Cell-mediated immunological responses in cervical and vaginal cancer patients immunized with a lipidated epitope of human papillomavirus type 16 E7

Human papillomavirus (HPV) infection has been causally associated with cervical cancer. We tested the effectiveness of an HLA-A*0201-restricted, HPV-16 E7 lipopeptide vaccine in eliciting cellular immune responses in vivo in women with refractory cervical cancer. In a nonrandomized Phase I clinical trial, 12 women expressing the HLA-A2 allele with refractory cervical or vaginal cancer were vaccinated with four E786-93 lipopeptide inoculations at 3-week intervals. HLA-A2 subtyping was also performed, and HPV typing was assessed on tumor specimens. Induction of epitope-specific CD8+ T-lymphocyte (CTL) responses was analyzed using peripheral blood leukapheresis specimens obtained before and after vaccination. CTL specificity was measured by IFN-gamma release assay using HLA-A*0201 matched target cells. Clinical responses were assessed by physical examination and radiographic images. All HLA-A*0201 patients were able to mount a cellular immune response to a control peptide. E786-93-specific CTLs were elicited in 4 of 10 evaluable HLA-A*0201 subjects before vaccination, 5 of 7 evaluable HLA-A*0201 patients after two vaccinations, and 2 of 3 evaluable HLA-A*0201 cultures after all four inoculations. Two of three evaluable patients' CTLs converted from unreactive to reactive after administration of all four inoculations. There were no clinical responses or treatment toxicities. The ability to generate specific cellular immune responses is retained in patients with advanced cervical cancer. Vaccination with a lipidated HPV peptide epitope appears capable of safely augmenting CTL reactivity. Although enhancements of cellular immune responses are needed to achieve therapeutic utility in advanced cervical cancer, this approach might prove useful in treating preinvasive disease.     

Electro‐optical transfer function preferences for LCD TVs: The effect of display brightness and surround illumination on preferred gamma

Abstract— Recent commercial liquid‐crystal‐display (LCD) televisions are larger and brighter than traditional televisions, thus impacting the viewing conditions in which they are viewed. These changes in viewing conditions may require different electro‐optical transfer functions (EOTFs) for LCD TVs than those for conventional TVs. Here, the way various EOTFs affect the preferred image quality of test images with changes in brightness and surround illumination conditions are examined. The first method used a gain, offset, and gamma (GOG) function with a range of gamma values, and the second method altered the intrinsic EOTFs. Image preference for the simulated EOTFs was determined using a paired‐comparison experiment for ten images. The first experiment took place in a darkened room at two display luminance levels. The results indicated that a gamma of 1.6 was most preferred overall although more so at a lower screen luminance level. In a second experiment, the procedure was repeated with a dim surround of 10% of the display's white point. With this surround, preference for a gamma value of around 1.6 at both screen luminance levels was more enhanced. These results indicated that image preference for different EOTFs is dependent on display luminance and that this dependence is maintained with a dim surround.     

Human papillomavirus-specific serologic response in vulvar neoplasia

We describe a case of positional dyspnea due to compression of the tracheobronchial tree by an extensive thoracic aneurysm. In a 77-year-old woman with long-standing systemic hypertension, intermittent anterior chest pain gradually developed over several years. She had no history of asthma or thoracic trauma. She was admitted to our hospital because of sudden, severe shortness of breath. The breathlessness was markedly worse when she lay on her back or on her right side. On physical examination, she was in acute respiratory distress with cyanosis, severe hypertension (180/110 mmHg), tachycardia, and inspiratory stridor. A chest X-ray film showed loss of volume and nearly complete radiopacity of the left hemithorax. Arterial blood gas analysis revealed an arterial oxygen partial pressure of 54.8 mmHg, a carbon dioxide partial pressure of 39.8 mmHg, and an oxygen saturation of 84.5 percent on room air. Computed tomographic examination of the thorax showed dilation of the aortic arch and descending aorta, and marked compression of the trachea and the left main bronchus. Examination with a fiberoptic bronchoscope revealed extrinsic compression of the trachea just proximal to the carina. The patient's symptoms stabilized. However, she did not undergo surgery because of her age and because of the size of the aneurysm. She died due to rupture of the aneurysm.     

