cssi/SciSciGPT-SciSciNet huggingface dataset:
Determining Which of Several Simultaneously Administered Vaccines Increase Risk of an Adverse Event

Childhood immunization schedules often involve multiple vaccinations per visit. When increased risk of an adverse event is observed after simultaneous (same-day) vaccinations, it can be difficult to ascertain which triggered the adverse event. This methods paper discusses a systematic process to determine which of the simultaneously administered vaccine(s) are most likely to have caused an observed increase in risk of an adverse event. We use an example from the literature where excess risk of seizure was observed 1 day after vaccination, but same-day vaccination patterns made it difficult to discern which vaccine(s) may trigger the adverse event. We illustrate the systematic identification process using a simulation that retained the observed pattern of simultaneous vaccination in an empirical cohort of vaccinated children. We simulated “true” effects for diphtheria–tetanus–acellular pertussis (DTaP) and pneumococcal conjugate (PCV) on risk of seizure the day after vaccination. We varied the independent and interactive effects of vaccines (on the multiplicative scale). After applying the process to simulated data, we evaluated risk of seizure 1 day after vaccination in the empirical cohort. In all simulations, we were able to determine which vaccines contributed to excess risk. In the empirical data, we narrowed the association with seizure from all vaccines in the schedule to three likely candidates, DTaP, PCV, and/or Haemophilus influenzae type B (HiB) (p < 0.01, attributable risk when all three were administered together: five per 100,000). Disentangling their associations with seizure would require a larger sample or more variation in the combinations administered. When none of these three were administered, no excess risk was observed. The process outlined could provide valuable information on the magnitude of potential risk from individual and simultaneousvaccinations. Associations should be further investigated with independent data as well as biologically based, statistically independent hypotheses.
Effect of Strain Rate on Deformation Response of Metastable High Entropy Alloys Upon Friction Stir Processing

Effect of strain rate on the tensile behavior of two friction stir-processed dual-phase high entropy alloys was investigated. The dual-phase high entropy alloys have a high fraction of metastable f.c.c. phase. Engineering the f.c.c. phase metastability through alloy chemistry leads to different levels of transformation and impacts the retained f.c.c. phase after deformation. These metastable high entropy alloys show dominance of transformation-induced plasticity (TRIP) irrespective of strain rates, unlike the observations in TRIP steels.
Planar-Locked Ru-PNN Catalysts in 1-Phenylethanol Dehydrogenation

Ru-PNN pincer catalysts of the general form [{PNN}Ru(H)(Cl)(CO)] can dehydrogenate alcohols through inner- and outer-sphere mechanisms, but determining the favored path is challenging. To address t...
Oral Communication in an Integrated STEM and Humanities First-Year Experience

This study looks at Purdue University's Integrated First-Year Experience of Design Thinking in Technology, Fundamentals of Speech Communication, and First-Year Composition and its effects on oral communication. We examined whether this three-course integration inspired by writing-across-the-curriculum and communication-across-the-curriculum would lead students to develop more effective oral communication skills than a nonintegrated course. Frameworks for 21st century skills and the National Association of Colleges and Employers (2017) have pinpointed the importance of oral and written communication skills and initiatives. Still, research has produced mixed results on how well universities are preparing students for the workplace. Our study investigated whether the integrated program had better end-of-semester group oral presentations than student groups enrolled only in our Design Thinking in Technology course. A quasi-experimental design and post-only analysis revealed that integrated sections had more effective oral presentations than the nonintegrated sections
The Small Margins Problem: How Abolishing the Electoral College Could Create a Future Election Crisis

This essay examines a potential unintended consequence of abolishing the Electoral College: the difficulty of identifying a national popular vote winner in the event of a close election. Under the Electoral College, the precise margin of victory is irrelevant in all but a handful of swing states decided by a small number of votes. The vast majority of states award all of their electoral votes to the candidate who finishes in first place, regardless of the candidate’s margin of victory. But if the United States elected the president through a nationwide popular vote, the precise vote totals in all 50 states would become crucially important. As recent elections have demonstrated, however, the quality of election administration in many states is sorely lacking. In a close presidential election, it might take several weeks for the states to produce an accurate and final vote total. California is a case in point. In 2016, California did not ascertain its official vote tabulation until mid-December, one month after election day. California’s slow vote-counting process would plunge the country into limbo in the event of a close nationwide popular vote. Recounts and litigation would likely further delay a conclusive determination of the popular vote. In such a scenario, the nation might not be able to ascertain an election winner before the January 20 inauguration date. Consequently, this essay concludes that a nationwide popular vote for president should not be adopted until Congress and the states establish uniform standards for tabulating presidential votes in a timely and accurate manner.
Seventy-Five Years of Traveler Connectivity: An Evolution Shaping U.S. Hospitality and Beyond:

As we celebrate the 75th anniversary of ICHRIE (International Council on Hotel, Restaurant, and Institutional Education) connecting the academic community, it seems fitting to reflect on the humble...
Susceptibility-Weighted Imaging of the Pediatric Brain after Repeat Doses of Gadolinium-Based Contrast Agent

