gebhart/patrepeval huggingface dataset:
Characterization of the p53 tumor suppressor pathway in cell lines of the National Cancer Institute anticancer drug screen and correlations with the growth-inhibitory potency of 123 anticancer agents. (1997)

In the present study, we report the characterization of the p53 tumor suppressor pathway in the 60 cell lines of the National Cancer Institute (NCI) anticancer drug screen, as well as correlations between the integrity of this pathway and the growth-inhibitory potency of 123 anticancer agents in this screen. Assessment of p53 status in these lines was achieved through complete p53 cDNA sequencing, measurement of basal p53 protein levels and functional assessment of (a) transcriptional activity of p53 cDNA from each line in a yeast assay, (b) gamma-ray-induced G1 phase cell cycle arrest, and (c) gamma-ray-induced expression of CIP1/WAF1, GADD45, and MDM2 mRNA. Our investigations revealed that p53 gene mutations were common in the NCI cell screen lines: 39 of 58 cell lines analyzed contained a mutant p53 sequence. cDNA derived from almost all of the mutant p53 cell lines failed to transcriptionally activate a reporter gene in yeast, and the majority of mutant p53 lines studied expressed elevated basal levels of the mutant p53 protein. In contrast to most of the wild-type p53-containing lines, cells containing mutant p53 sequence were also deficient in gamma-ray induction of CIP1/WAF1, GADD45, and MDM2 mRNA and the ability to arrest in G1 following gamma-irradiation. Taken together, these assessments provided indications of the integrity of the p53 pathway in the 60 cell lines of the NCI cell screen. These individual p53 assessments were subsequently used to probe a database of growth-inhibitory potency for 123 "standard agents," which included the majority of clinically approved anticancer drugs. These 123 agents have been tested against these lines on multiple occasions, and a proposed mechanism of drug action had previously been assigned to each agent. Our analysis revealed that cells with mutant p53 sequence tended to exhibit less growth inhibition in this screen than the wild-type p53 cell lines when treated with the majority of clinically used anticancer agents: including DNA cross-linking agents, antimetabolites, and topoisomerase I and II inhibitors. Similar correlations were uncovered when we probed this database using most of the other indices of p53 status we assessed in the lines. Interestingly, a class of agents that differed in this respect was the antimitotic agents. Growth-inhibitory activity of these agents tended, in this assay, to be independent of p53 status. Our characterization of the p53 pathway in the NCI cell screen lines should prove useful to researchers investigating fundamental aspects of p53 biology and pharmacology. This information also allows for the large-scale analysis of the more than 60,000 compounds tested against these lines for novel agents that might exploit defective p53 function as a means of preferential toxicity.
Photo-Cross-Linking and Cleavage Induced Reversible Size Change of Bio-Based Nanoparticles (2008)

Reversible size changes in degradable nanoparticles composed of bio-based cinnamate derivative copolymers, poly(3,4-dihydroxycinnamic acid-co-4-hydroxycinnamic acid) [P(3,4DHCA-co-4HCA)], were observed for the first time. The 860 nm diameter decreased to almost one-half (420 nm) during UV irradiation over 280 nm and rapidly recovered to 620 nm upon subsequent irradiation at 254 nm. Results from UV−vis and 1H NMR spectra suggested that diameter-changing phenomena corresponded to [2 + 2] cycloaddition formation and cleavage of the cinnamate groups. This significant diameter change was reproduced for at least three cycles, and the reason for this significant size change seemed to be due to the fact that all units of the copolymer contained photochromic groups. Furthermore, these photo-cross-linked bio-based nanoparticles showed various size change behaviors during hydrolytic degradation depending on the degree of cross-linking. Photosensitive degradable nanoparticles may be useful as novel, size-controllable carriers for environmental and biomedical fields.
A LIFE MORE PHOTOGRAPHIC (2008)

Twenty-two years since the arrival of the first consumer digital camera, Western culture is now characterized by ubiquitous photography. The disappearance of the camera inside the mobile phone has ensured that even the most banal moments of the day can become a point of photographic reverie, potentially shared instantly. Supported by the increased affordability of computers, digital storage and access to broadband, consumers are provided with new opportunities for the capture and transmission of images, particularly online where snapshot photography is being transformed from an individual to a communal activity. As the digital image proliferates online and becomes increasingly delivered via networks, numerous practices emerge surrounding the image’s transmission, encoding, ordering and reception. Informing these practices is a growing cultural shift towards a conception of the Internet as a platform for sharing and collaboration, supported by a mosaic of technologies termed Web 2.0. In this article we attempt to delineate the field of snapshot photography as this practice shifts from primarily being a print-oriented to a transmission-oriented, screen-based experience. We observe how the alignment of the snapshot with the Internet results in the emergence of new photographies in which the photographic image interacts with established and experimental media forms - raising questions about the ways in which digital photography is framed institutionally and theoretically.
Granulocyte colony-stimulating factor induces selective elevations of progenitor cells in the peripheral blood of mice. (1994)

