gebhart/patrepeval huggingface dataset:
Structural studies of protein–nucleic acid interaction: the sources of sequence-specific binding (1990)

Structural studies of DNA-binding proteins and their complexes with DNA have proceeded at an accelerating pace in recent years due to important technical advances in molecular genetics, DNA synthesis, protein crystallography and nuclear magnetic resonance. The last major review on this subject by Pabo &amp; Sauer (1984) summarized the structural and functional studies of the three sequence-specific DNA-binding proteins whose crystal structures were then known, the E. coli catabolite gene activator protein (CAP) (McKay &amp; Steitz, 1981; McKay et al. 1982; Weber &amp; Steitz, 1987), a cro repressor from phage λ (Anderson et al. 1981), and the DNA-binding proteolytic fragment of λcI repressor protein (Pabo &amp; Lewis, 1982) Although crystallographic studies of the E. coli lac repressor protein were initiated as early as 1971 when it was the only regulatory protein available in sufficient quantities for structural studies (Steitz et al. 1974), little was established about the structural aspects of DNA-binding proteins until the structure of CAP was determined in 1980 followed shortly thereafter by the structure of λcro repressor and subsequently that of the λ repressor fragment. There are now determined at high resolution the crystal structures of seven prokaryotic gene regulatory proteins or fragments [CAP, λcro , λcI repressor fragment, 434 repressor fragment (Anderson et al. 1987), 434 cro repressor (Wolberger et al. 1988), E. coli trp repressor (Schevitz et al. 1985), E. coli met repressor (Rafferty et al. 1989)], EcoR I restriction endonuclease (McClarin et al. 1986), DNAse I (Suck &amp; Ofner, 1986), the catalytic domain of γδ resolvase (Hatfull et al. 1989) and two sequence-independent double-stranded DNA-binding proteins [the Klenow fragment of E. coli DNA polymerase I (Ollis et al. 1985) and the E. coli Hu protein (Tanaka et al. , 1984)].
Environmental Contamination in Child Day-Care Centers (1991)

Enteropathogens associated with outbreaks of diarrhea in day-care centers are spread by the fecal-oral route through contaminated hands or environmental objects. This prospective study was undertaken to determine the prevalence of fecal coliform contamination in day care. Ten rooms in six centers housing 121 children less than 2 years of age were studied for 13 weeks (February to May 1988). Inanimate objects (n = 1,275), toy balls (n = 724), and hands (n = 954) were cultured 1-3 times per week. Fecal coliform contamination was common and was greater (p less than 0.05) for objects, toy balls, and hands of children in toddler compared with infant rooms. In five rooms in which clothes were worn over diapers, there was a significantly lower prevalence of fecal coliform contamination of toy balls (p less than 0.005), inanimate objects (p less than 0.05), and hands (p less than 0.001) when compared with rooms in which overclothes were not worn. Occurrence of diarrhea was significantly associated with increased contamination of hands (p = 0.001). Stool and environmental isolates from individual rooms had the same plasmid patterns, which were unique to each center. In summary, fecal coliform contamination of environmental objects and hands of children and caregivers in day-care centers is common; toy balls can serve as sentinels of contamination; fecal coliform contamination can be significantly decreased by use of overclothes; and Escherichia coli strains from stool showed the same plasmid patterns.
Serum fibrosis markers as predictors of an antifibrotic effect of interferon alfa in children with chronic hepatitis B (2005)

A 5 month IFN-alpha treatment has no marked effect on histological liver fibrosis in children with CHB, irrespective of virological response. The evolution of serum fibrosis markers suggests they may be more sensitive to detect minor antifibrotic effects than semiquantitative follow-up histology.
Catch and Release of Microwave Photon States (2013)

We demonstrate a superconducting resonator with variable coupling to a measurement transmission line. The resonator coupling can be adjusted through zero to a photon emission rate 1000 times the intrinsic resonator decay rate. We demonstrate the catch and release of photons in the resonator, as well as control of nonclassical Fock states. We also demonstrate the dynamical control of the release waveform of photons from the resonator, a key functionality that will enable high-fidelity quantum state transfer between distant resonators or qubits.
Expression and characterization of human lamin C (1990)

