Search results for "Pines"
showing 10 items of 421 documents
Efficacy of BET Bromodomain Inhibition in Kras-Mutant Non–Small Cell Lung Cancer
2013
Abstract Purpose: Amplification of MYC is one of the most common genetic alterations in lung cancer, contributing to a myriad of phenotypes associated with growth, invasion, and drug resistance. Murine genetics has established both the centrality of somatic alterations of Kras in lung cancer, as well as the dependency of mutant Kras tumors on MYC function. Unfortunately, drug-like small-molecule inhibitors of KRAS and MYC have yet to be realized. The recent discovery, in hematologic malignancies, that bromodomain and extra-terminal (BET) bromodomain inhibition impairs MYC expression and MYC transcriptional function established the rationale of targeting KRAS-driven non–small cell lung cance…
Phase I Assessment of New Mechanism-Based Pharmacodynamic Biomarkers for MLN8054, a Small-Molecule Inhibitor of Aurora A Kinase
2011
Abstract The mitotic kinase Aurora A is an important therapeutic target for cancer therapy. This study evaluated new mechanism-based pharmacodynamic biomarkers in cancer patients in two phase I studies of MLN8054, a small-molecule inhibitor of Aurora A kinase. Patients with advanced solid tumors received MLN8054 orally for 7 consecutive days in escalating dose cohorts, with skin and tumor biopsies obtained before and after dosing. Skin biopsies were evaluated for increased mitotic cells within the basal epithelium. Tumor biopsies were assessed for accumulation of mitotic cells within proliferative tumor regions. Several patients in the highest dose cohorts showed marked increases in the ski…
Cholinesterase Activity and Hematological Parameters as Biomarkers of Sublethal Molinate Exposure in Anguilla anguilla
2000
Cholinesterase (ChE) activity was measured in plasma, whole blood [using 5,5'-dithiobis(2-nitrobenzoic acid) and 2-PDS as chromophores], brain, and whole eyes of Anguilla anguilla exposed to a sublethal concentration of 11.15 mg/L (one-third of the 96-h LC(50)) of the carbamate herbicide molinate. ChE activity was evaluated after 6, 24, 48, 72, and 96 h of pesticide exposure. Results indicated that ChE activity in eel tissues decreased as time of exposure increased, especially in eel blood. Eels exposed to molinate were transferred to a pesticide-free water for a recovery period of 4 days and ChE activity was also evaluated. Results indicated that ChE activity for those animals with preexpo…
Neocortical Layer 6B as a Remnant of the Subplate - A Morphological Comparison.
2015
The fate of the subplate (SP) is still a matter of debate. The SP and layer 6 (which is ontogenetically the oldest and innermost neocortical lamina) develop coincidentally. Yet, the function of sublamina 6B is largely unknown. It has been suggested that it consists partly of neurons from the transient SP, however, experimental evidence for this hypothesis is still missing. To obtain first insights into the neuronal complement of layer 6B in the somatosensory rat barrel cortex, we used biocytin stainings of SP neurons (aged 0-4 postnatal days, PND) and layer 6B neurons (PND 11-35) obtained during in vitro whole-cell patch-clamp recordings. Neurons were reconstructed for a quantitative charac…
Efectos de la exposición crónica al etanol sobre el tráfico intracelular y citoesqueleto como factores implicados en la migración neuronal
2013
El consumo de etanol durante la gestación puede inducir una serie de alteraciones graves en el desarrollo del feto, la manifestación más extrema da lugar al Síndrome Alcohólico Fetal (SAF). La exposición prenatal al alcohol es la causa conocida y, además evitable, más importante de retraso mental en el mundo occidental. Además de déficits cognitivos, los niños con SAF presentan múltiples anomalías estructurales en el sistema nervioso central, como reducción de la masa cerebral, y a nivel celular, daños en la migración neuronal, en el proceso de formación de espinas dendríticas y establecimiento de sinapsis. En la actualidad, los mecanismos moleculares implicados en la teratogénesis inducida…
Revisiting the happy-productive worker thesis from a eudaimonic perspective: a systematic review
2021
The happy-productive worker thesis (HPWT) is considered the Holy Grail of management research, and it proposes caeteris paribus, happy workers show higher performance than their unhappy counterparts. However, eudaimonic well-being in the relationship between happiness and performance has been understudied. This paper provides a systematized review of empirical evidence in order to make a theoretical contribution to the happy-productive worker thesis from a eudaimonic perspective. Our review covers 105 quantitative studies and 188 relationships between eudaimonic well-being and performance. Results reveal that analyzing the eudaimonic facet of well-being provides general support for the HPWT…
The lack of the effect of DA-1 and DA-2 dopamine agonists on the isolated guinea-pig atria.
1987
1 The effects of dopamine and both DA-1 and DA-2 dopamine receptor agonists have been studied on the contractile force of electrically driven guinea-pig left atria and frequency of spontaneously beating right atria. 2 Pretreatment of animals with reserpine caused a parallel rightward shift of the concentration-response curve to dopamine of either preparation. 3 Propranolol, but not domperidone, shifted to the right the dose-response curve for the positive inotropic and chronotropic effects of dopamine. 4 Neither apomorphine, fenoldopam, bromocriptine nor piribedil had effects on the frequency and contractile force of the isolated guinea-pig atria. 5 These results suggest that DA-1 and DA-2 …
Influence of pH on the benzodiazepine-human serum albumin complex. Circular dichroism studies.
1974
The influence of pH on the binding of benzodiazepine derivatives to HSA was studied by circular dichroism measurements and by gel filtration. The binding of nearly all benzodiazepines is increased by rising the pH from 6.60 to 8.20. For flurazepam, clonazepam, and nitrazepam this increase in binding is due to an increase of the affinities, while for the other substances the affinity remains constant and the number of binding sites is increased from one to two. The changes in binding of the benzodiazepines by rising the pH are explained by a cationic amino acid residue near or at the benzodiazepine binding site of the HSA molecule. This second binding site is not detectable by circular dichr…
Association between obstructive apnea syndrome during sleep and damages to anterior labyrinth: Our experience
2019
The obstructive sleep apnea syndrome is a chronic condition characterized by frequent episodes of collapse of the upper airways during sleep. It can be considered a multisystem disease. Among the districts involved, even the auditory system was seen to be concerned. It was enrolled a population of 20 patients after polysomnographic diagnosis of OSAS (Apnea Hypopnea Index > 10) and a control group of 28 healthy persons (Apnea Hypopnea Index < 5). Each patient has been subjected to Pure Tone Audiometry, Tympanometry, study of Acoustic Reflex, Otoacoustic Emissions and Auditory Brainstem Response. Moreover they were submitted to endoscopy of upper airway with Muller Maneuver and Epworth …
Explorations on interactive interfaces using cuteness
2007
The experience of interactive systems can be a rather complex set of events. The perceptions appeal to the user's senses including visual, auditory, tactile, olfactory, and gustatory. Taken from a human factors approach, the sensitivity of the senses can be measured very closely and units of measurement arise from the "just noticeable difference." These differences can be mapped to the physics behind the stimuli and computer controlled systems very accurately provide sensation to the user through various user interfaces. The human mind also plays an important role in making sense of the experience not only from a physiological standpoint, but from a psychological and cultural reference poin…