cssi/SciSciGPT-SciSciNet huggingface dataset:
Automatic perceptual judgment using neural networks

The aim of the present study is to investigate the performance of automatic perceptual judgment models built with neural networks. In previous studies, Franco et al. (1997) used HMM-derived scores based on posterior probabilities of phone segments, demonstrating a high correlation with human raters. Deville et al. (1999) also used an HMM/ANN recognition approach, and showed how the results of automatic speech recognition can be used for perceptual judgments. However, since most previous studies made use of automatic speech recognition in their analysis, the present study provides a different approach: using features and raw data. Native speakers of English will listen to English sentences produced by native and non-native speakers of English, transcribe what they heard, and respond to one of three perceptual judgements: foreign-accentedness, fluency, and comprehensibility. The data will be fed into prediction models in three different ways; one with annotated features (pauses, durations, etc), another with Mel Frequency Cepstral Coefficients (MFCC), and the other with Mel-spectrograms. The performance of the models will be measured by analyzing the correlation between the judgments by models and by human raters. The preliminary results of this study will be used to build more accurate automatic proficiency judgment models.The aim of the present study is to investigate the performance of automatic perceptual judgment models built with neural networks. In previous studies, Franco et al. (1997) used HMM-derived scores based on posterior probabilities of phone segments, demonstrating a high correlation with human raters. Deville et al. (1999) also used an HMM/ANN recognition approach, and showed how the results of automatic speech recognition can be used for perceptual judgments. However, since most previous studies made use of automatic speech recognition in their analysis, the present study provides a different approach: using features and raw data. Native speakers of English will listen to English sentences produced by native and non-native speakers of English, transcribe what they heard, and respond to one of three perceptual judgements: foreign-accentedness, fluency, and comprehensibility. The data will be fed into prediction models in three different ways; one with annotated features (pauses, durations, etc), another wit...
Introduction and classification of inflammatory bowel diseases

Abstract Crohn’s disease and ulcerative colitis are the two primary forms of inflammatory bowel disease (IBD). However, IBD likely represents a wide disease spectrum based on the etiology, pathogenetic pathways, clinical presentation, and disease course. Overlaps exist between IBD and other immune-mediated disorders or chronic inflammatory disorders. On the other hand, the differential diagnosis can be difficult. Endoscopy along with histology plays a key role in the disease assessment. A detailed classification of IBD is proposed.
When Editors and Reviewers Disagree

I recall an occasion early in my career when a paper that I had reviewed and recommended for rejection was ultimately accepted by the journal editor. My initial response was to mumble “why did they...
Psychology, Politics, and Complex Thought: A Time for Postformal Thought in Politics

This chapter focuses on psychology, politics and postformal complex thought. This chapter offers a theoretical model of the components of the interaction between psychology and politics. What are the components of the current political change and drama that we all find so upsetting and confusing? Of course, there are many and this book offers a significant number of ideas. In this chapter the focus is on a few, suggesting that the situation today is influenced by elements of identity (either personal or group), by the pace of change (either fast or slow), by our ability (or lack of it) to solve these life problems in complex ways, and by emotions (especially related to fear). She examines the interconnection of those factors in the context of our current political experience (particularly our American experience) and discusses what we might do as individuals or groups to survive current upheavals by altering these factors using complex postformal problem solving.
Telehealth Use by Age and Race at a Single Academic Medical Center During the COVID-19 Pandemic: Retrospective Cohort Study.

Background: During the COVID-19 pandemic, many ambulatory clinics transitioned to telehealth, but it remains unknown how this may have exacerbated inequitable access to care. Objective: Given the potential barriers faced by different populations, we investigated whether telehealth use is consistent and equitable across age, race, and gender. Methods: Our retrospective cohort study of outpatient visits was conducted between March 2 and June 10, 2020, compared with the same time period in 2019, at a single academic health center in Boston, Massachusetts. Visits were divided into in-person visits and telehealth visits and then compared by racial designation, gender, and age. Results: At our academic medical center, using a retrospective cohort analysis of ambulatory care delivered between March 2 and June 10, 2020, we found that over half (57.6%) of all visits were telehealth visits, and both Black and White patients accessed telehealth more than Asian patients. Conclusions: Our findings indicate that the rapid implementation of telehealth does not follow prior patterns of health care disparities.
Book Reviews: African American Women in the News; Gender, Race and Class in Journalism

The representations of African American women are scattered across the multimedia landscapes of news and journalism. In her book, African American Women in the News: Gender, Race and Class in Journalism, Marian Meyers argues that these subjects are mostly hidden or portrayed in largely unflattering ways.
Context, Cognition, and Communication: Understanding how the Psychology of Location Affects Health and Medical Communication