We have expressed human lamin C cDNA in E. coli using a modification of the pLcII vector system. Protein produced in this way had seven additional amino acids at its N-terminus, but retained key lamin structural and assembly properties. The modified vector we produced may prove useful when difficulties are encountered in removal of the cII fusion peptide by factor X cleavage in the pLcII system. Shadowed preparations of expressed lamin C showed the presence of 50-nm rod-like particles that closely resembled those observed for native material. Isolated molecules had two globular domains at one end, indicating that they were constructed from two parallel polypeptide chains. The expressed material also formed paracrystals with a characteristic 22.5 nm axial repeat, indicating that its assembly properties had also been retained. We also used site-specific mutagenesis to engineer a lamin fragment that lacked the C-terminal non-helical domain of the molecule. This material formed paracrystals similar to those obtained with the intact molecule, indicating that the large C-terminal non-helical domain did not contain information vital for lamin assembly.
Identification of TRACs (T3 receptor-associating cofactors), a family of cofactors that associate with, and modulate the activity of, nuclear hormone receptors. (1996)

Nuclear hormone receptors are the largest known family of eukaryotic transcription factors and serve as critical effectors of vertebrate homeostasis, growth, and differentiation. The precise transcriptional response mediated by a given nuclear hormone receptor is dictated by hormone, promoter, and cellular context, and many nuclear hormone receptors function bimodally as both transcriptional activators and repressors. We report here the identification of a family of proteins, denoted TRACs (T3 receptor-associating cofactors), which physically interact with nuclear hormone receptors and can modulate the transcriptional properties of these receptors. TRACs associate with retinoic acid, retinoid X, and thyroid hormone receptors, as well as the PML-RAR alpha and v-Erb A oncoproteins. Certain TRAC forms attenuate target gene expression and may serve as corepressors, whereas other TRAC family members appear to counteract these effects. We suggest that TRACs and related cofactors may participate in dictating the pleiotropic transcriptional capacities of the nuclear hormone receptors.
Anti-tumor and anti-metastatic effects of human-vascular-endothelial-growth-factor-neutralizing antibody on human colon and gastric carcinoma xenotransplanted orthotopically into nude mice (1998)

In order to determine whether the inhibition of vascular-endothelial-growth-factor (VEGF) activity by administration of an immunoneutralizing antibody could suppress tumor growth and metastasis in spontaneous metastatic models of human colon and gastric carcinoma, 4 human carcinoma xenografts, 2 human colon carcinomas (TK4 and TK 13) and 2 gastric carcinomas (MT2 and MT5) were transplanted orthotopically into nude mice. The anti-VEGF antibody (MV833, 100 microg/mouse) or the same volume of saline was administered i.p. on alternative days from day 10 after transplantation. With each of the 4 xenografts, administration of MV833 significantly inhibited not only primary tumor growth but also macroscopic liver metastasis, although the growth rate varied. The inhibitory effect of MV833 on primary tumor growth appeared to have no correlation with the level of VEGF in tumor. Body-weight gain in each treated group was comparable with that in the control group. No toxicity of the antibody was observed. These results suggest that an anti-VEGF antibody can be effective against a wide variety of cancers, and that VEGF may be a possible target for cancer therapy.
A Varactor-Based, Inductively Coupled Wireless pH Sensor (2010)

An inductively coupled, wireless sensor was fabricated for remote measurement of pH. The sensor consisted of a planar spiral inductor connected to a surface mount varactor, which was a voltage controlled capacitor, forming an inductive-capacitive (LC) resonant circuit. The pH electrodes, made of a thick-film antimony/antimony oxide sensing electrode and a thick-film silver/silver chloride reference electrode, were connected in parallel to the varactor. A voltage change across the electrodes due to the pH variation in the test medium would change the capacitance of the varactor, shifting the resonant frequency of the LC circuit. By inductively coupling the spiral inductor with a detection coil, the resonant frequency of the LC circuit was remotely monitored, allowing measurement of the pH. The advantage of the described pH sensor is its wireless and passive nature, which allows for long-term pH monitoring in inaccessible area. The sensor will be useful for remote monitoring of pH during industrial or food processes. When miniaturized, the sensors can also be used for biomedical applications such as remote tracking of gastric or esophageal pH on patients suffering from gastroesophageal reflux disease.
Interleaved bi-directional Dual Active Bridge DC-DC converter for interfacing ultracapacitor in micro-grid application (2010)

