cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract IA26: Learning from and Addressing Racial and Ethnic Disparities in Cancer Clinical Trials: The ECOG-ACRIN Experience

Although breast cancer incidence and mortality have declined by about 35% in the United States since 1990, mortality rates have declined less in Black women, contributing to a widening of the racial gap which has contributed to about a 35% higher mortality rate for Black women compared with others. Black women are more likely to present with advanced stage disease, have triple negative breast cancer (TNBC), exhibit greater non-adherence and poorer tolerance to chemotherapy and endocrine therapy, and have more comorbidities and experience more disparities in care. With regard to ethnicity, Hispanic women also exhibit higher rates of TNBC, but otherwise experience similar outcomes as non-Hispanic women. In order to disentangle factors that may be contributing to inferior outcome associated with Black race, we evaluated the association between Black race or Hispanic ethnicity and recurrence in the population served by Montefiore Medical Center and in 3 clinical trials (E1199, E5103, TAILORx) coordinated by the ECOG-ACRIN Cancer Research Group, as summarized in Table 1. The results were remarkably consistent – Black race was associated with significantly higher recurrence risk (1.39-1.84-fold) in multivariate models in ER+ breast cancer, but not ER-negative breast cancer. Similar findings were not observed for Hispanic women. In the TAILORx trial, there were no significant differences in distribution of 21-gene recurrence score, nor ER, PR, or HER2 RNA expression levels, by race or ethnicity. In other analysis, we have reported specific genetic variants associated with higher risk of taxane-induced neuropathy in Black women (PMID: 26138065). Our findings highlight the need for greater representation of racial and ethnic minorities in clinical trials, and that additional studies designed specifically to determine if socioeconomic factors, biological factors, and/or other factors contribute to these disparities. ECOG-ACRIN is currently conducting a clinical trial to prospectively validate genetic variants associated with higher risk of peripheral neuropathy in Black women with breast cancer receiving taxane therapy (EAZ171; NCT04001829). Citation Format: Joseph A. Sparano. Learning from and Addressing Racial and Ethnic Disparities in Cancer Clinical Trials: The ECOG-ACRIN Experience [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr IA26.
Partisan Differences in Physical Distancing Predict Infections and Mortality During the Coronavirus Pandemic

Few things bind disparate groups together like a common obstacle. Yet, numerous polls suggest that the COVID-19 pandemic has been subject to a deep partisan divide. Using geo-tracking data of over 17 million smartphone users around the United States, we examined whether partisan differences predict objective physical-distancing behaviors. U.S. counties that voted for Donald Trump over Hillary Clinton in 2016 exhibited 16% less physical distancing from March 9 to May 8, 2020, as assessed by overall movement and visits to nonessential services (e.g., restaurants). Counties that watched more conservative media (i.e., Fox News) also exhibited reduced physical distancing, as did states with higher Trump approval. Contrary to our preregistered predictions, these differences did not weaken with time and remained even in pro-Trump states with active stay-at-home orders. Finally, lower physical distancing in strongly pro-Trump counties (those whose pro-Trump margin was 2 SDs above the mean) was associated with a 27% higher growth rate in COVID-19 infections. Taken together, these data suggest that behavior during the COVID-19 pandemic is not immune to the partisan divide in the United States and that partisan differences in physical distancing predict subsequent coronavirus infections and fatalities.
Increased utilization of buprenorphine and methadone in 2018 compared to 2015 among Seattle-area persons who inject drugs.

Abstract Objective To describe utilization patterns of methadone and buprenorphine among persons who inject drugs (PWID) in the Seattle area in 2018, compared to 2015. Methods Data from the 2018 National HIV Behavioral Surveillance (NHBS) system were used to compare the proportions of PWID reporting treatment with buprenorphine or methadone to survey responses in 2015. Temporal trends were assessed by calculating adjusted prevalence ratios (aPR) using Poisson regression. Results The sample included 498 PWID, of whom 39.2% (95% CI: 34.8–43.6%) reported past-year treatment with methadone and 21.9% (95% CI: 18.3–25.8%) reported buprenorphine. Participants in 2018 were significantly more likely to report past year receipt of buprenorphine (aPR = 4.43, 95% CI: 2.81–7.01) or methadone (aPR = 1.38, 95% CI: 1.02–1.87) compared to 2015. Most buprenorphine treated participants (67.6%) reported that they had received buprenorphine through low-barrier, community, or nonprofit programs. Conclusions Among PWID who use opioids in the Seattle area, methadone use increased 38%, and buprenorphine use more than quadrupled from 2015 to 2018. Approximately half of surveyed PWID who use opioids still reported no treatment with either medication, highlighting remaining treatment gaps.
Inactivation of Presenilin in inhibitory neurons results in decreased GABAergic responses and enhanced synaptic plasticity.

