximum body temperature of 102.3 °F with lymphopenia and thrombocytopenia. She was diagnosed with severe acute respiratory syndrome coronavirus 2 infection on the basis of a positive result from a reverse transcriptase–polymerase chain reaction of a nasopharyngeal swab sample. Contrast-enhanced chest computed tomography revealed multifocal, subpleural ground-glass opacities with nodular consolidations bilaterally. Computed tomography also demonstrated atypical bilateral hilar lymphadenopathy, a rarely reported imaging feature of COVID-19. Chest computed tomography 1 month before the presentation did not show focal consolidations or lymphadenopathy. This indicated that the findings were due to the patient’s severe acute respiratory syndrome coronavirus 2 infection. She received 5 days of oral hydroxychloroquine and experienced resolution of her symptoms. Chest computed tomography has been used extensively to diagnose and characterize the distinguishing radiological findings associated with viral pneumonia. It has emerged as an integral part of the diagnosis of COVID-19 alongside reverse transcriptase–polymerase chain reaction assays. Clinicians must be aware of uncommon clinical and radiological findings in order to diagnose this entity. Hilar lymphadenopathy is commonly seen with fungal infections, mycobacterial infections, and sarcoidosis. An extensive literature review found that bilateral hilar lymphadenopathy has not been reported in the setting of COVID-19. More data are needed to establish the clinical impact of this novel finding.
Attachment, acculturative stress, and mental health of Mexican immigrants

Mexican immigrants in the United States (US) account for 11.4 million individuals, yet little psychological research has examined the role of adult attachment on their acculturation experience and ...
The redesign of an advanced practice registered nurse professional evaluation process and tool at a midwest academic medical center: A pilot project.

BACKGROUND Inconsistency and a lack of clarity exist regarding the advanced practice registered nurse peer review process in hospitals throughout the country. LOCAL PROBLEM The current APRN peer review process in place for over a decade at an academic medical center has never been evaluated, and neither fulfills ongoing professional practice evaluation requirements nor meets the expectations of peer review. METHODS Pre-post intervention quality improvement project (Standards for Quality Improvement Reporting Excellence checklist). INTERVENTIONS Using current professional standards and guidelines that meet the requirements for ongoing professional practice evaluation and nursing peer review, a redesigned process and tool was created and piloted in three specialty groups of nurse practitioners (NPs) at the medical center. Satisfaction before and after the pilot survey was measured using a Likert-type scale, and results were compared and analyzed following the completion of the pilot survey. RESULTS The posttest measure revealed a statistically significant improvement in satisfaction with the redesigned professional evaluation tool compared with the prepilot peer review tool. CONCLUSIONS The redesign project demonstrated that using current professional standards and guidelines, a comprehensive process and tool for professional evaluation and peer review is achievable across NP specialties.
A Neural Marker of Speech Intention: Evidence From Contingent Negative Variation

Purpose This study investigated whether changes in brain activity preceding spoken words can be used as a neural marker of speech intention. Specifically, changes in the contingent negative variati...
Antitrust concerns in Ad-Tech: formalizing the combined effect of multiple conducts and behaviours

We present an economic model of competition in the ad tech “stack”. We use this model to understand how the complex web of conducts implemented by Google – and under scrutiny by both U.S. and Europ...
A Proof-of-Concept Study on Utilizing a Novel Non-invasive Sensor for Detection of Thin Biofilm in Simulated Water Pipes

A novel acoustic real-time detection of sub-wavelength biofilm in simulated water pipes is presented in this study. The novelty of this technique is that it requires no need for secondary methods to validate the receiver data and requires sensors with lower frequency compared to 20 MHz ultrasound sensor. The significance of this technology is that biofilms are of concern in many industries, such as healthcare, water, food, and others, leading to loss of profits, high downtime, and health concerns. Therefore, the quicker biofilm can be monitored, the greater the chances to avoid these issues. In this study, voltage and phase shifts of a pair of sensors positioned on each side of plastic chambers simulating water pipes were evaluated when random materials were positioned in between the sensors indicating their ability to detect materials with thickness greater than 40 µm, suggesting that the sensor arrangement can be used to detect biofilm of thickness greater than 40 µm in a closed piping system. Further, experiments performed with biofilm simulated by PolyHEMA and actual Escherichia coli (E. coli) bacteria biofilm indicated that as the thickness of the testing medium changes, the phase shift and the voltage levels change in response, indicating the ability of the sensors to detect not only the presence of biofilm, but also its growth. Real-time monitoring of the system provides instantaneous results thus enabling the user to take quick actions on controlling the formation of biofilm.
Less is more: Detecting clinical deterioration in the hospital with machine learning using only age, heart rate, and respiratory rate.

