gebhart/patrepeval huggingface dataset:
PapD-like chaperones provide the missing information for folding of pilin proteins (2000)

A fundamental question in molecular biology is how proteins fold into domains that can serve as assembly modules for building up large macromolecular structures. The biogenesis of pili on the surface of Gram-negative bacteria requires the orchestration of a complex process that includes protein synthesis, folding via small chaperones, secretion, and assembly. The results presented here support the hypothesis that pilus subunit folding and biogenesis proceed via mechanisms termed donor strand complementation and donor strand exchange. Here we show that the steric information necessary for pilus subunit folding is not contained in one polypeptide sequence. Rather, the missing information is transiently donated by a strand of a small chaperone to allow folding. Providing the missing information for folding, via a 13-amino acid peptide extension to the C-terminal end of a pilus subunit, resulted in the production of a protein that no longer required the chaperone to fold. This mechanism of small periplasmic chaperone function described here deviates from classical hsp60 chaperone-assisted folding.
Biological and immunological properties of the carboxyl terminus of staphylococcal enterotoxin C1 (1989)

Comparisons of recently published primary sequences of staphylococcal and streptococcal pyrogenic toxins prompted an evaluation of biological and immunological properties of the C terminus of staphylococcal enterotoxin C1. The 59 N-terminal amino acids were deleted from the toxin by digestion with trypsin. The resulting fragment (Mr, 20,659) contained the remaining 180 C-terminal residues. This fragment (Trp F1) consisted of two polypeptide chains (Trp F1a and Trp F1b) linked by cysteine residues. Trp F1 was mitogenic, pyrogenic, and enhanced susceptibility of rabbits to lethal endotoxin shock. In addition, this fragment contained at least one antigenic epitope that cross-reacted with enterotoxin B.
Role of Bach1 and Nrf2 in up‐regulation of the heme oxygenase‐1 gene by cobalt protoporphyrin (2006)

Heme oxygenase (HO) catalyzes the conversion of heme to biliverdin with the release of iron and carbon monoxide. HO-1 is highly inducible by a large number of physical and chemical factors. CoPP is known to be a potent and effective inducer of HO-1 activity in many tissues. Here we report that CoPP up-regulates HO-1 via Bach1 and Nrf2 in human liver cells. CoPP did not influence hepatic Bach1 or Nrf2 mRNA levels, but markedly reduced Bach1 protein levels by increasing degradation of Bach1 protein (t(1/2) from 19 h to 2.8 h), and increased Nrf2 by decreasing degradation of Nrf2 protein (t(1/2) from 2.5 h to 9 h). Silencing Bach1 by Bach1-siRNA significantly increased levels of HO-1 mRNA and protein, and addition of CoPP up-regulated HO-1 mRNA and protein further. However, silencing Nrf2 mRNA by Nrf2-siRNA did not significantly change baseline HO-1 mRNA or protein levels, but significantly decreased 5-10 microM CoPP-mediated up-regulation of HO-1 mRNA levels compared with CoPP alone. Transfection with equal amounts of non-Bach1 or non-Nrf2 related control siRNA did not reduce Bach1 or Nrf2 mRNA or protein, confirming the specificity of Bach1- and Nrf2-siRNA in Huh-7 cells. We conclude that the pathway of CoPP-mediated induction of HO-1 involves the repression of Bach1 and up-regulation of the Nrf2 protein by post-transcriptional site(s) of action. Because CoPP, unlike heme, is neither a prooxidant nor a substrate for HO-1, it might be considered as a potential therapeutic agent in situations where up-regulation of HO-1 is desired.
Mechanisms of Nucleophilic Substitution in Phosphate Esters (1964)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMechanisms of Nucleophilic Substitution in Phosphate EstersJames R. Cox, Jr. and O. Bertrand RamsayCite this: Chem. Rev. 1964, 64, 4, 317–352Publication Date (Print):August 1, 1964Publication History Published online1 May 2002Published inissue 1 August 1964https://pubs.acs.org/doi/10.1021/cr60230a001https://doi.org/10.1021/cr60230a001research-articleACS PublicationsRequest reuse permissionsArticle Views2909Altmetric-Citations268LEARN 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
RNA primer used in synthesis of anticomplementary DNA by reverse transcriptase of avian myeloblastosis virus. (1980)