Mutations in the Presenilin genes are the major genetic cause of Alzheimer's disease (AD). Presenilin (PS) is highly expressed in the hippocampus, which is particularly vulnerable in AD. Previous studies of PS function in the hippocampus, however, focused exclusively on excitatory neurons. Whether PS regulates inhibitory neuronal function remained unknown. In the current study, we investigate PS function in GABAergic neurons by performing whole-cell and field-potential electrophysiological recordings using acute hippocampal slices from inhibitory neuron-specific PS conditional double knockout (IN-PS cDKO) mice at 2 months of age, before the onset of age-dependent loss of interneurons. We found that the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) is reduced in hippocampal CA1 neurons of IN-PS cDKO mice, whereas the amplitude of sIPSCs is normal. Moreover, the efficacy of inhibitory neurotransmission as assessed with synaptic input/output relations for evoked mono- and di-synaptic IPSCs is markedly lowered in hippocampal CA1 neurons of IN-PS cDKO mice. Consistent with these findings, IN-PS cDKO mice display enhanced paired-pulse facilitation, frequency facilitation and long-term potentiation in the Schaffer collateral-CA1 pathway. Interestingly, depletion of intracellular Ca2+ stores by inhibition of sarcoendoplasmic reticulum Ca2+ ATPase results in a reduction of IPSC amplitude in control hippocampal neurons but not in IN-PS cDKO neurons, suggesting that impaired intracellular calcium homeostasis in the absence of PS may contribute to the deficiencies in inhibitory neurotransmission. Furthermore, the amplitude of IPSCs induced by short trains of presynaptic stimulation and paired-pulse ratio are decreased in IN-PS cDKO mice. These findings show that inactivation of PS in interneurons results in decreased GABAergic responses and enhanced synaptic plasticity in the hippocampus, providing additional evidence for the importance of PS in the regulation of synaptic plasticity and calcium homeostasis.
Does the location of directors' additional positions matter? A new dimension of board structure

Abstract This paper analyzes the impact on firm value of directors with outside directorships and/or executive positions in the same geographic area (DSAs). The findings show that DSAs are associated with higher firm value because they better understand the local business environment and have better local connections. This value impact is more prominent for rural firms, innovative firms, and firms with high growth rates, indicating that DSAs' local information advantage is more important for firms in areas with less effective information transmission, firms with high R&D expenses, and firms facing high uncertainty. Also, DSAs help corporations better manage local economic shocks, improve financial reporting quality, and increase CEO incentive pay.
Meditation and the Relaxation Response

Publisher Summary This chapter discusses meditation; its psychological, behavioral, and physiological effects; and how it can be effectively incorporated into the routine care of individuals who require mental and medical interventions. The relaxation response is the biological consequence of a wide variety of mental focusing techniques, one of which is meditation. A variety of techniques can be used to elicit the relaxation response, including meditation, progressive muscle relaxation, autogenic training, yoga, exercise, repetitive prayer, and the presuggestion phase of hypnosis. Although all of these strategies result in the same physiological response, two components appear to be essential to achieving the relaxation response: mental focusing and adopting a passive attitude toward distracting thoughts. For many patients with psychological disturbances who might be hesitant to enter therapy, relaxation response training is a nonthreatening intervention that can be introduced prior to other more rigorous forms of therapy such as cognitive therapy or medication. Meditation and other modes of eliciting the relaxation response can be a means of preparing for standard psychotherapy by allowing the patient to observe thoughts and mental events. Relaxation-response training can also be used to facilitate behavior modification goals. The relaxation response has been associated with improvements in many medical conditions including hypertension, cardiac arrhythmias, chronic pain, insomnia, side effects of cancer therapy, side effects of AIDS therapy, infertility, and preparation for surgery and X-ray procedures.
Alteration of tumour response to radiation by interleukin-2 gene transfer

We have previously shown that BALB/c-derived EMT6 mammary tumours transfected with interleukin (IL)-2 have decreased hypoxia compared to parental tumours, due to increased vascularization. Since hypoxia is a critical factor in the response of tumours to radiation treatment, we compared the radiation response of IL-2-transfected tumours to that of parental EMT6 tumours. Because the IL-2 tumours have an altered host cell composition, which could affect the interpretation of radiation sensitivity as measured by clonogenic cells, we employed flow cytometric analysis to determine the proportion of tumour cells vs host cells in each tumour type. Using this approach, we were able to correct the plating efficiency based on the number of actual tumour cells derived from tumours, making the comparison of the two types of tumours possible. We also excluded the possibility that cytotoxic T-cells present in EMT6/IL-2 tumours could influence the outcome of the clonogenic cell survival assay, by demonstrating that the plating efficiency of cells derived from EMT6/IL-2 tumours remained unchanged after depletion of Thy-1+cells. The in vivo radiation response results demonstrated that IL-2-transfected tumours were more sensitive to radiation than parental EMT6 tumours. The hypoxic fraction of the EMT6/IL-2 tumours growing in vivo was markedly decreased relative to parental EMT6 tumours thus the increased sensitivity results from the increased vascularity we have previously observed in these tumours. These results indicate the potential therapeutic benefit of combining radiation and immunotherapy in the treatment of tumours. © 2000 Cancer Research Campaign
Short-time distribution of particle displacements due to swimming microorganisms

model where the particles undergo repeated ‘kicks’ due to the swimmers to explain the shape of the distribution as a function of the volume fraction of swimmers. The net displacement is determined by the self-convolution of the drift function caused by one swimmer, and by a Poisson distribution for the frequency of interactions. The only adjustable parameter is the strength of the stresslet term in our spherical squirmer model. The eective diusivity predicted by the model is consistent with the experiments, with no further parameter adjustments. The diusive scaling appears to be due to the particular form of the drift function, and is not statistical in origin. The model also suggests that the scaling disappears for longer times, when the swimmers undergo signicant reorientation.
Rethinking the Scientific Enterprise: In Defense of Reductionism

