gebhart/patrepeval huggingface dataset:
Abstract 1888: MM-111, a bispecific HER2 and HER3 antibody, inhibits trastuzumab-resistant tumor cell growth (2012)

Abstract Amplification of human epidermal growth factor receptor 2 (HER2) occurs in approximately 25% of breast cancers and is associated with increased disease recurrence and poor prognosis. Trastuzumab, a monoclonal antibody targeting HER2, has demonstrated clinical benefit in HER2 over-expressing tumors. However, acquired resistance and disease progression is widely observed in patients treated with trastuzumab. In this experiment our objectives were to dissect the dynamic, molecular mechanisms involved in acquired resistance to trastuzumab and to determine whether MM-111, a novel bispecific antibody fusion protein that specifically targets the HER2/HER3 heterodimer and blocks heregulin binding to HER3, has activity in trastuzumab-resistant tumor cells. BT474 cells were cultured in the presence of trastuzumab and cells were periodically tested for response to trastuzumab and MM-111. Samples were also collected for protein and RNA analyses. Resistance to trastuzumab gradually increased in BT474 cells after four months of exposure to trastuzumab, as measured by a cell proliferation assay. Quantitative flow cytometry analysis showed EGFR, HER2, and HER3 levels on the cell surface of resistant cells were similar to the parental cells. Phospho-protein kinase antibody arrays revealed that signaling pathways associated with the ERK cascade were activated during the development of drug resistance. Western blotting further confirmed that phosphorylation of EGFR, ERK, CREB, c-Jun, and AFT-1 was increased in the resistant cells. Real-time polymerase chain reaction also showed transcript levels of HER ligands, including HRG1α, HRG1α, betacellulin, amphiregulin, epigen, TGFβ, and HB-EGF, dramatically increased in tumor cells that acquired resistance to trastuzumab. Compared to the BT474 parental cells, MM-111 showed a greater inhibition in trastuzumab-resistant cells in a spheroid growth assay. Furthermore, trastuzumab-resistant cells became more sensitive to gefitinib and erlotinib, both EGFR inhibitors. The combination of gefitinib or erlotinib with MM-111 showed greater inhibition than either drug alone. In conclusion, our data suggest that one mechanism by which HER2 overexpressing breast cancer cells develop resistance to trastuzumab is to up-regulate ligand-dependent EGFR and HER3 signaling pathways. The use of MM-111 and EGFR inhibitors may provide an effective therapeutic strategy for the treatment of trastuzumab-resistant cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1888. doi:1538-7445.AM2012-1888
One Century of Aryne Chemistry (2003)

Arynes, which are formally derived from aromatic rings by abstraction of two hydrogen atoms, have been a focus of organic chemistry for 100 years. In contrast to ortho-benzyne, which is mentioned in almost every introductory textbook on organic reaction mechanisms as a reactive intermediate of nucleophilic aromatic substitution, the meta and para isomers were regarded as rather exotic until recently. This situation has changed dramatically with the discovery of the enediyne antibiotics, a promising new class of antitumor drugs, and has aroused the interest of research groups from all branches of chemistry. Nowadays, arynes and related compounds are among the most intensively studied systems in chemistry. However, many aspects of the chemistry of these reactive intermediates are not well understood yet. In this review we outline the historical developement with an emphasis on recent progress in this challenging field of research.
[A study on new computer-aided modeling method of hip joint]. (2004)

The main reason of invalidation of prosthetic hip joint is the prostheses flexibility and shift, dislocation and disjunction. Promoting the long time stability of the prostheses is the key of improving the long term hip joint replacement effect. Former research work was focused on the upper segment of femur, and assumed the acetabulum cup to be a spheric concave, and the external form of acetabulum prostheses was basically semi spheric. This paper presents a method of acquiring the point data on the surface of the hip bone using the reverse engineering technology. By analyzing the acetabulum surface fitting error we use rotating elliptical surface to fit the acetabulum surface, together with the optimal technique to build up the CAD model of acetabulum surface. We compare the fitting error between the sphere fitting and rotating elliptical surface fitting and get the result that the rotating elliptical surface fitting error is smaller than the sphere fitting error, and the rotating elliptical surface can describe the shape of the acetabulum better.
Analyse des vibrations et du rayonnement de la table d'harmonie d'un piano droit et conception d'un système de reproduction du champ acoustique (1997)