Prior research reveals that cognition – or how the mind processes information – often guides human behavior in familiar settings (St.Amant, 2018). Such factors can affect the communication practices persons use to convey information about health concepts or medical processes (Hamm, 2003; St.Amant, 2021). The challenge becomes anticipating such connections in order to create texts and visuals audiences can understand and use to meet healthcare needs. This article presents an approach to meeting this need by applying the concept of cognitive scripts to understand and address the communication expectations audiences often associated with health and medical settings. In presenting these ideas, the article begins with an explanation of how cognitive scripts can affect communication processes. From there, the author advocates applying script dynamics to health and medical communication practices. To do so, the author expands upon ideas in the literature on cognitive scripts to create a script-based approach for researching an audience’s expectations of healthcare situations. The author then describes how to apply the information collected from this research to create communication materials audiences can more easily use in healthcare contexts. The result is a three-factor method that focuses on applying cognitive scripts to identify and address an audience’s expectations for healthcare communication in a given context. Readers can then use this approach to design healthcare communication materials that audiences can easily and effectively use.
The revolution, 1917–1921

No event since the French Revolution has occasioned such an outpouring of historical scholarship and such passionate debate as the Russian Revolution. The interest and the engagement are understandable, for the issues are complex and the stakes are high. The revolution was not simply a most significant event in Russian history, transforming an antiquated society and changing the way of life of millions: it was also a catalyst in the development of our world. For better or worse, the interpretation of the revolution was not confined to historians; people from all segments of the political spectrum have always been aware of the political significance of historiography. All aspects of the revolution have been well covered by historians, but none has received as much attention as the history of the revolutionary movement. This is understandable: revolutionaries fighting against the repressive tsarist regime were often willing to sacrifice their lives for a cause they deeply believed in. Many of them were extraordinary men and women, and their stories are fascinating. However, it may be an error to look for an explanation of the revolution in the work of underground subversives, for neither the tsarist government nor the Provisional Government were brought down by revolutionaries, or even primarily by discontented workers and peasants. It may be more fruitful to think of the events of 1917 as the collapse of two different systems of government, first the autocratic and then the liberal. The decisive questions were not why the workers were dissatisfied and what exactly they wanted, but how and why different forms of government disintegrated. According to this view the revolutionary events were the manifestation of a crisis in authority. The fundamental question was a political one: how could Russia be governed? It follows from this understanding of the revolution that the Bolshevik success in October was not the culmination or end of the revolution, but the nadir of the crisis. The question of what form of government was necessary for Russia under exceptionally difficult circumstances was truly resolved only by the civil war.
Rumbling geysers (and volcanoes)

Volcanologists take an especial interest in geysers because in some respects they can act as proxies for the processes going on in volcanoes. Research into tremor (ground vibration) at Old Faithful in Yellowstone Park has however revealed no evidence of acoustic organ-pipe resonance in the geyser's water column, thereby casting doubt on the importance accorded to resonance in most models of volcanic tremor.
Possible effects of charge frustration in NaxCoO2: Bandwidth suppression, charge orders, and resurrected resonating valence bond superconductivity

Charge frustration due to further neighbor Coulomb repulsion can have dramatic effects on the electronic properties of NaxCoO2 in the full doping range. It can significantly reduce the effective mobility of the charge carriers, leading to a low degeneracy temperature epsilonF<~T. Such strongly renormalized Fermi liquid has rather unusual properties—from the point of view of the ordinary metals with epsilonFT—but similar to the properties that are actually observed in the NaxCoO2 system. For example, we show that the anomalous thermopower and Hall effect observed in Na0.7CoO2 may be interpreted along these lines. If the repulsion is strong, it can also lead to charge order; nevertheless, away from the commensurate dopings, the configurational constraints allow some mobility for the charge carriers, i.e., there remains some "metallic" component. Finally, the particularly strong bandwidth suppression around the commensurate x = 1/3 can help resurrect the resonating valence bond superconductivity, which would otherwise not be expected near this high doping. These suggestions are demonstrated specifically for a tJ-like model with an additional nearest-neighbor repulsion.
Predictors of all-cause and cardiovascular disease mortality in type 2 diabetes: Diabetes Heart Study

Background Many studies evaluated the best predictors for cardiovascular disease (CVD) events in individuals with type 2 diabetes (T2D), but few studies examined the factors most strongly associated with mortality in T2D. The Diabetes Heart Study (DHS), an intensively phenotyped family-based cohort enriched for T2D, provided an opportunity to address this question.
Microscopy in magnetic resonance imaging

The notion of using magnetic resonance imaging (MRI) as a microscopic tool for obtaining three-dimensional images of living and nonliving material was envisioned early in the history of this technology. In this review we begin with a short discussion highlighting how imaging time is drastically lengthened as image resolution is increased. Obtaining sufficient signal and contrast is crucial in any imaging experiment and of particular importance in microscopic resolution MRI because of the intrinsically low sensitivity of the magnetic resonance phenomenon. In Section 2, we consider sources and ways to deal with signal and noise. In Sections 3 and 4, sample characteristics and how they can be taken advantage of with different MR imaging methods to provide high information content images are discussed. q-Space (displacement) imaging discussed in Section 5 is somewhat peculiar to microscopic MRI, while the notion of multimodal imaging is gaining acceptance at all scales. Section 6 is devoted to recent applications across a broad spectrum, but emphasizing biological samples. We conclude with a brief discussion of prospects for achieving higher resolution images in reasonable time spans.
Argonaute Journeys into the Heart of RISC