In this essay, I argue that modern science is not the dichotomous pairing of theory and experiment that it is typically presented as, and I offer an alternative paradigm defined by its functions as a human endeavor. I also demonstrate how certain scientific debates, such as the debate over the nature of the quantum state, can be partially resolved by this new paradigm.
Aligning needles in a haystack: paraphrase acquisition across the web

This paper presents a lightweight method for unsupervised extraction of paraphrases from arbitrary textual Web documents. The method differs from previous approaches to paraphrase acquisition in that 1) it removes the assumptions on the quality of the input data, by using inherently noisy, unreliable Web documents rather than clean, trustworthy, properly formatted documents; and 2) it does not require any explicit clue indicating which documents are likely to encode parallel paraphrases, as they report on the same events or describe the same stories. Large sets of paraphrases are collected through exhaustive pairwise alignment of small needles, i.e., sentence fragments, across a haystack of Web document sentences. The paper describes experiments on a set of about one billion Web documents, and evaluates the extracted paraphrases in a natural-language Web search application.
Summary of CDC Consultation to Address Social Determinants of Health for Prevention of Disparities in HIV/AIDS, Viral Hepatitis, Sexually Transmitted Diseases, and Tuberculosis

Many scientists, physicians, and others are now considering the total ecology of population health outcomes, which includes complex, integrated, and overlapping social structures and economic systems, collectively referred to as social determinants of health (SDH). SDH are the economic and social conditions that influence the health of individuals, communities, and jurisdictions as a whole. SDH include, but are not limited to, conditions for early childhood development; education, employment, and work; food security, health services, housing, income, and income distribution; social exclusion; the social safety net; job security; and the economic and social conditions that influence the health of individuals, communities, and jurisdictions as a whole.1 In 1988 and 2003, the Institute of Medicine emphasized and reiterated the role of public health as a collective societal function to ensure health for all people.2,3 Likewise, the World Health Organization (WHO) called for addressing the hegemonic conditions and inequalities that contribute to disease morbidity and mortality in developed and developing countries. The WHO Commission on Social Determinants of Health4 charged public health officials worldwide to provide action to: “… improve the conditions of daily life—the circumstances in which people are born, grow, live, work, and age…. Tackle the inequitable distribution of power, money, and resources—the structural drivers of those conditions of daily life—globally, nationally, and locally…. Measure and understand the problem and assess the impact of action—measure the problem, evaluate action, expand the knowledge base, develop a workforce that is trained in the social determinants of health, and raise public awareness about the social determinants of health.”4
CNS neurons express two distinct plasma membrane electron transport systems implicated in neuronal viability.

Trans-plasma membrane electron transport is critical for maintaining cellular redox balance and viability, yet few, if any, investigations have studied it in intact primary neurons. In this investigation, extracellular reduction of 2,6-dichloroindophenol (DCIP) and ferricyanide (FeCN) were measured as indicators of trans-plasma membrane electron transport by chick forebrain neurons. Neurons readily reduced DCIP, but not FeCN unless CoQ1, an exogenous ubiquinone analog, was added to the assays. CoQ1 stimulated FeCN reduction in a dose-dependent manner but had no effect on DCIP reduction. Reduction of both substrates was totally inhibited by e-maleimidocaproic acid (MCA), a membrane-impermeant thiol reagent, and slightly inhibited by superoxide dismutase. Diphenylene iodonium, a flavoenzyme inhibitor, completely inhibited FeCN reduction but had no affect on DCIP reduction, suggesting that these substrates are reduced by distinct redox pathways. The relationship between plasma membrane electron transport and neuronal viability was tested using the inhibitors MCA and capsaicin. MCA caused a dose-dependent decline in neuronal viability that closely paralleled its inhibition of both reductase activities. Similarly capsaicin, a NADH oxidase inhibitor, induced a rapid decline in neuronal viability. These results suggest that trans-plasma membrane electron transport helps maintain a stable redox environment required for neuronal viability.
Expert system aided automated design, simulation and controller tuning of AC drive system

