gebhart/patrepeval huggingface dataset:
Transcription of an Expanded Genetic Alphabet (2009)

Expansion of the genetic alphabet with a third base pair would have immediate biotechnology applications and also lay the foundation for a semisynthetic organism with an expanded genetic code. A variety of unnatural base pairs have been shown to be formed efficiently and selectively during DNA replication, and the pairs formed between the unnatural nucleotide d5SICS and either dMMO2 or dNaM are particularly interesting because they have been shown to be replicated with efficiencies and fidelities that are beginning to approach those of a natural base pair. Not only are these unnatural base pairs promising for different applications, but they also demonstrate that nucleobase shape and hydrophobicity are sufficient to control replication. While a variety of unnatural base pairs have been shown to be substrates for transcription, none are transcribed in both possible strand contexts, and the transcription of a fully hydrophobic base pair has not been demonstrated. We show here that both of the unnatural base pairs d5SICS:dMMO2 and d5SICS:dNaM are selectively transcribed by T7 RNA polymerase and that the efficiency of d5SICS:dNaM transcription in both possible strand contexts is only marginally reduced relative to that of a natural base pair. Thus, as with replication, we find that hydrogen-bonding is not essential for transcription and may be replaced with packing and hydrophobic forces. The results also demonstrate that d5SICS:dNaM is both replicated and transcribed with efficiencies and fidelities that should be sufficient for use as part of an in vitro expanded genetic alphabet.
Strain rate effects in the mechanical response of polymer anchored carbon nanotube foams (2008)

Super-compressible foam-like carbon nanotube films have been reported to exhibit highly nonlinear viscoelastic behaviour in compression similar to soft tissue. Their unique combination of light weight and exceptional electrical, thermal and mechanical properties have helped identify them as viable building blocks for more complex nanosystems and as stand-alone structures for a variety of different applications. In the as-grown state, their mechanical performance is limited by the weak adhesion between the tubes, controlled by the van der Waals forces, and the substrate allowing the forests to split easily and to have low resistance in shear. Under axial compression loading carbon nanotubes have demonstrated bending, buckling8 and fracture9 (or a combination of the above) depending on the loading conditions and on the number of loading cycles. In this work, we partially anchor dense vertically aligned foam-like forests of carbon nanotubes on a thin, flexible polymer layer to provide structural stability, and report the mechanical response of such systems as a function of the strain rate. We test the sample under quasi-static indentation loading and under impact loading and report a variable nonlinear response and different elastic recovery with varying strain rates. A Bauschinger-like effect is observed at very low strain rates while buckling and the formation of permanent defects in the tube structure is reported at very high strain rates. Using high-resolution transmission microscopy
Construction of Smart Supramolecular Polymeric Hydrogels Cross-linked by Discrete Organoplatinum(II) Metallacycles via Post-Assembly Polymerization (2016)

Postassembly modification strategy has been successfully employed in the construction of discrete metallosupramolecular assemblies. However, the most known reports have been limited to the simple structural conversion through the easy covalent reactions, thus hindering the development of organometallic functional materials. In this study, we first combined coordination-driven self-assembly and postassembly reversible addition-fragmentation chain-transfer (RAFT) polymerization to produce a new family of star supramolecular polymers containing well-defined metallacycles as cores, which featured typical lower critical solution temperature (LCST) behavior in water because of the existence of poly(N-isopropylacrylamide) (PNIPAAM) moieties. Moreover, the obtained star polymers could further form supramolecular hydrogels cross-linked by discrete hexagonal metallacycles at room temperature without heating-cooling process. Interestingly, the resultant polymeric hydrogels exhibited stimuli-responsive behavior toward temperature and bromide anion as well as self-healing property. We demonstrated that the dynamic nature of Pt-N bonds in the hexagonal metallacycles played an important role in determining the stimuli-responsive and self-healing property of the final soft matters. Thus, merging coordination-driven self-assembly and postassembly polymerization provided a new avenue to the preparation of functional materials containing well-defined, discrete metal-organic assemblies as main scaffolds.
A modular IgG-scFv bispecific antibody topology (2009)