The absolute numbers and relative frequencies of progenitor cells in six nonerythroid lineages were monitored in the peripheral blood (PB), bone marrow (BM), and spleen of Balb/c mice during 8 days of granulocyte colony-stimulating factor (G-CSF) injections. G-CSF induced a dose-related increase, up to 570-fold, in progenitor cell numbers in the blood and up to 620-fold rise of these cells in the spleen. The relative frequency of megakaryocyte progenitor cells was significantly increased in the blood compared with values in the BM or spleen. Time-dependent variations were also observed in the relative frequencies of three lineages of progenitor cells in the blood (megakaryocyte, granulocyte, and macrophage), but not in the BM or spleen. The consistent differences induced in the relative frequencies of various progenitor cell types between the blood, marrow, and spleen were independent of G-CSF dose. These data suggest that the increase in progenitor cells in the blood induced by G-CSF cannot simply be explained by a nonselective release of progenitor cells from the marrow or spleen.
Heterogeneity of airways mucus: variations in the amounts and glycoforms of the major oligomeric mucins MUC5AC and MUC5B (2002)

Respiratory mucus contains a mixture of gel-forming mucins but the functional significance of these different mucin species is unknown. To help gain a better understanding of mucus in airways we therefore need to ascertain the concentration of each of the gel-forming mucins within respiratory secretions. Thus the aim of this study was to determine the amounts of specific gel-forming mucins directly from solubilized secretions of the airways and purified mucin preparations. We investigated the feasibility of using direct-binding ELISA employing mucin-specific antisera but were unable to obtain reliable data owing to interference with the immobilization of the mucins on the assay surface by 6M urea and high levels of non-mucin proteins. We therefore developed an alternative approach based on quantitative Western blotting after agarose-gel electrophoresis, which was not subject to these problems. Here we demonstrate that this procedure provides reliable and reproducible data and have employed it to determine the amounts of the MUC2, MUC5AC and MUC5B mucins in saline-induced sputa from healthy airways and spontaneous sputa from asthmatic airways. Additionally we have used this procedure to analyse these glycoproteins in mucin preparations purified from cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) mucus. Our findings indicate that MUC5AC and MUC5B are the major oligomeric mucins and that airways mucus contains variable amounts of these glycoproteins. By contrast, the MUC2 mucin comprised, at most, only 2.5% of the weight of the gel-forming mucins, indicating that MUC2 is a minor component in sputum. Finally, we show that the amounts and glycosylated variants of the MUC5AC and MUC5B mucins can be altered significantly in diseased airways with, for instance, an increase in the low-charge form of the MUC5B mucin in CF and COPD mucus.
Expression of the yeast plasma membrane [H+]ATPase in secretory vesicles. A new strategy for directed mutagenesis. (1991)

Secretory vesicles that accumulate in the temperature-sensitive sec6-4 strain of yeast have been shown to contain a vanadate-sensitive ATPase, presumably en route to the plasma membrane (Walworth, N. C., and Novick, P. J. (1987) J. Cell Biol. 105, 163-174). We have now established this enzyme to be a fully functional form of the PMA1 [H+]ATPase, identical in its catalytic properties to that found in the plasma membrane. In addition, the secretory vesicles are sealed tightly enough to permit the measurement of ATP-dependent proton pumping with fluorescent probes. We have gone on to exploit the vesicles as an expression system for site-directed mutants of the ATPase. For this purpose, a sec6-4 strain has been constructed in which the chromosomal PMA1 gene is under control of the GAL1 promoter; the mutant pma1 allele to be studied is introduced on a centromeric plasmid under the control of a novel heat shock promoter. In galactose medium at 23 degrees C, the wild-type ATPase is produced and supports normal vegetative growth. When the cells are switched to glucose medium at 37 degrees C, however, the wild-type gene turns off, the mutant gene turns on, and secretory vesicles accumulate. The vesicles contain a substantial amount of newly synthesized, plasmid-encoded ATPase (5-10% of total vesicle protein), but only traces of residual wild-type PMA1 ATPase and no detectable mitochondrial ATPase, vacuolar ATPase, or acid or alkaline phosphatase. To test the expression strategy, we have made use of pma1-105 (Ser368----Phe), a vanadate-resistant mutant previously characterized by standard methods (Perlin, D. S., Harris, S. L., Seto-Young, D., and Haber, J. E. (1989) J. Biol. Chem. 264, 21857-21864). In secretory vesicles, as expected, the plasmid-borne pma1-105 allele gives rise to a mutant enzyme with a reduced rate of ATP hydrolysis and a 100-fold increase in Ki for vanadate. Proton pumping is similarly resistant to vanadate. Thus, the vesicles appear well suited for the production and characterization of mutant forms of the PMA1 [H+]ATPase. They should also aid the study of other yeast membrane proteins that are essential for growth as well as heterologous proteins whose appearance in the plasma membrane may be toxic to the cell.
Improved Performance from Multilayer Quantum Dot Light‐Emitting Diodes via Thermal Annealing of the Quantum Dot Layer (2007)