Ultracapacitor in microgrid requires a high power and galvanic isolated bi-directional converter to interface and control power flow with load. In this paper, an interleaved bi-directional Dual Active Bridge (DAB) DC-DC converter is proposed for interfacing ultracapacitor in microgrid application. By using interleaved scheme in the converter, the input/output ripple frequency is increased by n times and the ripple magnitude is reduced to 1 over n times where the n is the number of the converters in parallel or series. This can significantly reduce the filter size and thus increase the power density. To avoid the inrush current in the start up time, a soft-start scheme is also proposed. Furthermore, a cascaded control loop is implemented to achieve the voltage regulation as well as to balance power distribution among the modules. A 4.8kW interleaved input parallel output series DAB converter is proposed and simulations are carried out to verify the proposed scheme.
The SCF–Fbw7 ubiquitin ligase degrades MED13 and MED13L and regulates CDK8 module association with Mediator (2013)

The Mediator complex is an essential transcription regulator that bridges transcription factors with RNA polymerase II. This interaction is controlled by dynamic interactions between Mediator and the CDK8 module, but the mechanisms governing CDK8 module-Mediator association remain poorly understood. We show that Fbw7, a tumor suppressor and ubiquitin ligase, binds to CDK8-Mediator and targets MED13/13L for degradation. MED13/13L physically link the CDK8 module to Mediator, and Fbw7 loss increases CDK8 module-Mediator association. Our work reveals a novel mechanism regulating CDK8 module-Mediator association and suggests an expanded role for Fbw7 in transcriptional control and an unanticipated relationship with the CDK8 oncogene.
Novel modulatory effects of neurosteroids and benzodiazepines on excitatory and inhibitory neurons excitability: a multi-electrode array recording study (2012)

The balance between glutamate- and GABA-mediated neurotransmission in the brain is fundamental in the nervous system, but it is regulated by the "tonic" release of a variety of endogenous factors. One such important group of molecules are the neurosteroids (NSs) which, similarly to benzodiazepines (BDZs), enhance GABAergic neurotransmission. The purpose of our work was to investigate, at in vivo physiologically relevant concentrations, the effects of NSs and BDZs as GABA modulators on dissociated neocortical neuron networks grown in long-term culture. We used a multi-electrode array (MEA) recording technique and a novel analysis that was able to both identify the action potentials of engaged excitatory and inhibitory neurons and to detect drug-induced network up-states (burst). We found that the NSs tetrahydrodeoxycorticosterone (THDOC) and allopregnanolone (ALLO) applied at low nanomolar concentrations, produced different modulatory effects on the two neuronal clusters. Conversely, at high concentrations (1 μM), both NSs, decreased excitatory and inhibitory neuron cluster excitability; however, even several hours after wash-out, the excitability of inhibitory neurons continued to be depressed, leading to a network long-term depression (LTD). The BDZs clonazepam (CLZ) and midazolam (MDZ) also decreased the network excitability, but only MDZ caused LTD of inhibitory neuron cluster. To investigate the origin of the LTD after MDZ application, we tested finasteride (FIN), an inhibitor of endogenous NSs synthesis. FIN did not prevent the LTD induced by MDZ, but surprisingly induced it after application of CLZ. The significance and possible mechanisms underlying these LTD effects of NSs and BDZs are discussed. Taken together, our results not only demonstrate that ex vivo networks show a sensitivity to NSs and BDZs comparable to that expressed in vivo, but also provide a new global in vitro description that can help in understanding their activity in more complex systems.
Influence of glycosylation pattern on the molecular properties of monoclonal antibodies (2014)

