gebhart/patrepeval huggingface dataset:
Chemical synthesis of echistatin, a potent inhibitor of platelet aggregation from Echis carinatus: synthesis and biological activity of selected analogs. (1989)

Echistatin, a polypeptide from the venom of the saw-scaled viper, Echis carinatus, containing 49 amino acids and 4 cystine bridges was synthesized by solid-phase methodology in 4% yield. In the final step, air oxidation of the octahydroderivative was found to be optimal at pH 8. The synthetic product was shown to be physically and biologically indistinguishable from native material. It inhibits fibrinogen-dependent platelet aggregation stimulated by ADP with IC50 = 3.3 x 10(-8) M and also prevents aggregation initiated by thrombin, epinephrine, collagen, or platelet-activating factor. Reduction of purified synthetic echistatin to octahydroechistatin with dithiothreitol followed by air oxidation regenerated homogeneous echistatin in quantitative yield. This highly specific refolding strongly suggests that the linear sequence of octahydroechistatin contains all of the information that is required for the proper folding of the peptide. The sequence Arg24-Gly-Asp of echistatin occurs also in adhesive glycoproteins that bind to the platelet fibrinogen receptor--a heterodimeric complex composed of glycoproteins IIb and IIIa. In an effort to evaluate the role of this putative binding site we have synthesized analogs of echistatin with substitution of Arg-24. Replacement with ornithine-24 (Orn-24) resulted in an analog having a platelet aggregation inhibitory activity with IC50 = 1.05 x 10(-7) M. Substitution with Ala-24 gave IC50 = 6.1 x 10(-7) M. The inhibitory activity of the corresponding short sequence analogs Arg-Gly-Asp-Phe (IC50 = 6 x 10(-6) M), Orn-Gly-Asp-Phe (IC50 = 1.3 x 10(-4) M), and Ala-Gly-Asp-Phe (IC50 = 5.0 x 10(-4) M) was also determined. These results suggest that arginine plays a more important role in the binding of the tetrapeptide than in that of echistatin.
MessageWorld (1995)

We describe a prototype system called Me~ageWorld designed to offer a new approach to online communication. MessageWorld provides an alternative to traditional group information sharing tools such as e-mail, online bulletin boards, and searchable storage archives. MessageWorld relieves message authors of the burden of addressing, while prospective readers are relieved of the burden of searching; the system provides a rendezvous mechanism for uniting readers with messages of interest to them. We rely on a variety of techniques including traditional content analysis and the correlation of user preferences. Adaptive algorithms serve to incorporate some of the knowledge of the user community in the system's assessment of each user's interests. 1
Voltage Control of Droplet Interface Bilayer Lipid Membrane Dimensions (2010)

A novel approach to control the area of anchor-free droplet interface bilayer (DIB) lipid membranes is presented. Unsupported DIB lipid membranes are formed at the interface of phospholipid-coated aqueous droplets dispensed in dodecane oil. Using electrodes inserted into the droplets, an external voltage is applied which modulates the effective DIB area. Electrical (capacitance or current) and optical (imaging of DIB lateral length) recordings were simultaneously performed. Alpha-hemolysin (αHL) single channel insertions into the DIB were recorded. Currents across the DIB were measured as a function of voltage and αHL concentration in the droplets. Nonlinear response is observed for current, DIB lateral length and area, and capacitance with respect to voltage. Voltage induced changes in interfacial tension modulated the DIB-oil contact angle and the membrane contact length, which provided control of membrane dimensions. Comparison of these results is made to the electrowetting effect, which is also governed by effect of voltage on the interfacial tension. This approach provides active control of the number of ion channels inserted into the DIB.
Long-Term Small Molecule and Protein Elution from TiO2 Nanotubes (2009)

In this study, TiO(2) nanotubes of various dimensions were used to elute albumin, a large protein molecule, as well as sirolimus and paclitaxel, common small molecule drugs. The nanotubes controlled small molecule diffusion for weeks and large molecule diffusion for a month. Drug eluted from the nanotubes was bioactive and decreased cell proliferation in vitro. Elution kinetics was most profoundly affected by tube height. This study demonstrates that TiO(2) nanotubes may be a promising candidate for a drug-eluting implant coating.
High-efficiency transposon mutagenesis by electroporation of a Pseudomonas fluorescens strain (2006)