Abstract Aim We sought to develop a machine learning analytic (eCART Lite) for predicting clinical deterioration using only age, heart rate, and respiratory data, which can be pulled in real time from patient monitors and updated continuously without need for additional inputs or cumbersome electronic health record integrations. Methods We utilized a multicenter dataset of adult admissions from five hospitals. We trained a gradient boosted machine model using only current and 24-hour trended heart rate, respiratory rate, and patient age to predict the probability of intensive care unit (ICU) transfer, death, or the combined outcome of ICU transfer or death. The area under the receiver operating characteristic curve (AUC) was calculated in the validation cohort and compared to those for the Modified Early Warning Score (MEWS), National Early Warning Score (NEWS), and eCARTv2, a previously-described, 27-variable, cubic spline, logistic regression model without trends. Results Of the 556,848 included admissions, 19,509 (3.5%) were transferred to an ICU and 5764 (1.0%) died within 24 hours of a ward observation. eCART Lite significantly outperformed the MEWS, NEWS, and eCART v2 for predicting ICU transfer (0.79 vs 0.71, 0.74, and 0.78, respectively; p Conclusion Using only three inputs, we developed a tool for predicting clinical deterioration that is similarly or more accurate than commonly-used algorithms, with potential for use in inpatient settings with limited resources or in scenarios where low-cost tools are needed.
Gemella morbillorum- and Capnocytophaga sp.-Related Mycotic Thoracic Aortic Aneurysm and Mediastinal Abscess: An Unusual Case Report, a Treatment Challenge, and a Review of Literature.

A thoracic mycotic aortic aneurysm is an uncommon entity that can complicate mediastinal abscesses. Gemella morbillorum and Capnocytophaga sp. are oral bacteria that are very rarely encountered in this setting, especially when occurring together and with other organisms, posing a difficult treatment challenge per the available guidelines and sensitivities. We present in detail this interesting case of a multi-organism mediastinal abscess and thoracic mycotic aortic aneurysm after a previous esophagogastroduodenoscopic procedure in a 51-year-old female with known achalasia who presented with upper abdominal pain, including a successful surgical and antibiotic treatment regimen and a literature review of the involved topics.
New Species of Paralomis (Decapoda, Anomura, Lithodidae) From a Sunken Whale Carcass in the San Clemente Basin Off Southern California

Paralomis manningi, new species, is described and illustrated from two immature males recovered from remains of a whale carcass sunken at a depth of 1,922 min the San Clemente Basin off southern California. While studying the ecology of whale-fall communities on the California margin with the aid of a remotely operated vehicle, we (CRS and ARB) collected the lithodid specimens from the organic-rich axial skeleton of an 11.7-m long juvenile gray whale, Eschrichtius robustus (Lilljeborg, 1861), that had been experimentally placed at the San Clemente floor for 39 months. In general outline of body, spination, and other ornamentation, the new species seems most closely related to four species of Paralomis that were described and figured by Macpherson (1988): P. pectinata Macpherson, P. serrata Macpherson, P. cristulata Macpherson, and P. africana Macpherson. The closest resemblance is to P. cristulata. A key to identification of these species is abridged from Macpherson (1988). Five species of squat lobsters, Galatheidae, were associated with the whale skeleton; Munidopsis cascadia Ambler, M. yaquiensis Ambler, M. verrilli Benedict, M. quadrata Faxon, and a possibly undescribed species of Munidopsis.
Sojourner on Mars and Lessons Learned for Future Plantery Rovers

In this paper, the rover navigation performance is analyzed on the basis of received rover telemetry, rover uplink commands and stereo images captured by the lander cameras.
The initial step of in vitro synthesis of deoxyribonucleic acid by the T4 deoxyribonucleic acid polymerase.

Abstract In the initial step of the Goulian-Lucas-Kornberg model for the in vitro synthesis of DNA by the T4 DNA polymerase, a short sequence of nucleotides at the 3' terminus of the single stranded DNA substrate base pairs with an internal nucleotide sequence of the same strand, forming a loop. With the use of the 3' terminus as a primer, the polymerase then replicates the rest of the strand to form a hairpin structure. In this communication, evidence for a refinement of this model is presented. It appears that the loop is formed by base pairing of two internal sequences, one near the 3' terminus and one further back on the same strand. The polymerase then binds to the unpaired 3' terminus and by virtue of its hydrolytic activity degrades it exonucleolytically. When the polymerase reaches the base-paired region it reverses direction and begins incorporating nucleotides, finally yielding the hairpin structure.
Protease-Activated Receptors in Hemostasis, Thrombosis and Beyond