Le piano, comme tous les instruments a cordes, rayonne de l'energie grace au couplage de ses cordes avec une plaque : la table d'harmonie. Dans ce travail, les vibrations de la table d'harmonie d'un piano droit sont etudiees avec les techniques d'analyse modale. Dix modes sont ainsi mis en evidence dans la plage frequentielle 50-350 hz. Tous ces modes presentent de bonnes similitudes avec des modes de plaques minces isotropes en appui simple vibrant en flexion pure. Les deformees modales sont ensuite utilisees pour calculer le rayonnement des modes de la table d'harmonie. La encore, le parallele avec le rayonnement des modes d'une plaque mince est effectue. On retrouve, pour la table d'harmonie, l'existence d'une frequence (frequence de coincidence) en dessous de laquelle les modes rayonnent tres peu d'energie. Le modele de la table d'harmonie fourni par l'analyse modale ainsi que les algorithmes de calcul de rayonnement sont valides par comparaison avec des mesures, apres quoi le rendement de la table d'harmonie est calcule. Il apparait qu'une forte proportion de l'energie est dissipee dans la plaque et non transmise au champ acoustique ; le parallele avec les plaques isotropes permet de prevoir que cette proportion pourrait etre inversee moyennant un changement de geometrie. Certains auteurs s'accordent a penser que les caracteristiques de rayonnement d'un instrument sont perceptivement importantes, et qu'ainsi, une reproduction de ces caracteristiques permettrait d'ameliorer la diffusion sur haut-parleurs. Dans la derniere partie de ce travail une methode de reproduction de figures de directivite a l'aide de sources multi-haut-parleurs est presentee. Elle est ensuite appliquee a une source dodecaedrique composee de douze haut-parleurs groupes en quatre sous-ensembles independants pour reproduire les premieres harmoniques spheriques. Les resultats sont presentes pour deux dispositifs : le meilleur des deux dispositifs nous a permis d'obtenir une bonne reproduction des directivites cibles sur la plage frequentielle 100-1000 hz. Les causes de ces limitations sont en basses frequences la directivite des haut-parleurs (trop omnidirectifs) et en hautes frequences la distance entre les haut-parleurs.
Synthesis and Properties of Polyamides and Polyesters On the basis of 2,2‘-Bipyridine-5,5‘-Dicarboxylic Acid and the Corresponding Polymer−Ruthenium Complexes (2000)

Two series of polyamides and polyesters derived from 2,2‘-bipyridine-5,5‘-dicarboxylic acid have been synthesized. Different types of aliphatic and aromatic diamine and diol monomers with different structure were polymerized with the diacid or diacid chloride by using different polymerization methods. Most of these polymers exhibited modest thermal stabilities with decomposition temperatures in the range 320−500 °C, depending on the structure of the polymer main chain. It was found that some polyamides with a rigid main chain formed a lyotropic mesophase when dissolved in concentrated sulfuric acid or HMPA−4% LiCl solvent systems. For those polyamides and polyesters with a more flexible main chain, a thermotropic liquid crystal phase was observed. If a long and flexible pendant chain was attached to the polyesters, side chain melting was observed before the onset of the crystalline−nematic transition. The 2,2‘-bipyridyl moieties were able to form a complex with ruthenium. These polymer−ruthenium complexes were either synthesized by metalation of the polymers or synthesized directly from the corresponding ruthenium-containing monomer. After the formation of ruthenium complexes, they were able to enhance the photosensitivity and charge carrier mobility of the polymers. The ruthenium-containing polymers also emit red light at ca. 700 nm owing to the emission from the metal−ligand charge-transfer excited states. Some polymers with good film forming properties were fabricated into simple single-layer light-emitting devices, and red light emission was observed when the devices were subjected to forward bias.
Novel Mid-Infrared Lasers With Compressively Strained InAsSb Active Regions (1997)