A method is described for mutagenesis of Pseudomonas fluorescens strains by electroporation with the transposon delivery vector pUT/mini-Tn5 Km. The transposition process was shown to be optimal at 12.5 kV cm-1 for a pulse time (Bowen and Koslak, 1992) of about 4 ms. The Pseudomonas fluorescens L6.5 target strain exhibited maximal electrocompetence when harvested at the middle of the exponential growth phase. As many as 7.7 10(5) mutants per picomole of delivery vector (7.5 kb) could be obtained, and these kanamycin-resistant mutants were shown to have lost the pUT plasmid. By external calibration with plasmids of increasing size (from 11.5 to 60.1 kb), the efficiency of the transformation process was evaluated to be approximately 1.31 x 10(8) transformants per picomole of delivery vector. Efficiency of the transposition process was 0.58%. This rapid method was used to tag for the cloning three independent chromosomal loci responsible for the Alk+ phenotype of Pseudomonas fluorescens L6.5 strain.
Wearable electrochemical sensors for in situ analysis in marine environments (2011)

The development of wearable screen-printed electrochemical sensors on underwater garments comprised of the synthetic rubber neoprene is reported. These wearable sensors are able to determine the presence of environmental pollutants and security threats in marine environments. Owing to its unique elastic and superhydrophobic morphology, neoprene is an attractive substrate for thick-film electrochemical sensors for aquatic environments and offers high-resolution printing with no apparent defects. The neoprene-based sensor was evaluated for the voltammetric detection of trace heavy metal contaminants and nitroaromatic explosives in seawater samples. We also describe the first example of enzyme (tyrosinase) immobilization on a wearable substrate towards the amperometric biosensing of phenolic contaminants in seawater. Furthermore, the integration of a miniaturized potentiostat directly on the underwater garment is demonstrated. The wearable sensor-potentiostat microsystem provides a visual indication and alert if the levels of harmful contaminants have exceeded a pre-defined threshold. The concept discussed here is well-suited for integration into dry- and wetsuits worn by divers and recreational surfers/swimmers, thereby providing them with the ability to continuously assess their surroundings for environmental contaminants and security hazards.
Cortical and cancellous bone thickness on the anterior region of alveolar bone in Korean: a study of dentate human cadavers (2012)

For implant placement on the anterior region, a careful evaluation and full knowledge on the thickness of the cortical and cancellous bone are necessary, therefore, these results may provide an anatomic guideline to clinicians.
Logo and word matching using a general approach to signal registration (2002)

The paper presents work in the field of logo and word recognition. The approach is based on a general theory for signal registration and is thus applicable to a broad variety of signal processing domains. It has been fruitfully applied to solve speech and handwriting recognition as well as tasks in the field of document analysis.
Hand-Washing Patterns in Medical Intensive-Care Units (1981)

ORGANISMS that cause nosocomial infections can be transmitted by the hands of physicians, nurses, technicians, and other hospital personnel.1 2 3 4 Hand washing is considered the single most important procedure in preventing nosocomial infections, and it has been recommended after contact with every patient by both the Centers for Disease Control and the Americal Hospital Association.5 , 6 The risk of acquiring organisms, transmitting them to others, or causing a nosocomial infection may vary with the susceptibility of the patient and the type of patient contact.7 However, because patients in intensive-care units are highly susceptible to nosocomial infections,7 , 8 it has been suggested that personnel . . .
Engineered Cementitious Composites with High-Volume Fly Ash (2007)

Peer Reviewed
Novel inhibition of archaeal family-D DNA polymerase by uracil (2013)

Archaeal family-D DNA polymerase is inhibited by the presence of uracil in DNA template strands. When the enzyme encounters uracil, following three parameters change: DNA binding increases roughly 2-fold, the rate of polymerization slows by a factor of ≈ 5 and 3'-5' proof-reading exonuclease activity is stimulated by a factor of ≈ 2. Together these changes result in a significant decrease in polymerization activity and a reduction in net DNA synthesis. Pol D appears to interact with template strand uracil irrespective of its distance ahead of the replication fork. Polymerization does not stop at a defined location relative to uracil, rather a general decrease in DNA synthesis is observed. 'Trans' inhibition, the slowing of Pol D by uracil on a DNA strand not being replicated is also observed. It is proposed that Pol D is able to interact with uracil by looping out the single-stranded template, allowing simultaneous contact of both the base and the primer-template junction to give a polymerase-DNA complex with diminished extension ability.
Residues on Both Faces of the First Immunoglobulin Fold Contribute to Homophilic Binding Sites of PECAM-1/CD31 (1997)