When either the homologous RNA (avian myeloblastosis virus RNA) or a heterologous RNA (poliovirus RNA) was used as a template, the anticomplementary DNA synthesized in vitro by avian myeloblastosis virus reverse transcriptase (RNA-directed DNA nucleotidyltransferase, EC 2.7.7.7) was primed by fragments of the original RNA template that usually had adenosine at their 3' ends. When we used phage T/ RNA ligase (EC 6.5.1.3) to label the 3' end of the RNA template fragments contained in the RNA . cDNA hybrid intermediate, adenosine was found to be the principal nucleoside carrying the label. We infer from these results that the ribonuclease H (hybrid nuclease) activity of the reverse transcriptase creates fragments of the original RNA template with adenosine as the principal 3' terminus and that these fragments serve as primers for the synthesis of anticomplementary DNA.
FDA Approval Summary: Ruxolitinib for Treatment of Steroid-Refractory Acute Graft-Versus-Host Disease (2019)

On May 24, 2019, the Food and Drug Administration approved ruxolitinib for steroid-refractory acute graft-versus-host disease (SR-aGVHD) in adult and pediatric patients 12 years and older. Approval was based on Study INCB 18424-271 (REACH-1; NCT02953678), an open-label, single-arm, multicenter trial that included 49 patients with grades 2-4 SR-aGVHD occurring after allogeneic hematopoietic stem cell transplantation. Ruxolitinib was administered at 5 mg twice daily, with dose increases to 10 mg twice daily permitted after 3 days in the absence of toxicity. The Day-28 overall response rate was 57.1% (95% confidence interval [CI]: 42.2-71.2). The median duration of response was 0.5 months (95% CI: 0.3-2.7), and the median time from Day-28 response to either death or need for new therapy for acute GVHD was 5.7 months (95% CI: 2.2 to not estimable). Common adverse reactions included anemia, thrombocytopenia, neutropenia, infections, edema, bleeding, and elevated transaminases. Ruxolitinib is the first drug approved for treatment of SR-aGVHD. IMPLICATIONS FOR PRACTICE: Ruxolitinib is the first Food and Drug Administration-approved treatment for steroid-refractory acute graft-versus-host disease in adult and pediatric patients 12 years and older. Its approval provides a treatment option for the 60% of those patients who do not respond to steroid therapy.
Computing with Chemicals: Perceptrons Using Mixtures of Small Molecules (2018)

Computation that can exploit the Avogadrian numbers of molecules in heterogeneous solutions, and the even larger number of potential interactions among these molecules, is a tantalizing dream. However, the lack of precise specificity/control of chemical interactions can be at odds with the dream. In this paper, we show how relatively simple chemistry can be used to produce a ubiquitous computational primitive (the multiply-accumulate or MAC operation) that forms the basis for a single-layer neural network called a perceptron. A chemical perceptron can be realized using distinct mixtures as inputs and different reagents as operations to produce the results of the perceptron MAC operation, that can be read out perhaps using simple indicators such as pH or fluorescence. With a moderately large chemical library, the number of potential inputs can be Avogadrian so that reagent addition implicitly performs a concomitantly large number of MAC operations in parallel.
Alteration of Product Specificity of Rhodobacter sphaeroides Phytoene Desaturase by Directed Evolution (2001)

Phytoene desaturases occurring in nature convert phytoene to either neurosporene or lycopene in most eubacteria. Approximately 10% of known phytoene desaturases, as in Rhodobacter, produce neurosporene, whereas the rest produce lycopene. These two types of enzymes, although similar in function, have relatively low similarity (below 60%) in terms of nucleotide or amino acid sequence. The mechanism controlling the product specificity of these enzymes is unclear. Here we used directed evolution to change the product of Rhodobacter sphaeroides phytoene desaturase (crtI gene product), a neurosporene-producing enzyme, to lycopene. Two generations of random mutagenesis were performed, from which three positive mutants were isolated and sequenced. We then used site-directed mutagenesis to determine the effect of each amino acid change. Gathering information from random mutagenesis, we further recombined the beneficial mutations by site-directed mutagenesis and increased the percent of lycopene production to 90%.
Electrospun fibers from poly(methyl methacrylate)/vapor grown carbon nanofibers (2006)

