cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract B071: Validating sequence similarity-driven neoepitope fitness models via immunogenomics on TCGA and multiregional tumor data

Clonal fitness and survival models for checkpoint blockade response prediction have recently been proposed on the basis of ranking neoepitopes via an interaction between a proxy of T-cell recognition, a nonlinear function of neoepitope sequence similarity to known antigens, and neoantigen relative MHC binding affinity. In this work we examine the SKCM (n = 337) and NSCLC (n = 305) TCGA datasets to explicitly test if sequence similarity to known antigens from the IEDB is associated with tumor infiltrating lymphocyte (TIL) burden in patients, as measured by TCR sequencing and CDR reconstruction in RNA-seq data. We find that there is no statistically significant association between either the inferred clonality or magnitude of TIL response and neoepitope sequence similarity to known antigens. We do, however, find significant, moderate associations of TIL response to neoepitope burden. Further, we examined the LIHC (n = 193) and UCEC (n = 245) TCGA cohorts to explicitly derive tumor and virally derived epitopes (HepB, HPV respectively) and ranked their relative predicted MHC binding affinity profiles. We find a greater MHC binding affinity bias exists towards neoepitopes compared to virally derived peptides in a natural setting where both viral and tumor antigens are simultaneously present. Moreover, we find low and significant associations between TIL burden and overall neoepitope burden, but no association with overall viral epitope or expression burden. Finally, we used multiregionally sampled data (12 patients, 72 regions) from HepB-positive HCC liver cancer patients to confirm preferential MHC binding affinity and TIL response bias towards neoepitopes still holds and is significant. Our results suggest that neoepitopes dominate in their recruitment potential of, and association with, TIL burden compared to viral-cofactors. They also suggest that neoepitope sequence similarity to known antigens does not recapitulate patient TIL burden to first approximation. Citation Format: Adrian Bubie, Nicholas Akers, Augusto Villanueva, Bojan Losic. Validating sequence similarity-driven neoepitope fitness models via immunogenomics on TCGA and multiregional tumor data [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B071.
Usefulness of a Positive Psychology-Motivational Interviewing Intervention to Promote Positive Affect and Physical Activity After an Acute Coronary Syndrome.

Most patients are not able to achieve recommended levels of physical activity following an acute coronary syndrome (ACS). Existing interventions to promote activity have not focused on promoting psychological well-being, which is independently linked to superior cardiac health. To address this gap, we developed and tested a combined positive psychology-motivational interviewing (PP-MI) intervention in post-ACS patients to assess its feasibility and explore potential benefits in an initial randomized trial. We compared a 12-week, phone-delivered, PP-MI intervention to an attention-matched, MI-based health education control condition among 47 post-ACS patients with low baseline health behavior adherence. Feasibility/acceptability were assessed through rates of session completion and participant session ratings; we also explored between-group differences in positive affect, other self-reported outcomes, and accelerometer-measured physical activity, through mixed effects regression models, at 12 and 24 weeks. PP-MI participants completed a mean of 10.0 (standard deviation 2.2) sessions (84%), and mean participant ratings of sessions’ ease/utility were >8/10, above a priori thresholds for success. Compared with the control condition, PP-MI was associated with greater improvements in positive affect at 12 and 24 weeks (12 weeks: estimated mean difference [EMD] = 3.90 [SE = 1.95], p = 0.045, effect size [ES] = 0.56; 24 weeks: EMD = 7.34 [SE = 2.16], p In conclusion, PP-MI was feasible in post-ACS patients and showed promising effects on well-being and physical activity; additional studies are needed to confirm these findings.
Eicosanoid Synthesis in Mammary Tumors of Rats Fed Varying Types and Levels of N-3 and/or N-6 Fatty Acids

In previous studies (1,2), we have shown that the incidences of dimethylbenzanthracene (DMBA)-induced mammary tumors are decreased in animals fed diets containing the n-6 fatty acid, gammalinolenic acid (GLA) as contained in primrose oil (PO); and the n-3 fatty acids contained in menhaden oil (MO). Synthesis of eicosanoids was decreased in mammary fat pads of control rats and in mammary tumors of DMBA-treated rats by feeding high fat diets containing the n-3 fatty acids. Feeding a GLA source increased the ratio of monoenoic to dienoic eicosanoids compared to feeding either 20% corn oil (CO) or MO diets (2). In a study designed to explore mechanism(s) by which n-3 and/or n-6 polyunsaturated fatty acids (PUFAs) inhibit or promote mammary tumorigenesis, difluoromethylornithine (DFMO) and/or indomethacin were given during mammary tumor promotion in rats fed high n-3 and/or n-6 fat diets (3). This study demonstrated that diets containing high n-6 fatty acids enhance synthesis of cyclooxygenase, lipoxygenase, and ornithine decarboxylase (ODC) in mammary tumors. However, promotion of tumorigenesis by a 20% corn oil diet was not inhibited by blocking cyclooxygenase and/or ODC activities without significantly blocking 5-lipoxygenase. The combination of DFMO with a diet containing an n-3/n-6 fatty acid ratio of 1.2 profoundly inhibited (72%) tumor promotion. This study demonstrated that simultaneous inhibition of the arachidonic acid cascade (both cyclooxygenase and lipoxygenase) as well as polyamine synthesis may be necessary to achieve the greatest inhibition of tumorigenesis. The present study was designed to determine the optimal levels of n-3 fatty acids and/or GLA needed in a 20% fat diet to significantly inhibit mammary tumor promotion.
Metabolic Regulation of Ion Channels