BACKGROUND AND PURPOSE Gadolinium complexes have paramagnetic properties; thus, we aimed to determine the susceptibility changes in the globus pallidus and dentate nucleus following administration of linear or macrocyclic gadolinium-based contrast agents in children. MATERIALS AND METHODS Thirty-three patients with linear gadolinium-based contrast agent gadopentetate dimeglumine administration, 33 age- and sex-matched patients with macrocyclic gadolinium-based contrast agent gadobutrol administration, and 33 age- and sex-matched control subjects without gadolinium exposure were enrolled in this retrospective study. The signal intensity on SWI and T1WI was determined in the dentate nucleus, middle cerebellar peduncle, globus pallidus, and pulvinar of the thalamus in an ROI-based analysis to calculate dentate nucleus-to-middle cerebellar peduncle and globus pallidus-to-thalamus ratios. A repeated measures ANOVA was performed to compare SWIminimum, SWImean, and T1WI signal intensity ratios between gadolinium-based contrast agent groups and control subjects. Pearson correlation analysis was performed to determine any correlation between signal intensity ratios and variables. RESULTS Dentate nucleus-to-middle cerebellar peduncle and globus pallidus-to-thalamus ratios for both SWImean and SWIminimum were lower for the linear gadolinium-based contrast agent group compared with macrocyclic gadolinium-based contrast agent and control groups (P .05). Both dentate nucleus-to-middle cerebellar peduncle and globus pallidus-to-thalamus ratios on T1WI in the linear gadolinium-based contrast agent group were higher than in the control group and the macrocyclic gadolinium-based contrast agent group (P < .05). A negative correlation was identified between SWImean and SWIminimum ratios and the number of linear gadolinium-based contrast agent administrations (dentate nucleus-to-middle cerebellar peduncle ratio: SWImean, r = -0.43, P = .005; SWIminimum, r = -0.38, P = .011; globus pallidus-to-thalamus ratio: SWImean, r = -0.39, P = .009; SWIminimum, r = -0.33, P = .017). CONCLUSIONS SWI analysis of the pediatric brain demonstrated a statistically significant decrease in SWIminimum and SWImean values for the dentate nucleus and globus pallidus after administration of linear gadolinium-based contrast agents but not macrocyclic gadolinium-based contrast agents.
A genetic variant conferred high expression of CAV2 promotes pancreatic cancer progression and associates with poor prognosis

Abstract Aim This study aimed to identify the functional genes and genetic variants associated with the prognosis of pancreatic ductal adenocarcinoma (PDAC) and reveal the mechanism underlying their prognostic roles. Methods First, we implement a two-stage exome-wide association study in a total of 1070 patients to identify the genetic variant correlated with PDAC prognosis. Then we performed fine mapping through bioinformatics analysis and dual-luciferase reporter assays to reveal the causal functional variant and prognostic gene. Next, we established the gene knockdown, knockout, and overexpression cell lines with small interfering RNA, CRISPR/Cas9, and lentivirus, respectively, and investigated the gene function on cell proliferation and migration in vivo and in vitro. Finally, we performed the RNA-seq to elucidate downstream genes and mechanisms altering PDAC prognosis. Results We identified the CAV1-CAV2 locus tagged by rs8940 was significantly associated with PDAC prognosis, and rs10249656 in the 3′untranslated region of CAV2 was the real functional variant, which upregulated CAV2 expression through abolishing miR-548s binding. We observed upregulated CAV2 in PDAC and the higher expression correlated with worse prognosis. Transient knockdown of CAV2 inhibited PDAC migration without affecting proliferation rate. Knockout of CAV2 suppressed PDAC progression and metastasis, whereas stable overexpression of CAV2 promoted. Overexpressed CAV2 promoted the PDAC progression and metastasis via perturbing genes in the focal adhesion (CCND1, IGTA1, and ZYX) and extracellular matrix organisation (PLOD2, CAST, and ITGA1) pathways mechanically. Conclusion These findings shed light on an important role of CAV2 on PDAC progression and the prognostic impact of its genetic variation.
Echocardiography for the Pregnant Heart.

Pregnancy is associated with significant hemodynamic changes, making it a potentially high-risk period for women with underlying cardiovascular disease. Echocardiography remains the preferred modality for diagnosis and monitoring of pregnant women with cardiovascular disease as it is widely available and does not require radiation. This paper reviews the role of echocardiography along the continuum of pregnancy in at-risk patients, with a focus on key cardiac disease states in pregnancy. In the preconception stage, risk stratification scores such as CARPREG II, ZAHARA and the modified WHO remain central to counseling and planning. As such, echocardiography serves an important role in assessing the severity of pre-existing structural disease. Among women with pre-existing cardiovascular disease who become pregnant—as well as those who develop cardiovascular symptoms during pregnancy—echocardiography is a key imaging tool for assessment of hemodynamic and structural changes and is recommended as the first-line imaging modality when appropriate by both the American College of Obstetricians and Gynecologists (ACOG) and the Food and Drug Administration (FDA). However, routine screening intervals during pregnancy for various cardiac lesions are not well defined, resulting in clinical heterogeneity in care. Echocardiography is the imaging modality of choice for defining, risk stratifying, and monitoring cardiovascular changes throughout pregnancy. Once identified, at-risk patients should receive careful individual counseling and follow-up with a multidisciplinary team. Echocardiography serves as a widely available tool for serial monitoring of pregnant women with cardiovascular disease throughout pregnancy and the postpartum period.
Measurement of effective Sr diffusion coefficients in IG-110 graphite