Expert systems, a branch of artificial intelligence (AI), are showing tremendous potential for application to power electronics and AC motor drive systems. The paper describes expert system-aided automated design, simulation and controller tuning of an AC motor drive system. It is an extension of earlier work that discussed the design and optimization of power converter systems. Based on the application and performance specifications from the user, the expert system selects a motor drive configuration consisting of the AC machine type, power converter and control topologies. The expert system embeds the design expertise of an experienced AC motor drive system designer to configure, design and fine-tune the AC motor drive system. Next, the expert system supervises an autonomous hybrid simulation where the controller software is fine-tuned in real-time before loading to an experimental AC motor drive system. The paper discusses the design methodology for AC motor drive systems, with particular emphasis on the configuration selection, AC motor sizing and control design and tuning. The expert system based control design is experimentally verified on an indirect vector controlled induction motor drive system with synchronous current control, using a 5 hp IGBT inverter, with the control implemented by a Texas Instruments DSP 320C25. The same principles can be extended to larger and more complex AC motor drive system applications.
On the Feasibility of Grasers

The cross section at resonance for induced gamma ray transitions in nuclear isomers would be adequate for gain if population inversion could be reconciled with recoilless (Mossbauer”) emission; the overriding consideration is inhomogeneous broadening from hyperfine interactions and isomer shifts. Feasibility of a graser in which the crystal is pumped by intense neutron burst depends upon the relative rates of isomer formation and development of lattice damage during the time required for neutron moderation and wave incubation; a major uncertainty is the isomer ratio. It appears feasible to isolate inverted populations of isomer in quantity adequate for preparing a graser by assembly after irradiation; the limiting factor will be the extent to which the recoilless line breadth can be controlled by as-yet-undemonstrated techniques. Decision on feasibility and identification of transitions suitable for either type of graser await better understanding of these factors.
Towards custom cloud services: using semantic technology to optimize resource configuration

In today's highly dynamic economy, businesses have to adapt quickly to market changes, be it customer, competition- or regulationdriven. Cloud computing promises to be a solution to the ever changing computing demand of businesses. Current SaaS, PaaS and IaaS services are often found to be too inflexible to meet the diverse customer requirements regarding service composition and Quality-of-Service. We therefore propose an ontology-based optimization framework allowing Cloud providers to find the best suiting resource composition based on an abstract request for a custom service. Our contribution is three-fold. First, we describe an OWL/SWRL based ontology framework for describing resources (hard- and software) along with their dependencies, interoperability constraints and meta information. Second, we provide an algorithm that makes use of some reasoning queries to derive a graph over all feasible resource compositions based on the abstract request. Third, we show how the graph can be transformed into an integer program, allowing to find the optimal solution from a profit maximizing perspective.
Dopaminochrome induces caspase‐independent apoptosis in the mesencephalic cell line, MN9D

Parkinson's disease is characterized by a deficiency in motor cortex modulation due to degeneration of pigmented dopaminergic neurons of the substantia nigra projecting to the striatum. These neurons are particularly susceptible to oxidative stress, perhaps because of their dopaminergic nature. Like all catecholamines, dopamine is easily oxidized, first to a quinone intermediate and then to dopaminochrome (DAC), a 5-dihydroxyindole tautomer, that is cytotoxic in an oxidative stress-dependent manner. Here we show, using the murine mesencephalic cell line MN9D, that DAC causes cell death by apoptosis, illustrated by membrane blebbing, Annexin V, and propidium iodide labeling within 3 h. In addition, DAC causes oxidative damage to DNA within 3 h, and positive terminal deoxynucleotidyl transferase dUTP nick end labeling fluorescence by 24 h. DAC, however, does not induce caspase 3 activation and its cytotoxic actions are not prevented by the pan-caspase inhibitor, Z-VAD-fmk. DAC-induced cytotoxicity is limited by the PARP1 inhibitor, 5-aminoisoquinolinone, supporting a role for apoptosis-inducing factor (AIF) in the apoptotic process. Indeed, AIF is detected in the nuclear fraction of MN9D cells 3 h after DAC exposure. Taken together these results demonstrate that DAC induces cytotoxicity in MN9D cells in a caspase-independent apoptotic manner, likely triggered by oxidative damage to DNA, and involving the translocation of AIF from the mitochondria to the nucleus.
Seeing Sesotho: art, history, and the visual language of South Sotho identity

When approaching the topic of cultural affiliation and formation in southern Africa, the litmus test for many ethnographic studies generally stands on the work of Nicholas Jacobus van Warmelo, Government Ethnologist for South Africa (1930–1969), whose classification of African languages and ‘tribes’ essentially fixed ‘tribal’ ethnicities, and outlined the relationships of one African people to another. However, because his scholarship is largely language-based, it often presents South Sotho speakers as a homogeneous cultural entity, excluding important cultural markers such as ritual, material culture, and socio-religious beliefs. This essay offers a new methodology toward our understanding of identity by analyzing South Sotho visual arts, and their relation to oral histories and culturally sensitive activities. By examining specific examples of the arts that date from the early nineteenth century to the present, one can see that the various Sotho-speaking clans asserted themselves as heterogeneous cultural entities in spite of shared language systems, and relied on visual symbols to advance clan identity and cultural specificity. Because the visual arts are focused expressions of identity, one can gain a nuanced understanding of South Sotho affiliation and variation through the examination of objects that have been previously overlooked for the sake of locating a cohesive whole.
Hybrid networks: cellular-relay architecture

