gebhart/patrepeval huggingface dataset:
NMR spectroscopy: a multifaceted approach to macromolecular structure (2000)

1. Introduction 29 2. Landmarks in NMR of macromolecules 32 2.1 Protein structures and methods development 32 2.1.1 Sequential assignment method 32 2.1.2 Triple-resonance experiments 34 2.1.3 Structures of large proteins 36 2.2 Protein–nucleic acid complexes 37 2.3 RNA structures 38 2.4 Membrane-bound systems 39 3. NMR spectroscopy today 40 3.1 State-of-the-art structure determination 41 3.2 New methods 44 3.2.1 Residual dipolar couplings 44 3.2.2 Direct detection of hydrogen bonds 44 3.2.3 Spin labeling 45 3.2.4 Segmental labeling 46 3.3 Protein complexes 47 3.4 Mobility studies 50 3.5 Determination of time-dependent structures 52 3.6 Drug discovery 53 4. The future of NMR 54 4.1 The ease of structure determination 54 4.2 The ease of making recombinant protein 55 4.3 Post-translationally modified proteins 55 4.4 Approaches to large and/or membrane-bound proteins 56 4.5 NMR in structural genomics 56 4.6 Synergy of NMR and crystallography in protein structure determination 56 5. Conclusion 57 6. Acknowledgements 57 7. References 57 Since the publication of the first complete solution structure of a protein in 1985 (Williamson et al . 1985), tremendous technological advances have brought nuclear magnetic resonance spectroscopy to the forefront of structural biology. Innovations in magnet design, electronics, pulse sequences, data analysis, and computational methods have combined to make NMR an extremely powerful technique for studying biological macromolecules at atomic resolution (Clore &amp; Gronenborn, 1998). Most recently, new labeling and pulse techniques have been developed that push the fundamental line-width limit for resolution in NMR spectroscopy, making it possible to obtain high-field spectra with better resolution than ever before (Dötsch &amp; Wagner, 1998). These methods are facilitating the study of systems of ever-increasing complexity and molecular weight.
FAM83D promotes cell proliferation and motility by downregulating tumor suppressor gene FBXW7 (2013)

Amplification of chromosome 20q is frequently found in various types of human cancers, including breast cancer. The list of candidate oncogenes in 20q has expanded over the past decade. Here, we investigate whether FAM83D (family with sequence similarity 83, member D) on chromosome 20q plays any role in breast cancer development. The expression level of FAM83D is significantly elevated in breast cancer cell lines and primary human breast cancers. High expression levels of FAM83D are significantly associated with poor clinical outcome and distant metastasis in breast cancer patients. We show that ectopic expression of FAM83D in human mammary epithelial cells promotes cell proliferation, migration and invasion along with epithelial-mesenchymal transition (EMT). Ablation of FAM83D in breast cancer cells induces apoptosis and consequently inhibits cell proliferation and colony formation. Mechanistic studies reveal that overexpression of FAM83D downregulates FBXW7 expression levels through a physical interaction, which results in elevated protein levels of oncogenic substrates downstream to FBXW7, such as mTOR, whose inhibition by rapamycin can suppress FAM83D-induced cell migration and invasion. The results demonstrate that FAM83D has prognostic value for breast cancer patients and is a novel oncogene in breast cancer development that at least in part acts through mTOR hyper-activation by inhibiting FBXW7.
Loop-miRs: active microRNAs generated from single-stranded loop regions (2013)

MicroRNAs (miRNAs) are key mediators of post-transcriptional gene regulation. The miRNA precursors are processed by the endonucleases Drosha and Dicer into a duplex, bound to an Argonaute protein and unwound into two single-stranded miRNAs. Although alternative ways to generate miRNAs have been discovered, e.g. pre-miRNA cleavage by Ago2 or cleavage products of snoRNAs or tRNAs, all known pathways converge on a double-stranded RNA duplex. Exogenous single-stranded siRNAs (ss-siRNAs) can elicit an effective RNA interference reaction; recent studies have identified chemical modifications increasing their stability and activity. Here, we provide first evidence that endogenous, unmodified, single-stranded RNA sequences are generated from single-stranded loop regions of human pre-miRNA hairpins, the so called loop-miRs. Luciferase assays and immunoprecipitation validate loop-miR activity and incorporation into RNA-induced silencing complexes. This study identifies endogenous miRNAs that are generated from single-stranded regions; hence, it provides evidence that precursor-miRNAs can give rise to three distinct endogenous miRNAs: the guide strand, the passenger strand and the loop-miR.
Heparan sulphate N-sulphotransferase activity: reaction mechanism and substrate recognition (2003)