Electrospinning has been used to obtain poly(methyl methacrylate) (PMMA) microfibers and nanofibers and PMMA/vapor grown carbon nanofibers (VGCNFs or CNFs) composite fibers with micrometer and nanometer size diameters. Thermogravimetric analysis (TGA) indicated that addition of CNFs caused a decrease in the thermal stability of the composite fibers. Scanning electron microscopy (SEM) was used to confirm the micro- and nano- nature of the fibers and transmission electron microscopy (TEM) was utilized to confirm the presence of CNFs embedded within the polymer matrix and along the surface. Copyright © 2006 John Wiley & Sons, Ltd.
A Unique Metalolic Sysdrone Causes Obesity in the Melanocortin-3 Receptor-Deficient Mouse (2000)

The central melanocortin system is critical for the long term regulation of energy homeostasis. Null mutations of the melanocortin-4 receptor (MC4-R) are associated with hyperphagia, obesity, and accelerated longitudinal growth in mice and humans. However, little is known about the function of another central melanocortin receptor, the MC3-R. To assess the role of the MC3-R in energy homeostasis, the majority of the mc3r coding sequence was deleted from the mouse genome. In contrast to the MC4-R knockout, which exhibits increased food intake, increased somatic growth, and defects in metabolism, mc3r-/- mice exhibit an exclusively metabolic syndrome. Homozygous null mc3r mice, while not significantly overweight, exhibit an approximately 50% to 60% increase in adipose mass. Mc3r-/- mice also exhibit an unusual increase in respiratory quotient when transferred onto high fat chow, suggesting a reduced ratio of fat/carbohydrate oxidation. Furthermore, male mc3r-/- mice also exhibit an approximately 50% reduction in locomotory behavior on the running wheel, suggesting reduced energy expenditure.
Total Synthesis of the Polycyclic Fungal Metabolite (±)‐Communesin F (2010)

What the Heck: The heptacyclic fungal alkaloid communesin F was the target of a total synthesis featuring a rare example of an intramolecular Heck cyclization of a tetrasubstituted alkene, a reductive cyclization of an N-Boc aniline, a stereoselective C allylation of a lactam, and an azide reduction/N-Boc-δ-lactam ring opening sequence (see scheme, BOM=benzyloxymethyl).
Stroke Prevention Using the Oral Direct Thrombin Inhibitor Ximelagatran in Patients with Non-Valvular Atrial Fibrillation (2006)

Fixed-dose oral ximelagatran without coagulation monitoring prevented stroke and systemic embolism as effectively as warfarin in patients with AF. Differences in the results of the two trials might relate to consistency of warfarin anticoagulation, different degree of blinding in the two trials, other concomitant therapies or chance. Further investigation is required to explore the long-term safety profile of ximelagatran.
The erbstatin analogue methyl 2,5-dihydroxycinnamate cross-links proteins and is cytotoxic to normal and neoplastic epithelial cells by a mechanism independent of tyrosine kinase inhibition. (1995)

Differentiation therapy is an attractive option for the treatment of superficial, localized neoplastic lesions of the skin. Topical application of agents that induce differentiation could selectively inhibit tumor cell growth, inducing a program of cell death with the production of cross-linked protein envelopes as the terminal event of this process at the skin surface, effectively eliminating the neoplastic phenotype. The nonspecific kinase inhibitor staurosporine induces cornified envelope assembly in neoplastic keratinocytes and causes tumor regression (A. A. Dlugosz and S. H. Yuspa, Cancer Res., 51: 4677-4684, 1991). In pursuit of less toxic agents, specific tyrosine kinase inhibitors were tested for the ability to induce differentiation in keratinocyte-derived cells. Of a range of inhibitors tested, only MC was able to induce cross-linked protein and consequent cell death in mouse and human primary normal keratinocytes, 308 neoplastic mouse keratinocytes, HPV-18-infected immortalized human keratinocytes, and human lines SQCC-Y1 (squamous carcinoma) and A431 (epidermoid carcinoma). MC increased cross-linked protein in a dose-dependent manner (0.05-1 mM). To confirm differentiation, MC-treated mouse primary normal keratinocytes were tested for activation of the endogenous cross-linking enzyme transglutaminase, but no association was found between transglutaminase activity and MC-induced protein cross-linking. MC also induced protein cross-linking in the fibroblast cell line NIH3T3 and in B16 melanoma cells, in which cornified envelope assembly is not part of the differentiation process. This cross-linking occurred at 4 degrees C, suggesting a nonphysiological process. Western blot analysis of an in vitro assay with purified EGF receptor showed that MC was able to cross-link the receptor. As in NIH3T3 cells, DTT inhibited cross-linking, suggesting that oxidation of MC or an acceptor group may be required for this effect. Thus, MC does not induce differentiation by a physiological mechanism in epithelial cells but causes chemical protein cross-linking into cornified envelope-like structures at high concentration.
Automatic Generation of Buffer Overflow Attack Signatures: An Approach Based on Program Behavior Models (2006)