Abstract Radionuclide transport and release from operating HTGR cores during normal and off-normal operations carries the possibility of increased exposure risk to reactor personnel as well as radionuclide release to the surrounding environment in the event of a depressurization accident. Diffusion is one of the primary processes by which this radionuclide transport takes place. 90Sr is one of several fission products which is commonly investigated within the context of high-temperature gas-cooled reactors due to its low volatility and ability to migrate through intact TRISO fuel particles. Effective diffusion coefficients for strontium in unirradiated IG-110 graphite have been experimentally determined over the temperature range 1773 K – 1973 K using a time-release method coupled to an inductively-coupled plasma mass spectrometer. The results of this work are: D S r , I G − 110 = ( 1.7 × 10 − 1 m 2 / s ) e x p ( − 3.46 × 10 5 J / m o l R T )
Defining the Molecular Hallmarks of T-Cell Memory

The pool of memory CD8 T cells is comprised of highly specialized subpopulations of cells with both shared and distinct functions. The ongoing study of T-cell memory is focused on how these different subpopulations arise, how the cells are maintained over the life of the host, and how the cells protect a host against reinfection. As a field we have used the convenience of a narrow range of surface markers to define and study these memory T-cell subsets. However, as we learn more about these cells, it is becoming clear that these broad definitions are insufficient to capture the complexity of the CD8 memory T-cell pool, and an updated definition of these cellular states are needed. Here, we discuss data that have recently arisen that highlight the difficulty in using surface markers to functionally characterize CD8 T-cell populations, and the possibility of using the epigenetic state of cells to more clearly define the functional capacity of CD8 memory T-cell subsets.
Efficacy of pruning in ultra-low precision DNNs

Quantization, or reducing the precision of variables and operations, and pruning, or removing neurons and connections are two popular approaches for improving the efficiency of DNNs. These directions have been pursued largely separately. In this work, we investigate combining DNN quantization and pruning as each of them is pushed to its limits. Specifically, we explore the efficacy of pruning DNNs for inference in the ultralow precision (sub-8 bit) regime. Pruning requires the use of sparse formats to store and access only the non-zero values. We provide analytical expressions for the storage required by these sparse formats. We demonstrate that with decreasing weight precision, the overhead of indexing non-zero locations starts to dominate, greatly diminishing the benefits of pruning. We specifically analyze the compression ratios of two popular sparse formats – Compressed Sparse Column (CSC) and Sparsity Map (Smap) – and demonstrate that they drop significantly, even degrading to <1 (inflation) in some cases. To address this challenge, we make a key observation that the best-performing sparse format varies across different precisions and sparsity levels. Based on this observation, we propose a hybrid compression scheme that dynamically chooses between sparse formats at both the network and layer-level granularities. We further propose a new scheme, compressed Sparsity Map (cSmap), to enhance the performance of hybrid compression. The cSmap scheme improves the Smap scheme by applying compression methods widely used in manufacturing test. Across 6 state-of-the-art Convolutional Neural Networks (CNNs) and Recurrent Neural Networks (RNNs), the proposed hybrid compression scheme improves the average compression ratio by 18.3% - 34.7% compared to previous approaches.
Quince años después: traducciones legales, globalización del plea bargaining y americanización del proceso penal

The paper answers the remarks advanced by Bachmaier, Eng- lander and Correa Robles on Langer s main paper
“Being at Home”, White Racism, and Minority Health

The negative health effects of stress are well documented in medical and psychological research, but these effects are underexplored in political philosophy. This essay evaluates these effects in relation to the explanatory and normative value of the concept that I call “being at home.” The phenomenological description of the state of being at home is the sense of feeling safe and at ease in your context, and therefore able to relax. Although it characterizes a particular state of being for an individual person, its conditions are relational. I show how the normative value of being at home can guide nonideal action-guiding recommendations to respond to racism in light of the claim that one of the negative effects of racism is a steady stream of disruptions to a person’s sense of ease in the world. Racism and microaggressions create stress, which then causes further negative health effects to the minority body. Consequently, the physical harms perpetrated by racist and sexist societies on the members of oppressed identities can be as great as the effects of actions standardly understood as violence. Demonstrating that a nonideal theoretical approach to bioethics is well suited to evaluating the philosophical ramifications of the bodily damage incurred by microaggressions, I recommend selective and episodic separatism from the perpetrators of microaggressions as a health-protective response to the realities of living in an unjust world.
Fluvastatin Enhances IL-33-mediated Mast Cell IL-6 and TNF Production