Human heparan sulphate N-deacetylase/N-sulphotransferase 1 sulphates the NH(3) (+) group of the glucosamine moiety of the heparan chain in heparan sulphate/heparin biosynthesis. An open cleft that runs perpendicular to the sulphate donor 3'-phosphoadenosine 5'-phosphosulphate may constitute the acceptor substrate-binding site of the sulphotransferase domain (hNST1) [Kakuta, Sueyoshi, Negishi and Pedersen (1999) J. Biol. Chem. 274, 10673-10676]. When a hexasaccharide model chain is docked into the active site, only a trisaccharide (-IdoA-GlcN-IdoA-) portion interacts directly with the cleft residues: Trp-713, His-716 and His-720 from alpha helix 6, and Phe-640, Glu-641, Glu-642, Gln-644 and Asn-647 from random coil (residues 640-647). Mutation of these residues either abolishes or greatly reduces hNST1 activity. Glu-642 may play the critical role of catalytic base in the sulphuryl group transfer reaction, as indicated by its hydrogen-bonding distance to the NH(3) (+) group of the glucosamine moiety in the model and by mutational data.
Hydrogen-Atom Abstraction/Cyclization in Synthesis. Direct Syntheses of Coumestan and Coumestrol (2000)

The synthesis of coumestrol has been achieved in five steps from 1, 3-dimethoxybenzene. The key step is a photochemical cyclization of a glyoxylate ester.
On the self-similar nature of Ethernet traffic (1993)

We demonstrate that Ethernet local area network (LAN) traffic is statistically self-similar, that none of the commonly used traffic models is able to capture this fractal behavior, and that such behavior has serious implications for the design, control, and analysis of high-speed, cell-based networks. Intuitively, the critical characteristic of this self-similar traffic is that there is no natural length of a "burst": at every time scale ranging from a few milliseconds to minutes and hours, similar-looking traffic bursts are evident; we find that aggregating streams of such traffic typically intensifies the self-similarity ("burstiness") instead of smoothing it.Our conclusions are supported by a rigorous statistical analysis of hundreds of millions of high quality Ethernet traffic measurements collected between 1989 and 1992, coupled with a discussion of the underlying mathematical and statistical properties of self-similarity and their relationship with actual network behavior. We also consider some implications for congestion control in high-bandwidth networks and present traffic models based on self-similar stochastic processes that are simple, accurate, and realistic for aggregate traffic.
A taxonomy of see-through tools (1994)

Article A taxonomy of see-through tools Share on Authors: Eric A. Bier Xerox PARC, 3333 Coyote Hill Rd., Palo Alto, CA Xerox PARC, 3333 Coyote Hill Rd., Palo Alto, CAView Profile , Maureen C. Stone Xerox PARC, 3333 Coyote Hill Rd., Palo Alto, CA Xerox PARC, 3333 Coyote Hill Rd., Palo Alto, CAView Profile , Ken Fishkin Xerox PARC, 3333 Coyote Hill Rd., Palo Alto, CA Xerox PARC, 3333 Coyote Hill Rd., Palo Alto, CAView Profile , William Buxton University of Toronto, CSRI, Toronto, ON, Canada, M5S 1A4 University of Toronto, CSRI, Toronto, ON, Canada, M5S 1A4View Profile , Thomas Baudel Université de Paris-Sud, LRI, 91 405 Orsay Cedex, France Université de Paris-Sud, LRI, 91 405 Orsay Cedex, FranceView Profile Authors Info & Claims CHI '94: Proceedings of the SIGCHI Conference on Human Factors in Computing SystemsApril 1994 Pages 358–364https://doi.org/10.1145/191666.191786Online:24 April 1994Publication History 83citation1,192DownloadsMetricsTotal Citations83Total Downloads1,192Last 12 Months17Last 6 weeks5 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteGet Access
Sugar transport by the bacterial phosphotransferase system. Structural and thermodynamic domains of enzyme I of Salmonella typhimurium. (1991)