Pseudo-T2 mapping for normalization of T2-weighted prostate MRI

Magnetic Resonance Materials in Physics, Biology and Medicine - Signal intensity normalization is necessary to reduce heterogeneity in T2-weighted (T2W) magnetic resonance imaging (MRI) for...     

R1-soar: an experiment in knowledge-intensive programming in a problem-solving architecture

This paper presents an experiment in knowledge-intensive programming within a general problem-solving production-system architecture called Soar. In Soar, knowledge is encoded within a set of problem spaces, which yields a system capable of reasoning from first principles. Expertise consists of additional rules that guide complex problem-space searches and substitute for expensive problem-space operators. The resulting system uses both knowledge and search when relevant. Expertise knowledge is acquired either by having it programmed, or by a chunking mechanism that automatically learns new rules reflecting the results implicit in the knowledge of the problem spaces. The approach is demonstrated on the computer-system configuration task, the task performed by the expert system R1.     

Mechanisms of cyclic softening in precipitation-hardening alloys—A ball model approach and tests at 78 K

Tests of random, alternating cuts on a ball-model of in Al–Cu alloy have been run to check the kinetics at which disordering occurs in an initially ordered precipitate subject to cyclic strain. In addition, fatigue tests at low temperature (78 K) and various microscopical observations have been made on Al–Ag alloy containing GP zones to check whether a structure containing an initially disordered precipitate will cyclically soften or not. It was thus found that the ball model disorders as a function of accumulated plastic strain consistently with the kinetics of cyclic softening in actual material. Further, Al–Ag alloy was found not to soften at 78 K. Both of these results supoort the disordering hypothesis of cyclic softening over the dissolution or shearing-off mechanisms, although other systems may be subject to these mechanisms. In spite of the low temperature at which the Al–Ag alloy was tested, small / precipitates were found to have formed in the longest lived test; however, this result did not interfere with the validity of the experiment as it did previously at room temperature. The fatigue lives at 78 K were much longer than those previously measured at room temperature although the failure mechanisms were not affected at high strain and only somewhat affected at low strain (there was increased incidence of transgranular crack nucleation and propagation).

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Résumé Des essais d'application de coups alternés et aléatoires sur un modèle de simulation par des billes de la phase dans les alliages de Cu–Al ont été effectués en vue de vérifier la cinétique suivant laquelle se produisent des désordres dans un précipité initialement ordonné et soumis à des déformations cycliques. En outre, des essais de fatigue à basse température (78°K) ainsi que diverses observations microscopiques ont été effectués sur un alliage Al–Ag comportant des zones GP en vue de vérifier si une structure comportant un précipité initialement en désordre subirait un adoucissement cyclique ou non. On a donc trouvé que le modèle de utilisant des billes fait état de désordres en fonction de l'accumulation de la déformation plastique et ce en rapport avec la cinétique d'adoucissement cyclique dans le matériau réel. En outre, l'alliage Al–Ag s'est révélé ne pas s'adoucir à 78°K. Ces deux résultats soutiennent l'hypothèse suivant laquelle un adoucissement cyclique s'accompagne de désordres plutôt que de mécanismes de disolution ou de séparation par cisaillement, bien que d'autres systèmes puissent être sujets à ces mécanismes. En dépit de la basse température à laquelle l'alliage Al–Ag a été essayé, on a trouvé de petits précipités / qui se sont formés au cours des essais, les plus longs. Cependant, ce résultat ne gène pas la validité de l'expérience comme c'était le cas précédemment à température ambiante. Les vies en fatigue à 78°K ont été trouvées bien plus longues que celles mesurées précédemment à température ambiante, en dépit du fait que le mécanisme de rupture n'ait pas été affecté sous les déformations élevées et ne l'a été que quelque peu sous les déformations faibles, auxquelles apparait une incidence croissante d'une nucléation et d'une propagation d'une fissure transgranulaire.