Abstract Statins are HMG-CoA reductase inhibitors prescribed for lowering cholesterol. They can also inhibit inflammatory responses by suppressing isoprenylation of small G proteins. Consistent with this, we previously found that fluvastatin suppresses IgE-mediated mast cell function. However, some studies have found that statins induced pro-inflammatory cytokines in macrophages and NK cells. In contrast to IgE signaling, we show that fluvastatin augments IL-33-induced TNF and IL-6 production by mast cells. This effect required the key mast cell growth factor, stem cell factor (SCF). Treatment of IL-33-activated mast cells with mevalonic acid or isoprenoids reduced fluvastatin effects, suggesting fluvastatin acts at least partly by reducing isoprenoid production. Fluvastatin also enhanced IL-33-induced NF-κB transcriptional activity and promoted neutrophilic peritonitis in vivo, a response requiring mast cell activation. Other statins tested did not enhance IL-33 responsiveness. Therefore, this work supports observations of unexpected pro-inflammatory effects of some statins and suggests mechanisms by which this may occur. Because statins are candidates for repurposing in inflammatory disorders, our work emphasizes the importance of understanding the pleiotropic and possible unexpected effects of these drugs.
Optical isolators: Nonlinear dynamic reciprocity

Kerr optical nonlinearities are known to be well suited for achieving optical isolation, but the fact that the degree of non-reciprocity is signal-level dependent brings new opportunities as well as limitations.
Globalization and a new human resource policy in Korea: Transformation to a performance‐ based HRM

Korean firms are in the process of transforming their human resource management (HRM) systems to compete effectively in the global market. Whereas the traditional HRM system emphasized group harmony and age norms, the “new HR policy” emphasizes a performance‐based system. Whether the new HR policy can achieve its objectives remains to be seen. This radical change from the traditional HRM system to a new one is likely to cause a variety of problems. Discusses, specifically, four potential problems in the case of Samsung.
Assessment of COSMO-CLM Performances in Simulating the Past Climate of Italy

This paper analyzes the capabilities of the regional climate model COSMO-CLM to simulate the main features of the observed climate over the entire Italian domain. Two simulations on the period 1971-2000, driven by ERA40 Reanalysis and by the CMCC-MED global model respectively, have been performed at a spatial resolution of 8 km. 2-meters mean temperature and daily precipitation have been analyzed comparing their values with EOBS observational dataset, along with an analysis of the total cloud cover and geopotential at 500hPa and 850hPa compared with ERA-Interim Reanalysis.
The role of local fields and interparticle pair correlations in light scattering by dense fluids

The polarized scattering intensity is calculated, in the Einstein-Smoluchowski approximation, for four thermodynamic states of a model diatomic; these are the same states for which the depolarized intensity was calculated in the first article (I) of this series. The polarized intensity is discussed in terms of an ‘effective isotropic polarizability’ α 0 eff and the ratio (α 0 eff/α 0)2, where α 0 is the gas-phase isotropic polarizability, and is both expressed formally and tabulated for the four states. Similarly in (I), depolarized intensities were discussed in terms of the ratio, (γ/Δα)2, where γ is the ‘effective polarizability anisotropy’ and Δα the gas-phase anisotropy. We find that (α 0 eff/α 0)2 lies much closer to unity than does (γ/Δα)2, in agreement with existing experimental data, which indicates that the introduction of effective polarizabilities is relatively unimportant or important, respectively, as polarized or depolarized scattering is considered.
Thermal and circulatory responses during exercise: effects of hypohydration, dehydration, and water intake

Armstrong, Lawrence E., Carl M. Maresh, Catherine V. Gabaree, Jay R. Hoffman, Stavros A. Kavouras, Robert W. Kenefick, John W. Castellani, and Lynn E. Ahlquist. Thermal and circulatory responses du...
Changing Forms of Inequality

Individual sorting models prevail in current explanations of inequality, but individual sorting systems form rarely and depend on extensive institutional infrastructure. Inequality results more generally from the conjunction of socially organized categories with (a) clique control of value-producing resources, (b) clique deployment of those resources in relations of exploitation and/or opportunity with members of subordinated or excluded categories, backed up by (c) emulation and adaptation. Historically, major value-producing resources in the production of inequality have included coercive means, labor, animals, land, commitment-maintaining institutions, machines, financial capital, information, media, and scientific-technical knowledge. In the future, financial capital, information, media, and scientific-technical knowledge will play increasing parts in the generation of social inequality. Language: en
Assessing the predictive value of teacher reports in a high risk sample for schizophrenia: A ROC analysis.

We examined teachers' reports to determine early patterns of school behavior that identify children who were diagnosed schizophrenic in adulthood. High risk subjects (n=207) in the Copenhagen High Risk for schizophrenia project were examined on a 25-item questionnaire completed by teachers. A likelihood ratio approach was used to create a classification index relating school report to DSM-IIIR diagnoses made 31 years later. A standard receiver operating characteristic (ROC) analysis was used to evaluate the efficacy of the classification indices for distinguishing preschizophrenics from children who later developed schizotypal disorder, other nonpsychotic disorders, and no mental illness. Different items predicted schizophrenia in males and females. To a significantly greater degree than their controls, preschizophrenic males were lonely and rejected, behaved inappropriately, were disciplinary problems, emotionally high strung, and were more likely to have repeated a grade; preschizophrenic females were nervous and passive. Both preschizophrenic males and females were judged by teachers to be vulnerable to future psychotic problems. These findings are consistent with our preliminary findings, as well as with other research. They highlight the ability of teachers to identify school behaviors that may be used to select future schizophrenics for early intervention.
β-Adrenergic Stimulation Down-Regulates Neutrophil Priming for Superoxide Generation, but Not Elastase Release

