gebhart/patrepeval huggingface dataset:
Nanoparticle‐biomolecular corona: A new approach for the early detection of non‐small‐cell lung cancer (2018)

Lung cancer (LC) is the most common type of cancer and the second cause of death worldwide in men and women after cardiovascular diseases. Non-small-cell lung cancer (NSCLC) is the most frequent type of LC occurring in 85% of cases. Developing new methods for early detection of NSCLC could substantially increase the chances of survival and, therefore, is an urgent task for current research. Nowadays, explosion in nanotechnology offers unprecedented opportunities for therapeutics and diagnosis applications. In this context, exploiting the bio-nano-interactions between nanoparticles (NPs) and biological fluids is an emerging field of research. Upon contact with biofluids, NPs are covered by a biomolecular coating referred to as "biomolecular corona" (BC). In this study, we exploited BC for discriminating between NSCLC patients and healthy volunteers. Blood samples from 10 NSCLC patients and 5 subjects without malignancy were allowed to interact with negatively charged lipid NPs, leading to the formation of a BC at the NP surface. After isolation, BCs were characterized by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). We found that the BCs of NSCLC patients was significantly different from that of healthy individuals. Statistical analysis of SDS-PAGE results allowed discriminating between NSCLC cancer patients and healthy subjects with 80% specificity, 80% sensitivity and a total discriminate correctness rate of 80%. While the results of the present investigation cannot be conclusive due to the small size of the data set, we have shown that exploitation of the BC is a promising approach for the early diagnosis of NSCLC.
Physical activity and human energy expenditure (2004)

In adults, within the normal physical activity index range, the distribution of time spent at activities with low and moderate intensity determines the physical activity level. High-intensity activity does not have much impact on daily energy expenditure. High-intensity activity is not required to increase the activity energy expenditure.
Spatially-Addressable Immobilization of Macromolecules on Solid Supports (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSpatially-Addressable Immobilization of Macromolecules on Solid SupportsSteven A. Sundberg, Ronald W. Barrett, Michael Pirrung, Amy L. Lu, Benjang Kiangsoontra, and Christopher P. HolmesCite this: J. Am. Chem. Soc. 1995, 117, 49, 12050–12057Publication Date (Print):December 1, 1995Publication History Published online1 May 2002Published inissue 1 December 1995https://pubs.acs.org/doi/10.1021/ja00154a003https://doi.org/10.1021/ja00154a003research-articleACS PublicationsRequest reuse permissionsArticle Views929Altmetric-Citations107LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Systematic OO programming with axiomatic design (1999)

Axiomatic design offers a systematic and orderly way to proceed through the software development process. The methodology ensures that developers make the best possible design decisions by providing decision-making criteria in the form of two axioms: the independence axiom suggests that the best designs maintain the independence of the functional requirements, ensuring that the design can achieve each function without inadvertently affecting any other function; the information axiom suggests that the best designs minimize their information content. Thus, the solution with the greatest likelihood of success is the simplest solution. Software developers can determine the quality of the design based upon the degree to which it satisfies the defined functional requirements; ensure that the design satisfies each function independently and that coupling, which could cause unintended consequences, does not occur; enjoy easier job assignment and team management because they can use the system architecture diagram to assign tasks and define the interrelationships between various modules or classes; and handle software change orders quickly and easily because the system architecture identifies the modules affected by a change. Axiomatic design lets the developer document the design fully, making it easier to change or add extensions.
Physics needs a physical theory of observation (2012)

The ubiquitous assumption that ``systems'' can be taken as ``given'' is wrong.  Viewing observation physically as entanglement allows this assumption to be dropped.  In the framework that results, initial conditions play no role, time is emergent, observers are ubiquitous, and both ``systems'' and the theories that describe them are purely model-theoretic entities.
Structural studies on minor components of saframycin group antibiotics saframycins F, G and H. (1988)