Quantum dot light-emitting diodes with high external quantum efficiency and luminous power efficiency are realized through in situ thermal annealing of a quasi-monolayer of colloidal nanocrystals on a crosslinked hole-transport layer. Partial desorption of quantum-dot surface ligands and improved film morphology contribute to better electrical injection from the organic layers to the quantum dots, resulting in a 3 to 4 fold enhancement of device efficiency with emission exclusively from the quantum dots. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2089/2007/c2373_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Modeling Stress Using Thermal Facial Patterns: A Spatio-temporal Approach (2013)

Stress is a serious concern facing our world today, motivating the development of better objective understanding using non-intrusive means for stress recognition. The aim for the work was to use thermal imaging of facial regions to detect stress automatically. The work uses facial regions captured in videos in thermal (TS) and visible (VS) spectrums and introduces our database ANU StressDB. It describes the experiment conducted for acquiring TS and VS videos of observers of stressed and not-stressed films for the ANU StressDB. Further, it presents an application of local binary patterns on three orthogonal planes (LBP-TOP) on VS and TS videos for stress recognition. It proposes a novel method to capture dynamic thermal patterns in histograms (HDTP) to utilize thermal and spatio-temporal characteristics associated in TS videos. Individual-independent support vector machine classifiers were developed for stress recognition. Results show that a fusion of facial patterns from VS and TS videos produced significantly better stress recognition rates than patterns from only VS or TS videos with p <; 0.01. The best stress recognition rate was 72% and it was obtained from HDTP features fused with LBP-TOP features for TS and VS videos respectively.
Address obfuscation: an efficient approach to combat a board range of memory error exploits (2003)

Attacks which exploit memory programming errors (such as buffer overflows) are one of today's most serious security threats. These attacks require an attacker to have an in-depth understanding of the internal details of a victim program, including the locations of critical data and/or code. Program obfuscation is a general technique for securing programs by making it difficult for attackers to acquire such a detailed understanding. This paper develops a systematic study of a particular kind of obfuscation called address obfuscation that randomizes the location of victim program data and code. We discuss different implementation strategies to randomize the absolute locations of data and code, as well as relative distances between data locations. We then present our implementation that transforms object files and executables at link-time and load-time. It requires no changes to the OS kernel or compilers, and can be applied to individual applications without affecting the rest of the system. It can be implemented with low runtime overheads. Address obfuscation can reduce the probability of successful attacks to be as low as a small fraction of a percent for most memory-error related attacks. Moreover, the randomization ensures that an attack that succeeds against one victim will likely not succeed against another victim, or even for a second time against the same victim. Each failed attempt will typically crash the victim program, thereby making it easy to detect attack attempts. These aspects make it particularly effective against large-scale attacks such as Code Red, since each infection attempt requires significantly more resources, thereby slowing down the propagation rate of such attacks.
Development of the Bridged and Pored Type of Metal Bond Diamond Wheel. (1991)

One of the ideal wheel with super-abrasive grains may be the pored type with metal bond which is easily able to remove chips from the surface of wheel and makes grinding temperature low due to the high ratio of heat conductivity. The present paper reports the developing process of metal bond diamond wheel with the bonding bridge and the porosity which the pored type of vitrified bond diamond wheel has. In order to establish the reliable adhesion between metal and diamond, the wettability and the thermal erosion of diamond are investigated for the several combinations of metals. The built bridges of bond are observed among diamond grains with metals heated in vacuum and are strengthened by the phosphorating treatment which provides 10 to 50 MPa of the bending strength to wheel. It is indicated in a few grinding tests that some of newly developed diamond wheels have the superiority to the pored type of vitrified bond diamond wheels.
Specification of Molecular Chirality (1966)

Abstract The topological analysis of chiral molecular models has provided the framework of a general system for the specification of their chirality. The application, made in and before 1956, of this system to organic‐chemical configurations is generally retained, but is redefined with respect to certain types of structure, largely in the light of experience gained since 1956 in the Beilstein Institute and elsewhere. The system is now extended to deal, on the one hand, with organic‐chemical conformations, and, on the other, with inorganic‐chemical configurations to ligancy six. Matters arising in connexion with the transference of chiral specifications from model to name are considered, notably that of the symbiosis in nomenclature of expressions of the general system and of systems of confined scope. For corrigendum see DOI: 10.1002/anie.196605111
MOLECULAR APPROACHES TO SPINAL CORD REPAIR (2003)