Identifying the "slicer" component of the RNA-induced silencing complex (RISC) complex has been a major goal of those interested in the RNA interference pathway of gene silencing. In their Perspective, [Sontheimer and Carthew][1] discuss a pair of recent studies ([ Liu et al .][2], [ Song et al .][3]) that identify the protein Argonaute2 as the slicer element of RISC that cleaves target messenger RNAs. [1]: http://www.sciencemag.org/cgi/content/full/305/5689/1409 [2]: http://www.sciencemag.org/cgi/content/short/305/5689/1437 [3]: http://www.sciencemag.org/cgi/content/short/305/5689/1434
Tryptophan hydroxylase 2 aggregates through disulfide cross-linking upon oxidation: possible link to serotonin deficits and non-motor symptoms in Parkinson's disease

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopamine neurons of the nigrostriatal system, resulting in severe motor disturbances. Although much less appreciated, non-motor symptoms are also very common in PD and many can be traced to serotonin neuronal deficits. Tryptophan hydroxylase (TPH) 2, the rate-limiting enzyme in the serotonin biosynthesis, is a phenotypic marker for serotonin neurons and is known to be extremely labile to oxidation. Therefore, the oxidative processes that prevail in PD could cause TPH2 misfolding and modify serotonin neuronal function much as is seen in dopamine neurons. Oxidation of TPH2 inhibits enzyme activity and leads to the formation of high molecular weight aggregates in a dithiothreitol-reversible manner. Cysteine-scanning mutagenesis shows that as long as a single cysteine residue (out of a total of 13 per monomer) remains in TPH2, it cross-links upon oxidation and only cysteine-less mutants are resistant to this effect. The effects of oxidants on TPH2 catalytic function and cross-linking are also observed in intact TPH2-expressing HEK293 cells. Oxidation shifts TPH2 from the soluble compartment into membrane fractions and large inclusion bodies. Sequential non-reducing/reducing 2-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting confirmed that TPH2 was one of a small number of cytosolic proteins that form disulfide-bonded aggregates. The propensity of TPH2 to misfold upon oxidation of its cysteine residues is responsible for its catalytic lability and may be related to loss of serotonin neuronal function in PD and the emergence of non-motor (psychiatric) symptoms.
Recent Photometric Observations of Nova-Like Variables

For a variety of reasons changes in the orbital periods of binary, nova-like variables are expected to occur. Photoelectric observations provide the most direct means of establishing such variations for those objects that have been found to eclipse. However, in the 15 to 20 years that have elapsed since periods for many were first determined, timings of additional minima have only been obtained sporadically. In many instances the coverage is neither complete nor up-to-date.
Tropical North Atlantic ocean-atmosphere interactions synchronize forest carbon losses from hurricanes and Amazon fires

©2015. American Geophysical Union. All Rights Reserved. We describe a climate mode synchronizing forest carbon losses from North and South America by analyzing time series of tropical North Atlantic sea surface temperatures (SSTs), landfall hurricanes and tropical storms, and Amazon fires during 1995-2013. Years with anomalously high tropical North Atlantic SSTs during March-June were often followed by a more active hurricane season and a larger number of satellite-detected fires in the southern Amazon during June-November. The relationship between North Atlantic tropical cyclones and southern Amazon fires (r = 0.61, p < 0.003) was stronger than links between SSTs and either cyclones or fires alone, suggesting that fires and tropical cyclones were directly coupled to the same underlying atmospheric dynamics governing tropical moisture redistribution. These relationships help explain why seasonal outlook forecasts for hurricanes and Amazon fires both failed in 2013 and may enable the design of improved early warning systems for drought and fire in Amazon forests.
Challenges in early operative approaches to intramedullary spinal cord tumors: Harvey Cushing's perspective.

Although Harvey Cushing was mostly known for his contributions to brain tumor surgery, he was also a pioneer in the development of spinal cord surgery. This lesser known facet of Cushing’s career can provide a fresh and unique perspective into how the founders of neurosurgery surmounted early challenges in the field. The authors bring to light and examine for the first time Cushing’s unpublished writing “Technique of Laminectomy” along with his first 3 documented intramedullary spinal cord tumor (IMSCT) cases at the Johns Hopkins Hospital. The authors draw lessons from the challenges in pathological classification, preoperative diagnosis, tumor localization, and surgical technique ofthat time. Although Cushing’s attempts at exploration and resection of IMSCT as described here were of limited success, his ability to adapt his clinical and surgical technique to the challenges of the time, as well as develop skills to successfully manipulate the spinal cord during these exploratory procedures without the pat...
Bacterial reduction of selenite to elemental selenium

Abstract It is well known that many microorganisms can reduce the highly toxic soluble selenium oxyanions (selenate and selenite) to a much less toxic insoluble form, namely elemental selenium. We are developing a bacterial treatment system to mitigate selenium-contaminated waste streams using Pseudomonas fuorescens and Bacillus subtilis , respectively, as model Gram (−) and (+) soil bacteria. Our studies demonstrate that both strains reduce selenite to elemental selenium. The selenite detoxification system is independent of nitrite and sulfite electron acceptors, but dependent on the substrate provided for growth. Elemental selenium is deposited as granules throughout the cell, or between the cell wall and the plasma membrane in P. fuorescens and B. subtilis , respectively. In B. subtilis , thioredoxin is induced in the presence of selenite.
Ethanol alters cellular activation and CD14 partitioning in lipid rafts.