Here we present a bispecific antibody (bsAb) format in which a disulfide-stabilized scFv is fused to the C-terminus of the light chain of an IgG to create an IgG-scFv bifunctional antibody. When expressed in mammalian cells and purified by one-step protein A chromatography, the bsAb retains parental affinities of each binding domain, exhibits IgG-like stability and demonstrates in vivo IgG-like tumor targeting and blood clearance. The extension of the C-terminus of the light chain of an IgG with an scFv or even a smaller peptide does appear to disrupt disulfide bond formation between the light and heavy chains; however, this does not appear to affect binding, stability or in vivo properties of the IgG. Thus, we demonstrate here that the light chain of an IgG can be extended with an scFv without affecting IgG function and stability. This format serves as a standardized platform for the construction of functional bsAbs.
Angiopoietin 1, PDGF‐B, and TGF‐β gene regulation in endothelial cell and smooth muscle cell interaction (2003)

The vascular wall is mainly composed of endothelial cells (ECs) and smooth muscle cells (SMCs). The crosstalking between these two cell types is critical in the vascular maturation process. Genetic studies suggest that the Tie2/angiopoietin 1 (Ang1) pathway regulates vascular remodeling. However, the molecular mechanism is unclear. PDGF is a potent chemoattractant for SMCs, and TGF-beta regulates SMC differentiation. Here, we examined gene regulation. PDGF-B stimulation upregulated Ang1 expression in SMCs through the PI3K and PKC pathways. PDGF-B stimulation also produced an acute induction of TGF-beta expression in SMCs through the MAPK/ERK pathway. Interestingly, TGF-beta negatively regulated Ang1 expression induced by the PDGF-B stimulation in SMCs. Reciprocally, we observed that stimulation of ECs with either Ang1 or TGF-beta slightly downregulated PDGF expression. A combination of both TGF-beta with Ang1 produced much stronger downregulation of PDGF. Our data showed complex gene regulations that include both positive and negative regulations between ECs and SMCs to maintain vascular homeostasis.
From the Cover: Negative regulation of defense responses in plants by a conserved MAPKK kinase (2000)

The enhanced disease resistance 1 (edr1) mutation of Arabidopsis confers resistance to powdery mildew disease caused by the fungus Erysiphe cichoracearum. Resistance mediated by the edr1 mutation is correlated with induction of several defense responses, including host cell death. Double mutant analysis revealed that all edr1-associated phenotypes are suppressed by mutations that block salicylic acid (SA) perception (nim1) or reduce SA production (pad4 and eds1). The NahG transgene, which lowers endogenous SA levels, also suppressed edr1. In contrast, the ein2 mutation did not suppress edr1-mediated resistance and associated phenotypes, indicating that ethylene and jasmonic acid-induced responses are not required for edr1 resistance. The EDR1 gene was isolated by positional cloning and was found to encode a putative MAP kinase kinase kinase similar to CTR1, a negative regulator of ethylene responses in Arabidopsis. Taken together, these data suggest that EDR1 functions at the top of a MAP kinase cascade that negatively regulates SA-inducible defense responses. Putative orthologs of EDR1 are present in monocots such as rice and barley, indicating that EDR1 may regulate defense responses in a wide range of crop species.
Effect of Inhaled Nitric Oxide on Gas Exchange in Patients with Congestive Heart Failure (1999)

Because nitric oxide inhalation improved gas exchange, it may be used as a supportive therapy when other conventional vasodilators worsen gas exchange.
The characterization of the invasion phenotype of uveal melanoma tumour cells shows the presence of MUC18 and HMG‐1 metastasis markers and leads to the identification of DJ‐1 as a potential serum biomarker (2006)

Uveal malignant melanoma (UM) is the most frequent primary intraocular tumour in adult humans. Because the survival rate of patients with UM has changed little in the past few decades, a better understanding of the molecular events governing UM development and the identification of markers indicating the potential for metastasis at the time of diagnosis are necessary to design improved and more specific treatments. In this study, we investigated UM tumour development by comparing two recently established UM cultures with different invasion potential by two-dimensional gel electrophoresis. Protein features expressed differentially were identified by mass spectrometric analysis. Potential markers were assayed in both cultures and in long-term established UM cell lines (UW-1, OCM-1, SP6.5 and 92.1) by Western blotting and their role in invasion analysed using Matrigel membranes. Comparative analysis revealed that UM cultures with low- and high-grade invasion potential differ in their cellular metabolism and, more interestingly, in several cancer-associated proteins, including those implicated in cell adhesion and migration, proliferation and various oncogenes. Our data indicate a correlation between MUC18 and HMG-1 expression and the invasiveness of UM cells. We also demonstrate the expression and secretion of DJ-1 oncoprotein by UM cells. We suggest a possible role for MUC18 and HMG-1 proteins in UM cell invasion. The secretion of DJ-1 by UM cells, and the ability to detect this protein in UM patients' sera implicate it as a potential noninvasive biomarker for this malignancy.
Bone markers : biochemical and clinical perspectives (2001)

