gebhart/patrepeval huggingface dataset:
Quantitative proteomics analysis of adsorbed plasma proteins classifies nanoparticles with different surface properties and size (2011)

Nanoparticle biological activity, biocompatibility and fate can be directly affected by layers of readily adsorbed host proteins in biofluids. Here, we report a study on the interactions between human blood plasma proteins and nanoparticles with a controlled systematic variation of properties using (18)O-labeling and LC-MS-based quantitative proteomics. We developed a novel protocol to both simplify isolation of nanoparticle bound proteins and improve reproducibility. LC-MS analysis identified and quantified 88 human plasma proteins associated with polystyrene nanoparticles consisting of three different surface chemistries and two sizes, as well as, for four different exposure times (for a total of 24 different samples). Quantitative comparison of relative protein abundances was achieved by spiking an (18)O-labeled "universal" reference into each individually processed unlabeled sample as an internal standard, enabling simultaneous application of both label-free and isotopic labeling quantification across the entire sample set. Clustering analysis of the quantitative proteomics data resulted in distinctive patterns that classified the nanoparticles based on their surface properties and size. In addition, temporal data indicated that the formation of the stable protein corona was at equilibrium within 5 min. The comprehensive quantitative proteomics results obtained in this study provide rich data for computational modeling and have potential implications towards predicting nanoparticle biocompatibility.
A Gene-Expression Inhibitor that Targets an α-Helix-Mediated Protein Interaction (2003)

Protein-protein interactions are harder to target by small organic molecules than by enzymes or nuclear hormone receptors. Here we report the discovery of an organic compound that inhibits the expression of the Her2 oncogene by disrupting an alpha-helix-mediated protein interaction. The druglike molecule we named adamanolol competitively inhibited the interaction between the two cancer-linked nuclear proteins, ESX (an epithelial-specific transcription factor) and Sur-2/DRIP130 (a Ras-linked subunit of the human mediator complex), which is important for the overexpression of Her2 gene in malignant breast cancer cells. Adamanolol impaired Her2 expression and caused cell death selectively in Her2-positive breast cancer cells. NMR signals of adamanolol suggest that its rigid conformation plays a role in forming a helixlike surface for the interaction.
Subcellular localization of activating transcription factor 2 in melanoma specimens predicts patient survival. (2003)

The transcription factor activating transcription factor 2 (ATF2) has been shown to be associated with melanocytic oncogenesis and melanoma tumor proliferation in preclinical models. The clinical significance of ATF2 expression is unknown. To determine the prognostic value of ATF2 in melanoma, we evaluated the pattern and level of ATF2 expression in a large cohort of melanoma specimens. Immunohistochemical staining was performed on a tissue microarray representing 544 patients with a mean follow-up time of 60 months. Expression was evaluated semiquantitatively and correlated with overall survival and other clinicopathological data. Strong cytoplasmic ATF2 expression was associated with primary specimens rather than metastases (P < 0.0001) and with better survival (P = 0.0003). Strong nuclear ATF2 expression was associated with metastatic specimens (P < 0.0001) and with poor survival (P = 0.0008). Patients who had both weak cytoplasmic and strong nuclear ATF2 staining had the worst outcome, both among the full cohort of patients (P < 0.0001) and among the patients with localized disease (n = 269; P < 0.0001). On multivariate analysis of the primary cutaneous specimens, weak cytoplasmic staining and strong nuclear staining was an independent predictor of poor outcome, as was Clark level. Nuclear ATF2 is likely to be transcriptionally active, whereas cytoplasmic ATF2 probably represents an inactive form. These findings support other preclinical findings in which transcriptionally active ATF2 is involved in tumor progression-proliferation in melanoma. Moreover, our findings suggest that ATF2 might be a useful prognostic marker in early-stage melanoma.
Measuring Residual Estrogen Receptor Availability during Fulvestrant Therapy in Patients with Metastatic Breast Cancer (2014)

Serial imaging of tumor estrogen uptake by FES-PET can give insight into the dose needed for ER antagonists to completely abolish ER. FES-PET showed significant residual ER availability in tumors during fulvestrant therapy in 38% of patients, which was associated with early progression.
Inhibition of murine monocyte proliferation by a colony-stimulating factor-1 antisense oligodeoxynucleotide. Evidence for autocrine regulation. (1990)