Protease-activated receptors (PARs) provide a mechanism by which thrombin and related proteases can regulate the behavior of platelets and other cells. Overall, the coagulation cascade and PARs together provide an elegant system that links mechanical information in the form of disruption of vascular integrity to appropriate cellular responses involved in hemostasis, inflammation, repair, and even pain perception. This talk will focus on lessons from ex vivo studies of human platelets, animal models and human clinical trials that speak to the roles of PARs in platelet activation, hemostasis and thrombosis and on work in progress that speaks to roles for this system in blood vessel formation and other processes in the vertebrate embryo.
Autonomous Mental Development by Robots and Animals

The scope of mental development includes cognitive, behavioral, emotional, and all other mental capabilities that are exhibited by humans, higher animals, and artificial systems. Computational principles of autonomous mental development in humans and the synthesis of developmental programs for robots and other artificial systems are beginning to be actively studied. Robots that develop their mental skills autonomously represent a fundamental change from the traditional paradigm for constructing intelligent machines. Support for this new field should lead to advances in science, engineering, economy, and understanding of the mind.
A study of Islamic herstory: Or how did we ever get into this mess?: To the memory of my mother, Yusra Mīdāni, who was an active, independent, and capable Muslim woman

To write about ‘Women and Islam’ is to write about a host of issues only one of which is ‘the Status of Women in Islam’. For Islam and Women have shared an enduring though often turbulent relationship throughout the patriarchal upheavals of the past 1400 years in the Arab World. To comprehend this relationship fully, we must comprehend first the socio-political conditions affecting women in the Arab peninsula before the rise of Islam, and the subsequent impact of Islam upon the lives of these women, as well as upon society as a whole. We also need to comprehend the dynamics of rising Patriarchy in the Arab World during the era of Jahiliyyah, and the ensuing power struggles among various patriarchal factions. These struggles raged for many centuries destroying most notably the original Khilf for, as the word of God, it transcends all ideology. Among these, we can distinguish two groups: those who believe that Islam as it is today is fair and just to women, and those who believe that Islam as it is pructised today is utterly patriarchal, but that true Islam is not. This latter group upholds the position that Islam is not only different from Patriarchy, but that through an historical process of cooptation, Patriarchy was able to devour Islam and quickly make it its own after the death of Prophet Muhammad.’ I should like to lend some credence to this last view regardless of whether one believes that Islam transcends all ideology. I shall not attempt to provide in this article a detailed and profound study of the relation of Women to Islam, or of Patriarchy to Islam, simply because such a study requires nothing less than rewriting Arab history from a feminist perspective. However, I do intend to provide some preliminary data to that end. It is best to approach this rich and complicated topic by focusing first on the relation between Islam and Patriarchy.
The Effects of a Pickling Process on the Reduction of Escherichia coli O157:H7, Listeria monocytogenes, Salmonella spp. and Staphylococcus aureus Inoculated onto Hard-Cooked Eggs

Traditional methods of food preservation, such as pickling, have reemerged as popular approaches for home and commercial food processing. The process of pickling hard-cooked eggs (HCE) can be an effective method of preventing the growth and survival of pathogenic microorganisms. Because of the variety of pickling processes, HCE manufacturers must validate their pickling process for Food and Drug Administration (FDA) approval and demonstrate 5-log reductions of pathogens associated with the product. In this study, a rapid one-step pickling process was evaluated for its ability to reduce Salmonella spp., Listeria monocytogenes, Staphylococcus aureus and Escherichia coli O157:H7 inoculated onto HCE for 14 days at room temperature. All pathogens inoculated onto HCE were reduced by (>5.0 logs) within 24 h and were undetectable following enrichment. The data obtained in this study may be of interest to regulatory officials and processors of HCE seeking pathogen reduction validation for their products. Practical Applications Pickling of HCE is an effective preservation method capable of preventing pathogen growth and survival. Although the use of organic acids for food preservation is not a new concept, few published studies have scientifically validated the ability of pickling methods to inhibit pathogen growth and survival on specific foods. Because of the regulatory requirements set forth by the FDA, acidified foods sold commercially must be validated through scientific studies, which demonstrate 5-log reductions of pathogens associated with the product. Previous studies have utilized a two-step pickled egg pickling process and demonstrated complete kill of various pathogens within 96 h. In this study, we evaluate a rapid one-step pickling process utilizing a reformulated pickling solution and produce a complete kill of selected pathogens within 24 h, drastically reducing the cost and increasing the efficiency of a commercial pickled egg pickling process.
The spectrum of histopathologic patterns secondary to the topical application of EMLA® on vulvar epithelium: clinicopathological correlation in three cases