Summary form only given. Inter-vehicle communication, an important component of intelligent transportation system, performs crucial functions in collision avoidance, road-hazard notification, and coordinated driving system. An inter-vehicle communication network is an instantiation of a mobile ad hoc network, which is characterized by multi-hop wireless communications among mobile nodes without any centralized control infrastructure. However, automotive ad hoc networks behaves in fundamentally different ways than the models that predominate mobile ad hoc network research. Driver behavior, constraints on mobility and high speeds create unique characteristics in such networks. They are characterized by rapid but somewhat predictable topology changes, with frequent fragmentation, a small effective network diameter, and redundancy that is limited temporally and functionally. The motivation of this research is to propose an effective approach to topology management under these constraints. Apparently flat structure is not suited to vehicular ad hoc networks since it is impossible for every node to acquire the global topology information. All participating nodes must be organized hierarchically so that only local information is required to exchange and global information is hidden for single node. Clustering is an important technique to implement hierarchical structure. Several heuristic clustering techniques have been proposed to choose cluster heads in an ad hoc network. These are lowest-ID, highest-degree and node-weight heuristics. However they cannot be deployed directly in ad hoc vehicular networks since their design objectives are not for highly mobility vehicular networks. The metrics used in these proposals are frequently changed. In this paper, we propose a new clustering technique, position-based hierarchical clustering, which incorporates position information into a novel hierarchical clustering technique. Each node knows its own position through a Global Positioning System. The cluster structure is determined by the geographic position of nodes. Each cluster has one node as the cluster head. Not only is the election of cluster heads based on nodes' position, but also the association and dissociation of clusters are determined by each node's position. The predefined maximum distance between the cluster head and its members then controls the cluster size. It enables nodes to move during cluster setup and maintenance. Furthermore, it allows asynchronous operation for cluster head election. A vehicular ad hoc network can be considered as a one-dimension network by taking the number of lanes into account. We give some mathematical analysis about the performance under some assumptions. Our simulation results show that it gains better stability of the cluster structure, and needs smaller communication overhead for maintaining the cluster structure than the existing approaches do.
Sociocultural and behavioral influences on weight gain during pregnancy

Studies have consistently identified a positive association between prenatal weight gain and birth weight. Much less, however, is known about factors that may influence women to gain weight within currently recommended ranges. The importance of this issue is suggested by recent reports indicating that only 30-40% of women actually gain weight within these ranges. This paper examines demographic, sociocultural, and behavioral factors that are associated with, and may influence risk of, low prenatal weight gain among adult women with low and normal body mass indexes. Available data suggest that these factors include ethnicity, socioeconomic status, age, education, pregnancy intendedness or wantedness, prenatal advice, and psychosocial characteristics such as attitude toward weight gain, social support, depression, stress, anxiety, and self-efficacy. Potential theoretical models for these associations include biological, behavioral, and mixed pathways. The design of targeted intervention studies will depend on further identification and characterization of sociocultural and behavioral risk factors that, along with reproductive and nutritional characteristics, may predict which women are most likely to have inadequate prenatal weight gain.
The effects of an oral contraceptive containing ethinyloestradiol and norgestrel on CYP3A activity.

Aims To examine the effects of an oral contraceptive containing ethinyloestradiol and norgestrel on intestinal and hepatic CYP3A activity using midazolam as a probe substrate. Methods In a nonblinded sequential study, nine healthy women received simultaneous doses of intravenous midazolam (0.05 mg kg−1) and oral 15N3-midazolam (3 mg) on days 0, 4, 6, 8, and 14. On study day 5, Ovral™ (50 µg ethinyloestradiol/500 µg norgestrel) was administered for 10 days. Serum and urine samples were assayed for midazolam, 15N3-midazolam and metabolites by liquid chromatography-mass spectrometry. A Digit Symbol Substitution Test (DSST) was used to assess changes in the pharmacodynamic activity of midazolam. Results Moderate (% CV 26–46) interindividual variability in the pharmacokinetics of midazolam were observed. Compared with baseline, AUC(0,∞)iv ratios (95% CIs) after 2, 4, and 10 days treatment with OC were 89% (79, 101), 96% (85, 109), and 88% (77, 99), respectively. The AUC(0,∞)oral ratios (95% CIs) were 101% (82, 125), 105% (85, 130), and 114% (92, 141), respectively, after 2, 4, and 10 days OC treatment compared with baseline. Concomitant administration of the oral contraceptive, Ovral™ for 2, 4 or 10 days did not significantly alter the area under the curve, clearance, or half-life of midazolam after either oral or intravenous administration. No alterations in pharmacodynamic effects of midazolam were observed between treatment days. Mean DSST scores strongly correlated with mean total midazolam blood concentrations (r = −0.936). Conclusions Administration of Ovral™ for 10 days had no impact on intestinal or hepatic CYP3A activity as determined by midazolam metabolism.
The First Publication of Grace Ellery Channing's Tribute to Whitman

Reprints the recently rediscovered first publication of Channing's poem "Walt Whitman" from the Boston Transcript, September 10, 1892.
Progressive multifocal leukoencephalopathy from JC virus in a patient with advanced mycosis fungoides