Three minor components of saframycin group antibiotics, saframycins F, G and H were isolated and their structures were determined by comparison with the spectral data of UV, IR, and 1H and 13C NMR of already reported saframycins A and D. Saframycins F, G and H were 21-cyanosaframycin D, 14-hydroxysaframycin A and 25-dihydro-25-beta-ketopropyl-saframycin A, respectively.
Optimized Expression of Full-Length IgG1 Antibody in a Common E. coli Strain (2010)

Multi-polypeptide proteins such as antibodies are difficult to express in prokaryotic systems such as E. coli due to the complexity of protein folding plus secretion. Thus far, proprietary strains or fermenter cultures have been required for appreciable yields. Previous studies have shown that expression of heterologous proteins in E. coli can be enhanced by the reduction of protein translation rates. In this paper, we demonstrate that useful quantities of full-length IgG can be expressed and purified from the common E. coli laboratory strain HB2151 in standard shaking culture using a simple strategy of reduced inducer concentration combined with delayed induction times to modulate translation rates. Purified IgG had only marginally reduced avidity compared to mammalian derived IgG. This indicates that this technique can be used to derive antibodies of potentially equal utility as those expressed in mammalian cell culture, particularly for applications where effector functions mediated by the glycosylated residues in the Fragment Crystallizable (Fc) portion of the immunoglobulin are not required.
Characteristics of Friendships Between Children with and without Mild Disabilities (2003)

Friendship is a very important component in human lives, but it is difficult for children with disabilities to make friends with their typical peers. This study investigated quality of play behaviors in friendships between children with and without disabilities and analyzed how typical peers perceive friendships with children with disabilities. Fifteen pairs of children with and without disabilities who chose each other as friends were selected in elementary regular classrooms. Fifteen pairs of children without disabilities and their normal friends were also selected. Each pair's play behaviors were observed twice for 30 minutes. Then children without disabilities were interviewed about their perception of friendship with their friends with disabilities. Results showed that play role and positive/neutral affect of dyads without and with disabilities was different from dyads of normal peers. Children without disabilities perceived children with disabilities as playing mates, but they noted that limitations in communication, as well as behavior problems made it difficult to maintain friendship. Future research directions were discussed.
Safety and Tolerability of the Glutamate Antagonist CGS 19755 (Selfotel) in Patients With Acute Ischemic Stroke (1995)

We conclude that a single intravenous dose of 1.5 mg/kg CGS 19755 is safe and tolerable in patients with acute ischemic stroke. An efficacy trial is indicated.
Discovery of QCA570 as an Exceptionally Potent and Efficacious Proteolysis Targeting Chimera (PROTAC) Degrader of the Bromodomain and Extra-Terminal (BET) Proteins Capable of Inducing Complete and Durable Tumor Regression (2018)

Proteins of the bromodomain and extra-terminal (BET) family are epigenetics "readers" and promising therapeutic targets for cancer and other human diseases. We describe herein a structure-guided design of [1,4]oxazepines as a new class of BET inhibitors and our subsequent design, synthesis, and evaluation of proteolysis-targeting chimeric (PROTAC) small-molecule BET degraders. Our efforts have led to the discovery of extremely potent BET degraders, exemplified by QCA570, which effectively induces degradation of BET proteins and inhibits cell growth in human acute leukemia cell lines even at low picomolar concentrations. QCA570 achieves complete and durable tumor regression in leukemia xenograft models in mice at well-tolerated dose-schedules. QCA570 is the most potent and efficacious BET degrader reported to date.
Cyclotron Resonance Experiments in Uniaxially Stressed Silicon: Valence Band Inverse Mass Parameters and Deformation Potentials (1963)