Enzyme I, the first in the sequence of phosphocarrier proteins of the bacterial phosphoenolpyruvate:glycose phosphotransferase system, is a potential critical point for regulating sugar uptake. The thermal stability of Enzyme I was studied by high sensitivity differential scanning calorimetry. At pH 7.5, thermal unfolding of the protein exhibits two peaks with maxima (Tm) at 47.6 and 55.1 degrees C, indicating that the protein comprises two cooperative unfolding structures. Interaction between the two domains is markedly dependent on pH within the range 6.5-8.5. At pH 7.5, catalytic activity was unaffected by heating through the first transition but was lost by heating through the second. Cleavage of Enzyme I (63.5 kDa) by trypsin, chymotrypsin, or Staphylococcus aureus V8 protease yields a 30-kDa fragment, EI-N, containing the NH2 terminus and the active site, His-189. Protease and differential scanning calorimetry experiments show that EI-N is the structural domain corresponding to the cooperative region in the intact enzyme that unfolds at the higher Tm. EI-N catalyzes one activity of Enzyme I; it accepts a phosphoryl group from phosphohistidine-containing phosphocarrier protein but cannot be phosphorylated by phospho-Enzyme I or phosphoenolpyruvate. The phosphoryl transfer between EI-N and the histidine-containing phosphocarrier protein is reversible. Portions of the Salmonella typhimurium ptsI DNA sequence are known; the complete sequence is presented here and compared to Escherichia coli ptsI.
Pain Assessment of Subcutaneous Injections (1996)

The pain of a subcutaneous injection is related to injection volume in the thigh. The results show that increasing the volume from 0.5 to 1.0 mL increases the pain significantly. The findings from this study should be considered when injection preparations for subcutaneous administration are formulated. The volume should generally be less than 1.0 mL if injected into the thigh.
EPR investigations of non‐oxidized silicon nanoparticles from thermal pyrolysis of silane (2011)

Abstract Electron paramagnetic resonance (EPR) investigations of non‐oxidized crystalline silicon nanoparticles (SiNP) from thermal silane pyrolysis revealed that the dangling bond (db) concentration strongly depends on the synthesis temperature. For SiNP synthesized at 1000‐1200 °C and processed entirely in inert atmosphere, approximately 10 13 cm ‐2 dbs were found which is at least one order of magnitude higher than the values previously reported for oxidized SiNP. After the synthesis, the dbs can be quenched by the addition of bromine (Br 2 ) that proves their location at the particle surface. (© 2011 WILEY‐VCH Verlag GmbH &amp; Co. KGaA, Weinheim)
Dramatic Aggregation of Alzheimer Aβ by Cu(II) Is Induced by Conditions Representing Physiological Acidosis (1998)

The cortical deposition of Abeta is an event that occurs in Alzheimer's disease, Down's syndrome, head injury, and normal aging. Previously, in appraising the effects of different neurochemical factors that impact upon the solubility of Abeta, we observed that Zn2+ was the predominant bioessential metal to induce the aggregation of soluble Abeta at pH 7.4 in vitro and that this reaction is totally reversible with chelation. We now report that unlike other biometals tested at maximal biological concentrations, marked Cu2+-induced aggregation of Abeta1-40 emerged as the solution pH was lowered from 7.4 to 6.8 and that the reaction was completely reversible with either chelation or alkalinization. This interaction was comparable to the pH-dependent effect of Cu2+ on insulin aggregation but was not seen for aprotinin or albumin. Abeta1-40 bound three to four Cu2+ ions when precipitated at pH 7.0. Rapid, pH-sensitive aggregation occurred at low nanomolar concentrations of both Abeta1-40 and Abeta1-42 with submicromolar concentrations of Cu2+. Unlike Abeta1-40, Abeta1-42 was precipitated by submicromolar Cu2+ concentrations at pH 7.4. Rat Abeta1-40 and histidine-modified human Abeta1-40 were not aggregated by Zn2+, Cu2+, or Fe3+, indicating that histidine residues are essential for metal-mediated Abeta assembly. These results indicate that H+-induced conformational changes unmask a metal-binding site on Abeta that mediates reversible assembly of the peptide. Since a mildly acidic environment together with increased Zn2+ and Cu2+ are common features of inflammation, we propose that Abeta aggregation by these factors may be a response to local injury. Cu2+, Zn2+, and Fe3+ association with Abeta explains the recently reported enrichment of these metal ions in amyloid plaques in Alzheimer's disease.
Sheath fluid control to permit stable flow in rapid mix flow cytometry (1999)