Buffer overflows have become the most common target for network-based attacks.They are also the primary mechanism used by worms and other forms of automated attacks.Although many techniques have been developed to prevent server compromises due to buffer overflows, these defenses still lead to server crashes.When attacks occur repeatedly, as is common with automated attacks, these protection mechanisms lead to repeated restarts of the victim application, rendering its service unavailable.To overcome this problem, we develop a new approach that can learn the characteristics of a particular attack, and filter out future instances of the same attack or its variants.By doing so, our approach significantly increases the availability of servers subjected to repeated attacks.The approach is fully automatic, does not require source code, and has low runtime overheads.In our experiments, it was effective against most attacks, and did not produce any false positives.
Silicon based replication technology of 3D-microstructures by conventional CD-injection molding techniques (2002)

A novel and rapid mass fabrication process for replicated polymeric 3D-microstructures of almost any arbitrary geometrical shape is presented. In this approach the master is fabricated using relatively inexpensive silicon bulk micromachining (wet or dry etching). This together with a slightly modified conventional CD-injection molding process can substantially reduce the production cycle times. The process was used to form microstructured replicas with micrometer precision and with structure depths down to 470 /spl mu/m at a cycle time less than 10 seconds.
Review: Application of Stem Cells for Vascular Tissue Engineering (2005)

As the prevalence of vascular disease has continued to expand, the need for a suitable arterial replacement has prompted researchers to look beyond synthetic and autologous grafts toward the field of tissue engineering. Advances in vascular tissue engineering have utilized both mesenchymal and hematopoietic stem cells as a cell source in an attempt to create a fully engineered small-diameter graft. Stem cells offer enormous potential as a cell source because of their proliferative and growth potential, and the application of stem cell technology has far-reaching implications for future applications. The innovative use of stem cells for vascular tissue engineering has opened new possibilities for a fully engineered blood vessel. The purpose of this review is to summarize the current perspective on the use of stem cells for vascular tissue engineering. It focuses principally on the classes of stem cells used, techniques for differentiation scaffolding technology, and the successes and failures of models.
Synthetic lipopeptide Pam3CysSer(Lys)4 is an effective activator of human platelets (1994)

Lipopeptide analogues of the NH2-terminus of bacterial lipoprotein are known to induce activation of macrophages, neutrophils, and lymphocytes. We studied the effect of the lipopeptide N-palmitoyl-S-[2,3-bis(palmitoyloxy)-(2RS)-propyl]-(R)-cysteinyl-( S)-seryl-(S)-lysyl-(S)-lysyl-(S)-lysyl-(S)-lysine [Pam3CysSer(Lys)4] on several functions of human platelets. Pam3CysSer(Lys)4 led to the aggregation of platelets and induced the secretion of serotonin with an effectiveness similar to thrombin. These cellular effects of Pam3CysSer(Lys)4 were concentration dependent, being half maximal at 2-3 microM and maximal at 10-30 microM. Another lipopeptide also induced platelet aggregation and serotonin secretion but was less potent and less effective than Pam3CysSer(Lys)4. The lipid moiety and the peptide moiety of Pam3CysSer(Lys)4 alone were without any effect. Lipopeptides also stimulated tyrosine phosphorylation of several proteins with molecular masses similar to those found to be tyrosine phosphorylated in response to thrombin, and Pam3CysSer(Lys)4 led to an increase in the cytosolic calcium concentration. All studied responses of platelets to lipopeptides were inhibited by the prostacyclin receptor agonist cicaprost. Taken together, our data show that lipopeptides are effective activators of human platelets and that this activation is susceptible to the action of physiological platelet inhibitors.
Carotid Chemoreceptor Modulation of Regional Blood Flow Distribution During Exercise in Health and Chronic Heart Failure (2007)