EMLA(®) (eutectic mixture of local anesthetics, 2.5% each of lidocaine and prilocaine in an oil and water emulsion) is used as a topical anesthetic. We report three cases of EMLA(®) -induced histopathologic changes on the vulvar epithelium. While there are some similar histopathologic features to those reported in extragenital skin, we describe additional findings on vulvar epithelium, which, to our knowledge, have not been reported previously. The patients presented with clinical signs suggestive of lichen sclerosus or erosive lichen planus (LP), but were all confirmed histopathologically as LP. The biopsy was taken after 15 min of EMLA(®) application and intradermal injection of 1% lidocaine. Blistering prior to intradermal lidocaine and the biopsy procedure was observed in two patients. The histopathologic changes observed in the epithelium included pallor of the upper epidermis, mild spongiosis, intraepidermal subcorneal and suprabasal acantholysis, congestion of the papillary dermal capillaries and extravasated erythrocytes. Basophilic granules were present, but rare, while the necrosis with multifocal clefting was more marked than in extragenital skin. It is important to be aware of these changes occurring on genital mucosa; these may occur in the absence of clinical signs and may obscure the primary underlying pathology, thus representing a diagnostic pitfall.
Fast Scheduling of Distributable Real-Time Threads with Assured End-to-End Timeliness

We consider networked, embedded real-time systems that operate under run-time uncertainties on activity execution times and arrivals, node failures, and message losses. We consider the distributable threads abstraction for programming and scheduling such systems, and present a thread scheduling algorithm called QBUA. We show that QBUA satisfies (end-to-end) thread time constraints in the presence of crash failures and message losses, has efficient message and time complexities, and lower overhead and superior timeliness properties than past thread scheduling algorithms. Our experimental studies validate our theoretical results, and illustrate the algorithm's effectiveness.
Cell death precedes rod neurogenesis in embryonic teleost retinal development

We measured cell death in the retinas of embryonic and adult teleost fish using TUNEL staining. Following a wave of cell birth during embryogenesis that generates all retinal cell types except rods, cell death occurs in all three nuclear layers. The lack of a corresponding pattern of cell death in the growing adult margin suggests different roles for death during embryogenesis and adult neurogenesis.
Integrated hardware and software designs in mechatronics laboratory courses

Abstract Concurrent design is a concept of engineering design where all aspects of a design problem are considered simultaneously. Mechatronics is a specialization of concurrent design to problems dealing with the integration of mechanical and electrical components into specialized modular devices. This paper illustrates this concept of design through student projects drawn from the files of Mechanical Engineering microprocessor design courses at the Georgia Institute of Technology. The design projects show the integration of mechanical devices, controls concepts, electronic hardware, and microprocessor software using the concurrent design philosophy.
Acyl-CoA synthetase 2 overexpression enhances fatty acid internalization and neurite outgrowth.

During neurodevelopment neurons increase phospholipid synthesis to generate additional plasma membrane that makes up the growing neurites. Compared with most cell types, neurons contain a high percentage of the polyunsaturated fatty acids (PUFAs) arachidonic acid (AA) and docosahexaenoic acid (DHA). By utilizing PC12 cell lines as a model neuronal cell line, we examined the internalization rate of AA, DHA, and non-essential oleic acid (OA), as well as their effects on neurite outgrowth. When wild type cells were differentiated, the rate of AA and DHA internalization increased 50% more than the rate of OA internalization. When media were supplemented with AA or DHA, the average neurite length was increased by ∼40%, but supplementation with the same amount of OA had no effect. We also increased the levels of acyl-CoA synthetase-1 (ACS1) and ACS2 proteins to determine whether they contribute to PUFA internalization or neurite outgrowth. Overexpression of ACS1 increased the rate of OA internalization by 55%, and AA and DHA uptake was increased by 25%, but there was no significant change in neurite outgrowth. In ACS2-overexpressing cells, in contrast, the rate of OA internalization increased by 90%, AA by 115%, and DHA by 70%. The average aggregate neurite length in ACS2-overexpressing cells was increased by ∼40% when the media were supplemented with PUFAs, but there was no change with OA supplementation. Taken together, these results support the hypotheses that ACSs are rate-limiting for fatty acid internalization and that ACS2 enhances neurite outgrowth by promoting PUFA internalization.
Interaction of phosphatidylcholine and apolipoprotein-alanine: electron microscopic studies.

Abstract Protein-lipid complexes of apolipoprotein-alanine and phosphatidylcholine were studied by electron microscopy using the technique of negative staining. An unfractionated sonicated dispersion of phosphatidylcholine vesicles of varying size was combined with apolipoprotein-Ala without exposure to further sonication. The resulting complexes appeared as linear arrays of stacked discs varying in length from 500 to 5000 A. These stacks appeared to form by two processes: (1) by the transverse cleavage of segments of discs from multilamellar vesicles; and (2) by alignment of bilamellar vesicles into linear arrays. When fractionated bilamellar vesicles of uniform diameter (250 A) were titrated with increasing amounts of apolipoprotein-Ala, the vesicles underwent a series of morphological changes from free vesicles to stacked discs to parallel groups of stacked discs to myelin figures.
Regular Work, Underground Jobs, and Hustling: An Examination of Paternal Work and Father Involvement