This use of automated syringes to control both sheath and sample flow provides a potential for robust sample handling applicable to kinetic as well as high throughput flow cytometric analysis.
Molecular aspects of phosphate transport in Escherichia coli (1990)

Escherichia coli transports inorganic phosphate (Pi) by the low-affinity transport system, Pit. When the level of the external Pi is lower than 20 microM, another transport system, Pst, is induced with a Kt of 0.25 microM. An outer-membrane porin, PhoE, with a Km of about 1 microM is also induced. The outer membrane allows the intake of organic phosphates which are degraded to Pi by phosphatases in the periplasm. The Pi-binding protein will capture the free Pi produced in the periplasm and direct it to the transmembrane channel of the cytoplasmic membrane. The channel consists of two proteins, PstA and PstC, which have six and five transmembrane helices, respectively. On the cytoplasmic side of the membrane the channel is linked to the PstB protein, which carries a nucleotide (probably ATP)-binding site. PstB probably provides the energy required by the channel to free Pi. The Pst system has two functions in E. coli: (i) the transport of Pi, and (ii) the negative regulation of the phosphate regulon (a complex of 20 proteins mostly related to organic phosphate transport). It is remarkable that these two functions are not related, since the repressibility of the regulon depends on the integral structure of Pst (PiBP + PstA + PstC + PstB) and not on the Pi transported. Another gene of the pst operon, phoU, produces a protein involved in the negative regulation of the Pho regulon, but the mechanism of this function has not been explained. Thus the regulatory function of the Pst system remains obscure. Its basal level, present when Pi is abundant, is sufficient to repress the Pho regulon but the negative regulatory function is lost upon Pi starvation.
Sequence organization of the circular plasmid pKDl from the yeastKluyveromyces drosophilarum (1986)

pKD1 is the only circular plasmid known in the genus Kluyveromyces. Nucleotide sequence analysis has revealed that this 4757 base-pairs long plasmid contained three major open reading frames, A, B, and C, and a pair of inverted repeats of 346 base-pairs. The molecule exists in two isomeric forms generated by internal recombination at these repeats. The functional organization of pKD1 genome appears to be quite analogous to that of the 2u plasmid of Saccharomyces cerevisiae. There is however little homology of sequences between these plasmids, except that the gene A has a dispersed but significant homology with the FLP recombinase gene of the 2u plasmid. S.cerevisiae cells can be transformed by derivatives of pKD1 carrying URA3 gene as a selection marker.
Fast-Forward Aging in a Mutant Mouse? (1997)

When the television or the toaster oven breaks down a week after its warranty expires, it's tempting to believe the manufacturer designed it to do so. Similarly, the infirmities and breakdowns that herald old age are so predictable that some scientists believe our genes evolved with their own kind of warranty, one that runs out shortly after reproductive age. These researchers speculate that if they could figure out which genes underlie this planned obsolescence, they might be able to delay it—in effect, extending the warranty. Now, by studying mutant mice that resemble senior citizens by the time they're only 60 days old, a team in Japan may have discovered what such a gene would look like.
Cytoplasmic dynein participates in the centrosomal localization of the Golgi complex. (1992)

The localization of the Golgi complex depends upon the integrity of the microtubule apparatus. At interphase, the Golgi has a restricted pericentriolar localization. During mitosis, it fragments into small vesicles that are dispersed throughout the cytoplasm until telophase, when they again coalesce near the centrosome. These observations have suggested that the Golgi complex utilizes a dynein-like motor to mediate its transport from the cell periphery towards the minus ends of microtubules, located at the centrosome. We utilized semi-intact cells to study the interaction of the Golgi complex with the microtubule apparatus. We show here that Golgi complexes can enter semi-intact cells and associate stably with cytoplasmic constituents. Stable association, termed here "Golgi capture," requires ATP hydrolysis and intact microtubules, and occurs maximally at physiological temperature in the presence of added cytosolic proteins. Once translocated into the semi-intact cell cytoplasm, exogenous Golgi complexes display a distribution similar to endogenous Golgi complexes, near the microtubule-organizing center. The process of Golgi capture requires cytoplasmic tubulin, and is abolished if cytoplasmic dynein is immunodepleted from the cytosol. Cytoplasmic dynein, prepared from CHO cell cytosol, restores Golgi capture activity to reactions carried out with dynein immuno-depleted cytosol. These results indicate that cytoplasmic dynein can interact with isolated Golgi complexes, and participate in their accumulation near the centrosomes of semi-intact, recipient cells. Thus, cytoplasmic dynein appears to play a role in determining the subcellular localization of the Golgi complex.
<title>Planarization of deep trenches</title> (2001)