Using a combination of v-myc and v-ras oncogenes, we have established a growth factor-independent monocyte cell line from murine fetal liver (FL-ras/myc). Biologic and molecular characterization demonstrated that the gene for the macrophage growth factor CSF-1 and the c-fms proto-oncogene (CSF-1 receptor) are expressed in this cell line, thus suggesting autocrine regulation as a possible mechanism for the unregulated growth of these cells. To study this possibility, we used 1) mAb, to neutralize the CSF-1 protein produced by the cell line, and 2) antisense oligomers, to inhibit CSF-1 gene products by specific base-pairing of complementary nucleic acids. We report here that both approaches inhibited in vitro cell growth by 60 to 70%, whereas the combination of oligomer and mAb inhibited proliferation by 95%. However, control antisense oligomers (50% bp mismatch with CSF-1 mRNA) did not inhibit FL-ras/myc cell growth. Furthermore, the inhibitory effects of mAb and oligomers were reversible when they were removed from the media. Detection of cell-associated CSF-1 protein by immunofluorescence showed that cells treated with the antisense oligomer expressed significantly less CSF-1 protein. These results indicate that the FL-ras/myc cell line requires CSF-1 for autonomous growth and that oligomers can efficiently block production of autocrine growth factors.
Structure ofStreptococcus agalactiaeglyceraldehyde-3-phosphate dehydrogenase holoenzyme reveals a novel surface (2014)

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a conserved cytosolic enzyme, which plays a key role in glycolysis. GAPDH catalyzes the oxidative phosphorylation of D-glyceraldehyde 3-phosphate using NAD or NADP as a cofactor. In addition, GAPDH localized on the surface of some bacteria is thought to be involved in macromolecular interactions and bacterial pathogenesis. GAPDH on the surface of group B streptococcus (GBS) enhances bacterial virulence and is a potential vaccine candidate. Here, the crystal structure of GBS GAPDH from Streptococcus agalactiae in complex with NAD is reported at 2.46 Å resolution. Although the overall structure of GBS GAPDH is very similar to those of other GAPDHs, the crystal structure reveals a significant difference in the area spanning residues 294-307, which appears to be more acidic. The amino-acid sequence of this region of GBS GAPDH is also distinct compared with other GAPDHs. This region therefore may be of interest as an immunogen for vaccine development.
Impact of Precision Medicine in Diverse Cancers: A Meta-Analysis of Phase II Clinical Trials (2015)

Comprehensive analysis of phase II, single-agent arms revealed that, across malignancies, a personalized strategy was an independent predictor of better outcomes and fewer toxic deaths. In addition, nonpersonalized targeted therapies were associated with significantly poorer outcomes than cytotoxic agents, which in turn were worse than personalized targeted therapy.
Pharmacodynamics of RP 59500 (quinupristin-dalfopristin) administered by intermittent versus continuous infusion against Staphylococcus aureus-infected fibrin-platelet clots in an in vitro infection model (1997)