Platelet-activating factor (PAF) concordantly primes neutrophils (PMNs) for superoxide generation and elastase release. beta-Adrenergic stimulation of PMNs enhances cAMP-dependent protein kinase A (PKA) activity and has been shown to inhibit PAF-mediated NADPH-oxidase activity. PMN superoxide generation is thought to play a predominate microbicidal role, whereas elastase is known to mediate untoward PMN-endothelial interactions. We hypothesized that beta-adrenergic neutrophil stimulation has disparate effects on PAF-mediated PMN superoxide generation versus elastase release. Human PMNs were isolated using a standard Ficoll/Hypaque gradient. PMNs were then primed with PAF (200 nM) and activated with fMLP (1 microM). Subsets of PMNs were pretreated for 5 min with a beta agonist (10(-4) M isoprotereno) or an adenylate cyclase agonist (10(-5) M forskolin). Superoxide generation was determined by superoxide dismutase inhibitive cytochrome c reduction. Elastase activity was measured by the cleavage of n-methoxylsuccinyl-A-A-P-V-p-nitroanilide. Pretreatment with isoproterenol and forskolin yielded superoxide generation of 3.2 +/- 0.6 and 3.1 +/- 1.2 nmole/2.5 x 10(5) PMN/min compared to 9.0 +/- 0.6 nmole/2.5 x 10(5) PMN/min for PAF/fMLP alone, whereas isoproterenol and forskolin did not significantly affect PAF-mediated neutrophil elastase release, 22.4 +/- 5.3 and 24.0 +/- 3.6%, respectively, compared to 39.4 +/- 9.1% for PAF/fMLP alone. Disparate PMN signal transduction for superoxide generation versus elastase release may explain the SICU clinical paradox, in which patients are both susceptible to infection and vulnerable to PMN-mediated multiple organ failure.
Molecular Physiology of Glucose Transporters

Molecular cloning of cDNA encoding the human erythrocyte facilitated-diffusion glucose transporter (GT) has elucidated its structure and has permitted a careful study of its tissue distribution and of its involvement in processes such as insulin-stimulated glucose uptake by adipose cells or transformation-induced increase in glucose metabolism. An important outcome of these studies was the discovery that additional isoforms of this transporter were expressed in a tissue-specific manner; these comprise a family of structurally and functionally related molecules. Their tissue distribution, differences in kinetic properties, and differential regulation by ambient glucose and insulin levels suggest that they play specific roles in the control of glucose homeostasis. Herein, we will discuss the structure of three members of the GT family: erythroid/brain GT, liver GT, and adipose cell/muscle GT. In the light of their tissue-specific expression, kinetic parameters, and susceptibility to insulin action, we discuss their possible specific functions.
Further investigations on the hydrolytic degradation of poly (DL-lactide)

The hydrolytic degradation of poly(DL-lactide) (PLA50) material was investigated in order to elucidate the effects of temperature and acidity of the external medium on the degradation characteristics. It was observed that at 60 degrees C and at pH = 7.4, degradation was extremely rapid as compared with degradation at 37 degrees C. After only 2 days, heterogeneous degradation was observed due to larger internal autocatalysis. On the other hand, in the case of degradation at 37 degrees C in an acidic medium with pH = 3.7, the heterogeneous degradation was preceded by a much longer lag time. Water absorption was found to be pH dependent. At pH = 7.4, water absorption was increased due to the osmotic pressure driving the buffer solution into the polymer matrix to neutralize acidic endgroups, which was not the case for degradation at pH = 3.7. In both cases, the oligomeric stereocomplex was obtained as degradation residue at the end of the degradation period.
Handbook of Creative Cities

Handbook of Creative Cities, David Emanuel Andersson, Ake E. Andersson and Charlotta Mellander (Eds), Edward Elgar, Cheltenham (2011). ix + 555 pp. US$270.00. £160.00 (hbk). ISBN 978 1 84980 150 9....
The normative environment for drug use: comparisons among American Indian and white adolescents.

The current study examined the influence of descriptive norms, injunctive norms, perceived outcome expectancies, and ethnicity on marijuana and inhalant use among 2334 American Indian (AI) and White high school students who lived on or near reservations in the United States. Hierarchical multiple regression analyses were conducted with survey data collected during the 2009–2010 and 2010–2011 school years. Results suggest differences between ethnicities in the influence of the normative environment and outcome expectancies on both marijuana and inhalant use. Study limitations are noted, and future research is suggested.
Oral clonidine prolongs lidocaine spinal anesthesia in human volunteers.