1. Introduction 2. Potential Candidates for Bone Turnover Markers: N-Telopeptide Cross Links of Type I Collagen 3. C-Telopeptides 4. Pyridinium Crosslinks as Bone Resorption Markers 5. Bone Specific Alkaline Phosphatase 6. Osteocalcin 7. The N- and C-Terminal Propeptides of Human Procollagen Type I (PINP and PICP) Bone Sialoprotein 8. Biochemical Markers of Bone Turnover: 9. Age, Gender, and Race as Sources of Biological Variability 10. Circadian Rhythm Studies of Serum Bone Resorption Markers: Implications for Optimal Sample Timing and Clinical Utility 11. Sources of Biological Bone Marker Variability 12. The Effects of Fracture or Disease on Biochemical Markers of Bone Remodelling 13. Variation in Biochemical Markers of Bone Turnover: Sources, Quantification, Minimisation 14. The Use of Biochemical Markers of Bone Turnover for Monitoring Treatment of Osteoporosis 15. The Use of Biochemical Markers of Bone Turnover to Monitor Response to Therapy: Statistics and Logic 16. Prediction of Response in Bone Mass by Biochemical Markers of Bone Turnover During Anti-Resorptive Therapy for Prevention of Osteoporosis 17. Biochemical Markers of Bone Turnover as Predictors of Bone Loss and Response to Therapy 18. Assessment of Fracture Risk 19. Markers of Bone Turnover, Endogenous Hormones, Rate of Bone Loss and Fracture Risk in the OFELY Study 20. Prediction of Hip Fractures with Markers of Bone Turnover in the EPIDOS Study 21. Which Fractures are Associated with High Bone Resorption in Elderly Women: The Rotterdam Study 22. The Study of Osteoporotic Fractures 23. The Association Between Bone Turnover and Fracture Risk: The Sheffield Osteoporosis Study 24. Panel Discussions
Structure and autoregulation of the metJ regulatory gene in Escherichia coli. (1984)

The nucleotide sequence of the Escherichia coli metJ regulatory gene (312 nucleotides) has been determined as well as that of two mutations located within the gene. Analysis of the sequence downstream from the metJ gene has revealed inverted repeats homologous to several intercistronic regions, also reported to occur between operons. A hybrid protein that contains the 55 first amino acid residues of the metJ protein substituting for the 8 amino acid residues at the NH2 terminus of beta-galactosidase was produced by gene fusion. The hybrid protein retaining beta-galactosidase activity was purified. Its amino-terminal sequence was determined and this allowed us to locate the translational start codon of the metJ gene. Evidence was provided for autoregulation by repression of the metJ gene. By sequencing upstream from metJ, the region situated between the metJ and metB genes was found to contain putative operator structures that we propose to call "Met boxes."
Influenza virus entry and infection require host cell N-linked glycoprotein (2004)

A widely held view of influenza virus infection is that the viral receptor consists of cell surface carbohydrate sialic acid, which can be present as glycoprotein or glycolipid. Here, we examined influenza virus entry and infection in Lec1 cells, a mutant CHO cell line deficient in terminal N-linked glycosylation caused by a mutation in the N-acetylglucosaminyltransferase I (GnT1) gene. We show that influenza virus cannot infect Lec1 cells, despite having full capacity to undergo virus binding and fusion. Lec1 cells also show no virus replication defect, and infection was restored in Lec1 cells expressing wild-type GnT1. Viruses were apparently arrested at the level of internalization from the plasma membrane and were not endocytosed. Lec1 cells were refractory to infection by several strains of influenza virus, including H1 and H3 strains of influenza A, as well as influenza B virus. Finally, cleavage of N-glycans from wild-type CHO cells markedly reduced infection by influenza virus. We suggest that influenza virus specifically requires N-linked glycoprotein for entry into cells, and that sialic acid, although acting as an efficient attachment factor, is not sufficient as an influenza virus receptor in vivo.
Role of the Gag Matrix Domain in Targeting Human Immunodeficiency Virus Type 1 Assembly (2000)