Progressive multifocal leukoencephalopathy is a central nervous system disease due to reactivation of the human polyoma JC virus in immunocompromised patients. Advanced mycosis fungoides patients are intrinsically immunosuppressed and susceptible to infections, but only rarely have been reported to develop progressive multifocal leukoencephalopathy. We report a case of progressive multifocal leukoencephalopathy developing in an advanced mycosis fungoides patient without prior history of immunosuppressive therapy.
The synthesis of 5- and 6-hydroxy-2-methylisoquinuclidine

The reduction of the isomeric 5,6-epoxy-2-carboethoxyisoquinuclidines with lithium aluminum hydride afforded 5- and 6-hydroxy-2-methylisoquinuclidine. Contrary to expectation essentially single epimers were obtained for each alcohol.
Effect of Angiotensin II on Adrenal and Pituitary Function in Man

ABSTRACT The acute effect of angiotensin II on plasma cortisol, aldosterone and immunoassayable ACTH (I-ACTH) was studied in normal subjects and in 3 patients with hypopituitarism. Angiotensin II, in a pressor dose given by constant infusion for 1 hr, increased plasma aldosterone to 28.5 ±5 (sd) ng/100 ml, while ACTH had a significantly greater effect, increasing aldosterone to 64 ±10 mean ±(sd) ng/100 ml. ACTH (0.1 μg/kg/hr, βl–24) increased cortisol 3- to 4- fold; however, angiotensin II in a subpressor dose did not increase cortisol. A pressor dose of angiotensin significantly increased I-ACTH from 27.8 ±8.8 (sd) to 60.4 ±20 (sd) pg/ml (p<0.01). A rise was noted in every angiotensin infusion despite an apparent fall in cortisol whether administered in the morning or afternoon. In contrast, a subpressor infusion (1/3 pressor dose), or a pressor infusion of angiotensin after an overnight dexamethasone dose (1 mg q 12 hr), did not increase the plasma I-ACTH. In 3 patients with pituitary insufficiency, who...
Contributions to the History of Psychology: XLVI. The Pioneer Work of Alfred Binet on Children as Eyewitnesses:

The pioneer work of Alfred Binet (1857–1911) on eyewitness testimony (1900) often is cited today in support for a traditional view of the extreme suggestibility of children. Binet, on the other hand, interpreted his findings as showing that suggestibility is not a static trait among children but rather is a function of cognitive and social factors associated with attempts to influence during interrogation. Ironically, those conclusions made nearly 90 years ago are mirrored in modern conceptualizations of the nature of children's suggestibility. In light of renewed interest in historical work on this topic, this paper provides general information about Binet's La suggestibilite (1900) and of some reactions surrounding its publication.
Lattice gauge theories and the continuum limit in two dimensions

Lattice gauge theories in two dimensions are studied with regard to investigating the continuum limit. The effective interaction is calculated for the lattice gauge theories for QED [U(1)] and $\mathrm{SU}(N)$ to all orders in the gauge coupling and is shown to reproduce the usual Schwinger and 't Hooft models, respectively, in the limit of zero lattice spacing. However, lattice gauge theories in strong coupling have, in general, qualitatively different $S$ matrices than their expected continuum analogs. Except for the $\mathrm{SU}(N)$ lattice gauge theory in the formal limit $N\ensuremath{\rightarrow}\ensuremath{\infty}$, ${g}^{2}N$ fixed, the lattice introduces additional four-or-more-body forces which are not present in the continuum.
Suppression of T helper function: An immunoregulatory effect of rosette inhibitory factor in hepatitis B virus infection

The potential immunoregulatory effects of rosette inhibitory factor (RIF) were evaluated using lymphocyte subpopulations defined by monoclonal antibodies (OKT4, OKT8). Initial experiments indicated that RIF inhibits E-rosette formation by T cells that provide helper/inducer function (OKT4+). Subsequently, experiments were done to assess if RIF had an inhibitory effect on in vitro immunoglobulin and anti-HBs production. These studies used peripheral blood mononuclear cells from convalescent and hepatitis B-vaccinated donors. The results indicated that RIF-positive low-density lipoprotein, but not RIF-negative low-density lipoprotein, inhibits in vitro production of IgG and IgM by 60 to 70% and totally ablates anti-HBs synthesis. In order to determine if RIF directly affected the proliferative response of T4 lymphocytes, these cells were cultured in the presence of optimal mitogen concentrations and either RIF-positive or RIF-negative low-density lipoprotein. The experiments demonstrated that RIF-treated T4 cells are hyporesponsive to pokeweed mitogen and phytohemagglutinin when compared to T4 cells cultured in the absence of RIF. In contrast, B cell proliferation in response to soluble T helper factors was not affected by incubation with RIF. As the production of soluble helper factors by T4 cells was inhibited by exposure to RIF-positive but not RIF-negative low-density lipoprotein, we conclude that the suppressive effect of RIF on immunoglobulin and anti-HBs synthesis is due to inhibition of this specific helper T cell function.
Spiritual practices children understand: an analysis of Madeleine L’Engle’s fantasy, A Wind in the Door