During the last 30 years a great deal of progress has been made in our understanding of how neurotransmitters can regulate the activity of excitable cells. Much of our knowledge has come from studies on the vertebrate neuromuscular junction, in part because the preparation is easily accessible for experimental manipulation, but perhaps more importantly because a series of brilliant investigators have made it the focus of their highly imaginative studies. The resulting body of work has given us a detailed molecular picture of the nicotinic acetylcholine receptor/channel as a single macromolecular complex that can both bind acetylcholine and mediate the transport of ions across the plasma membrane. The opening of the channel (and transport of ions) is rapid in onset after the binding of acetylcholine to the receptor and is rapidly reversible when the receptor is no longer occupied by the agonist. Figure 1A summarizes schematically this way of thinking of rapidly reversible changes in the activity of an ion channel as being dependent on the continued occupation of a closely associated receptor by an agonist.
Race, Culture and Disability: Rehabilitation Science and Practice

Race, Culture and Disability: Rehabilitation Science and Practice is a guide to understanding the research and practical implications related to race, culture and disability in rehabilitation science. Edited and contributed by leading experts, this multidisciplinary work examines the intersection of the constructs of race, culture and disability in order to identify strategies for improving the effectiveness of rehabilitation practice with ethnic minority consumers. This text is an extremely timely and relevant contribution for students, researchers, and practitioners in the rehabilitation fields. Key topics covered include disability identity, psychological testing, evidence-based practice, community infrastructure, employment issues and much more.
Presidential Review: The President’s Statutory Authority Over Independent Agencies

Many presidents have been interested in asserting authority over independent regulatory agencies, such as the Federal Trade Commission, the Federal Communications Commission, the Nuclear Regulatory Commission, the Securities and Exchange Commission, and the Federal Reserve Board. The underlying debates raise large constitutional questions, above all about the meaning and justification of the idea of a “unitary executive.” In the first instance, however, the president’s authority over independent agencies depends not on the Constitution, but on a common statutory phrase, which allows the president to discharge the heads of such agencies for “inefficiency, neglect of duty, or malfeasance in office.” This phrase – the INM standard – is best understood to create a relationship of presidential review and a particular remedy for legal delinquency flowing from that review. It allows the president to discharge members of independent agencies not only for laziness and torpor (“inefficiency”) or for corruption (“malfeasance”), but also for neglect of their legal duty, which includes clearly erroneous decisions of policy, law, or fact, either repeatedly or on unusually important matters. Connecting this understanding to the Take Care Clause, we reject both a minimalist approach, which deprives the president of any kind of decisionmaking authority over policy made by independent agencies, and also a maximalist approach, which would treat the independent agencies as essentially identical to executive agencies, in terms of presidential oversight authority. This approach has strong implications for how to understand the President’s supervisory authority over the independent agencies; it suggests that he has such authority insofar as he is attempting to ensure against “neglect of duty” but not if he is displacing their policymaking discretion.
FDA approved calcium channel blockers inhibit SARS CoV 2 infectivity in epithelial lung cells

Abstract COVID-19 has infected more than 22 million people worldwide causing over 750.000 deaths. The disease is caused by the severe acute respiratory syndrome coronavirus (CoV) 2 (SARS-CoV-2), which shares a high sequence similarity to SARS-CoV. Currently there are no vaccinations available to provide protection and the only antiviral therapy in active use in patients is remdesivir, which currently provides only limited benefit. Hence, there is an urgent need for antiviral therapies against SARS-CoV2. SARS-CoV requires Ca2+ ions for host cell entry and based on the similarity between SARS-CoV and SARS-CoV-2 it is highly likely that the same requirements exist for the two viruses. Here, we tested whether FDA-approved calcium channel blocker (CCB) drugs are efficacious to inhibit the spread of SARS-CoV-2 in cell culture. Our data shows that amlodipine, felodipine, and nifedipine limit the growth of SARS-CoV-2 in epithelial kidney (Vero E6) and epithelial lung (Calu-3) cells. We observed some differences in the inhibition efficacy of the drugs in the two different cell lines, but with felodipine and nifedipine having the greatest effect. Overall, our data suggest that CCBs have a high potential to treat SARS-CoV-2 infections and their current FDA approval would allow for a fast repurposing of these drugs.
Including Neuroscience in Social Work Education: Introducing Graduate Students to the Neurosequential Model of Therapeutics.

To fill a gap in research on the incorporation of neuroscience in social work education, this article describes Master of Social Work (MSW) student and alumni experiences learning a neuroscience-in...
Linezolid to treat urinary tract infections caused by vancomycin-resistant Enterococcus.

Background:Vancomycin-resistant Enterococcus can cause urinary tract infection. Linezolid possesses antimicrobial activity against vancomycin-resistant Enterococcus but has limited urinary excretio...
Determining the Basaltic Source Rocks of Enigmatic Cogged Stones From Southern California

Enigmatic cogged stones, found in southern California, are hand-sized Native American artifacts carved into the shape of a cogged wheel. They are found in 8,000–3,500-year-old sites, but their func...
Does the Degree of Platelet Adenosine Diphosphate and Arachidonic Acid Receptor Inhibition Correlate With the Severity of Injury in Non-Brain-Injured Trauma Patients?