BACKGROUND Premedication with oral clonidine may improve the quality and duration of lidocaine spinal anesthesia, but this effect has not been examined in a quantitative fashion. METHODS Eight volunteers received 50 mg lidocaine (1.5% dextrose free) both with and without 0.2 mg oral clonidine 1.5 h before spinal anesthesia in a randomized, double-blind, placebo-controlled, crossover fashion. Sensory block was assessed by pinprick, transcutaneous electric stimulation equivalent to surgical incision, and duration of tolerance to pneumatic thigh tourniquet. Motor block at the quadriceps and gastrocnemius muscles was assessed by isometric force dynamometry. Episodes of bradycardia, hypotension, and sedation were recorded. RESULTS Regression of pinprick was unchanged with clonidine. However, duration of tolerance to electric stimulation was increased at the knee (28 +/- 24 min) and ankle (31 +/- 28 min) with clonidine (P < 0.05). The duration of tolerance to tourniquet-induced pain was increased with clonidine (14 +/- 12 min; P < 0.05). The duration of motor block was increased at the quadriceps (20 +/- 13 min) and gastrocnemius (33 +/- 24 min) muscle groups with clonidine (P < 0.05). Although clonidine decreased systolic blood pressure (13 +/- 4 mmHg, P < 0.003) and heart rate (13 +/- 5 beats/min; P = 0.02), no subjects had hypotension or bradycardia. The incidence of sedation was greater with clonidine than with plain lidocaine (50% vs. 0%, P < 0.04). DISCUSSION Premedication with oral clonidine prolonged sensory and motor block from lidocaine spinal anesthesia. The exact mechanism whereby oral clonidine prolongs spinal anesthesia remains to be determined.
Efficiency of separation of DNA mutations by constant denaturant capillary electrophoresis is controlled by the kinetics of DNA melting equilibrium

Constant denaturant capillary electrophoresis (CDCE) separation takes place in the heated portion of the capillary where faster-moving, unmelted DNA fragments are in equilibrium with slower-moving, partially melted forms. Within a certain temperature range, the position of the melting equilibrium and thus the average electrophoretic mobility of each mutant is different. The resulting difference in mobility allow sequences containing single base pair point mutations to be separated from each other. We report the results of experiments in which we explored the rules defining separation efficiency by varying the parameters of CDCE. We discovered an unusual peak broadening mechanism. In contrast to most other DNA electrophoresis systems, peak width in CDCE steadily decreases with the square root of the separation speed. Moreover, the peak width displays a sharp maximum at a specific temperature. To account for these observations, we use a model which describes CDCE separation as a random walk. According to this model, peaks in CDCE are broad because the kinetics of the melting equilibrium are slow and there-fore the number of random walk steps represented by melting/renaturation transitions is relatively small. In addition to providing a satisfactory interpretation of the data, the model also predicts that separation efficiency will increase as the ionic strength of the running buffer is increased and as the concentration of denaturant in the buffer is decreased. These predictions were verified and were used to establish conditions for high-resolution CDCE suitable for separating complex mixtures of single base pair mutants.
Immunosuppression of Thyroiditis

Immunization of mice with 50 micrograms human thyroglobulin (TG) in complete Freund's adjuvant leads to histological thyroiditis; production of IgG, IgA, and IgM anti-TG antibodies; and in vitro proliferative responses after incubation of lymphocytes with TG. Oral administration of 500 micrograms TG at four intervals before Tg immunization and once afterward causes up to 80% suppression of these responses. The effect is antigen specific and dose dependent. Feeding TG after immunization produces a 40% reduction in responses. We wished to define the mechanism of this antigen-specific oral tolerization. Popliteal lymph nodes (PLN) of orally tolerized animals (T) are reduced in size compared to those in immunized (I) animals not fed TG. PLN and mesenteric lymph nodes (MLN) of I animals produce interleukin-2 (IL-2) and interferon-gamma (IFN gamma) after in vitro incubation with TG, typical of an inflammatory immune response. PLN and MLN of tolerized animals do not proliferate in response to antigen, do not pro...
Amino acid residues in Std1 protein required for induction of SUC2 transcription are also required for suppression of TBPDelta57 growth defect in Saccharomyces cerevisiae

The STD1 gene of Saccharomyces cerevisiae was isolated independently as a multicopy suppressor of a dominant negative mutation in the TATA-binding protein and of a mutation in the Snf1/Snf4 kinase complex, suggesting that Std1 might couple the Snf1 kinase signaling pathway to the transcriptional machinery. In order to identify the protein domains that specify these activities of the Std1 protein, a plasmid library of randomly mutagenized STD1 genes was screened for loss of function alleles using complementation of the raffinose growth defect of a std1-, mth1- strain as an assay. One missense allele (P236S) with complete loss of function at 30 degreesC and four missense alleles (L173F, E225K, S269L and E274K) that conferred a temperature sensitive phenotype were identified. The C-terminal 20 residues of Std1 were essential for SUC2 derepression, whereas the deletion of the N-terminal 96 residues did not affect SUC2 gene induction. Std1 mutants that lost the ability to induce SUC2, were also unable to suppress the growth defect caused by the expression of the dominant negative TBPDelta57 protein, suggesting that these two genetic screens may be detecting the same biological activity.
Renal Prostaglandins: Possible Regulators of the Renal Actions of Pressor Hormones