Abstract Alcohol consumption interferes with innate immunity. In vivo EtOH administration suppresses cytokine responses induced through Toll-like receptor 4 (TLR4) and inhibits TLR4 signaling. Actually, EtOH exhibits a generalized suppressive effect on signaling and cytokine responses induced by through most TLRs. However, the underlying mechanism remains unknown. RAW264.7 cells were treated with LPS or co-treated with EtOH or with lipid raft-disrupting drugs. TNF-α production, IRAK-1 activation, and CD14 partition were evaluated. EtOH or nystatin, a lipid raft-disrupting drug, suppressed LPS-induced production of TNF-α. The suppressive effect of EtOH on LPS-induced TNF-α production was additive with that of methyl-β-cyclodextrin (MCD), another lipid raft-disrupting drug. EtOH interfered with IRAK-1 activation, an early TLR4 intracellular signaling event. Cell fractionation analyses show that acute EtOH altered LPS-related partition of CD14, a critical component of the LPS receptor complex. These results suggest a novel mechanism of EtOH action that involves interference with lipid raft clustering induced by LPS. This membrane action of EtOH might be one of the mechanisms by which EtOH acts as a generalized suppressor for TLR signaling.
Lymphatic vascular integrity is disrupted in type 2 diabetes due to impaired nitric oxide signalling

Aims Lymphatic vessel dysfunction is an emerging component of metabolic diseases and can lead to tissue lipid accumulation, dyslipidaemia, and oedema. While lymph leakage has been implicated in obesity and hypercholesterolaemia, whether similar lymphatic dysfunction exists in diabetes has not been investigated. Methods and results To measure the lymphatic integrity of transgenic mice, we developed a new assay that quantifies the solute permeability of murine collecting lymphatic vessels. Compared with age-matched wild-type (WT) controls, the permeability of collecting lymphatics from diabetic, leptin receptor-deficient ( db/db ) mice was elevated >130-fold. Augmenting nitric oxide (NO) production by suffusion of l-arginine rescued this defect. Using pharmacological tools and eNOS−/− mice, we found that NO increased WT lymphatic permeability, but reduced db/db lymphatic permeability. These conflicting actions of NO were reconciled by the finding that phosphodiesterase 3 (PDE3), normally inhibited by NO signalling, was active in db/db lymphatics and inhibition of this enzyme restored barrier function. Conclusion In conclusion, we identified the first lymphatic vascular defect in type 2 diabetes, an enhanced permeability caused by low NO bioavailability. Further, this demonstrates that PDE3 inhibition is required to maintain lymphatic vessel integrity and represents a viable therapeutic target for lymphatic endothelial dysfunction in metabolic disease.
Pulsed-ion study of ultrasonically generated turbulence in superfluid 4He

Abstract A pulsed-ion method is used to investigate the turbulent field generated by a beam of ultrasound. Basic information about how ions interact with the vortex tangle is obtained. Global line-density profiles which show how the turbulence convects away from the excited region are also presented.
Where the Jobs Are: Employment Access and Crime Patterns in Cleveland

Economists and criminologists have long tried to establish linkages between job markets and crime. Most prior research, however, used large areas such as the whole nation, states, metropolitan areas, or counties to identify job markets. Such large units are heterogeneous, and there may be more variation within such units than between them. This research uses two GIS–based methods to measure job access across census tracts in Cleveland, Ohio in 1990. The first is a ratio of jobs to resident workers (JR ratio) within catchment areas defined by reasonable commuting times. The second approach is a gravity–based job–accessibility index, which accounts for job competition among workers and longer commute times for public transit riders. Controlling for spatial autocorrelation, we find consistent inverse relationships between gravity–based job accessibility and crime rates. These relationships tend to be stronger for economic crimes than for crimes of violence.
Fetal Heart Rate Classification Using Generative Models

This paper presents novel methods for classification of fetal heart rate (FHR) signals into categories that are meaningful for clinical implementation. They are based on generative models (GMs) and Bayesian theory. Instead of using scalar features that summarize information obtained from long-duration data, the models allow for explicit use of feature sequences derived from local patterns of FHR evolution. We compare our methods with a deterministic expert system for classification and with a support vector machine approach that relies on system-identification and heart rate variability features. We tested the classifiers on 83 retrospectively collected FHR records, with the gold-standard true diagnosis defined using umbilical cord pH values. We found that our methods consistently performed as well as or better than these, suggesting that the use of GMs and the Bayesian paradigm can bring significant improvement to automatic FHR classification approaches.
The present status of irradiation of foods in the U.S.A.--milk and milk products.

Milk is one of the most sensitive of all foods to flavor and odor changes that occur during irradiation. Work in eliminating the off-flavor constituents from milk and milk products during irradiation is reviewed. (C.H.)
Mechanisms of blood pressure elevation in pyelonephritic rats after sodium loading.