BackgroundDirect correlations between platelet adenosine diphosphate (ADP) and arachidonic acid (AA) receptor inhibition have been described in the traumatic brain injury (TBI) population. Our goal...
Neoliberal nationalism: Immigration and the rise of the populist right: by Christian Joppke, Cambridge, Cambridge University Press, 2021, vii + 328 pp., $25.99 (paperback), ISBN 978-1-108-7106-3

Christian Joppke presents us with an important puzzle that is hard to resolve. On its face, it appears that neoliberalism and neonationalism are ideological and policy opposites. Nevertheless, he a...
Deleuze, a Stoic

Ryan Johnson reveals that Deleuze's provocative reading of ancient Stoicism produced many of his most singular and powerful ideas. Including previously untranslated French Stoic scholarship, Johnson unearths new possibilities for bridging contemporary and ancient philosophy.
Severe hypertriglyceridemia following sirolimus use in an infant

Inhibitors of mammalian target of rapamycin function to downregulate cell growth and proliferation and have off-label use in pediatrics for vascular malformations. Hypertriglyceridemia is a known side effect of mammalian target of rapamycin (mTOR) inhibitors. Further studies to better understand the incidence and treatment of hypertriglyceridemia in infants and neonates are warranted.
The Versailles Treaty and Its Legacy: The Failure of the Wilsonian Vision

1. The international order on trial 2. The road to Paris 3. Versailles: a study in arrogance 4. The retreat to utopia 5. Manchuria and the triumph of non-recognition 6. The rise of Hitler 7. Challenge of the dictators 8. The illusive response 9. Munich: the continuing escape from reality 10. The road to Prague 11. The Soviet quest for collective security 12. The coming of war.
Shifting Trajectories of Salafi/Ahl-Sunna Reformism in Ghana

This article explores the shifting trajectories of Salafi-inclined reforms in Ghana since the 1950s. I illustrate that Ghanaian expressions of Salafism emerged in the 1950s from local doctrinal debates between members of the Tījāniyya Sufi brotherhood and those who opposed Sufism. The opposition against the Tījāniyya evolved to become part of the worldwide Salafi reform movement. Tracing the movement’s development, I illustrate further that the Ghanaian expressions of Salafism was neither homogenous nor static in its strategies of proselytization or its doctrinal emphases. Rather, many local Salafi scholars continuously defined and sharpened their ideas and strategies to accommodate changing local and global realities. Moreover, while seeking intellectual and financial support of Salafi sponsors in the Arab world, Ghanaian Salafis remained focused on local needs. The history of Ghanaian Salafiyya will thus sharpen our knowledge of the dynamism of global Salafiyya, and the processes by which local doctrinal concerns find affinities with debates in other parts of the Muslim world.
Rhizobium trifolii 0403 Is Capable of Growth in the Absence of Combined Nitrogen.

Rhizobium trifolii 0403 was treated with 16.6 mM succinate and other nutrients and thereby induced to grow in nitrogen-free medium. The organism grew microaerophilically on either semisolid or liquid medium, fixing atmospheric nitrogen to meet metabolic needs. Nitrogen fixation was measured via 15N incorporation (18% 15N enrichment in 1.5 doublings) and acetylene reduction. Nitrogen-fixing cells had a Km for acetylene of 0.07 atm (ca. 7.09 kPa), required about 3% oxygen for optimum growth in liquid medium, and showed a maximal specific activity of 5 nmol of acetylene reduced per min per mg of protein at 0.04 atm (ca. 4.05 kPa) of acetylene. The doubling time on N-free liquid medium ranged from 1 to 5 days, depending on oxygen tension, with an optimum temperature for growth of about 30°C. Nodulation of white clover by the cultures showing in vitro nitrogenase activity indicates that at least part of the population maintained identity with wild-type strain 0403. Images
Bragg cavity polaritons in disordered planar lattices

We investigate polaritons resulting from excitons localized in arrays with energy and oscillator strength fluctuations embedded in microcavities. The polariton emission shape remains robust under oscillator strength fluctuations, but is more sensitive to energy fluctuations.
Children's Beliefs About Violating Gender Norms: Boys Shouldn't Look Like Girls, and Girls Shouldn't Act Like Boys

This research examined 3- to 11-year-old children's knowledge of and beliefs about violating several gender norms (e.g., toys, play styles, occupations, parental roles, hairstyles, and clothing) as compared to social and moral norms. Knowledge of the norms and understanding that norm violations were possible increased with age. The children's evaluations of violations of gender norms varied from item to item. Violations concerning becoming a parent of the other gender were devalued in both boys and girls, whereas most toy and occupation violations were not especially devalued in either. Boys with feminine hairstyles or clothing were evaluated more negatively than girls with masculine hairstyles or clothing. On the other hand, girls who played in masculine play styles were devalued relative to boys who played in feminine styles. Evaluations of norm violations were not consistently related to age.
Bringing Hidden Dimensions into View

Warped Passages . Unraveling the Mysteries of the Universe's Hidden Dimensions / Unravelling the Universe's Hidden Dimensions. By Lisa Randall . Ecco, New York, 2005. 512 pp. $27.95, C$37.95. ISBN 0-06-053108-8. / Allen Lane, London. £25, C$40. ISBN 0-713-99699-4. A researcher known for her argument as to how extra dimensions could be large and still hidden discusses the possibilities of proving their existence and explores their implications.
"Heart rate-dependent" electrocardiographic diagnosis of left ventricular hypertrophy.