Human immunodeficiency virus type 1 (HIV-1) particle formation and the subsequent initiation of protease-mediated maturation occur predominantly on the plasma membrane. However, the mechanism by which HIV-1 assembly is targeted specifically to the plasma membrane versus intracellular membranes is largely unknown. Previously, we observed that mutations between residues 84 and 88 of the matrix (MA) domain of HIV-1 Gag cause a retargeting of virus particle formation to an intracellular site. In this study, we demonstrate that the mutant virus assembly occurs in the Golgi or in post-Golgi vesicles. These particles undergo core condensation in a protease-dependent manner, indicating that virus maturation can occur not only on the plasma membrane but also in the Golgi or post-Golgi vesicles. The intracellular assembly of mutant particles is dependent on Gag myristylation but is not influenced by p6(Gag) or envelope glycoprotein expression. Previous characterization of viral revertants suggested a functional relationship between the highly basic domain of MA (amino acids 17 to 31) and residues 84 to 88. We now demonstrate that mutations in the highly basic domain also retarget virus particle formation to the Golgi or post-Golgi vesicles. Although the basic domain has been implicated in Gag membrane binding, no correlation was observed between the impact of mutations on membrane binding and Gag targeting, indicating that these two functions of MA are genetically separable. Plasma membrane targeting of Gag proteins with mutations in either the basic domain or between residues 84 and 88 was rescued by coexpression with wild-type Gag; however, the two groups of MA mutants could not rescue each other. We propose that the highly basic domain of MA contains a major determinant of HIV-1 Gag plasma membrane targeting and that mutations between residues 84 and 88 disrupt plasma membrane targeting through an effect on the basic domain.
Researching from the spaces in between? The politics of accountability in studying the British military (2016)

This paper is an exploration of the embodied experience of attempting to occupy the spaces in between collaboration and disengagement in conducting feminist-informed, critical research on the British military, and the ethical questions raised by doing so. It draws for illustration on a qualitative study of domestic abuse in the British Armed Forces, which began independently of the institution before seeking support from and ethical clearance through the military at a later date. The paper discusses the risk that research based on high levels of access to the military may be co-opted by the institution and its priorities; that is, that such research may become militarized. Drawing on feminist work on the politics of accountability, it also highlights the importance of reflecting upon the ways in which research on military populations may be taken up by the institutions themselves. In opposition, it explores the political and ethical quandaries raised by pursuing such research in detachment from the military institution, and the lack of nuance likely to characterize the findings of such a study. The paper thus reflects upon some of the researcher’s embodied experience of negotiating a space between these two poles as well as on the political and ethical questions which this position, too, engenders.
Function of a relaxed-like state following temperature downshifts in Escherichia coli (1992)

Temperature downshifts of Escherichia coli throughout its growth range resulted in transient growth inhibition and a cold shock response consisting of transient induction of several proteins, repression of heat shock proteins, and, despite the growth lag, continued synthesis of proteins involved in transcription and translation. The paradoxical synthesis of the latter proteins, which are normally repressed when growth is arrested, was explored further. First, by means of a nutritional downshift, a natural stringent response was induced in wild-type cells immediately prior to a shift from 37 to 10 degrees C. These cells displayed decreased synthesis of transcriptional and translational proteins and decreased induction of cold shock proteins; also, adaptation for growth at 10 degrees C was delayed, even after restoration of the nutrient supplementation. Next, the contribution of guanosine 5'-triphosphate-3'-diphosphate and guanosine 5'-diphosphate-3'-diphosphate, collectively abbreviated (p)ppGpp, to the alteration in cold shock response was studied with the aid of a mutant strain in which overproduction of these nucleotides can be artificially induced. Induction of (p)ppGpp synthesis immediately prior to shifting this strain from 37 to 10 degrees C produced results differing only in a few details from those described above for nutritional downshift of the wild-type strain. Finally, shifting a relA spoT mutant, which cannot synthesize (p)ppGpp, from 24 to 10 degrees C resulted in a greater induction of the cold shock proteins, increased synthesis of transcriptional and translational proteins, decreased synthesis of a major heat shock protein, and faster adaptation to growth than for the wild-type strain. Our results indicate that the previously reported decrease in the (p)ppGpp level following temperature downshift plays a physiological role in the regulation of gene expression and adaptation for growth at low temperature.
Intracavity phase measurement towards sub nanometer resolution (2009)