Mid-infrared lasers grown by MOCVD with AlAsSb claddings and strained InAsSb active regions are reported. A 3.8--3.9 {micro}m injection laser with a pseudomorphic InAsSb multiple quantum well active region lased at 210 K under pulsed operation. A semi-metal layer acts as an internal electron source for the injection laser. An optically pumped laser with an InAsSb/InAsP strained-layer superlattice active region was demonstrated at 3.7 {micro}m, 240 K.
In Saccharomyces cerevisiae, the Inositol Polyphosphate Kinase Activity of Kcs1p Is Required for Resistance to Salt Stress, Cell Wall Integrity, and Vacuolar Morphogenesis (2002)

A problem for inositol signaling is to understand the significance of the kinases that convert inositol hexakisphosphate to diphosphoinositol polyphosphates. This kinase activity is catalyzed by Kcs1p in the yeast Saccharomyces cerevisiae. A kcs1Delta yeast strain that was transformed with a specifically "kinase-dead" kcs1p mutant did not synthesize diphosphoinositol polyphosphates, and the cells contained a fragmented vacuolar compartment. Biogenesis of the yeast vacuole also required another functional domain in Kcs1p, which contains two leucine heptad repeats. The kinase activity of Kcs1p was also found to sustain cell growth and integrity of the cell wall and to promote adaptive responses to salt stress. Thus, the synthesis of diphosphoinositol polyphosphates has wide ranging physiological significance. Furthermore, we showed that these phenotypic responses to Kcs1p deletion also arise when synthesis of precursor material for the diphosphoinositol polyphosphates is blocked in arg82Delta cells. This metabolic block was partially bypassed, and the phenotype was partially rescued, when Kcs1p was overexpressed in the arg82Delta cells. This was due, in part, to the ability of Kcs1p to phosphorylate a wider range of substrates than previously appreciated. Our results show that diphosphoinositol polyphosphate synthase activity is essential for biogenesis of the yeast vacuole and the cell's responses to certain environmental stresses.
Blocking Effect in the Transitional Nuclei<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline"><mml:mrow><mml:mmultiscripts><mml:mrow><mml:mi mathvariant="normal">Au</mml:mi></mml:mrow><mml:mprescripts/><mml:mrow/><mml:mrow><mml:mn>1</mml:mn><mml:mn>8</mml:mn><mml:mn>9</mml:mn><mml:mo>,</mml:mo><mml:mn>1</mml:mn><mml:mn>9</mml:mn><mml:mn>1</mml:mn><mml:mo>,</mml:mo><mml:mn>1</mml:mn><mml:mn>9</mml:mn><mml:mn>3</mml:mn></mml:mrow><mml:mrow/><mml:mrow/></mml:mmultiscripts></mml:mrow></mml:math> (1976)

The study of high-spin states in $^{189,191,193}\mathrm{Au}$ revealed that the ${h}_{\frac{11}{2}}$ proton-hole rotation-aligned bands are terminated by isomeric ${\frac{27}{2}}^{\ensuremath{-}}$ states most probably of ${(\ensuremath{\pi}h_{\frac{11}{2}}^{\ensuremath{-}3})}_{{\frac{27}{2}}^{\ensuremath{-}}}$ configuration. The relatively low excitation energies of these isomers can be understood qualitatively if the concept of blocking as used in the rotation-alignment model is modified by taking into account a reduction of the proton pairing gap energy in these odd-mass Au nuclei.
A Mathematical Method of Comparing Spectrochemical Results (1958)

A mathematical method is described for comparing spectrochemical results, by calculating and comparing the areas of the contour ellipses which surround the points of density scatter diagrams. By employing this comparison method, it was found that, when using lithium carbonate as a buffer for plant ash analysis, the best results are obtained when the arc is burned with a surrounding air stream, as first suggested by Stallwood, but with a constant current generator used as the energy source.
Toward a high performance distributed memory climate model (2002)

As part of a long range plan to develop a comprehensive climate systems modeling capability, the authors have taken the atmospheric general circulation model originally developed by Arakawa and collaborators at UCLA and have recast it in a portable, parallel form. The code uses an explicit time-advance procedure on a staggered three-dimensional Eulerian mesh. They have implemented a two-dimensional latitude/longitude domain decomposition message passing strategy. Both dynamic memory management and interprocess communication are handled with macro constructs that are preprocessed prior to compilation. The code can be moved about a variety of platforms, including massively parallel processors, workstation clusters, and vector processors, with a mere change of three parameters. Performance on the various platforms as well as issues associated with coupling different models for major components of the climate system are discussed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Prognosis for Wilms' tumor patients with nonmetastatic disease at diagnosis--results of the second National Wilms' Tumor Study. (1985)