CD31 (PECAM-1) is a member of the immunoglobulin superfamily whose extracellular domain is comprised of six immunoglobulin-like domains. It is widely expressed on endothelium, platelets, around 50% of lymphocytes, and cells of myeloid lineage. CD31 has been shown to be involved in interendothelial adhesion and leukocyte-endothelial interactions, particularly during transmigration. CD31-mediated adhesion is complex, because CD31 is capable of mediating both homophilic and multiple heterophilic adhesive interactions. Here we show that the NH2-terminal (membrane-distal) immunoglobulin domain of CD31 is necessary but not sufficient to support stable homophilic adhesion. Key residues forming the binding site within this domain have been identified by analysis of 26 single point mutations, representing the most systematic analysis of a fully homophilic interaction between immunoglobulin superfamily family members to date. This revealed five mutations that affect homophilic binding. Uniquely, the residues involved are exposed on both faces of the immunoglobulin fold, leading us to propose a novel mechanism for CD31 homophilic adhesion.
Chitinase Inhibitors and Chitin Mimetics for Crop Protection (2008)

Pathogen and pest management is a key element in agriculture. The Integrated Pest Management concept relies on the availability of an array of protective measures having different but complementary mechanisms. As a consequence, alternative strategies have to be developed. Because chitin occurs in the cell wall of fungi and in various structural components of arthropods, its metabolism has been considered as a suitable target to manage pathogens and pests. Disruption of chitinase metabolism is one of the strategies that have been considered. Studies led to the discovery of new molecules which interact with chitinases and induce antibiotic, antifungal or insecticidal effects. These compounds present different ranges of activity, depending on their biochemical classification, their structure and the nature of the targeted chitinase. Some are oligo- and polysaccharides (e.g. allosamidin, FPS-1) and others are peptides (e.g. argadin, argifin, cyclic dipeptides or psammaplin A). These natural molecules directly interact with the catalytic site of chitinases, mimicking chitin structure. In this review we will present a synthesis of the recent works that aimed to disrupt chitin metabolism by chitinase inhibition with the ultimate objective of developing new applications for crop protection.
Antimetabolites (1992)

Research efforts over the past year further elucidate the determinants of sensitivity and mechanisms of resistance to the antimetabolites fluorouracil, methotrexate, and cytarabine. Progress has been made in clarifying the complex regulation of target enzyme expression for these antimetabolites. Advances in analytical methodology should facilitate quantitation of thymidylate synthase content in tumor tissue prior to and following fluorouracil-based therapy. Information concerning the basis for certain drug interactions may guide rational dose rates and schedules for clinical trials. A better understanding of the clinical pharmacology of these agents has suggested strategies to minimize their toxicity while maintaining therapeutic activity.
Loss of 5‐hydroxymethylcytosine is accompanied with malignant cellular transformation (2012)

Dysregulated DNA methylation followed by abnormal gene expression is an epigenetic hallmark in cancer. DNA methylation is catalyzed by DNA methyltransferases, and the aberrant expression or mutations of DNA methyltransferase genes are found in human neoplasm. The enzymes for demethylating 5-methylcytosine were recently identified, and the biological significance of DNA demethylation is a current focus of scientific attention in various research fields. Ten-eleven translocation (TET) proteins have an enzymatic activity for the conversion from 5-methylcytosine to 5-hydroxymethylcytosine (5-hmC), which is an intermediate of DNA demethylation. The loss-of-function mutations of TET2 gene were reported in myeloid malignancies, suggesting that impaired TET-mediated DNA demethylation could play a crucial role in tumorigenesis. It is still unknown, however, whether DNA demethylation is involved in biological properties in solid cancers. Here, we show the loss of 5-hmC in a broad spectrum of solid tumors: for example, a significant reduction of 5-hmC was found in 72.7% of colorectal cancers (CRCs) and 75% of gastric cancers compared to background tissues. TET1 expression was decreased in half of CRCs, and a large part of them was followed by the loss of 5-hmC. These findings suggest that the amount of 5-hmC in tumors is often reduced via various mechanisms, including the downregulation of TET1. Consistently, in the in vitro experiments, the downregulation of TET1 was clearly induced by oncogene-dependent cellular transformation, and loss of 5-hmC was seen in the transformed cells. These results suggest the critical roles of aberrant DNA demethylation for oncogenic processes in solid tissues.
Fibroblast growth factor receptor 4 is a high affinity receptor for both acidic and basic fibroblast growth factor but not for keratinocyte growth factor. (1993)