WE describe here the release from the kidney by angiotensin II and noradrenaline of substances which have the properties of prostaglandins. This observation may help to account for the antihypertensive function of the kidney first suggested by Fasciolo1, who demonstrated that removal of the kidney contralateral to an ischaemic kidney produced sustained hypertension in dogs. We have adapted the bioassay method of Vane2, the super-fused blood-bathed organ technique, for the detection of prostaglandins in renal venous blood in response to infusions of arigioteiisin II or noradrenaline into the renal artery.
Community Behavior and Spatial Regulation within a Bacterial Microcolony in Deep Tissue Sites Serves to Protect against Host Attack

Bacterial pathogens express virulence-specific transcriptional programs that allow tissue colonization. Although phenotypic variation has been noted in the context of antibiotic exposure, no direct evidence exists for heterogeneity in virulence-specific transcriptional programs within tissues. In a mouse model of Yersinia pseudotuberculosis infection, we show that at least three subpopulations of bacteria develop within a single tissue site in response to distinct host signals. Bacteria growing on the exterior of spleen microcolonies responded to soluble signals and induced the nitric oxide (NO)-detoxifying gene, hmp. Hmp effectively eliminated NO diffusion and protected the interior bacterial population from exposure to NO-derived inducing signals. A third subpopulation, constituting the most peripherally localized bacteria, directly contacted neutrophils and transcriptionally upregulated a virulence factor. These studies demonstrate that growth within tissues results in transcriptional specialization within a single focus of microbial replication, facilitating directed pathogen counterattack against the host response.
Interferon regulatory factor-2 physically interacts with NF-κB in vitro and inhibits NF-κB induction of major histocompatibility class I and β2-microglobulin gene expression in transfected human neuroblastoma cells

Most neural cells constitutively lack major histocompatibility complex (MHC) class I and beta 2-microglobulin gene expression. Cytokines and viruses may, however, induce expression of these genes in some neural cells, and this correlates with factor binding to the NF-kappa B and interferon stimulated response elements of these genes. Here, we demonstrate that NF-kappa B is capable of inducing MHC class I and beta 2-microglobulin gene expression when transiently co-transfected into CHP-126 neuroblastomas, and that IRF-2 represses this induction. Interferon regulatory factor-2 (IRF-2) repression of MHC class I and beta 2-microglobulin gene expression in CHP-126 neuroblastomas may demonstrate a mechanism by which virus persists in neural cells. We show here that IRF-2 physically interacts in vitro with NF-kappa B. This interaction may contribute to the repression of the expression of these genes. Our demonstration that IRF family members, in addition to IRF-2, physically interact in vitro with NF-kappa B (p50 and p65), provides a general mechanism by which these transcription factors may, in concert, regulate the expression of a variety of genes involved in immune responses in the brain.
The information revealed in infinitely-repeated games of incomplete information

Zero-sum two-person games with incomplete information on one side are considered. It is shown that the information revealed by the informed player in an infinitely-repeated game with simultaneous moves is essentially the same as the information revealed by him in a one-stage game in which he must move first.
Speeding-up network reconfiguration by minimum cost maximum flow based branch exchanges

We propose a novel and efficient heuristic algorithm for solving the distribution network reconfiguration problem for loss reduction. We formulate the problem of finding incremental branch exchanges as a minimum cost maximum flow (MCMF) problem. This novel approach finds the best set of concurrent branch exchanges during each iteration of the algorithm and leads to larger loss reductions and a reduced number of iterations, hence significantly reducing the computational runtime. Experiments using distribution systems with sizes of up to 10476 buses demonstrate that the proposed technique leads to an average speed-up of 2.3x with similar or better solution quality compared to the Baran's reconfiguration technique [32].
A self-paced CAI package for selecting statistical methods

TREELAB is a package of FORTRAN IV programs, files, work sheets, and assignments for self-paced instruction in selecting statistical methods for a broad variety of empirical research purposes. It complements traditional statistics course curricula by giving students extensive practice in evaluating data sets and selecting appropriate methods according to their theoretical needs.
Overview of HZETRN and BRNTRN Space Radiation Shielding Codes

The NASA Radiation Health Program has supported basic research over the last decade in radiation physics to develop ionizing radiation transport codes and corresponding data bases for the protection of astronauts from galactic and solar cosmic rays on future deep space missions. The codes describe the interactions of the incident radiations with shield materials where their content is modified by the atomic and nuclear reactions through which high energy heavy ions are fragmented into less massive reaction products and reaction products are produced as radiations as direct knockout of shield constituents or produced as de-excitation products in the reactions. This defines the radiation fields to which specific devices are subjected onboard a spacecraft. Similar reactions occur in the device itself which is the initiating event for the device response. An overview of the computational procedures and data base with some applications to photonic and data processing devices will be given.
Reliability of diagnosis in older psychiatric patients using the structured clinical interview for DSM-III-R