Axon growth inhibitors associated with myelin and the glial scar contribute to the failure of axon regeneration in the injured adult mammalian central nervous system (CNS). A number of these inhibitors, their receptors, and signaling pathways have been identified. These inhibitors can now be neutralized by a variety of approaches that point to the possibility of developing new therapeutic strategies to stimulate regeneration after spinal cord injury.
On the effects of weak bases and monensin on sorting and processing of lysosomal enzymes in human cells. (1987)

The weak bases chloroquine, primaquine, NH4Cl and the ionophore monensin exert similar but not identical effects on sorting, transport and processing of cathepsin D in several human cell lines (fibroblasts, HepG2 cells, U937, monocytes). The drugs inhibit the segregation of newly synthesized cathepsin D from the secretory route. The kinetics of transport of nonsegregated cathepsin D precursor along the secretory route is retarded resulting in a delayed hypersecretion. Higher concentrations of the drugs can arrest the intracellular transport completely. The extent of inhibition of segregation varies among the different human cell types tested. Thus, in fibroblasts the secretion can be stimulated to exceed 80%, while in U937 cells the secretion cannot be enhanced above 50% although both cell types have the same basal rate of secretion (approximately 10% of the synthesized cathepsin D). We suggest that pH-independent sorting mechanisms contribute to the targeting of cathepsin D in U937 cells. Processing of the cathepsin D remaining in cells is characteristically changed depending on the drug. The proteolytic processing is strongly inhibited by chloroquine and is rather insensitive to monensin. Unlike the other drugs, monensin blocks the formation of complex oligosaccharides in cathepsin D and allows for extensive secretion solely of molecules that are sensitive to endo H.
Peptidoglycan-associated polypeptides of Mycobacterium tuberculosis (1990)

Important protein-based immunoreactivities have long been associated with the cell wall core of mycobacteria. In order to explore the molecular basis of such activities, purified cell walls of Mycobacterium tuberculosis were extracted with sodium dodecyl sulfate to produce an insoluble residue composed of the mycolylarabinogalactan-peptidoglycan complex and about 2% of unextractable protein. Treatment of the product from an avirulent strain of M. tuberculosis with trifluoromethanesulfonic acid released a single polypeptide with a molecular size of 23 kilodaltons, accounting for all of the insoluble cell wall protein. Extensive purification and then analysis of the 23-kilodalton protein demonstrated the absence of diaminopimelic acid, muramic acid, or other peptidoglycan components, pointing to either a novel linkage between protein and peptidoglycan or a noncovalent but tenacious association. The released 23-kilodalton protein showed amino acid homology and other similarities to the outer membrane protein OmpF of Escherichia coli. Although a similar product was released in small quantities from cell walls of the virulent M. tuberculosis Erdman and H37Rv by lysozyme treatment, the cell walls of virulent bacilli were dominated by the presence of poly-alpha-L-glutamine, accounting for as much as 10% of their weight. The poly-alpha-L-glutamine was successfully separated from the cell wall proper, demonstrating again the absence of a covalent association between peptidoglycan and the polymer. The antigenicity of these products is demonstrated, and their roles vis-a-vis analogous polypeptides from other bacteria in immunogenicity, pathogenicity, and bacterial physiology are discussed.
α7 Nicotinic Receptor Agonists: Potential Therapeutic Drugs for Treatment of Cognitive Impairments in Schizophrenia and Alzheimer’s Disease (2010)

Accumulating evidence suggests that α7 nicotinic receptors (α7 nAChRs), a subtype of nAChRs, play a role in the pathophysiology of neuropsychiatric diseases, including schizophrenia and Alzheimer's disease (AD). A number of psychopharmacological and genetic studies shown that α7 nAChRs play an important role in the deficits of P50 auditory evoked potential in patients with schizophrenia, and that (α nAChR agonists would be potential therapeutic drugs for cognitive impairments associated with P50 deficits in schizophrenia. Furthermore, some studies have demonstrated that α7 nAChRs might play a key role in the amyloid-β (Aβ)-mediated pathology of AD, and that α7 nAChR agonists would be potential therapeutic drugs for Aβ deposition in the brains of patients with AD. Interestingly, the altered expression of α7 nAChRs in the postmortem brain tissues from patients with schizophrenia and AD has been reported. Based on all these findings, selective α7 nAChR agonists can be considered potential therapeutic drugs for cognitive impairments in both schizophrenia and AD. In this article, we review the recent research into the role of α7 nAChRs in the pathophysiology of these diseases and into the potential use of novel α7 nAChR agonists as therapeutic drugs.