A case is presented revealing the common phenomenon of heart rate-dependent diagnosis of electrocardiographic (ECG) diagnosis of left ventricular hypertrophy (LVH), which consists of satisfaction of LVH criteria only at faster rates whereas ECGs with a slow heart rate do not satisfy such criteria. The mechanism of the phenomenon has been attributed to the tachycardia-mediated underfilling of the left ventricle bringing the electrical “centroid” of the heart closer to the recording electrodes, which results in augmentation of the amplitude of QRS complexes, particularly in leads V2–V4. (PACE 2013; 36:e136–e137)
Application of ionospheric topside-sounding results to magnetospheric physics and astrophysics

[1] A brief review is presented to illustrate how the knowledge and experience gained from investigations of ionospheric topside-sounder ionograms has benefited scientific research beyond the ionosphere. In particular, to the interpretation of (1) natural radio emissions from space plasmas, (2) sounder-stimulated echoes and plasma emissions, and plasma diagnostics in planetary magnetospheres and (3) X-ray spectra of disks around neutron stars and black holes. The relevant data are from 60 satellite years of ionospheric topside-sounder operations by the four satellites of the International Satellites for Ionospheric Studies (ISIS) program from 1963 through 1989. Not all of these data were reduced to ionograms on 35-mm film. An ongoing effort at the NASA Goddard Space Flight Center is producing digital topside-sounder ionograms directly from a selected subset of the original telemetry tapes. More than 300,000 digital ionograms are now in the National Space Science Data Center at the NASA GSFC (http://nssdc.gsfc.nasa.gov/space/isis/isis-status.html).
Update on the Methodological Quality of Research Published in The American Journal of Sports Medicine Comparing 2011-2013 to 10 and 20 Years Prior

Background:In recent years, the number of articles in The American Journal of Sports Medicine (AJSM) has risen dramatically, with an increasing emphasis on evidence-based medicine in orthopaedics and sports medicine.Hypothesis:Despite the increase in the number of articles published in AJSM over the past decade, the methodological quality of articles in 2011-2013 has improved relative to those in 2001-2003 and 1991-1993.Study Design:Meta-analysis.Methods:All articles published in AJSM during 2011-2013 were reviewed and classified by study design. For each article, the use of pertinent methodologies, such as prospective data collection, randomization, control groups, and blinding, was recorded. The frequency of each article type and the use of evidence-based techniques were compared relative to 1991-1993 and 2001-2003 by use of Pearson χ2 testing.Results:The number of research articles published in AJSM more than doubled from 402 in 1991-1993 and 423 in 2001-2003 to 953 in 2011-2013. Case reports decreased...
Changing the face of computing

The demand for computing professionals continues to grow, while women and minorities remain severely underrepresented at all levels. This opening SIGCSE 2013 keynote asks the crucial question "What can WE do to change the face of computing?" Several answers to this question will be provided in an unusual format with the following all-star cast. Each speaker will take five minutes to share 20 slides (which automatically advance every 15 seconds) to provide a stimulating presentation that ends with "What can YOU do to change the face of computing?"
To Supplement or Not to Supplement: The U.S. Preventive Services Task Force Recommendations on Calcium and Vitamin D

In this issue, the U.S. Preventive Services Task Force plunges headlong into ongoing debates about whether healthy adults—those who show no signs of vitamin D deficiency or osteoporosis—should be a...
Oxidative phosphorylation in guinea pig mammary gland mitochondria during various functional states.

Abstract Oxidative phosphorylation was measured in the mammary gland mitochondria of guinea pigs during pregnancy, at parturition, and during lactation and retrogression. The phosphorylation concomitant with oxidation of succinate, α-ketoglutarate, and β-hydroxybutyrate was shown to be uncoupled in mitochondria from glands at all functional states except during lactation. The phosphorylative capacity could be restored by the in vitro addition of bovine serum albumin to the reaction system. Mitochondrial and microsomal fractions prepared from retrogressing guinea pig mammary glands completely uncoupled phosphorylation concomitant with oxidation of succinate in a rat liver mitochondrial preparation. The supernatant fraction from these glands had no effect on either the oxidative or phosphorylative capacity of the liver mitochondria. Preliminary evidence is presented to suggest that a specific uncoupling factor for oxidative phosphorylation is present in mammary tissue preparations during specific functional states.
Sex differences in the discriminative stimulus effects of m-chlorophenylpiperazine and ethanol withdrawal.