Previous work has shown sensitization of carotid chemoreceptor (CC) responsiveness during exercise as well as in chronic heart failure (CHF). Accordingly, we hypothesized that the CCs contribute to the sympathetic restraint of skeletal muscle blood flow during exercise and CHF. We examined the effect of transient CC inhibition on total (Con(T)) and hindlimb (Con(L)) conductance, and blood pressure at rest and during exercise (2.5 miles per hour, 5% grade) in chronically instrumented dogs. Via a carotid arterial catheter, CCs were inhibited using dopamine (5 to 10 microg/kg) or hyperoxic lactated Ringer's solution. Although vasodilation did not occur with CC inhibition in resting healthy dogs, CC inhibition during exercise caused an immediate vasodilatory response (increase in Con(T) and Con(L) and decrease in blood pressure). When comparing the peak Con(L) response from CC inhibition versus alpha-adrenergic blockade (phentolamine), we found that the CCs accounted for approximately one-third of the total sympathetic restraint during exercise. CHF was then induced by chronic rapid cardiac pacing and characterized by impaired cardiac function, enhanced chemosensitivity, and greater sympathetic restraint at rest and during exercise. In contrast to healthy dogs, CC inhibition in resting CHF dogs produced vasodilation, whereas a similar vasodilatory response was observed during exercise in CHF as compared with healthy dogs. The vasodilation following CC inhibition during exercise and in CHF was abolished with alpha-adrenergic blockade and was absent in healthy exercising animals after carotid body denervation. These results establish an important role for the CCs in cardiovascular control in the healthy animal during exercise and in the CHF animal both at rest and during exercise.
Differential expression of the human mu opiate receptor from different primary vascular endothelial cells. (2004)

The individual variations in mu receptor expression in these vascular tissues may explain the large variance in graft survival using saphenous veins for coronary artery bypass surgery.
Synthesis, Characterization, and Viscoelastic Properties of High Molecular Weight Hyperbranched Polyglycerols (2006)

Very high molecular weight (Mn up to 700 000) and narrowly polydispersed (PDI = 1.1−1.4) hyperbranched polyglycerols (HPG) were synthesized by ring-opening multibranching polymerization of glycidol using dioxane as an emulsifying agent. Broader molecular weight distributions with low molecular weight fractions were obtained when diglyme was used as the emulsifying agent. But the low molecular weight fractions could be removed by dialysis. Isolated yields in both the cases were 70−90%. The different result in the case of dioxane may be due to faster cation exchange which leads to low polydispersites. HPGs of various molecular weights were characterized by a GPC system coupled with a multiangle laser light scattering detector and a triple detector array. The intrinsic viscosities were low for these polymers and did not increase with molecular weight. The dimensions of these polymers (Rg, Rh, Rη) and their dependence on molecular weights are described. The hydrodynamic radii were very small with dimensions similar to those of dendrimers. Our results show that these polymers are very compact and have spherical conformations in water with no indications of aggregate formation. The melt viscoelastic properties were also studied. Despite their self-similar structures, depending on the type of solvent used to synthesize them (diglyme vs dioxane), topologically restricted configurations are produced that result in completely different entanglement dynamics.
A new approach for modelling kinematic dependencies for monitoring locations of objects in closed kinematic chains (Part 2) (2002)

Location monitoring systems for surgical applications are getting more and more common in clinical daily life. Navigation treatment systems are also a form of a location monitoring system. These systems always consist of an optical, US-, electromagnetic or mechanical navigation system. If two or more navigation systems are combined or one navigations system is combined with a robot system the kinematic model of the entire system consists of closed kinematic loops. In this paper, an approach is presented to gain more information from the closed kinematic chains instead of breaking the kinematic loops. This is the second part of [1].