Glycosylation is an important post-translational modification during protein production in eukaryotic cells, and it is essential for protein structure, stability, half-life, and biological functions. In this study, we produced various monoclonal antibody (mAb) glycoforms from Chinese hamster ovary (CHO) cells, including the natively glycosylated antibody, the enriched G0 form, the deglycosylated form, the afucosylated form, and the high mannose form, and we compared their intrinsic properties, side-by-side, through biophysical and biochemical approaches. Spectroscopic analysis indicates no measureable secondary or tertiary structural changes after in vitro or in vivo modification of the glycosylation pattern. Thermal unfolding experiments show that the high mannose and deglycosylated forms have reduced thermal stability of the CH2 domain compared with the other tested glycoforms. We also observed that the individual domain's thermal stability could be pH dependent. Proteolysis analysis indicates that glycosylation plays an important role in stabilizing mAbs against proteases. The stability of antibody glycoforms at the storage condition (2-8 °C) and at accelerated conditions (30 and 40 °C) was evaluated, and the results indicate that glycosylation patterns do not substantially affect the storage stability of the antibody we studied.
Dynorphin-(1–8) inhibits the release of substance P-like immunoreactivity in the spinal cord of rats following a noxious mechanical stimulus (1997)

This study was conducted to determine the effect of the opioid peptide dynorphin-(1-8) on the release of substance P-like immunoreactivity in the dorsal horn during mechanical activation of peripheral nociceptors. A push-pull cannula was used to perfuse the dorsal horn of decerebrate/spinal transected rats before, during and following the application of a noxious mechanical stimulus to the ipsilateral hindpaw and lower limb. The collected perfusates were assayed for substance P-like immunoreactivity using radioimmunoassay. Dynorphin-(1-8) applied to the spinal cord at a concentration of 1 microM reduced the basal release of substance P-like immunoreactivity by 28 +/- 11% and prevented the mechanically evoked release of substance P-like immunoreactivity. This effect of dynorphin-(1-8) was reversed by 2 microM of the selective kappa-opioid receptor antagonist nor-binaltorphimine. Moreover, blockade of the kappa-opioid receptors by nor-binaltorphimine resulted in a 33 +/- 5% increase in the basal release of substance P-like immunoreactivity. These data show that activation of nor-binaltorphimine-sensitive sites by dynorphin-(1-8) results in inhibition of the release of substance P-like immunoreactivity in the dorsal horn of the rat.
Oxazolines. X. Synthesis of .gamma.-butyrolactones (1974)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTOxazolines. X. Synthesis of .gamma.-butyrolactonesA. I. Meyers, Edward D. Mihelich, and Robert L. NolenCite this: J. Org. Chem. 1974, 39, 18, 2783–2787Publication Date (Print):September 1, 1974Publication History Published online1 May 2002Published inissue 1 September 1974https://pubs.acs.org/doi/10.1021/jo00932a023https://doi.org/10.1021/jo00932a023research-articleACS PublicationsRequest reuse permissionsArticle Views417Altmetric-Citations47LEARN 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
Octagonal washer DC SQUIDs and integrated susceptometers fabricated in a planarized sub- mu m Nb-AlO/sub x/-Nb technology (1993)

The authors have designed, fabricated, and measured a number of Nb-AlO/sub x/-Nb octagonal washer DC superconducting quantum interference devices (SQUIDs) and miniature DC SQUID susceptometers having minimum feature size down to 0.5 mu m. With SQUID inductance values on the order of 100 pH, typical noise performance is better than 1 mu Phi /sub 0// square root Hz. The small minimum feature size of input coils and pickup loop structures will facilitate tight coupling to a wide variety of systems ranging from submicron particles and structures to conventional approximately mu H input circuits. A single-washer SQUID with an 80-turn 0.5- mu m-linewidth, 630-nH input coil has user-friendly V- Phi (voltage-flux) curves and a coupled energy sensitivity of 20 h at 4.2 K. Susceptometers with pickup loops ranging from 20- mu m to 0.8- mu m across have very user-friendly V- Phi curves and a resolution of order 100 mu /sub B// square root Hz at 4.2 K for devices with the smallest loops.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Inhibition of Chikungunya Virus Infection in Cultured Human Muscle Cells by Furin Inhibitors (2008)