We evaluated the bactericidal activity of RP 59500 (quinupristin-dalfopristin) against fibrin-platelet clots (FPC) infected with two clinical isolates of Staphylococcus aureus, one constitutively erythromycin and methicillin resistant (S. aureus AW7) and one erythromycin and methicillin susceptible (S. aureus 1199), in an in vitro pharmacodynamic infection model. RP 59500 was administered by continuous infusion (peak steady-state concentration of 6 microg/ml) or intermittent infusion (simulated regimens of 7.5 mg/kg of body weight every 6 h (q6h) q8h, and q12h. FPCs were infected with S. aureus to achieve an initial bacterial density of 10(9) CFU/g. Model experiments were run in duplicate over 72 h. Two FPCs were removed from each model at 0, 12, 24, 36, 48, and 72 h, and the bacterial densities (in CFU per gram) were determined and compared to those of growth control experiments. Additional samples were also removed from the model over the 72-h period for pharmacokinetic evaluation. All regimens significantly (P < or = 0.01) decreased bacterial densities in the infected FPCs for both isolates compared to growth controls. This occurred even though MBCs were equal to or greater than the RP 59500 concentrations achieved in the models. There were no significant differences found between the dosing frequencies and levels of killing when examining each isolate separately. However, examination of the residual bacterial densities (CFU per gram at 72 h) and visual inspection of the overall killing effect (killing curve plots over 72 h) clearly demonstrated a more favorable bactericidal activity against 1199 than against the AW7 isolate. This was most apparent when the q8h and the q12h AW7 regimens were compared to all 1199 treatment regimens by measuring the 72-h bacterial densities (P < or = 0.01). Killing (99.9%) was not achieved against the AW7 isolate. However, a 99.9% kill was demonstrated for all dosing regimens against the 1199 isolate. The area under the concentration-time curve from 0 to 24 h was found to be significantly correlated with reduction in bacterial density for the AW7 isolate (r = 0.74, P = 0.04). No resistance was detected during any experiment for either isolate. RP 59500 efficacy against constitutively erythromycin- and methicillin-resistant S. aureus may be improved by increasing organism exposure to RP 59500 as a function of dosing frequency.
A New Approach to the Synthesis of γ-Keto-α-Amino Acids: Synthesis of Optically Pure 5-Hydroxy-4-oxo-L-norvaline, L-HON (1993)

The nucleophilic ring opening of activated monocyclic (β-lactams by trimethylsulphoxonium ylide, lithiated sulphones and cuprates is reported. Conversion of the resultant ring opened forms to a variety of funtionalised γ-keto-α-amino acids is described as exemplified by a short synthesis of the natural product 5-hydroxy-4- oxo-L????-noivaline, L????-HON.
Electronic structure of the amorphous oxide semiconductor a‐InGaZnO4–x: Tauc–Lorentz optical model and origins of subgap states (2009)

Abstract This paper discusses an optical model and subgap electronic states for a representative amorphous oxide semiconductor, InGaZnO 4 (a‐IGZO). Parameterized optical models were developed based on the Tauc–Lorentz model combined with a Lorentz‐type oscillator. The measured optical absorption spectra exhibit nearly linear dependences on photon energy ( E ) between 3 eV &lt; E &lt; 5 eV, which requires the transition energies in the Tauc–Lorentz model ( E 0,TL ) being around 4 eV. The optimized parameters for the fixed E 0,TL of 3.7 eV are provided for four different a‐IGZO films with root‐mean‐square errors less than 1%. Formation energies of crystalline IGZO, stoichiometric a‐IGZO, oxygen deficient a‐IGZO and their constituent oxides were calculated by the density functional theory using the local density approximation (LDA) and generalized gradient approximation with PBE96 functionals (PBE). PBE gives larger unit cell volumes at the ground states and better agreement in the formation energies than LDA does. The formation energies of an oxygen deficiency in a‐IGZO were calculated to be 3.2–3.5 eV. The calculated electronic structures of stoichiometric a‐IGZO models exhibit somewhat large dispersions for conduction bands (CB), which are not largely affected by the disordered structure in a‐IGZO, while the dispersions of the valence bands (VBs) are very small, unlike the crystalline IGZO, showing that a‐IGZO have strongly localized states at the VB maximums (VBMs). Oxygen‐deficient a‐IGZO models showed that oxygen deficiencies form both a deep localized state at 0.4–1 eV above VBM and a shallow donor state depending on local atomic configurations. An oxygen deficiency that forms a deep state breaks the dispersion of the CB, which could be an origin of the subgap states observed near CB. (© 2009 WILEY‐VCH Verlag GmbH &amp; Co. KGaA, Weinheim)
Remote plasma treatment of Si surfaces: Enhanced nucleation in low-temperature chemical vapor deposition (2009)

The nucleation density on Si(100):H is increased by two orders of magnitude after exposing the surface to a remote argon plasma. We study HfB2 growth from Hf(BH4)4 and MgO growth from Mg(DMDBA)2 plus H2O. In the latter case, pretreatment allows the growth of MgO films with an rms roughness below 0.5 nm, whereas in absence of plasma treatment no nucleation is observed. The plasma does not damage the substrate and is compatible with microelectronics technology. We propose that H desorption is the key mechanism leading to nucleation enhancement, and that remote plasma activation is likely to be generally applicable.
A sequence of cells (1994)