SummaryRats with experimental chronic pyelonephritis were given a high sodium diet with fluid ad libitum and their body composition was determined. The rats with more severe pyelonephritis developed mild to moderate hypertension but analysis of fluid volumes and body electrolyte composition revealed no significant differences from normotensive pyelonephritic rats and nonpyelonephritic rats given the same diet. The results suggest that the elevation of blood pressure which develops in these rats is a consequence of an eventual increase in peripheral resistance, which results from processes of autoregulation following exposure to the increased sodium and fluid load.
GAS CHROMATOGRAPHY AND TITRIMETRY FOR THE ANALYSIS OF CERTAIN MEDICINAL AMINES IN AEROSOLS.

A comparison was made of various methods which could be utilized to determine quantitatively various medicinal amines used in a pressurized dosage form. The medicinal amines investigated during this study were atropine N.F., butacaine, ephedrine (anhydrous) N.F., tuaminoheptane, and propylhexedrine U.S.P. The conditions necessary for the chromatographic analysis were established initially using liquid samples of the medicinal amines dissolved in acetone, nitrobenzene, ethanol, and/or chloroform. Once these conditions were established, the aerosol formulation containing the medicinal amine was analyzed by gas chromatography. A procedure for sampling the aerosol was developed, so that those medicinal aerosol products containing amines also could be analyzed by several existing methods of analysis. A titrimetric method was used for each aerosol as a means of comparison for the gas chromatographic analysis. Atropine and butacaine aerosols could not be determined by gas chromatography. Tuaminoheptane and propylhexedrine were assayed by gas chromatography from a nitrobenzene solution, while ephedrine was assayed from an acetone solution. The results of this investigation indicate the effectiveness of these two methods and show their application to the analysis of aerosol products.
Self-care intervention to reduce oral candidiasis recurrences in HIV-seropositive persons: a pilot study.

– Objectives: This single-blind randomized controlled pilot study evaluated the efficacy of a behavioral intervention program, PRO-SELF: Candidiasis, to reduce time to recurrence of oral candidiasis over 6 months in susceptible HIV-seropositive persons. The intervention involved instruction by dentists on improving oral hygiene, minimizing sugar intake, and self-diagnosing candidiasis. Methods: Participants were adults with oral candidiasis responsive to antifungals who presented to the UCSF Stomatology Clinic between 1997 and 2000. At 2–3 weeks of follow-up visits, a dentist ‘examiner’, masked to group assignment, quizzed participants as to the presence of candidiasis, and assessed candidiasis status. A second, unmasked dentist ‘instructor’ then delivered the program to intervention participants. Participants recorded dietary and oral hygiene practices in 24-h recall diaries: intervention participants at each visit and controls at initial and final visits. Results: At randomization, CD4+ cell counts (cells/mm3) were 298 ± 188 among 18 intervention participants and 396 ± 228 among 17 controls. The candidiasis recurrence rates at 6 months were 78% among intervention compared with 88% among control participants (hazard ratio 0.72; 95% CI 0.35–1.50). Performing oral hygiene after meals/snacks showed the largest relative improvement: intervention–control difference in proportion of meals/snacks affected was 24% (95% CI −1 to 48%). Self-diagnoses of candidiasis were inaccurate, possibly because of mild episodes. Conclusions: The results weakly indicate that regular instruction from healthcare professionals helps patients delay candidiasis recurrence by improving oral hygiene. Among HIV-seropositive persons, those with poor oral hygiene, and high-sugar diets are most likely to benefit.
Numerical Modelling for the Hydraulic Performance Prediction of Automotive Monotube Dampers

SUMMARY A computer model of an automotive monotube damper is developed based on fundamental principles of mechanics. The model can identify the required damper valve and/or size for the desired performance and hence speed the design process. Also, a parametric study can be easily conducted to understand the effects of parameters on the performance. A typical monotube damper is introduced and numerical formulations are described. Satisfactory agreement is achieved between model results and test data for a wide range of parameters including stroke conditions, valve combinations, and gas charge pressure. Some of these results are presented including the correlation at low and high speed strokes, cavitation simulation, and thermal effects on the performance.
Modeling Transient Pupillary Light Reflex Induced by a Short Light Flash

A pupillary light reflex (PLR) model was proposed in this paper by considering the iris muscle mechanical properties and modulation inputs from both parasympathetic and sympathetic systems. The model can describe very well the experimental PLR responses induced by a short light flash of various intensities. In addition, an inverse method was developed to fit numerically this model to experimental PLR data. The model was tested in experimental human PLR data to extract separately the parasympathetic and sympathetic modulations during PLR. The results indicated a higher parasympathetic and a lower sympathetic activity in females than in males, which was consistent with previous findings in cardiovascular studies. This new model may help improve our understanding of the PLR process and could be applied to analyze autonomic nervous interaction during pupillary responses.
Generation of stable CD4+ and CD8+ T cell lines from patients immunized with ras oncogene-derived peptides reflecting codon 12 mutations.