This paper analyzes data from the Fragile Families and Child Wellbeing Study to examine a sample of urban fathers, a majority of whom were unwed at the time of their child’s birth. Integrating research on race/ethnicity, poverty, family, work, and crime, this study explores how fathers’ participation in regular work, underground employment, and illicit hustles is related to engagement with their children; it also investigates how these relationships vary by race. The results show that the more time fathers spend in illegal hustling, the less engaged they are with their children. In contrast, time spent working in the formal economy has a positive effect on father engagement. Importantly, the effects of work on father engagement vary by race/ethnicity. The positive relationship between fathers’ participation in regular work and engagement with children is even greater for African Americans than whites. In addition, underground work has a more positive association with father engagement for African American fathers than white fathers. Finally, hustling has a more negative effect on engagement among African American fathers than among Latino fathers.
Characterization of meningococcal polysaccharides by light‐scattering spectroscopy. IV. Molecular weight distribution of group B meningococcal polysaccharide in buffer solution

We report the first characterization of group B meningococcal polysaccharide at 28°C in 0.4M KCl and 0.05M sodium acetate at pH 5.61 and in pure water by means of light-scattering spectroscopy. In buffer solution, the weight-average molecular weight Mr = 1.46 × 105 g/mol, the Z-average radius of gyration 〈rg2〉z1/2 = 26.3 nm, the second virial coefficient A2 = (2.12 ± 0.17) × 10−4 cm3 mol/g2, and the second virial coefficient of the diffusion expansion kD ≈ 79 g/g. By using a histogram approximation on the correlation function profile analysis, we observed size fractions of two sizes with rhL/rhS = 298 A/50 A and AL/AS = 82/18, where rh and A are the respective effective hydrodynamic radius and the integrated intensity and the subscripts L and S denote the large and small size fractions. In pure water, rhL/rhS = 402 A/29 A with AL/AS = 84/16. The linewidth results are consistent with the measurements on the angular distribution of scattered intensity. Furthermore, if we take the large fraction to behave more like solid spheres, we are able to determine a molecular weight distribution of B-polysaccharide in buffer solution in a bimodal size distribution function.
Historical Perspectives on Microwave Field Theory

Microwave Field Theory furnishes the foundation for all of the microwave circuitry that made possible the great advances achieved by the microwave field. It is important to understand that microwave field theory is only a portion of electromagnetic field theory in general, and to appreciate how it is distinguished from it. In addition, the network formulation of microwave field theory has been fundamental to the rapid progress made by the microwave community; the formulation in network terms has been so intertwined with the development and understanding of the field concepts and behavior that the network formulation should be viewed as an integral part of microwave field theory. The first part of this introduction explains the point of view indicated in the above paragraph. The second part of the introduction outlines the scope of the historical review presented here.
Inhibition of P-glycoprotein Activity at the Primate Blood-Brain Barrier Increases the Distribution of Nelfinavir into the Brain but Not into the Cerebrospinal Fluid

P-glycoprotein (P-gp) expression at the rodent blood-brain barrier (BBB) limits the central nervous system (CNS) distribution of anti-human immunodeficiency virus (HIV) protease inhibitors (PIs). However, it is not clear whether P-gp activity at the human BBB is as effective as that in rodents in preventing the distribution of PIs into the CNS. If it is, inhibition of P-gp at the human BBB could increase the distribution of the PIs into the CNS and, therefore, their efficacy against HIV-associated dementia. Because the distribution of the PIs into the human brain cannot be directly measured, we conducted studies in a more representative animal, the nonhuman primate. Specifically we investigated the distribution of nelfinavir (a PI and a P-gp substrate; 6 mg/kg i.v.) into the brain and cerebrospinal fluid (CSF) of nonhuman primates (cynomolgus monkeys, Macaca fascicularis) in the presence and absence of the potent and selective P-gp inhibitor, zosuquidar, and whether changes in brain nelfinavir concentration, after inhibition of P-gp, paralleled those in the CSF. Our data indicate that nelfinavir has poor penetration into the macaque's brain and CSF, and P-gp inhibition at the BBB by zosuquidar enhanced the distribution of nelfinavir into the brain by 146-fold. However, the concentration of nelfinavir in the CSF was unaffected by coadministration of zosuquidar (p > 0.05). In conclusion, P-gp inhibition at the nonhuman primate BBB significantly enhanced the distribution of nelfinavir into the brain, and this effect was not observed in the CSF. Therefore, as is common in human studies investigating P-gp inhibition at the BBB, CSF concentration of a drug should not be used as a surrogate marker for brain drug concentration.
Modification of the positive inotropic effects of catecholamines, cardiac glycosides and Ca2+ by the orally active male contraceptive, gossypol, in isolated guinea-pig heart.