Using intracavity phase measurement technique, we designed a linear laser cavity with two pulses per cavity operation, that provides a sample/reference arm. We demonstrate the conversion of nanometer positioning of a mirror into kHz bandwidth.
Double Cycloisomerization as a Novel and Expeditious Route to Tricyclic Heteroaromatic Compounds:  Short and Highly Diastereoselective Synthesis of (±)-Tetraponerine T6 (2002)

[reaction: see text] Cu-Assisted double cycloisomerization of bis-alkynylpyrimidines afforded the 5-6-5 tricyclic heteroaromatic skeleton. This transformation was used as a key step in the highly diastereoselective total synthesis of (+/-)-tetraponerine T6.
An investigation of non-compensatory decision strategies utilized in transportation carrier selection for outbound surface shipments of general commodity freight (1997)

The primary objective of this study was to gain further insight into the decision strategies used by shippers to select transportation services providers and in particular, to verify the idea that transportation carrier selection criteria importance is a multidimensional concept.The results indicate that shippers utilize a combination
Direct synthesis of pyrrole nucleosides by the stereospecific sodium salt glycosylation procedure (1987)

Abstract A stereospecific high‐yield glycosylation of preformed fully aromatic pyrroles has been accomplished for the first time. Reaction of the sodium salt of pyrrole‐2‐carbonitrile ( 1a ) and pyrrole‐2,4‐dicarbonitrile ( 1b ) with 1‐chloro‐2‐deoxy‐3,5‐di‐ O ‐ p ‐toluoyl‐α‐D‐ erythro ‐pentofuranose ( 2 ) gave exclusively the corresponding blocked nucleosides with β‐anomeric configuration 3a and 3b , which on deprotection gave 1‐(2‐deoxy‐β‐D‐ erythro ‐pentofuranosyl) derivatives of 1a ( 3c ) and 1b ( 3d ). Functional group transformation of 3c and 3d provided a number of 2‐monosubstituted 4a‐c and 2,4‐disubstituted 4d‐f derivatives of 1‐(2‐deoxy‐β‐D‐ erythro ‐pentofuranosyl)pyrrole. Similar glycosylation of the sodium salt of 1a and 1b with 1‐chloro‐2,3,5‐tri‐ O ‐benzyl‐α‐D‐arabinofuranose ( 5 ) and further functional group transformation of the intermediate blocked nucleosides 6a and 6b provided 1‐β‐D‐arabinofuranosyl derivatives of pyrrole‐2‐carboxamide ( 7b ) and pyrrole‐2,4‐dicarboxamide ( 7d ). The synthetic utility of this glycosylation procedure for the preparation of 1‐β‐D‐ribofuranosylpyrrole‐2‐carbonitrile ( 12 ) has also been demonstrated by reacting the sodium salt of 1a with 1‐chloro‐2,3‐ O ‐isopropylidene‐5‐ O ‐( t ‐butyl)dimethylsilyl‐α‐D‐ribofuranose ( 10 ) and subsequent deprotection of the blocked intermediate 11 . This study provided a convenient route to the preparation of aromatic pyrrole nucleosides.
Reduced Adverse Event Profile of Orally Inhaled DHE (MAP0004) vs IV DHE: Potential Mechanism (2009)

The mechanism by which nausea was experienced with IV DHE--yet not with MAP0004--was not associated with classic nausea pathways/targets (dopamine, 5-HT(3), or muscarinic receptors) or with peripheral action in the intestine via enterochromaffin cells. Importantly, the maximum DHE concentrations following MAP0004 administration were insufficient to interact with receptors implicated in cardiovascular (5-HT(2B) and beta(1)) and pulmonary effects (beta(2), adenosine, muscarinic, and leukotriene).