Previous studies have identified and characterized both murine in vivo and human in vitro T cell responses reflecting specific mutations in the ras proto-oncogenes at codon 12, 13, or 61. In an attempt to determine whether peptide epitopes reflecting point mutations in the ras oncogenes are immunogenic in humans for the production of CD4+ and/or CD8+ T cell responses, a phase I clinical trial was initiated in metastatic carcinoma patients whose primary tumors harbor mutations in the K-ras proto-oncogenes at codon 12. The peptides used here as immunogens, which were administered in Detox adjuvant, spanned the ras sequence 5-17 and reflected the amino acid substitution of glycine (Gly) at position 12 to aspartic acid (Asp), cysteine (Cys), or valine (Val). Three of eight evaluable patients have demonstrated peptide-specific cell-mediated immunity, as determined by the production of T cell lines resulting from the vaccination. First, an antigen (Ag)-specific, major histocompatibility complex (MHC) class II (DP)-restricted CD4+ T cell line was established in vitro from postvaccination lymphocytes of a non-small cell lung carcinoma patient whose primary tumor contained a Cys12 mutation when cultured on the immunizing peptide. Moreover, CD4+ proliferation was inducible against the corresponding mutant K-ras protein, suggesting productive T cell receptor recognition of exogenously processed Ag. Second, an Ag-specific, MHC class I (HLA-A2)-restricted CD8+ cytotoxic T lymphocyte (CTL) line was established in vitro from postvaccination lymphocytes of a colon carcinoma patient whose primary tumor contained an Asp12 mutation. To that end, a 10-mer peptide, nested within the 13-mer immunizing peptide, was identified [i.e., ras5-14(Asp12)], which was shown to bind to HLA-A2 and display specific functional capacity for expansion of the in vivo primed CD8+ CTL precursors. Third, both Ag-specific, MHC class II (DQ)-restricted CD4+ and MHC class I-restricted (HLA-A2) CD8+ T cell lines were generated from a single patient with duodenal carcinoma whose primary tumor contained a Val12 mutation when cultured on the immunizing 13-mer peptide or a nested 10-mer peptide [i.e., ras5-14(Val12)], respectively. Evidence is thus provided that vaccination with mutant ras oncogene peptides in adjuvant may induce specific anti-ras cellular immune responses, with no detectable cross-reactivity toward normal proto-ras sequences. Moreover, we have identified for the first time human HLA-A2-restricted, CD8+ CTL epitopes reflecting specific point mutations in the K-ras oncogenes at codon 12 which, in concert with the activation of the CD4+ T cell response, may have important implications for both active and passive immunotherapies in selected cancer patients.
Optical monitoring of transmitter release and synaptic vesicle recycling at the frog neuromuscular junction

1. Frog cutaneous pectoris motor nerve terminals were loaded with the fluorescent dye FM1-43, which produced a series of discrete spots along the length of terminals, each spot evidently marking a cluster of synaptic vesicles. Terminals were imaged for 2-10 min as they destained during repetitive nerve stimulation. Endplate potentials (EPPs) were recorded simultaneously from the muscle fibres innervated by these terminals; their summed amplitudes provided a measure of cumulative transmitter release. 2. Individual fluorescent spots in any one terminal varied in initial brightness but destained at similar fractional rates. 3. The rates of cumulative transmitter release and destaining increased with stimulus frequency in the range 2-30 Hz. At 40 Hz, however, both transmitter release and destaining were slower than at 30 Hz. 4. In twenty-six experiments, rates of dye loss and transmitter release were compared quantitatively. When the time course of summed EPPs was scaled to fit the time course of dye loss during the first 30-60 s of destaining, the two curves usually diverged at later times, the dye loss curve falling below the summed EPP curve. Thus, assuming that dye loss and transmitter release are proportional at early times, at later times the rate of dye loss decreases relative to the rate of transmitter release. 5. At stimulus frequencies from 2 to 30 Hz, the results could be fitted by a simple model in which vesicles lose their dye during exocytosis and, after a fixed recycle 'dead time', they re-enter the vesicle pool, mixing randomly with other vesicles. 6. Unlike stimulation at lower frequencies, at 40 Hz dye loss and summed EPP amplitude curves did not significantly diverge. Stimulation periods lasted up to about 2 min. Interpreted according to the model of vesicle recycling, this suggests that vesicle recycling is inhibited at 40 Hz. 7. The model led to predictions about the relative number, N, of vesicles (labelled and unlabelled) in the terminal at any time during stimulation. The calculated value of N decreased at times less than the recycle 'dead time', and then increased, reflecting the appearance of recycled vesicles in the vesicle pool. 8. From estimates of N and recorded EPP amplitudes, the fraction of vesicles released per shock, F, could be calculated during the entire stimulation period. At low stimulus frequencies (2-5 Hz), after an initial rapid fall, F decreased slowly and monotonically by about 50% in 6 min. At higher stimulus frequencies, a different process was observed.(ABSTRACT TRUNCATED AT 400 WORDS)
Equine oocyte in vitro maturation: influences of sera, time, and hormones.