Abstract Gossypol is an orally active male contraceptive with cardio-depressant side effects. To understand the mechanism of its cardiac actions, the interaction of gossypol with positive inotropic grugs was examined in isolated atrial muscle preparations obtained from guinea- pig heart. Gossypol delayed the onset of arrhythmias caused by digoxin. In the presence of gossypol, the positive inotropic effect of isoproterenol declined rapidly, and the effect of isoproterenol to increase tissue cyclic AMP concentrations was smaller. Pretreatment of atrial muscle with the combination of gossypol and isoproterenol markedly reduced effects of isoproterenol on developed tension and cyclic AMP concentrations when these effects were tested after the washout of the first dose of isoproterenol. These effects, however, were not specific to isoproterenol. The gossypol-isoproterenol pretreatment reduced the positive inotropic effect of ouabain or extracellular Ca 2+ These results indicate that gossypol has pharmacodynamic interactions with several positive inotropic agents that are known to enhance developed tension by increasing intracellular Ca 2+ transients.
Mobility of Mercury Ions in Mercury Vapor

Measurements of mercury ion drift velocities and mobilities in mercury vapor by the Hornbeck technique have been made over a range of electric-field strength divided by reduced pressure ($\frac{E}{{p}_{0}}$) from 40 to 1500 V / (cm\ifmmode\times\else\texttimes\fi{}mm Hg). Two stable mercury ions, believed to be ${\mathrm{Hg}}^{+}$ and $\mathrm{Hg}_{2}^{}{}_{}{}^{+}$, have been observed. The zero-field mobility of the two ions found by a long extrapolation gives the atomic ion ${\mathrm{Hg}}^{+}$ a zero-field mobility of 0.24\ifmmode\pm\else\textpm\fi{}0.03 ${\mathrm{cm}}^{2}$/V-sec while the molecular ion mobility is estimated at 0.45\ifmmode\pm\else\textpm\fi{}0.05 ${\mathrm{cm}}^{2}$/V-sec. The atomic ion value is in good agreement with theory; the molecular ion value is appreciably lower than the theoretical prediction. Charge exchange cross sections for ${\mathrm{Hg}}^{+}$ in Hg computed from present data are higher by a factor of nearly 1.5 than values measured directly but are qualitatively in line with rare-gas values measured by the present method. The secondary electron emission coefficient from a surface due to positive ion bombardment ${\ensuremath{\gamma}}_{i}$ has been calculated for the two cathodes used: ${\ensuremath{\gamma}}_{i}$ for molybdenum is estimated by 5\ifmmode\times\else\texttimes\fi{}${10}^{\ensuremath{-}5}$ electron per positive ion striking the cathode surface; ${\ensuremath{\gamma}}_{i}$ for an oxide-coated nickel surface is estimated at 2\ifmmode\times\else\texttimes\fi{}${10}^{\ensuremath{-}2}$ electron per positive ion striking the cathode.
Removal of Aerosol Particles and Fractional Separation of HDO-H2O During Snowstorms

Abstract The concentrations of both deuterium and water-insoluble particles in snow collected during snowstorms in the mountains of Colorado were found to be proportional to the size of snowflakes. Large snowflakes were associated with high particle concentration and high deuterium content. Small snow crystals appear to have originated in deuterium and aerosol-particle depleted air. The small snow crystals appeared at times of highest ice-forming nuclei concentration in air. The ratios of concentrations of different sized particles present in snow collected during a brief snowshower in March reveal that the predominant particles within small snow crystals are indeed those corresponding to the size range of ice nuclei. The relationship between the number of different sized particles present in a single snow crystal and the mass of snow crystals is given. Analyses of trajectories of moisture-bearing air parcels explained the large difference between the deuterium content of snow from the two snowfalls.
SU-FF-T-320: The Radiological Physics Center's Annual TLD Machine Calibration Audit and Its Impact On Clinical Trials