Rationale: The serotonergic system plays a role in regulation of anxiety and ethanol withdrawal (EW). Nevertheless, few studies have assessed sex differences in serotonergic effects on EW. Objectives: This study examined sex differences in the anxiogenic stimu-li induced by a serotonin (5-HT)1b/2 agonist, meta- chlorophenylpiperazine (mCPP), prior to ethanol and during EW. Methods: Gonadectomized or sham-operated adult male and female rats and 17β-estradiol (2.5 mg, 21-day release, s.c.) -replaced ovariectomized (OVX) rats were trained to discriminate mCPP (1.2 mg/kg, i.p.) from saline in a two-lever choice task for food. Latency to the first lever press and mCPP lever selection were measured following mCPP (0–1.2 mg/kg). Rats then received chronic ethanol-containing liquid diet (6.5%) for 10 days and were tested for mCPP lever selection 12 h and 36 h after removal of ethanol. Results: Fewer sham female and β-estradiol-replaced OVX rats selected the mCPP lever than male or OVX rats, and showed an increased initiation latency after mCPP injection. During EW (12 h and 36 h), fewer sham female and β-estradiol-replaced OVX rats responded on the mCPP-lever after saline injection as well as after mCPP challenge than male or OVX rats. Castration did not alter any response of male rats to mCPP. Conclusions: (1) mCPP discrimination is a useful measure of EW in male and female rats; and (2) sham female and β-estradiol-replaced OVX rats are less sensitive to the discriminative stimulus prior to and during EW, but more sensitive to impaired behavioral initiation induced by mCPP than male or OVX rats.
Paper: Removing the assumption of conditional independence from Bayesian decision models by using artificial neural networks: Some practical techniques and a case study

The article describes how artificial neural networks with special designs can be applied to approximate a subjective Bayesian decision model without the assumption of conditional independence. New techniques are proposed to resolve some of the practical difficulties during the processes of problem structuring, knowledge elicitation, quantitative modeling, and model interpretation. A Bayesian model considering the conditional dependencies to predict a teenager's marijuana use was constructed by experts using these techniques, and compared to another conventional Bayesian model which assumed conditional independence. The new approach without the assumption of conditional independence had predictive power (r = 0.7) in the test of linearity compared to the conventional approach (r = 0.58) on a data set (n = 129). Its receiver operating characteristic curve dominated the alternative approach within the range (true positive fraction > 0.7) that we were interested in. The interpretations of the possible conditional dependencies provided by the artificial neural network after the training process were consistent with the expert's descriptions.
Assumptions and Evidence Behind Sex Offender Laws: Registration, Community Notification, and Residence Restrictions

Since the mid-1990s legislators have enacted a series of laws regulating convicted sex offenders who have returned to communities. Policymakers crafted these laws to appease a worried public, but they were based on assumptions about sex offenders’ behaviors that were not well supported by research evidence. In this paper we examine the social context within which these laws were passed and the assumptions behind the three most common sex offender laws – mandatory registration, community notification, and residence restrictions. Next we review the research that has been conducted so far to evaluate the effectiveness of these laws and their unintended consequences. We conclude with a discussion of the lessons learned from these sex offender laws for both policymaking and future research.
What are the Odds

Abstract Students and mathematicians alike have long struggled to understand the nature of probability. This article explores the use of gambling activities as a basis for defining probabilities.
Taurine and glycine in the gills of the clam Protothaca staminea exposed to chlorinated seawater.

In the present study, individuals of the clam Protothaca staminea were exposed to chlorinated seawater for 26 days and the free amino acid levels of the gill tissue were measured. This experiment represents yet another condition of stress and a fourth bivalve species with respect to the available literature on the taurine:glycine ratio in stressed molluscs. Chlorine is commonly used as either a biocide or disinfectant in coastally located electric power plants or domestic waste treatment systems, respectively, and has been reported to adversley impact marine organisms.
Growth and protein phosphorylation in the Nb2 lymphoma: Effect of prolactin, cAMP, and agents that activate adenylate cyclase

The Nb2 T lymphoma is unique in that these lymphocytes proliferate in response to prolactin as well as in response to interleukin-2. In this study, we have examined the responsiveness of the adenylate cyclase system in Nb2 cells and the role of this signaling system in regulating proliferation and protein phosphorylation. An analog of cAMP inhibited prolactin-stimulated proliferation and blocked a prolactin-induced decrease in protein phosphorylation. Forskolin, a potent activator of adenylate cyclase in T lymphocytes, did not elevate cAMP levels in Nb2 cells and was not an effective inhibitor of prolactin-induced proliferation. In fact, one preparation of forskolin stimulated proliferation of quiescent Nb2 cells. Like forskolin, prostaglandin E2 did not stimulate cAMP production in Nb2 cells even though, it increased cAMP in a preparation of rat peripheral blood lymphocytes. Cholera toxin appeared to ADP-ribosylate a stimulatory guanine nucleotide-binding protein in Nb2 cells, but the toxin did not increase intracellular levels of cAMP nor was it a potent anti-mitogenic agent. Pertussis toxin, an agent that can increase cAMP production through suppression of the inhibitory guanine nucleotide-binding protein, exerted only minor anti-proliferative actions on prolactin-stimulated Nb2 cells. These data suggest that cAMP inhibits Nb2 cell proliferation and prolactin-induced changes in protein phosphorylation but that the adenylate cyclase system in our clone of Nb2 cells responds poorly to agents that normally increase cAMP.
Satellite observation of the subaerial growth of the Atchafalaya Delta, Louisiana