Process sequence cell layouts (PSCL) have been proposed as a method of arranging processing equipment which will enable kanban signals to control material movements within high variety/low volume manufacturing environments. PSCLs involve allocating items of equipment to cells according to their position within the operation route of components. Each cell, therefore, represents a stage in the processing sequence of components manufactured within a company. Individual cells also provide a suitable environment for the setting up of a JIT intfrastructure in terms of providing conditions for operators to take responsibility for such functions as quality monitoring, routine maintenance and achieving lead time targets.
A reliable assessment of 8-oxo-2-deoxyguanosine levels in nuclear and mitochondrial DNA using the sodium iodide method to isolate DNA (2001)

A major controversy in the area of DNA biochemistry concerns the actual in vivo levels of oxidative damage in DNA. We show here that 8-oxo-2-deoxyguanosine (oxo8dG) generation during DNA isolation is eliminated using the sodium iodide (NaI) isolation method and that the level of oxo8dG in nuclear DNA (nDNA) is almost one-hundredth of the level obtained using the classical phenol method. We found using NaI that the ratio of oxo8dG/10(5 )deoxyguanosine (dG) in nDNA isolated from mouse tissues ranged from 0.032 +/- 0.002 for liver to 0.015 +/- 0.003 for brain. We observed a significant increase (10-fold) in oxo8dG in nDNA isolated from liver tissue after 2 Gy of gamma-irradiation when NaI was used to isolate DNA. The turnover of oxo8dG in nDNA was rapid, e.g. disappearance of oxo8dG in the mouse liver in vivo after gamma-irradiation had a half-life of 11 min. The levels of oxo8dG in mitochondrial DNA isolated from liver, heart and brain were 6-, 16- and 23-fold higher than nDNA from these tissues. Thus, our results showed that the steady-state levels of oxo8dG in mouse tissues range from 180 to 360 lesions in the nuclear genome and from one to two lesions in 100 mitochondrial genomes.
Application of point distribution models to the automated analysis of echocardiograms (2002)

We have recently described how a Point Distribution Model (PDM) can be used to automatically detect structures in medical images. The method has two stages. Initially a statistical model of the shape variability is generated from a set of training images. Structures are located in experimental data by placing an instance of the model in the image and iteratively refining its shape and location to better fit the data. Whilst fitting to the image the model can only adopt shapes which are consistent with the training data. We call the combination of a PDM and the iterative refinement procedure an Active Shape Model (ASM). We have 'trained' models of the left ventricle and associated structures as seen in both long axis and short axis echocardiograms. We show that ASM search using these models is able to detect the structures of interest rapidly accurately and reliably.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
T lymphocytes infiltrating sites of tumor rejection and progression display identical V beta usage but different cytotoxic activities. (1995)

Abstract Most tumors grow progressively and overwhelm the host. The rare but documented cases of spontaneous regression of primary tumors are indicative of the potential of tumor-bearing hosts to develop a significant antitumor response. Because most tumors grow progressively in the host, it is not surprising that the majority of studies have focused on T lymphocytes that infiltrate these tumors. Although these studies have generated significant and useful information during the period of tumor growth, they can only speculate on the mechanisms that are involved in tumor rejection. We have used a well developed sponge model of concomitant tumor immunity that allows us to compare the immunologic events that occur during tumor progression vs rejection. In this model, an animal harboring a primary EMT6 mammary tumor is challenged with a secondary tumor implant through a pre-implanted gelatin sponge. During the manifestation of concomitant tumor immunity, the secondary tumor is rejected and the effector cells mediating the response are retained within the sponge matrix. Using this model we analyzed the TCR usage, cytotoxic activity of lymphocytes, and cytokine production at both tumor sites. The data revealed that tumor-rejecting lymphocytes isolated from the site of secondary tumor implant were cytotoxic toward EMT6 cells, whereas tumor-infiltrating lymphocytes isolated from the progressing primary tumor were not. Interestingly, the TCR-V beta repertoire of the tumor-infiltrating lymphocytes and tumor-rejecting lymphocytes were identical with V beta 1 and V beta 8 being predominant at both sites. Furthermore, the rejection site showed higher gene expression of IFN-gamma, TNF-alpha, and IL-10 whereas TGF-beta expression was slightly higher in the progressing tumors. These findings suggest that the disparate effector functions observed during tumor progression vs rejection are not caused by different T cell phenotypes but may be due instead to influences exerted by cytokines produced at the tumor sites.
Expression genetics in cancer: Shifting the focus from DNA to RNA (1997)