The following essay is a close reading of Madeleine L’Engle’s science fantasy novel, A Wind in the Door, in which young Meg Murry travels first to outer space and then into her younger brother’s ailing cells. The novel is a fine example of high fantasy (also known as heroic fantasy) wherein a humble protagonist is called to a quest to fight a cosmic battle between good and evil. The essay analyzes specific expressions of evil in the novel: impersonality, narcissism, despair and blind empiricism. Meg’s quest demonstrates particular spiritual practices that promote spiritual maturation and the ability to overcome evil: ‘kything’, Naming, deepening and holding. L’Engle portrays these practices in a fresh way that can help both children and adults incorporate them into their day‐to‐day lives. Moreover, there are links between kything and holding and the metta and tonglen, two types of Buddhist meditation. L’Engle affirms children’s innate relational consciousness and presents spiritual practices that are rela...
Effect of Surface Radiation on Natural Convection in Parabolic Enclosures

The interaction of natural convection and surface radiation in two-dimensional parabolic cavities heated from below with insulated walls and flat top and bottom walls is studied numerically. The shape of the cavities arises from the design of non-imaging optics-based compound parabolic concentrators (CPC). A numerical model based on finite differences is developed to solve the mass, momentum, and energy equations. A coordinate transformation is used to map the parabolic shape into a rectangular domain where the governing equations are solved. The results show that surface radiation significantly changes the temperature distribution and local Nusselt number inside the parabolic enclosure. Solutions are obtained for two different parabolic geometries that correspond to two different levels of concentration.
Some Joys and Trials of Mathematical Neuroscience

I describe the basic components of the nervous system—neurons and their connections via chemical synapses and electrical gap junctions—and review the model for the action potential produced by a single neuron, proposed by Hodgkin and Huxley (HH) over 60 years ago. I then review simplifications of the HH model and extensions that address bursting behavior typical of motoneurons, and describe some models of neural circuits found in pattern generators for locomotion. Such circuits can be studied and modeled in relative isolation from the central nervous system and brain, but the brain itself (and especially the human cortex) presents a much greater challenge due to the huge numbers of neurons and synapses involved. Nonetheless, simple stochastic accumulator models can reproduce both behavioral and electrophysiological data and offer explanations for human behavior in perceptual decisions. In the second part of the paper I introduce these models and describe their relation to an optimal strategy for identifying a signal obscured by noise, thus providing a norm against which behavior can be assessed and suggesting reasons for suboptimal performance. Accumulators describe average activities in brain areas associated with the stimuli and response modes used in the experiments, and they can be derived, albeit non-rigorously, from simplified HH models of excitatory and inhibitory neural populations. Finally, I note topics excluded due to space constraints and identify some open problems.
Efficient PCR‐based random mutagenesis of sub‐genic (100 bp) DNA fragments

Here we describe a method for performing a PCR-driven random mutagenesis of 100 bp DNA fragments that yields mutations at a useful frequency. The method is a modification of the manganese ion substitution PCR technique, and neither creates ‘hot-spots’ nor favors transition mutations over transversions. © 1998 John Wiley & Sons, Ltd.
Tacrolimus, cyclosporine and plasma lipoproteins in renal transplant recipients

To compare the effect of tacrolimus (FK506) and cyclosporine (CsA) on plasma lipoproteins in renal transplant recipients receiving maintainance therapy, the following prospective study was undertaken. Blood from nineteen recipients on tacrolimus (FK group) and from twenty-one on CsA (CsA group) was collected at baseline, 3-, 6-, and 10-month intervals. Plasma lipids, lipoproteins and oxidation properties of lipoproteins were determined. Plasma total cholesterol, low density lipoprotein (LDL) cholesterol, and apolipoprotein B (apoB) were substantially increased in both groups, although only the CsA group showed significant differences at all time intervals and at the baseline. High density lipoprotein cholesterol, triglycerides, and apolipoprotein A varied in both groups at time intervals from the baseline, but not significantly. The susceptibility to oxidation of LDL isolated from the FK group at all times was uninfluenced by the tacrolimus treatment, and values were comparable to those obtained from LDL isolated from healthy individuals. A significantly higher susceptibility to oxidation as indicated by the shorter time required to start the formation of conjugated dienes was observed in LDL isolated from the CsA group at 3 and at 6 months of therapy. Tacrolimus-treated patients appear to have less hyperlipidemic and have LDL less susceptible to oxidation than patients treated with CsA.
Metal quenching of radiative emission in metal-clad nanolasers