Objectives of the present research were to determine the influences of types of media, sera, time and hormones on equine oocyte in vitro maturation (IVM). The following types of media and sera were evaluated: Menezo's B2 medium (B2), modified Tissue Culture Medium 199 (TCM), Defined Medium (DM), fetal calf serum (FCS), mare serum collected on the first day of estrus (MS), and mare serum collected on the day of ovulation (MSO). Resultant oocyte maturation was compared with the control: DM with bovine serum albumin (BSA). Effect of culture time (0, 15, and 32 hr) and the following hormones on oocyte IVM were evaluated: none, bovine luteinizing hormone (bLH; 1, 10, 100 μg/ml), equine luteinizing hormone (eLH; 100 μg/ml), bovine follicle-stimulating hormone (FSH; 5 μg/ml), and equine chorionic gonadotropin (eCG; 1 and 100 IU/ml). Cumulus expansion in the media and sera experiments was 50% (DM with BSA), 80% (TCM, B2, and DM with MS or MSO), and 100% (FCS with any medium). The proportion of metaphase II (MII) oocytes was significantly (P < 0.05) increased by MS, MSO, and FCS as compared with the control (BSA). In vitro culture for either 15 or 32 hr significantly (P < 0.05) increased the percentage of MII oocytes as compared with 0 hr of culture. Cumulus expansion in the hormone experiments was 80% (none, bLH, and eLH), and 100% (eCG and FSH). Freshly prepared bLH significantly (P < 0.05) inhibited nuclear maturation of equine oocytes. In summary, 15 hr of culture was sufficient time for equine oocyte IVM and all combinations of medium, serum, and hormone addition were equally effective in achieving IVM except fresh bLH and DM with BSA.
Measuring the structure of expertise

This report reviews work on defining and measuring conceptual structures of expert and novice fighter pilots. Individuals with widely varying expertise were tested. Cognitive structures were derived using multidimensional scaling (MDS) and link-weighted networks (Pathfinder). Experience differences among pilots were reflected in the conceptual structures. Detailed analyses of individual differences point to factors that distinguish experts and novices. Analysis of individual concepts identified areas of agreement and disagreement in the knowledge structures of experts and novices. Applications in selection, training and knowledge engineering are discussed.
Cross-modal re-organization in adults with early stage hearing loss.

Cortical cross-modal re-organization, or recruitment of auditory cortical areas for visual processing, has been well-documented in deafness. However, the degree of sensory deprivation necessary to induce such cortical plasticity remains unclear. We recorded visual evoked potentials (VEP) using high-density electroencephalography in nine persons with adult-onset mild-moderate hearing loss and eight normal hearing control subjects. Behavioral auditory performance was quantified using a clinical measure of speech perception-in-noise. Relative to normal hearing controls, adults with hearing loss showed significantly larger P1, N1, and P2 VEP amplitudes, decreased N1 latency, and a novel positive component (P2’) following the P2 VEP. Current source density reconstruction of VEPs revealed a shift toward ventral stream processing including activation of auditory temporal cortex in hearing-impaired adults. The hearing loss group showed worse than normal speech perception performance in noise, which was strongly correlated with a decrease in the N1 VEP latency. Overall, our findings provide the first evidence that visual cross-modal re-organization not only begins in the early stages of hearing impairment, but may also be an important factor in determining behavioral outcomes for listeners with hearing loss, a finding which demands further investigation.
Rosette-type tegumental glands associated with aesthetasc sensilla in the olfactory organ of the Caribbean spiny lobster, Panulirus argus

The lateral antennular flagellum of decapod crustaceans bears unique olfactory sensilla, namely the aesthetascs, and other sensilla types. In this study, we identify a new major tissue in the lateral flagellum of the Caribbean spiny lobster, Panulirus argus, namely "aesthetasc tegumental glands" (ATGs), based on immunostaining with antibodies against CUB serine protease (Csp), in situ hybridization with csp-specific probes, labeling with the F-actin marker phalloidin, labeling with the nuclear marker Hoechst 33258, and staining with methylene blue. Each ATG has 12-20 secretory cells arranged in a rosette. Each secretory cell has a Csp-immunoreactive basal portion and an apical portion containing granular material (metachromatic staining indicative of acid mucopolysaccharides). At the center of each secretory rosette is a phalloidin-positive common locus that gives rise to a main drainage duct projecting toward the cuticle. Scanning electron and light microscopy show that thin ducts traverse the cuticle and connect to "peg pores" proximal to the bases of the aesthetascs, with 3.4 peg pores per aesthetasc. Since the number of common loci is correlated with the number of peg pores, we conclude that each pore represents the outlet of one ATG, and that the secretions are released from them. We conclude further that ATGs and aesthetascs are functionally linked. We hypothesize that ATG secretions have antifouling and/or friction-reducing properties, and that they are spread over the surface of the aesthetascs by antennular grooming. A review of the literature suggests that ATGs are common in decapod crustacean antennules, and that rosette glands and grooming might be functionally coupled in other body areas.
Maternal inheritance of Cre activity in a Sox2Cre deleter strain