Cyclotron resonance of holes in unstressed or "cubic" silicon fails to specify uniquely the valence band parameters because of the complex shape of the warped energy surfaces. The application of uniaxial stresses to the crystal lifts the cubic symmetry and removes the degeneracy at k=0 of the valence band which is responsible for the warping of the surfaces. The ellipsoidal energy surfaces of the decoupled bands give cyclotron resonance masses amenable to simple interpretation. From the measured masses (at 1.26\ifmmode^\circ\else\textdegree\fi{}K and \ensuremath{\sim}9000 Mc/sec) the following quantities have been determined: the inverse mass band parameters (in units of $\frac{{\ensuremath{\hbar}}^{2}}{2{m}_{0}}$) $A=\ensuremath{-}4.28\ifmmode\pm\else\textpm\fi{}0.02$, $|B|=0.75\ifmmode\pm\else\textpm\fi{}0.04$, and $|N|=9.36\ifmmode\pm\else\textpm\fi{}0.10$; the absolute value of the ratio of the band splitting deformation potentials $|\frac{D_{u}^{}{}_{}{}^{\ensuremath{'}}}{{D}_{u}}|=1.31\ifmmode\pm\else\textpm\fi{}0.03$; and the signs of the quantities $B{D}_{u}&lt;0$ and $ND_{u}^{}{}_{}{}^{\ensuremath{'}}&lt;0$. The interaction of the spin-orbit split-off band with the valence band edge under strain allows the signs and magnitudes of the deformation potentials to be obtained. They are ${D}_{u}=+(2.04\ifmmode\pm\else\textpm\fi{}0.20)$ eV and $D_{u}^{}{}_{}{}^{\ensuremath{'}}=+(2.68\ifmmode\pm\else\textpm\fi{}0.25)$ eV. The results indicate that the ${M}_{J}=\ifmmode\pm\else\textpm\fi{}\frac{1}{2}$ band moves "up" and the ${M}_{J}=\ifmmode\pm\else\textpm\fi{}\frac{3}{2}$ band "descends" under compressive stresses along the [001] and [111] crystallographic axes. This fact in conjunction with the ratio of deformation potentials shows that the quantization and band energy splitting are approximately isotropic with respect to the direction of stress. Finally, the signs of $B$ and $N$ were determined to be negative, the negative sign of $B$ being contrary to that predicted by band theory. An investigation of the shape of the split-band hole resonance confirms the line-broadening mechanism proposed by Hasegawa.
Transcriptome analysis by strand-specific sequencing of complementary DNA (2009)

High-throughput complementary DNA sequencing (RNA-Seq) is a powerful tool for whole-transcriptome analysis, supplying information about a transcript's expression level and structure. However, it is difficult to determine the polarity of transcripts, and therefore identify which strand is transcribed. Here, we present a simple cDNA sequencing protocol that preserves information about a transcript's direction. Using Saccharomyces cerevisiae and mouse brain transcriptomes as models, we demonstrate that knowing the transcript's orientation allows more accurate determination of the structure and expression of genes. It also helps to identify new genes and enables studying promoter-associated and antisense transcription. The transcriptional landscapes we obtained are available online.
Discovery and characterisation of an antibody that selectively modulates the inhibitory activity of plasminogen activator inhibitor-1 (2019)

Plasminogen activator inhibitor-1 (PAI-1) is a serine protease inhibitor (serpin) that regulates fibrinolysis, cell adhesion and cell motility via its interactions with plasminogen activators and vitronectin. PAI-1 has been shown to play a role in a number of diverse pathologies including cardiovascular diseases, obesity and cancer and is therefore an attractive therapeutic target. However the multiple patho-physiological roles of PAI-1, and understanding the relative contributions of these in any one disease setting, make the development of therapeutically relevant molecules challenging. Here we describe the identification and characterisation of fully human antibody MEDI-579, which binds with high affinity and specificity to the active form of human PAI-1. MEDI-579 specifically inhibits serine protease interactions with PAI-1 while conserving vitronectin binding. Crystallographic analysis reveals that this specificity is achieved through direct binding of MEDI-579 Fab to the reactive centre loop (RCL) of PAI-1 and at the same exosite used by both tissue and urokinase plasminogen activators (tPA and uPA). We propose that MEDI-579 acts by directly competing with proteases for RCL binding and as such is able to modulate the interaction of PAI-1 with tPA and uPA in a way not previously described for a human PAI-1 inhibitor.
Differential Regulation of AMPA Receptor and GABA Receptor Trafficking by Tumor Necrosis Factor-α (2005)