Chikungunya virus (CHIKV) is a mosquito-transmitted Alphavirus that causes in humans an acute infection characterized by polyarthralgia, fever, myalgia, and headache. Since 2005 this virus has been responsible for an epidemic outbreak of unprecedented magnitude. By analogy with other alphaviruses, it is thought that cellular proteases are able to process the viral precursor protein E3E2 to produce the receptor-binding E2 protein that associates as a heterodimer with E1. Destabilization of the heterodimer by exposure to low pH allows viral fusion and infection. We show that among a large panel of proprotein convertases, membranous furin but also PC5B can process E3E2 from African CHIKV strains at the HRQRR(64) / ST site, whereas a CHIKV strain of Asian origin is cleaved at RRQRR(64) / SI by membranous and soluble furin, PC5A, PC5B, and PACE4 but not by PC7 or SKI-1. Using fluorogenic model peptides and recombinant convertases, we observed that the Asian strain E3E2 model peptide is cleaved most efficiently by furin and PC5A. This cleavage was also observed in CHIKV-infected cells and could be blocked by furin inhibitor decanoyl-RVKR-chloromethyl ketone. This inhibitor was compared with chloroquine for its ability to inhibit CHIKV spreading in myoblast cell cultures, a cell-type previously described as a natural target of this virus. Our results demonstrate the role of furin-like proteases in the processing of CHIKV particles and point out new approaches to inhibit this infection.
Engineering the proteolytic specificity of activated protein C improves its pharmacological properties (2003)

Human activated protein C (APC) is an antithrombotic, antiinflammatory serine protease that plays a central role in vascular homeostasis, and activated recombinant protein C, drotrecogin alfa (activated), has been shown to reduce mortality in patients with severe sepsis. Similar to other serine proteases, functional APC levels are regulated by the serine protease inhibitor family of proteins including alpha(1)-antitrypsin and protein C inhibitor. Using APC-substrate modeling, we designed and produced a number of derivatives with the goal of altering the proteolytic specificity of APC such that the variants exhibited resistance to inactivation by protein C inhibitor and alpha(1)-antitrypsin yet maintained their primary anticoagulant activity. Substitutions at Leu-194 were of particular interest, because they exhibited 4- to 6-fold reductions in the rate of inactivation in human plasma and substantially increased pharmacokinetic profiles compared with wild-type APC. This was achieved with minimal impairment of the anticoagulant/antithrombotic activity of APC. These data demonstrate the ability to selectively modulate substrate specificity and subsequently affect in vivo performance and suggest therapeutic opportunities for the use of protein C derivatives in disease states with elevated serine protease inhibitor levels.
Cyclotides: a novel type of cytotoxic agents. (2002)

Cytotoxic activities of three naturally occurring macrocyclic peptides (cyclotides) isolated from the two violets, Viola arvensis Murr. and Viola odorata L., were investigated. A nonclonogenic fluorometric microculture assay was used to examine cytotoxicity in a panel of 10 human tumor cell lines representing defined types of cytotoxic drug resistance. Additionally, primary cultures of tumor cells from patients, and for comparison normal lymphocytes, were used to quantify cytotoxic activity. All three cyclotides, varv A, varv F, and cycloviolacin 02, exhibited strong cytotoxic activities, which varied in a dose-dependent manner. Cycloviolacin 02 was the most potent in all cell lines (IC50 0.1-0.3 microM), followed by varv A (IC50 2.7-6.35 microM) and varv F (IC50 2.6-7.4 microM), respectively. Activity profiles of the cyclotides differed significantly from those of antitumor drugs in clinical use, which may indicate a new mode of action. This, together with the exceptional chemical and biological stability of cyclotides, makes them interesting in particular for their potential as pharmacological tools and possibly as leads to antitumor agents.
Amidation of triglycerides by amino alcohols and their impact on plant oil-derived polymers (2016)

Amidation of plant oils with amino alcohols was methodologically examined.