Since the early 1970s a new subaerial delta has been forming along the central Louisiana coast, an area traditionally characterized by coastal retreat. This delta of the Lower Atchafalaya River has been monitored by using data from the Landsat satellite. With these data, the formation and year-to-year growth of a major new deltaic lobe of this Mississippi River distributary have been measured for the first time. The analyses show that the formation of new land coincides with flood pulses of the river and that, as would be expected, intertidal lands below mean sea level accrete at a faster rate than lands above mean sea level. Measurements indicate that by early 1976 approximately 32.5 km 2 of new land had been formed at an average growth rate of 6.5 km 2 /yr. Delta growth initiated bay filling and shoreline progradation; the result was creation of extensive new marshlands along the south-central portion of the Louisiana coast.
Associations between drinking-water nitrate and the productivity and health of farrowing swine

Abstract The associations between nitrate contained in drinking water and farrowing swine health and productivity were examined. The study was conducted from November 1989 through February 1991 on 571 randomly selected swine farms (27 207 farrowing swine) in the United States. At the beginning and end of each farm's 3-month monitoring period, the drinking water provided to the farrowing swine was tested for nitrate. Data on farrowing swine health and productivity were observed and recorded daily by the animal caretaker. Data were analyzed on a farm basis. Nitrate was detected in 53.2% (304/571) of well-water samples, with a median concentration of 2.1 ppm. No association was seen between the nitrate concentration of drinking water and the farm litter size (P = 0.94), proportion of the pigs stillborn (P = 0.48), or the risk of having an above median percentage of the litter born mummified (OR= 1.0; 95% CI 0.99,1.00). No association was seen between nitrate and the health of farrowing swine as measured by the risk of having an above median percentage of farrowing swine ill (OR = 1.0; 95% CI 0.99, 1.00) or dead (OR = 0.99; 95% CI 0.98,1.01) due to farrowing problems, other reproductive problems (ill OR = 1.0, 95% CI 1.00, 1.01; dead OR = 1.0, 95% CI 0.98, 1.01 ), other known health problems (ill OR = 1.0, 95% CI 0.99, 1.00; dead OR= 1.0, 95% CI 0.99, 1.01), or unknown health problems (ill OR = 1.0, 95% CI 0.99, 1.01; dead OR= 1.0, 95% CI 0.99, 1.01). The results of this study indicate that nitrate contained in drinking water, at the concentrations seen during the National Swine Study, is not associated with the farrowing swine health or productivity parameters studied.
Inhibition of cyclooxygenase-2 protects motor neurons in an organotypic model of amyotrophic lateral sclerosis

The pathogenesis of motor neuron loss in amyotrophic lateral sclerosis (ALS) is thought to involve both glutamate-mediated excitotoxicity and oxidative damage due to the accumulation of free radicals and other toxic molecules. Cyclooxygenase-2 (COX-2) may play a key role in these processes by producing prostaglandins, which trigger astrocytic glutamate release, and by inducing free radical formation. We tested the effects of COX-2 inhibition in an organotypic spinal cord culture model of ALS. The COX-2 inhibitor (SC236) provided significant protection against loss of spinal motor neurons in this system, suggesting that it may be useful in the treatment of ALS.
HFIR irradiation facilities improvements — Completion of the HIFI project

Abstract The HFIR Irradiation Facilities Improvements (HIFI) Project has now been completed. In August 1986, Phase I of the project was completed, providing the capability to perform instrumented irradiation experiments in the target region of the HFIR. In June 1987, Phase II of the project was completed with the assembly in the reactor mockup of all the components necessary to operate up to eight 46-mm-diameter instrumented experiments in the removable beryllium region of the HFIR. In conjunction with the installation of Phase I components, the first instrumented target capsule was installed to determine more accurately the probable temperature in the uninstrumented target capsules previously irradiated as part of the Japan/US fusion materials program. Data from this experimant indicate close agreement with expected temperatures in all positions except those at the extreme ends of the capsule. These data provide a more accurate axial gamma heating rate profile that will allow for better design of future HFIR target irradiation capsules.
Cyst(e)ine Dependency Presenting with Growth Failure and Steatorrhea

Initial study of a first-born male Caucasian child with classical celiac syndrome failed to reveal the cause of his growth failure: birth wt. 3.0 kg, age 12 weeks 3.3 kg. At age 16 weeks the child was admitted to hospital with an acute bout of diarrhea and dehydration. On fat-free intake, steatorrhea disappeared but hyperphagia and watery diarrhea with sugar-free stools persisted. Weight gain was less than normal for age. Following oral feeding of Amigen with glucose, alopecia occurred, and blood levels of methionine, ½ cystine, and taurine were > 115, <1.5, and 3.0 μM/dl respectively. Homocysting in blood and urine, and cystathionine in blood, were undetectable by ion exchange chromatography. Cystathionine was excreted in urine at less than 15 mg daily, dietary methionine averaging 6.5 μM daily. These findings suggested a block in the conversion of methionine to homocysteine. The essential nature of cystine for growth was documented in a series of feeding experiments. Three basic diets were used, providing the percentage distribution of calories as shown in the table. Caloric intake averaged 150 cal/kg/d. Weight gain was calculated from the average weight of the day before, day of, and day after a diet change. Diet were fed at least 6 days without significant change. Catch-up growth in body length and head circumference has occurred with dietary supplementation. Mental development seems normal but physical weakness persists.
Leveraging Technology to Improve Intent to Purchase