The ability of various deposition processes and materials to fill and planarize topographical features (trenches deeper than 10 micrometers ) is investigated in this work. Three different deposition processes are considered: LPCVD (Ge), PECVD (Ge, Si<SUB>3</SUB>N<SUB>4</SUB>, SiO<SUB>2</SUB>) and spin coating (BCB, resist, polyimide). Comparing LPCVD and PECVD processes show that, for the same trench width, thick PECVD layers can close off trenches from the top, while thick LPCVD layers fill the trenches completely. The use of PECVD layers is thus advantageous for sealing applications, where a low bottom step coverage is desired. LPCVD layers on the other hand are very useful for planarization purposes where a low ratio between the deposited film thickness and the planarized trench width is desired. Also the deposition of polymers by spin coating yields excellent planarization results with a simpler process and lower thermal budget compared to LPCVD processes. All polymers investigated fill the trenches totally. If these planarization layers are used as sacrificial layers, they should be etched isotropically and selectively with respect to the structural layer. Ge can be etched in oxidizing solutions (H<SUB>2</SUB>O<SUB>2</SUB>/H<SUB>2</SUB>O) and the sacrificial etch of Ge is selective towards Si, SiO<SUB>2</SUB> and many other layers. SiO<SUB>2</SUB> can be removed by wet or vapor HF, and resist, polyimide and BCB can be removed by O<SUB>2</SUB> or O<SUB>2</SUB>/SF<SUB>6</SUB> plasma. Which layer should be used depends on the trench fill requirements, the thermal budget and the further processing needed.
The Development of New Monometallic Bifunctional Catalysts with Lewis acidand Lewis Base Properties, and their Application in Asymmetric Cyanation Reactions (2001)

Bifunctional catalysts can drastically improve the efficiency of asymmetric processes with respect to enantioselectivity and/or conversion rate. A new type of chiral bifunctional catalyst has been developed recently in the Shibasaki group that contains both Lewis acid and Lewis base moieties. These monometallic and bifunctional phosphinoyl-containing catalysts are able to coordinate both nucleophilic and electrophilic substrates in the transition state. Several successful applications of this new catalytic concept in the field of asymmetric cyanation reactions have already been reported, for example, the asymmetric hydrocyanation of aldehydes and imines as well as the asymmetric Reissert reaction. The development and principle of this catalytic concept as well as main applications thereof are reviewed in this article.
Cell surface expression and orientation in membranes of the 44-amino-acid SH protein of simian virus 5 (1988)

Antiserum was raised against a synthetic peptide containing the N-terminal hydrophilic domain of the small hydrophobic protein (SH) of simian virus 5 (SV5) and used to characterize properties of the SH protein. SH demonstrated properties of an integral membrane protein. Indirect immunofluorescence experiments showed that the protein is involved in the exocytotic pathway, and isolation of plasma membranes from SV5-infected cells showed an enrichment of SH, indicating that SH is transported to the infected-cell surface. Biochemical analysis of the orientation of SH in membranes by proteolysis of intact SV5-infected cell surfaces and intracellular microsomal vesicles indicated that SH is oriented in membranes with its N-terminal hydrophilic domain exposed on the cytoplasmic face of the plasma membrane and the C terminus of approximately five amino acid residues exposed at the cell surface. These data are discussed with respect to positive-acting signals being necessary in the ectodomain of SH for cell surface expression.
Vagus nerve stimulation therapy, epilepsy, and device parameters (2002)

Our understanding of a precise dose-response relationship for vagus nerve stimulation (VNS) therapy in the treatment of seizures is still evolving. Because several parameters are involved in VNS therapy, the individual contribution of each is not well understood. This review discusses the efficacy of stimulation parameters used in the VNS clinical trials. The background, influence on safety and efficacy, and role in helping to achieve seizure control are discussed for each VNS device parameter: output current, pulse duration, frequency, and duty cycle. Finally, we provide an algorithm for the adjustment of VNS device settings (see Appendices).