Summary: The Sox2 gene is expressed in several undifferentiated cell types. In an earlier study we described a Sox2Cre transgene that mediates epiblast-specific Cre-mediated modification of gene activity in the embryo. Here we report that this transgene is active in the female germline. Consequently, all offspring that arise from female mice heterozygous for the Sox2Cre transgene have demonstrable Cre activity irrespective of whether they inherit the transgene itself. Maternal inheritance of Cre activity allows the efficient modification of gene activity for functional analysis. genesis 37:51–53, 2003. © 2003 Wiley-Liss, Inc.
Ceguera nocturna y xeroftalmía tras cirugía de obesidad mórbida

espanolCaso clinico: Se describen los hallazgos oculares debidos a un deficit de vitamina A en un varon de 50 anos. Fue sometido a una cirugia de bypass intestinal dos anos antes. Despues de tratamiento con vitamina A oral, los sintomas mejoraron. Discusion: La incidencia de obesidad morbida sigue aumentando alarmantemente en todo el mundo, siendo actualmente el tratamiento mas adoptado en la mayoria de los pacientes la cirugia de bypass intestinal. Este tipo de cirugia puede provocar un deficit de vitamina A, con importantes consecuencias oftalmologicas, que podrian incluso llegar a la ceguera sin un correcto tratamiento. Por consiguiente, se deberia considerar seriamente esta patologia hasta ahora poco frecuente en paises desarrollados. EnglishCase report: We describe ocular findings due to a vitamin A deficiency in a 50-year-old man. The patient had undergone intestinal bypass surgery two years before. After therapy with oral vitamin A the symptoms improved. Discussion: The incidence of morbid obesity is increasing throughout much of the developed world, with intestinal bypass surgery the treatment of choice for most people with the condition. This type of surgery can lead to a vitamin A deficiency, with remarkable ophthalmological consequences, which without correct treatment may ultimately cause blindness. For this reason, the pathology, even though rare at present, must considered seriously.
The significance of stimuli on conservation of number with educable mentally retarded children.

Summary. This investigation studied the differential effects of the significance of stimuli on educable mentally retarded (EMR) children in a conservation of number experiment. The sample consisted of 30 low and 30 middle SES children attending classes for the EMR. The effect of using candies or paper-clips was investigated in Piaget's one-to-one correspondence task. A significant interaction between SES and the significance of stimuli was found. This was discussed in terms of the possible misdiagnosis of lower class children, multiple criteria diagnostic procedures, and the relevance of cues.
Simple delayed discrimination of tastes in the rat

Although taste memory has been extensively studied within the context of long-delay taste aversion learning, little attention has been devoted to taste memory within more traditional memory designs, for example, simple delayed discriminations. This was examined in the present experiment. Specifically, following taste discrimination training during which responding was reinforced following exposure to only one of two tastes, delays were imposed between sampling of the initial taste and the opportunity to respond. On the average, subjects were able to perform the simple delayed taste discrimination with an accuracy of 80% or better at a delay of 45 sec. Discrimination performance returned to chance at an average delay of 58 sec. Taste memory within the simple delayed discrimination paradigm is discussed and compared with other assessments of short-term memory in the rat and other species.
Metabolic engineering of Methylobacterium extorquens AM1 for 1-butanol production

Butanol is a promising next generation fuel and a bulk chemical precursor. Although clostridia are the primary industrial microbes for the fermentative production of 1-butanol, alternative engineered hosts have the potential to generate 1-butanol from alternative carbon feedstocks via synthetic metabolic pathways. Methylobacterium extorquens AM1, a facultative methylotrophic α-proteobacterium, is a model system for assessing the possibility of generating products such as 1-butanol from one-carbon and two-carbon feedstocks. Moreover, the core methylotrophic pathways in M. extorquens AM1 involve unusual coenzyme A (CoA)-derivative metabolites, such as crotonyl-CoA, which is a precursor for the production of 1-butanol. In this work, we engineered a modified CoA-dependent pathway in Methylobacterium extorquens AM1 to produce 1-butanol. Engineered strains displayed different 1-butanol titers using ethylamine as a substrate. A strain overexpressing Treponema denticola trans-enoyl-CoA reductase, Clostridium acetobutylicum alcohol dehydrogenase, and native crotonase was able to generate the highest 1-butanol titer (15.2 mg l-1). In vitro isotopic tracing of metabolic flux and in vivo metabolite analysis showed the accumulation of butyryl-CoA, demonstrating the functionality of the synthetic pathway and identifying targets for future improvement. We demonstrated the feasibility of using metabolic intermediates of the ethylmalonyl-CoA pathway in M. extorquens AM1 to generate value-added chemicals, with 1-butanol as the test case. This will not only establish the biotechnological potential of the ethylmalonyl-CoA pathway, but will also introduce M. extorquens AM1 as a potential platform to produce value-added chemicals.
Temperature dependence of impurity mode frequencies in a displacive ferroelectric

Abstract The temperature dependence of impurity phonon modes in a displacive ferroelectric has been investigated above the Curie point. It is predicted that the frequencies of these modes will in general show a dip at the Curie temperature due to the presence of soft mode. An anomalous behaviour for a very low frequency resonance mode is discussed. Estimates of the magnitude of the frequency shifts indicates that they should be measurable.