Distribution of deceptive counterfeit goods via online marketplaces such as Amazon and eBay has introduced a particularly burdensome decision making process for the consumers. The consumers need to spend additional time in the information search step, reading product and seller reviews to assist with counterfeit detection. Automated counterfeit detection could assist with this process. This paper presents the conceptual framework that employs artificial intelligence techniques, such as natural language processing and topic analysis, in order to automatically detecting counterfeit goods. Specifically, online reviews of products and sellers can be downloaded and parsed using natural language processing. Topic analysis methods can be performed against the resulting text corpus to detect the most frequent terms in the reviews and to examine the reviews for a collection of keywords related to fraudulent products. The implications of this research are to alert consumers to potentially counterfeit products thereby increasing trust and efficiency in the online marketplace.
Numerical solutions of the Lamm equation. III. Velocity centrifugation

We have generated solutions to the Lamm equation to examine the effects of concentration dependence on velocity experiments. Two forms of c dependence are considered: s/s0 = 1 – kc and s/s0 = (1 + kc)−1. Features of these solutions are discussed. The magnitude of the errors resulting from the usual procedure of measuring the rate of movement of schlieren maxima or of the position at which the concentration is one half the plateau value have been examined. These errors are usually negligible after sufficient centrifugation time. The errors in using the half-plateau concentration are less than those using the movement of the peak. We have also examined a technique due to Fujita for determining D from boundary spreading when s/s0 = (1+kc)−1. This method is satisfactory when s/s0 is actually of this form, or under certain limitations when s/s0 = (1 + kc)−1. Creeth has shown that under certain conditions the concentration gradient, curve remains virtually unchanged in shape after separating from the meniscus. When this occurs it is possible to estimate s/D from the data. The condition for such a steady state is that kc0 be sufficiently large. Numerical confirmation of this method is presented in the final section.
Emergency Presentations of Cancer in Childhood

Childhood cancer is an important area for pediatricians and emergency physicians to have an up-to-date knowledge based on both diagnostic and therapeutic issues. Clinical cases of some common childhood cancers will be presented as the basis for the review of how these potentially lethal disorders can present. Patient assessment and initial workup and pertinent components of the differential diagnosis will be discussed. With a growing number of children successfully treated for cancer, long-term care–related issues are also reviewed. Childhood leukemia, neuroblastoma and Wilms tumor will be reviewed in more depth. The goal of this paper is to guide the reader in these relatively uncommon, although extremely important, clinical presentations of cancer in children.
Induction of basal cell carcinoma features in transgenic human skin expressing Sonic Hedgehog

Hedgehog (HH) signaling proteins mediate inductive events during animal development. Mutation of the only known HH receptor gene, Patched (PTC), has recently been implicated in inherited and sporadic forms of the most common human cancer, basal cell carcinoma (BCC). In Drosophila, HH acts by inactivating PTC function, raising the possibility that overexpression of Sonic Hedgehog (SHH) in human epidermis might have a tumorigenic effect equivalent to loss of PTC function. We used retroviral transduction of normal human keratinocytes to constitutively express SHH. SHH-expressing cells demonstrated increased expression of both the known HH target, BMP-2B, as well as bcl-2, a protein prominently expressed by keratinocytes in BCCs. These keratinocytes were then used to regenerate human skin transgenic for long terminal repeat-driven SHH (LTR-SHH) on immune-deficient mice. LTR-SHH human skin consistently displays the abnormal specific histologic features seen in BCCs, including downgrowth of epithelial buds into the dermis, basal cell palisading and separation of epidermis from the underlying dermis. In addition, LTR-SHH skin displays the gene expression abnormalities previously described for human BCCs, including decreased BP180/BPAG2 and laminin 5 adhesion proteins and expression of basal epidermal keratins. These data indicate that expression of SHH in human skin recapitulates features of human BCC in vivo, suggest that activation of this conserved signaling pathway contributes to the development of epithelial neoplasia and describe a new transgenic human tissue model of neoplasia.
Integrated System for Remediation of Contaminated Soils

A pilot-scale study was conducted to evaluate an integrated system for the remediation of soils contaminated primarily with pentachlorophenol (PCP), a wood preserver. The integrated soil remediation system consisted of three unit processes: (1) soil solvent washing; (2) solvent recovery; and (3) biotreatment of the contaminant residual. Pilot-scale countercurrent solvent washing was carried out using a 95% ethanol solution—a solvent that in an earlier bench-scale study was found to be effective in removing PCP and hydrocarbons (HCs) from soils. Three-stage countercurrent solvent washing of a field-contaminated soil was performed using batches of 7.5 kg of soil and 30 L of solvent (1 kg:4 mL soil-to-solvent contact ratio). The washed soil was rinsed with water in a single stage after three countercurrent wash stages. Pilot-scale, three-stage countercurrent solvent washing with 95% ethanol reduced the PCP and HC contamination on the soil by 98% and 95%, respectively. The spent solvent and the spent rinse water were combined as the spent wash fluid for further treatment. A pilot-scale distillation unit was used to recover the ethanol from the spent wash fluid. The HC constituents of the spent wash fluid were removed by pH adjustments prior to feeding the spent wash fluid to a distillation unit. Greater than 96% of the ethanol in the spent wash fluid was recovered in the distillate stream, whereas PCP was captured in the bottoms stream. The bottoms stream was treated sequentially in anaerobic and aerobic granular-activated carbon fluidized-bed reactors. Complete mineralization of PCP was achieved using this treatment train.
Use of spin traps in biological systems