     

Knowledge-directed Adaptation in Multi-level Agents

Most work on adaptive agents have a simple, single layerarchitecture. However, most agent architectures support three levels ofknowledge and control: a reflex level for reactive responses, a deliberatelevel for goal-driven behavior, and a reflective layer for deliberateplanning and problem decomposition. In this paper we explore agentsimplemented in Soar that behave and learn at the deliberate and reflectivelevels. These levels enhance not only behavior, but also adaptation. Theagents use a combination of analytic and empirical learning, drawing from avariety of sources of knowledge to adapt to their environment. We hypothesize that complete, adaptive agents must be able to learn across all three levels.     

Force generation during friction stir welding of AA2024-T3

Force measurement in friction stir welding (FSW) provides a significant insight into the process in terms of machine and tool limitations and design. In the present research the tool forces were investigated experimentally using a rotating component dynamometer and through the development of a finite element model. The model correlated well with experimental temperatures and tool forces and was capable of predicting tool forces for different welding parameters, predicting regions were tool failure is likely to occur and identifying tool pin designs which can process the workpiece more efficiently.     

Building dampness diagnosing the causes

In our January/February issue last year, Jim Smith described the insights he had gained as the human expert being ‘mined’ by the knowledge engineers for an expert system to aid diagnosis of the causes of dampness in buildings. An overview of that BREDAMP project is presented here, explaining the background to the project and its objectives, and the way the expert system was created, discussing in detail the methods used to capture the depth of knowledge available.     

Spectroscopic study of carbaryl sorption on smectite from aqueous suspension

Sorption of carbaryl (1-naphthyl-N-methyl-carbamate) from aqueous suspension to smectite was studied using Fourier transform infrared (FTIR), high-performance liquid chromatography (HPLC) (for batch sorption), and quantum chemical methods. The amount of carbaryl sorbed was strongly dependent on the surface-charge density of the smectite with more sorption occurring on the two "low" surface-charge density smectites (SHCa-1 and SWy-2) compared to that of the high surface-charge SAz-1 smectite. In addition, the amount of carbaryl sorbed was strongly dependent on the nature of the exchangeable cation and followed the order of Ba approximately Cs approximately Ca > Mg approximately K > Na approximately Li for SWy-2. A similartrend was found for hectorite (SHCa-1) of Cs > Ba > Ca > K approximately Mg > Na approximately Li. Using the shift of the carbonyl stretching band as an indicator of the strength of interaction between carbaryl and the exchangeable cation, the observed order was Mg > Ca > Ba approximately K > Na > Cs. The position of the carbonyl stretching band shifted to lower wavenumbers with increasing ionic potential of the exchangeable cation. Density functional theory predicted a cation-induced lengthening of the C=O bond, resulting from the carbonyl group interacting directly with the exchangeable cation in support of the spectroscopic observations. Further evidence was provided by a concomitant shift in the opposite direction by several vibrational bands in the 1355-1375 cm(-1) region assigned to stretching bands of the carbamate N-Ccarbonyl and Oether-Ccarbonyl bonds. These data indicate that carbaryl sorption is due, in part, to site-specific interactions between the carbamate functional group and exchangeable cations, as evidenced by the FTIR data. However, these data suggest that hydrophobic interactions also contribute to the overall amount of carbaryl sorbed. For example, the FTIR data indicated thatthe weakest interaction occurred when Cs+ was the exchangeable cation. In contrast, the highest amount of carbaryl sorption was observed on Cs-exchanged smectite. Of all the cations studied, Cs has the lowest enthalpy of hydration. It is suggested that this low hydration energy provides the carbaryl with greater access to the hydrophobic regions of the siloxane surface.