Purpose: Demonstrate the importance of the annual TLD machine calibration audit for clinical trial patient dosimetry.Material and Methods: The RPC TLD postal audit program, begun in 1977, currently monitors ∼14,000 megavoltage beams at ∼1700 institutions that participate in NCI sponsored cooperative group clinical trials. This TLD audit uses capsules containing LiF powder and mini‐phantoms that are shipped to institutions annually. The TLD are irradiated, returned to and read by the RPC. The TLDdose is compared to the institution's stated dose. The RPC's acceptance criterion is ±5% and results falling outside the ±5% criterion are investigated to resolve potential dosimetry errors. Results: At the 770 institutions that contribute the majority of the clinical trial patients, ∼5% of the beams audited fall outside the 5% criterion. Correspondingly, 15–20% of the institutions have one or more beams with a potential calibration error. The standard deviation of the RPC/Inst. TLD results is 2.1% about a mean of 0.999. Most institutions rarely have dosimetry errors in two consecutive years. If the frequency of the audit were to occur biennially then the number of potential errors detected would nearly double during that time period (700 vs. 1200 beams) to include ∼33% of the institutions. As the number of uncorrected calibration errors increases, the uncertainty in dose delivered to trial patients also increases. An increase in clinical trial patient dose uncertainty, even at the 2–3% level, can reduce a trial's ability to show differences between experimental arms. Conclusions: Megavoltage beam calibration is the one dosimetry parameter that is unique to each machine and highly dependent on personnel. An independent TLD annual audit serves to detect potential calibration errors. These errors can be resolved, reducing the uncertainty in the doses delivered to clinical trial patients. Work supported by CA010953, CA081647 awarded by NCI, DHHS
E3 ubiquitin protein ligase, E6-associated protein (E6-AP) regulates PI3K-Akt signaling and prostate cell growth ☆

This study elucidates the role of E6-associated protein, E6-AP (a dual function steroid hormone receptor coactivator and ubiquitin-protein ligase) in the regulation of PI3K-Akt signaling pathway, prostate gland growth and proliferation. Here, we report the generation of transgenic mice and prostate cancer cell line, LNCaP cells that overexpress E6-AP protein. Using these models we show that the levels of total Akt and phosphorylated Akt (active Akt) are increased in E6-AP overexpressing prostate gland and LNCaP cells suggesting that E6-AP regulates the PI3K-Akt signaling pathway. The prostate glands in our transgenic mice are ~20% larger and produce preneoplastic lesions at the age of 18 months. Our data also suggest that E6-AP modulates PI3K-Akt signaling pathway by both androgen-independent and -dependent mechanisms. In the androgen-independent mechanism, E6-AP modulates PI3K-Akt signaling by regulating the protein levels of RhoA, a small GTPase, which is a negative regulator of the Akt signaling pathway. Further, we show that E6-AP, a known coactivator of AR, amplifies the androgen-dependent activation of PI3K-Akt signaling pathway. In addition, we show that stable overexpression of E6-AP in prostate cancer cells results in increased cell size and proliferation. Overall our data suggests that E6-AP regulates both the positive and negative modulators of the PI3K-Akt pathway in prostate cells which results in increased prostate cell growth, proliferation and decreased apoptosis.This article is part of a Special Issue entitled The 26S Proteasome: When degradation is just not enough!
Reduction during metamorphism of four ordinary chondrites

Abstract Three type 3 chondrite finds, Willaroy, Suwahib (Buwah) and Moorabie, and one type 4 find, Cerro los Calvos, are ordinary chondrites (OC) in all respects except redox state: (a) they have OC abundances of refractory lithophiles (Cerro los Calvos data are ambiguous), Zn and other taxonomic elements, (b) they have OC matrix/chondrule abundance ratios, and their chondrule sizes are consistent with bulk-siderophile indicators of group membership—H for Willaroy and Cerro los Calvos, L for Suwahib (Buwah) and Moorabie, and (c) their oxygen isotope compositions are far closer to those of OC than to those of any other chondrite group. In each of the four chondrites the range of olivine compositions is relatively narrow; fayalite modes and means are distinctly below those of other members of their respective groups having similar or greater degrees of equilibration. The most plausible explanation of these properties is that these four OC experienced reduction during metamorphism. This is consistent with reverse zoning in olivine from one type II chondrule in Willaroy. The reducing agents may have been foreign clasts incorporated during an earlier accretional history; alternatively, these chondrites could themselves have been foreign materials incorporated into a reduced regolith. Examples of reducing clasts are the C-rich aggregates in Sharps; examples of reducing host regoliths are the host materials in Bencubbin and Cumberland Falls. Confirmation of this interpretation will require identification of the reduced foreign material or their relicts in the four reduced OC; initial searches have been unsuccessful.
Ethchlorvynol Ingestion: Interpretation of Blood Concentrations and Clinical Findings

AbstractThirty-eight patients who ingested ethchlorvynol were seen at our institution over an 8.7 year period. Eleven involved ethchlorvynol alone (“pure”) while the remainder included at least one other drug (“mixed”). Twenty-three of the patients were women. Six patients required hospitalization. Five patients were chronic users of the drug. Admission ethchlorvynol blood concentrations ranged from 3 to 46 mg/L (“pure”) and from 3 to 75 mg/L (“mixed”). For the “pure cases the most common physical findings were depressed level of consciousness (10 cases), dysarthria (7), mydriasis (6), nystagmus (6), areflexia (4), tachycardia (4), and hypotension, ataxia, and respiratory depression (2 cases each). Following “pure” ingestion, ethchlorvynol concentrations greater than 19 mg/L were usually associated with dysarthria, mydriasis, nystagmus, and tachycardia. When concentrations exceeded 38 mg/L, coma, areflexia, hypotension, and respiratory depression were generally noted as well. All patients recovered with s...
The type I human T-cell leukemia virus (HTLV-I) Rex trans-activator binds directly to the HTLV-I Rex and the type 1 human immunodeficiency virus Rev RNA response elements.