Abstract Free radicals including superoxide have been proposed to mediate a variety of cellular responses including phagocytosis, ischemic tissue injury, aging and cancer. However, it has only been in recent years that procedures have been developed which allows one to study the role free radicals play in cellular injury. One such method that has received considerable attention is spin trapping. This technique consists of using a nitrone or a nitroso compound to “trap” the initial unstable free radical as a “long-lived” nitroxide that can be observed at room temperature using convention ESR spectrometric procedures. This review examines how a number of investigators have employed spin trapping methodologies to study the generation of free radicals as a consequence of biological activation by drugs and other foreign compounds.
Natural work groups

Explains how the collection and subsequent analysis of information on the personal interactions within an organization, and the identification of natural work groups, can provide a powerful diagnostic tool to evaluate the organizational health of a company, measuring internal customer/supplier relationships, the degree of cross‐functional working, the level of teamwork, and the dominant management style.
Evaluation of Al3Mg2 Precipitates and Mn-Rich Phase in Aluminum-Magnesium Alloy Based on Scanning Transmission Electron Microscopy Imaging

Scanning transmission electron microscopy (STEM) and energy dispersive X-ray spectroscopy (EDS) were used to observe intergranular and intragranular β-phase (Al3Mg2) formation and growth in as-received sample and long-term (~1 year) thermally treated samples of 5083-H131 alloy. Rod-shaped and equiaxed particles rich in Mn, Fe, and Cr were present in the as-received and heat treated samples. The β-phase precipitated along grain boundaries as well as around and between preexisting Mn-Fe-Cr rich particles. The measured thickness of β-phase along grain boundaries was lower than Zener–Hillert diffusion model predicted value and the potential reasons were theoretically analyzed. Dislocation networks, grain boundaries, and different preexisting particles were observed to contribute to Mg diffusion and β-phase precipitation.
Reply to 'Does neutrophil CD38 have a role in Ca ++ signaling triggered by β 2 integrin?'

Reply to 'Does neutrophil CD38 have a role in Ca ++ signaling triggered by β 2 integrin?'
Bovine Serum Lipid Analysis

Abstract An improved technique was devised for complete analysis of bovine blood serum. Three milliliters of blood serum were lyophilized and then extracted in a Soxhlet apparatus with chloroform: methanol 2:1. The extract was evaporated to dryness, and taken up in petroleum ether. A portion of the extract was removed for total lipid analysis. The lipid fractions were separated by using 1g of silica gel G packed in a micro-column. The fractions were forced through the column with nitrogen. The elution solvents and fractions were as follows: I. 20ml of 1% ethyl ether in petroleum ether (cholesterol esters). II. 27ml of 10% ethyl acetate in petroleum ether (triglycerides and free cholesterol). III. 25ml of ethyl ether (free fatty acids, mono-, and diglycerides). IV. 30ml glacial acetic acid :methanol :ethyl ether 4:9:27 (phospholipids). In preparation for gas chromatography, total lipids and Fractions I and II were first saponified before methylation. Fractions III and IV were methylated without further preparation. All were extracted with petroleum ether from an aqueous solution, evaporated to dryness, and made up in 27 μ l of hexane. Three microliters of this solution were then analyzed by gas-liquid chromatography for individual fatty acids.
A Parameter-Driven Router

We describe a routing algorithm which is adjustable in its operation. The routing medium is composed of cells with variable parameters such as depth, via density, channel density, etc. Routing is carried out within these parametric bounds on an abstract board, which is then mapped to the physical board in a postprocessing step. The internal details of the routing process are presented. Some results are presented which show the influence of placement, channel density and layering on routability.
Induction of Alzheimer-specific tau epitope AT100 in apoptotic human fetal astrocytes

In Alzheimer's and other neurodegenerative diseases, hyperphosphorylated tau accumulates in affected neuronal and glial cells in the form of paired helical filaments (PHFs). This tau binds antibody AT100, which recognizes the double phosphorylation site (Thr212/Ser214) that is not present in normal biopsy tau. In primary cultures, highly enriched (>98%) in astrocytes of human fetal brain, three polypeptides of 52, 64, and 70 kD showed immunoreactivity with tau antibodies against non-phosphorylated epitopes, accounting for 88, 12, and <1%, respectively, of the total reactivity. All three polypeptides were phosphorylated at the PHF-1 epitope but not at the epitopes Tau-1, 12E8, AT8, and AT100. Treatment of cultures with okadaic acid resulted in apoptosis characterized by the blebbing of the plasma membrane, condensation of nuclear chromatin, and fragmentation of the nucleus. This treatment also resulted in a 3- to 5-fold increase in the content of both tau protein and phosphorylation. The increases were observed in all phosphorylation sites examined, and included the AT100 site. The AT100 site has been proposed to be generated by protein kinase B/Akt and Cdc2. Since okadaic acid can induce an AD-like hyperphosphorylated state of normal tau in primary cultures of human brain cells, a simple cellular model is available permitting study of self-aggregation of tau and phosphorylation events characteristic of neurodegeneration.