The proinflammatory cytokine tumor necrosis factor-alpha (TNFalpha) causes a rapid exocytosis of AMPA receptors in hippocampal pyramidal cells and is constitutively required for the maintenance of normal surface expression of AMPA receptors. Here we demonstrate that TNFalpha acts on neuronal TNFR1 receptors to preferentially exocytose glutamate receptor 2-lacking AMPA receptors through a phosphatidylinositol 3 kinase-dependent process. This increases excitatory synaptic strength while changing the molecular stoichiometry of synaptic AMPA receptors. Conversely, TNFalpha causes an endocytosis of GABA(A) receptors, resulting in fewer surface GABA(A) receptors and a decrease in inhibitory synaptic strength. These results suggest that TNFalpha can regulate neuronal circuit homeostasis in a manner that may exacerbate excitotoxic damage resulting from neuronal insults.
Zeolitic Polyoxometalate-Based Metal−Organic Frameworks (Z-POMOFs): Computational Evaluation of Hypothetical Polymorphs and the Successful Targeted Synthesis of the Redox-Active Z-POMOF1 (2009)

The targeted design and simulation of a new family of zeolitic metal-organic frameworks (MOFs) based on benzenedicarboxylate (BDC) as the ligand and epsilon-type Keggin polyoxometalates (POMs) as building units, named here Z-POMOFs, have been performed. A key feature is the use of the analogy between the connectivity of silicon in dense minerals and zeolites with that of the epsilon-type Keggin POMs capped with Zn(II) ions. Handling the epsilon-Keggin as a building block, a selection of 21 zeotype structures, together with a series of dense minerals were constructed and their relative stabilities computed. Among these Z-POMOFs, the cristobalite-like structure was predicted to be the most stable structure. This prediction has been experimentally validated by the targeted synthesis of the first experimental Z-POMOF structure, which was strikingly found to possess the cristobalite topology, with three interpenetrated networks. Crystals of [NBu(4)](3)[PMo(V)(8)Mo(VI)(4)O(36)(OH)(4)Zn(4)(BDC)(2)].2H(2)O (Z-POMOF1) have been isolated under hydrothermal conditions from the reduction of ammonium heptamolybdate in the presence of phosphorous acid and Zn(II) ions. Tetrabutylammonium cations play the role of counterions and space-filling agents in this tridimensional interpenetrated framework. Moreover, the electrochemistry of the epsilon-Keggin POM is maintained and can be exploited in the insoluble Z-POMOF1 framework, as demonstrated by the electrocatalytic reduction of bromate.
Fuse or die: how to survive the loss of Dam in Vibrio cholerae (2013)

Dam methylates GATC sequences in γ-proteobacteria genomes, regulating several cellular functions including replication. In Vibrio cholerae, which has two chromosomes, Dam is essential for viability, owing to its role in chr2 replication initiation. In this study, we isolated spontaneous mutants of V. cholerae that were able to survive the deletion of dam. In these mutants, homologous recombination and chromosome dimer resolution are essential, unless DNA mismatch repair is inactivated. Furthermore, the initiator of chr2 replication, RctB, is no longer required. We show that, instead, replication of chr2 is insured by spontaneous fusion with chr1 and piggybacking its replication machinery. We report that natural fusion of chr1 and chr2 occurred by two distinct recombination pathways: homologous recombination between repeated IS elements and site-specific recombination between dif sites. Lastly, we observed a preferential fusion of the two chromosomes in their terminus of replication.
RNA Interference of Human α-Synuclein in Mouse (2017)

α-Synuclein is postulated to play a key role in the pathogenesis of Parkinson's disease (PD). Aggregates of α-synuclein contribute to neurodegeneration and cell death in humans and in mouse models of PD. Here, we use virally mediated RNA interference to knockdown human α-synuclein in mice. We used an siRNA design algorithm to identify eight siRNA sequences with minimal off-targeting potential. One RNA-interference sequence (miSyn4) showed maximal protein knockdown potential <i>in vitro</i>. We then designed AAV vectors expressing miSyn4 and injected them into the mouse substantia nigra. miSyn4 was robustly expressed and did not detectably change dopamine neurons, glial proliferation, or mouse behavior. We then injected AAV2-miSyn4 into Thy1-hSNCA mice over expressing α-synuclein and found decreased human α-synuclein (hSNCA) in both midbrain and cortex. In separate mice, co-injection of AAV2-hSNCA and AAV2-miSyn4 demonstrated decreased hSNCA expression and rescue of hSNCA-mediated behavioral deficits. These data suggest that virally mediated RNA interference can knockdown hSNCA <i>in vivo</i>, which could be helpful for future therapies targeting human α-synuclein.
Rapid analysis of poplar lignin monomer composition by a streamlined thioacidolysis procedure and near‐infrared reflectance‐based prediction modeling (2009)