Expression genetics is a conceptually different approach to the identification of cancer-related genes than the search for mutations at the genome level. While mutations lie at the heart of cancer, at least in its early stages, what is recognized here are phenotypic changes usually many steps removed from the initiating mutation. Classically cancer geneticists have concentrated on genomic changes and have ignored the productive potential of examining downstream events based on screening for differential gene expression between tumor cells and well matched normal counterparts. Genes involved in cancer affect the normal functions of many cellular processes: not only proliferation but cell-cell and cell-matrix interactions, DNA repair, invasion and motility, angiogenesis, senescence, apoptosis, and others. Yet very few cancer-related genes affecting these processes have been identified in human cancers by classical methods to find mutated genes despite enormous efforts. I report here our success in readily isolating more than 100 candidate tumor suppressor genes from human tissue, estimated to represent roughly 20% of the total genes recoverable by this approach. Half of the genes are unknown and the other half include representatives of most known cancer processes. Because their expression is lost during cancer progression, they may be useful tumor markers for diagnosis and prognosis. Because these genes are not mutated, they provide opportunities for pharmacological intervention by inducing their reexpression.
In vitrovolatile organic compound profiling using GC×GC-TOFMS to differentiate bacteria associated with lung infections: a proof-of-concept study (2016)

Chronic pulmonary infections are the principal cause of morbidity and mortality in individuals with cystic fibrosis (CF). Due to the polymicrobial nature of these infections, the identification of the particular bacterial species responsible is an essential step in diagnosis and treatment. Current diagnostic procedures are time-consuming, and can also be expensive, invasive and unpleasant in the absence of spontaneously expectorated sputum. The development of a rapid, non-invasive methodology capable of diagnosing and monitoring early bacterial infection is desired. Future visions of real-time, in situ diagnosis via exhaled breath testing rely on the differentiation of bacteria based on their volatile metabolites. The objective of this proof-of-concept study was to investigate whether a range of CF-associated bacterial species (i.e. Pseudomonas aeruginosa, Burkholderia cenocepacia, Haemophilus influenzae, Stenotrophomonas maltophilia, Streptococcus pneumoniae and Streptococcus milleri) could be differentiated based on their in vitro volatile metabolomic profiles. Headspace samples were collected using solid phase microextraction (SPME), analyzed using comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry (GC×GC-TOFMS) and evaluated using principal component analysis (PCA) in order to assess the multivariate structure of the data. Although it was not possible to effectively differentiate all six bacteria using this method, the results revealed that the presence of a particular pattern of VOCs (rather than a single VOC biomarker) is necessary for bacterial species identification. The particular pattern of VOCs was found to be dependent upon the bacterial growth phase (e.g. logarithmic versus stationary) and sample storage conditions (e.g. short-term versus long-term storage at -18 °C). Future studies of CF-associated bacteria and exhaled breath condensate will benefit from the approaches presented in this study and further facilitate the production of diagnostic tools for the early detection of bacterial lung infections.
USP11 regulates p53 stability by deubiquitinating p53 (2014)

The p53 tumor suppressor protein coordinates the cellular responses to a broad range of cellular stresses, leading to DNA repair, cell cycle arrest or apoptosis. The stability of p53 is essential for its tumor suppressor function, which is tightly controlled by ubiquitin-dependent degradation primarily through its negative regulator murine double minute 2 (Mdm2). To better understand the regulation of p53, we tested the interaction between p53 and USP11 using co-immunoprecipitation. The results show that USP11, an ubiquitin-specific protease, forms specific complexes with p53 and stabilizes p53 by deubiquitinating it. Moreover, down-regulation of USP11 dramatically attenuated p53 induction in response to DNA damage stress. These findings reveal that USP11 is a novel regulator of p53, which is required for p53 activation in response to DNA damage.