Nanolasers made from III–V active materials and metal-clad cavities have attracted research interest because of the small volume possible with metal nanocavities.1 Proposed applications include intrachip optical interconnects and optical sensors. The metal-clad nanocavities are one of several cavity approaches being studied, and differ from dielectric and semiconductor nanocavities in their high optical loss coefficients. Despite high absorption loss that increases with decreasing cavity size, several reports of lasing have been made.2,3 Clear trends exist, however, that the temperature at which lasing can be achieved decreases with the metal nanocavity volume. At least part of the temperature limit is due directly to the optical absorption of the metal walls of the nanocavity. In this talk we present a second mechanism that is highly deleterious to lasing in metal clad nanocavities, and analyze recent reported results of emission properties in a metal-clad nanocavity. The second mechanism is metal quenching of the radiative emission of the gain material, which is separate from the optical absorption of the cavity mode by the metal walls. Metal quenching occurs instead from the gain materials is nonradiative energy transfer between the gain's near-field and metal walls.4,5
Factor XI contributes to thrombin generation in the absence of factor XII

During surface-initiated blood coagulation in vitro, activated factor XII (fXIIa) converts factor XI (fXI) to fXIa. Whereas fXI deficiency is associated with a hemorrhagic disorder, factor XII deficiency is not, suggesting that fXI can be activated by other mechanisms in vivo. Thrombin activates fXI, and several studies suggest that fXI promotes coagulation independent of fXII. However, a recent study failed to find evidence for fXII-independent activation of fXI in plasma. Using plasma in which fXII is either inhibited or absent, we show that fXI contributes to plasma thrombin generation when coagulation is initiated with low concentrations of tissue factor, factor Xa, or α-thrombin. The results could not be accounted for by fXIa contamination of the plasma systems. Replacing fXI with recombinant fXI that activates factor IX poorly, or fXI that is activated poorly by thrombin, reduced thrombin generation. An antibody that blocks fXIa activation of factor IX reduced thrombin generation; however, an antibody that specifically interferes with fXI activation by fXIIa did not. The results support a model in which fXI is activated by thrombin or another protease generated early in coagulation, with the resulting fXIa contributing to sustained thrombin generation through activation of factor IX.
Approximation method for electrolyte diffusion through a fixed charge medium

The diffusion of a binary salt through media containing uniformly dispersed immobile ions is formally equivalent to the diffusion of a nonelectrolyte with a concentration-dependent diffusion coefficient. This permits the application of a quasi-steady-state approximation, developed in a previous paper (Bull. Math. Biophysics,21, 19–32, 1959), to problems of transient diffusion. Free diffusion across an interface involving a discontinuity in immobile ion concentration is considered and expressions for the salt concentration and electrical potential at any point are developed. The dependence of electrical potential on the fixed charge density, ionic mobilities, as well as on the boundary concentrations is illustrated by a numerical example. This particular example is suggested by experiments on connective tissue.
MR imaging of the breast with rotating delivery of excitation off resonance: clinical experience with pathologic correlation.

An investigative study was undertaken to determine the potential for a new magnetic resonance (MR) imaging technique, RODEO (rotating delivery of excitation off resonance), for use as a diagnostic imaging tool for the breast. The RODEO technique provides fat suppression with T1 weighting and is ideal for gadolinium-enhanced breast imaging. It is a short repetition time, steady-state sequence for high-resolution three-dimensional acquisitions and provides a clinically efficient imaging time of approximately 5 minutes for 128 sections. Imaging findings were correlated with serially sectioned pathologic specimens in 30 breasts with 47 malignant and 27 benign lesions. MR imaging had a sensitivity of 94% and a specificity of 37%. MR imaging depicted additional cancers not seen at mammography in 11 of the 30 patients (37%). The lesions not seen at mammography varied in size from 3 mm to 12 cm. RODEO MR imaging may be used to improve diagnosis of breast cancer in patients with mammographically dense breasts or s...
Exchange contributions to optical-model potentials

The optical potential is computed exactly for a two-channel 1s-2s model in electron-hydrogen scattering. Exchange contributions in the 2s channel are calculated explicitly and compared to other terms in the nonlocal optical potential. It is concluded that exchange effects in excited states cannot be neglected in calculating optical potentials for low-energy electron-atom scattering.
Neural Correlates of Cognitive Reappraisal in Children: An ERP Study

Cognitive emotion regulation strategies, such as reappraising the emotional meaning of events, are linked to positive adjustment and are disrupted in individuals showing emotional distress, like anxiety. The late positive potential (LPP) is sensitive to reappraisal: LPP amplitudes are reduced when unpleasant pictures are reappraised in a positive light, suggesting regulation of negative emotion. However, only one study has examined reappraisal in children using the LPP. The present study examined whether directed reappraisals reduce the LPP in a group of 5- to 7-year-olds, and correlate with individual differences in fear and anxiety. EEG was recorded from 32 typically developing children via 64 scalp electrodes during a directed reappraisal task. Mothers reported on child anxiety. Fearful behavior was observed. As predicted, LPP amplitudes were larger to unpleasant versus neutral pictures;counter to predictions, the LPP was not sensitive to reappraisal. The degree to which unpleasant versus neutral pictures elicited larger LPPs was correlated with greater anxiety and fear. Results suggest that reappraisal in young children is still developing, but that the LPP is sensitive to individual differences related to fear and anxiety. The utility of the LPP as a measure of cognitive emotion regulation and emotional processing biases in children is discussed.