Determination of the physico-chemical attributes of plant cell walls, such as lignin content and composition, is of paramount importance in germplasm screening and for evaluating the results of plant breeding and genetic engineering. There are escalating needs for analyses to be robust, reproducible, accurate, and efficient. We have recently modified an established protocol for discrimination of lignin monomers, thioacidolysis, with the goal of increasing sample throughput while maintaining accuracy and reducing equipment load and consumption of reagents. Numerous methodological changes related to volume scaling, selection of the processing vessel, and sample handling were addressed. The revised protocol permitted rapid processing of some 50 or more samples per person per day. A direct comparison between methods using hybrid poplar (Populus alba x tremula) wood samples, resulted in quantities of p-hydroxyphenyl (H), guaiacyl (G), and syringyl (S) lignin monomers that were equivalent to those derived from the original protocol. The revised methodology was then applied to quickly generate phenotypic trait data from 267 hybrid poplar trees (including wild type and eight C4H::F5H transgenic lines), for the development of a near-infrared-based model for predicting the proportion of lignin monomers across a broad phenotypic range of S:G. The resulting partial least squares regression model performed well under full cross-validation, giving strong, linear relationships between actual and predicted monomer proportions, and very high predictive accuracy for the predominant G and S monomers. This research brings considerable refinement to the thioacidolysis procedure, and establishes a method for rapidly and accurately quantifying cell-wall lignin composition that could effectively be employed in routine phenotypic screening platforms.
RP 59500: a proposed mechanism for its bactericidal activity (1992)

RP 59500 is a combination of RP 57669 and RP 54476, which are semisynthetic water soluble derivatives of pristinamycin IA (PIA) and pristinamycin IIA (PIIA), respectively. Like their precursors, these molecules are bacteristatic in their own right. In association, they exert bactericidal activity against a variety of Gram-positive bacteria. Experiments involving the binding of these antibiotics to the target bacterial ribosome showed that both the binding sites and the mechanism of action of the components of RP 59500 are identical to those of the parent molecules. By affinity-labelling with a structural analogue of RP 57669, it was demonstrated that L24, a protein of the 70S ribosomal subunit, was specifically labelled. Experiments using radioactive N-ethylmaleimide to label proteins possessing a thiol residue, indicated that proteins L24, L10 and L11 are not only close to each other in the ribosomal structure, but are also adjacent (if not actually part of) the channel through which newly synthesized proteins are extruded. We propose that the mechanism of action of these compounds is to close or narrow the extrusion channel of these proteins, which could lead to their accumulation on the ribosome. We cannot exclude, of course, the possibility that this accumulation disturbs peptidyl-tRNA hydrolase (PHT) activity, thereby depleting free tRNAs within the cell and inhibiting protein synthesis.
Cadmium Increases Tissue Factor (Coagulation Factor III) Activity by Facilitating Its Reassociation with Lipids (1980)

The coagulant activity of partially purified and delipidated tissue factor (TF) (coagulation Factor III) has previously been recovered by dialysis of the apoprotein after addition of mixed brain lipids and deoxycholate. Inclusion of cadmium chloride in the relipidation mixture greatly increases the recovered activity of highly purified TF from human placenta by promoting incorporation of TF into phospholipid vesicles; TF that had not been incorporated into vesicles showed no coagulant activity. Thus, TF must be present in a lipid bilayer for expression of coagulant activity. In vitro, cadmium induces fusion of lipid vesicles and may contribute to the incorporation of proteins in membranes.