Multivariate statistical methods were used to study prognosis for 632 patients entered on the second National Wilms' Tumor Study who had nonmetastatic, unilateral disease at diagnosis. Separate analyses were conducted for each of four endpoints: abdominal recurrence, distant metastasis, relapse without regard to site, and death. The two most important predictors for metastasis and general relapse were an unfavorable (anaplastic or sarcomatous) histology and the presence of microscopically confirmed disease in the regional lymph nodes. Operative spillage of tumor increased the rates of abdominal recurrence and death, even after accounting for histology and lymph node effects. The presence of a tumor thrombus in the renal vein or IVC increased the risk of metastasis, and intrarenal vascular invasion was associated with general relapse after accounting for histology, lymph nodes, and spillage. However, these latter associations were weaker, and some uncertainty remains regarding the true prognostic import of such findings due to a high degree of collinearity among variables. By contrast to the results of a similar data analysis for the first National Wilms' Tumor Study, specimen weight had no bearing on outcome, and the effects of age at diagnosis were entirely explained by the association of age with other more critical factors.
Voluntary Exercise in Mesothelioma: Effects on Tumour Growth and Treatment Response in a Murine Model (2020)

Abstract Objective There is substantial evidence that exercise can safely reduce the risk of cancer and improve survival in different human cancer populations. Long latency periods associated with carcinogeninduced cancers like asbestos induced mesothelioma provide an opportunity to implement exercise as an intervention to delay or prevent disease development. However, there are limited studies investigating the ability of exercise to prevent or delay cancer, and exercise as a preventive strategy has never been assessed in models with a known carcinogen. We investigated the potential of voluntary exercise (VE) to delay development of asbestos related disease (ARD) in our well-characterised, asbestos induced MexTAg model of mesothelioma. Results Asbestos exposed MexTAg mice were given continuous or delayed access to VE and ARD assessed over time. We found that the addition of VE did not affect ARD development in asbestos exposed MexTAg mice. However, nonasbestos exposed, aged matched control mice participated in significantly more VE behaviours, suggesting subclinical development of ARD after asbestos exposure had a greater impact on VE participation than age alone. These data highlight the importance of model choice and the potential limitation that some preclinical studies may not accurately represent the clinical paradigm, particularly in the context of prevention studies.
Effects of 4‐Methylpyrazole on Ethanol Neurobehavioral Toxicity in CD‐1 Mice (2004)

Pretreatment with 4-MP significantly prolonged ethanol neurobehavioral toxicity in CD-1 mice, presumably by inhibiting its metabolism by ADH. Further investigation is warranted to evaluate this interaction.
Development of SI-Engine based Extended MVEMs for use in Estimators for Engine Health Management (2012)

<div class="section abstract"><div class="htmlview paragraph">Mean Value Engine Models (MVEM) represent average behaviour of an engine over one or more thermodynamic cycles and have been designed for automotive control and diagnosis applications. However, most MVEMs are limited to the description of the dynamics of few engine sub-systems. The diagnostic capabilities of a vehicular engine health management (VEHM) system that uses such MVEMs are limited. In this paper, the process of deriving an MVEM for an entire engine system from an instantaneous within-cycle crank-angle model (WCCM) is described. This is expected to be more beneficial for fault diagnosis in VEHMs since such MVEMs in the context of state observers, can be used to detect a broader range of faults and also generate a larger number of fault signatures for better fault detection and isolation (FDI). Extended Kalman Filter (EKF) based estimators are developed that use this MVEM for state estimation. The quality of estimation results was significantly improved by modelling the inaccuracy of the MVEM as a bias and extending the MVEM with the knowledge of these bias tables. Fault residue generators are designed using various MVEM-based fault models in a state observer.</div></div>
Effects of pinealectomy, oestradiol and melatonin on plasma prolactin and LH secretion in ovariectomized sheep (1984)