Abstract The Rex protein of the type I human T-cell leukemia virus (HTLV-I) is essential for the replication of this pathogenic retrovirus and, surprisingly, can also replace the function of the structurally distinct Rev protein of the type 1 human immunodeficiency virus (HIV-1). Rex action requires a 255-nucleotide viral RNA stem-loop structure termed the Rex RNA response element (RexRE) located in the 3' retroviral long terminal repeat. Rex function leads to the induced cytoplasmic expression of the incompletely spliced family of viral mRNAs that uniquely encode the HTLV-I structural and enzymatic proteins (Gag, Pol, and Env). Our studies now demonstrate that Rex acts by binding directly to the RexRE in a sequence-specific manner. These effects of Rex require the presence of a 10-nucleotide subregion of the RexRE that is essential for Rex function in vivo. Dominant-negative mutants of Rex also bind to the RexRE with high affinity, while a recessive-negative Rex mutant altered within its arginine-rich, positively charged domain fails to engage the RexRE. Analogously, both the wild-type and dominant-negative Rex proteins specifically bind to the structurally distinct HIV-1 Rev response element, a finding that likely underlies the respective stimulatory and inhibitory effects of these HTLV-I proteins in the heterologous HIV-1 system. However, consistent with their lack of amino acid homology, the binding sites for Rex and Rev within the HIV-1 Rev response element are distinct.
Photometric analysis of proteins and peptides at 191–194 mμ

Abstract The light absorption band of the peptide bond at 191–194 mμ has been used for quantitative measurement of purified peptides and proteins with the Beckman DBG spectrophotometer. In comparison to measurement of proteins at 280 mμ those conducted at 191–194 mμ are approximately 40–80 times more sensitive, depending on the protein. This is a significant advantage, especially in monitoring of effluents from chromatographic columns. Specific absorbance values of different proteins at 191–194 mμ vary less widely than those at 280 mμ and, therefore, in cases in which proteins cannot be analyzed in terms of nitrogen or protein weight, analysis by photometry at 191–194 mμ is subject to less uncertainty than that at 280 mμ. The average specific absorbance (A1cm1%) for 5 proteins was 686 with the Beckman DBG spectrophotometer. With this instrument we have observed direct proportionality between absorbance and concentration up to an absorbance of about 0.7. All anions except fluoride interfere since they absorb near 190 mμ. Therefore, the only electrolytes which can be used in appreciable concentration are those containing fluoride as anion.
Attribute Illumination of Basement Faults, Cuu Long Basin, Vietnam

Geometric attributes such as coherence and curvature have been very successful in delineating faults in sedimentary basins. While not a common exploration objective, fractured and faulted basement forms important reservoirs in Mexico, India, Yemen, and Vietnam. Because of the absence of stratified, coherent reflectors, illumination of basement faults is more problematic than illumination of faults within the sedimentary column. In order to address these limitations we make simple modifications to wellestablished vector attributes including structural dip and azimuth, amplitude gradients, and maximum and minimum curvature, to provide greater interpreter interaction. We apply these modifications to better characterize faults in the granite basement of the Cuu Long Basin, Vietnam, that form an unconventional, but very important oil reservoir.
Flow and Heat Transfer of a Stably Stratified Fluid Through an Enclosure

The flow of a stably stratified fluid, or thermocline, through a cubical enclosure with: (a) strongly conducting; and (b) weakly conducting side-walls, was investigated experimentally. The flow Peclet number and enclosure aspect ratio were varied in the experiment. Flow visualization revealed buoyancy-affected motions in both side-wall configurations. During the charging period of an energy storage cycle, for the strongly conducting side-wall case, axial heat conduction along the side-wall induced an upward-directed buoyant force on the fluid adjacent to the wall in the lower (colder) part of the enclosure. This was in contrast to a downward-directed force on near-wall fluid in the weakly conducting side-wall case. However, the motions induced by the forces were relatively weak compared to the main flow, and in the weakly conducting wall case appeared to be confined to thin fluid layers adjacent to the enclosure side-walls. The cumulative influence of buoyant forces was most noticeable for long times, in flows with small Peclet number and conducting side-walls. Measurements of temperature and of the energy storage performance characteristics of the thermocline were made as a function of time. Predictions of these quantities based on the analytical solution of the transient, one-dimensional, energy conservation equation are in goodmore » agreement with the measurements.« less