We conducted one of the few studies that has examined the reliability of the Structured Clinical Interview for DSM-III-R Axis I (SCID-I) with a mixed inpatient and outpatient population of adults 55 years old and over (range, 56–84 years; mean, 67.33 years). All SCID interviews were videotaped or audiotaped and were administered by Master's-level clinicians working toward their doctorate degrees in clinical psychology. Interrater reliability estimates (kappa and percentage agreement) were calculated for current major depressive episode (47% base rate) and the broad diagnostic categories of anxiety disorders (15% base rate) and somatoform disorders (12% base rate). Kappa values were .70, .77, and 1.0. Respective percentage agreement was 85% for major depression, 94% for anxiety disorders, and 100% for somatoform disorders. Overall percentage agreement was 91%. We conclude that the SCID-I can be effectively administered by relatively inexperienced clinicians to diagnose older psychiatric patients reliably. Directions that future research might take are offered.
Effect of clinically modeled regimens on the growth response and development of resistance in human colon carcinoma cell lines

Two human colon cell lines, HCT-8 and HT-29, were exposed to 5-fluorouracil (FUra) under conditions similar to the human plasma pharmacokinetic profile achieved by a single bolus dose or a sustained i.v. infusion. The bolus treatment for 5 days caused a substantial cell kill; however, only a moderate inhibition in cell growth was obtained with sustained exposure to the clinically relevant level of 2 microM. To achieve a cell kill equivalent to the bolus method, a sustained concentration of 10 microM was required. This would constitute a 60% increase in the total area under the curve (AUC) compared with the bolus treatment. After three courses of therapy with each of the schedules, emerging cell lines displayed a similar degree of resistance. HT-29 resistant cell lines returned to the original sensitivity within a few weeks, and most of the enzymes involved in the metabolic activation of FUra returned to their pretreatment activities. However, resistance and enzymatic modifications remained in the HCT-8 line for at least 3 months. In the HCT-8 cell line derived from bolus treatment, resistance was associated with a 50-60% reduction in uridine kinase activity. In the line derived from continuous exposure, there was a 35-40% reduction in uridine kinase in addition to a greater reduction in the activity of orotate phosphoribosyltransferase. These changes in both resistant cell lines resulted in a decreased incorporation of [3H]FUra into nucleic acids and a reduced formation of di- and triphosphate nucleotides of FUra.
Bilirubin Dynamics in the Gunn Rat during Phototherapy

Abstract Bilirubin dynamics were studied in homozygous Gunn rats under normal room lighting conditions and under conditions simulating phototherapy. A kinetic model was developed for the formation, distribution, and elimination of bilirubin. The decrease in plasma bilirubin concentration during illumination with low intensity [300 footcandles (fc)] and high intensity (1000–1100 fc) light was studied. The plasma bilirubin concentration in the rats decreased under phototherapy until a new steady-state concentration was reached, the decline being more rapid under high intensity light conditions. Gunn rats were also injected with a tracer dose of 14 C-bilirubin following a period during which the rats were illuminated with low or high intensity light. The distribution and elimination of the labeled bilirubin were followed under continuous illumination. The chosen kinetic model, when adapted to the set of data under investigation, fit all of the data concerning bilirubin kinetics in Gunn rats under continuous illumination.
A phase II trial of prolonged oral etoposide (VP-16) as second-line therapy for advanced and recurrent endometrial carcinoma: A Gynecologic Oncology Group study

Prolonged oral etoposide is an active regimen in small and nonsmall cell carcinoma of the lung, carcinomas of the breast and ovary, germ cell tumors, and in lymphoma. A Phase II trial was conducted by the Gynecologic Oncology Group to determine its activity in endometrial carcinoma. Twenty-six patients with advanced or recurrent endometrial carcinoma were entered into study; one patient was ineligible because of an incorrect cell type. The remaining eligible patients were treated with etoposide at a starting dose of 50 mg/m2/day (30 mg/m2/day with prior radiotherapy) for 21 days. Based on hematologic toxicity, a dose escalation to a maximum dose of 60 mg/m2/day was prescribed. Twenty-two patients were evaluable for response and 25 were evaluable for toxicity. Fourteen had received prior radiotherapy and 24 had received prior chemotherapy. A median of two courses were given (range, 1-10). Grade 3 or 4 leukopenia occurring in 52% was the most common complication (grade 3, 36%; grade 4, 16%). Grade 4 thrombocytopenia occurred in 16% of patients. There were no objective responses including four patients with serous papillary carcinoma. This regimen is not significantly active as second-line therapy in endometrial carcinoma.
Molecular basis for evasion of plant host defence in bacterial spot disease of pepper

A fundamental objective in studying host-pathogen interactions is to determine how a pathogen evolves to overcome the defences of a previously resistant host. In mammalian systems, evolution of a pathogen population is often directed towards avoiding recognition by an immune system1–3. Although plants lack circulating antibodies and the memory response of mammalian immune systems, it is becoming increasingly clear that active resistance in plants involves recognition of the pathogen by its host4,5. In this paper we present the first molecular evidence to indicate that plant pathogens evolve to overcome resistance by evading host recognition and response. The bacterial pathogen Xanthomonas campestris pathovar vesicatoria mutates to overcome genetically defined resistance in pepper, Capsicum annuum, by the transposon-induced mutation of avrBs1 a bacterial gene that provokes the plant's resistance response.