The study examines whether the pineal gland mediates in the seasonal rhythm in the response of the hypothalamo-pituitary axis to oestrogen in the sheep. Five groups of ewes, each comprised of five sham-pinealectomized ewes and five pinealectomized ewes, were maintained under field conditions over a 2-year period. Group I ewes were ovariectomized and treated with two oestradiol capsules in the first year and one oestradiol capsule in the second year; group 2 ewes were ovariectomized and treated with two oestradiol capsules and three melatonin sachets in the first year and one oestradiol capsule and three melatonin sachets in the second year; group 3 ewes were ovariectomized and treated with three melatonin sachets in the first year and one oestradiol capsule in the second year; group 4 ewes were ovariectomized and treated with empty implants; group 5 had intact ovaries. Blood samples were taken at weekly intervals for determination of plasma prolactin, LH and FSH levels. Cyclic ovarian activity, determined by rams fitted with a marking harness, occurred in both sham-pinealectomized and pinealectomized ewes in group 5 during December to May in both years. A circannual rhythm in plasma prolactin levels was apparent in all ten groups of animals. The levels were highest in spring (September to November) and decreased before the onset of breeding activity in midsummer (December). Ovariectomized ewes with intact pineal glands and treated with oestradiol capsules (group 1) exhibited marked changes in LH and FSH concentrations during the study.(ABSTRACT TRUNCATED AT 250 WORDS)
Overexpression of transforming growth factor‐<i>β</i>1 in teeth results in detachment of ameloblasts and enamel defects (2006)

Transforming growth factor-beta1 (TGF-beta1) is a key regulator of many cellular processes, including cell adhesion, the immune response and synthesis of extracellular matrix proteins. In the present study, we report the characterization of enamel defects in a transgenic mouse model overexpressing TGF-beta1 in odontoblasts and ameloblasts, its expression being driven by the promoter sequences of the dentin sialophosphoprotein gene. As reported earlier, these mice develop distinct dentin defects similar to those seen in human dentin dysplasia and dentinogenesis imperfecta. A further detailed examination of enamel in these mice revealed that from the early secretory stage, ameloblasts began to detach from dentin to form cyst-like structures. A soft X-ray analysis revealed that this cyst-like structure had a disorganized and partially mineralized matrix with an abnormal mineralization pattern and a globular appearance. In the molars, the enamel was not only pitted and hypoplastic, but enamel rods were completely lost. Thus, altered TGF-beta1 expression in the tooth seems to trigger detachment of ameloblasts and abnormal secretion and deposition of minerals in the cyst-like structures adjoining the dentin. We speculate that the altered expression of TGF-beta1 in teeth impacts the adhesion process of ameloblasts to dentin.
[Metabolic activity of adipose tissue in the goat during gestation and at the beginning of lactation]. (1978)

In 5 French Alpine goats, omental adipose tissue acetyl-CoA carboxylase, glucose-6-phosphate deshydrogenase, malic enzyme and lipoprotein lipase activities significantly decreased during the third month of gestation, whereas plasma non-esterified fatty acid and triacyglycerol contents increased. This probably reflects an early decreasing rate of adipose tissue anabolism during gestation in the Goat. At the third week of lactation, anabolic activities relative to DNA content of adipose tissue were extremely low, and the tissue weight relative to DNA was lower than during gestation. Metabolic alterations of omental adipose tissue in early lactation do not seem to be related to milk production level. These results could contribute to a better control of the kinetic of body lipid stores during the reproductive cycle in high milk yielding ruminants.
A KNOWLEDGE-BASED SYSTEM TO MODEL HUMAN SUPERVISORY CONTROL IN DYNAMIC PLANNING (2004)

With the increases in the levels of automation and computerization, supervisory control systems are becoming increasingly common in commercial and military applications. A supervisory control system consists of one or more human operators interacting with highly automated components such as those seen in satellite ground control, flexible manufacturing systems, or nuclear power plants. Humans typically perform cognitively intense tasks such as monitoring, planning, real-time control, and troubleshooting, and are ultimately responsible for the safe and efficient operation of the overall system. Although developments on supervisory control have led to useful applications in interface design and automation, there is a scarcity of research that empirically evaluates human decision making in supervisory control through emulation of task performance using knowledge-based systems. In the context of dynamic planning involving simulated search and rescue missions using ground based autonomous robots and uninhabited aerial vehicles, we developed a knowledge-based system that mimics supervisory control performance. This paper describes the application domain, the details of the simulation model, and the implementation and assessment of a knowledge-based system that mimics human supervisory control performance.