A cDNA predicted to encode a transmembrane tyrosine kinase receptor with sequence features characteristic of known fibroblast growth factor (FGF) receptors was isolated from an expression library constructed from the human mammary epithelial cell line B5/589. This cDNA, designated cl44, encodes a product of 803 amino acid residues and was readily distinguishable from known FGF receptors. During the course of our studies, Partanen et al. (Partanen, J., Makela, T. P., Eerola, E., Korhonen, J., Hirvonen, H., Claesson, W. L., and Alitalo, K. (1991) EMBO J. 10, 1347-1354) isolated a new FGF receptor, designated FGFR4, from the human leukemia cell line, K562. Its amino acid sequence is identical to that of cl44 with the exception of 1 residue. The 5'-untranslated sequences of the two cDNAs diverged far upstream of the initiation codon. A myoblast line, L6E9, which lacks FGF receptors, was utilized to express high levels of FGFR4. We found, in contrast to Partenen et al., who reported only binding of acidic FGF, that FGFR4 bound both acidic and basic FGF with dissociation constants of 10-15 and 120 pM, respectively. No detectable binding of keratinocyte growth factor was observed. In studies aimed to determine whether FGF receptors contribute to the development of human tumors, we screened RNAs prepared from cell lines derived from a variety of solid tumors. High levels of the cl44 transcript were detected in 8 of 14 and 6 of 9 human mammary and kidney carcinomas, respectively, but only infrequently in other types of tumors. In contrast, FGFR1 was found to be frequently expressed in kidney, but not in breast tumor cells, suggesting a possible role for FGFR4 in human mammary cancer.
Inhibition of leukotriene synthesis with MK‐886 prevents a rise in blood pressure and reduces noradrenaline‐evoked contraction in L‐NAME‐treated rats (2003)

(1) Long-term treatment of rats with Nomega-nitro-l-arginine methyl ester (l-NAME) induces hypertension associated with inflammatory and vascular changes. Leukotrienes are proinflammatory vasoactive products that are suspected to be involved in the pathogenesis of hypertension. We investigated, in rats chronically treated with l-NAME, the involvement of leukotrienes in the in vivo regulation of blood pressure and the in vitro contraction elicited by noradrenaline in isolated aorta. (2) Rats were randomly assigned to four groups and orally treated for 3 weeks with l-NAME (1 mg ml-1), l-NAME (1 mg ml-1) plus the leukotriene biosynthesis inhibitor MK-886 (0.1 mg ml-1), MK-886 (0.1 mg ml-1) alone or vehicle (Methocel, 0.1%). All the drugs were added to the drinking fluid. (3) The mean arterial blood pressure (MABP) increased significantly in l-NAME-treated rats (173.3+/-9.4 mmHg (n=25)) vs Methocel-treated rats (110.7+/-4.8 mmHg (n=11), P<0.001). Chronic treatment with MK-886 prevented this rise in MABP. (4) Aortic rings with or without endothelium were suspended in organ baths for recording isometric changes in response to noradrenaline. Pretreatment with either MK-886 (10 microm), the CysLT1 receptor antagonist MK571 (1 microm) or the dual CysLT1/CysLT2 receptor antagonist BAY-u9773 (0.1 microm) reduced (P<0.05) noradrenaline-induced contractions in intact aortic rings from l-NAME-treated rats only. (5) Noradrenaline (0.3 microm) induced a two-fold increase in cysteinyl leukotriene (CysLT) release (measured by enzyme immunoassay) in intact aortic rings from l-NAME-treated rats only. (6) These data suggested (1) a role for the 5-lipoxygenase pathway in the regulation of blood pressure in l-NAME-treated rats and (2) the involvement of endothelial CysLTs in noradrenaline-induced contraction in aorta from l-NAME-treated rats.
α1A-Adrenoceptors Activate Glucose Uptake in L6 Muscle Cells through a Phospholipase C-, Phosphatidylinositol-3 Kinase-, and Atypical Protein Kinase C-Dependent Pathway (2004)

The role of alpha1-adrenoceptor activation on glucose uptake in L6 cells was investigated. The alpha1-adrenoceptor agonist phenylephrine [pEC50 (-log10 EC50), 5.27 +/- 0.30] or cirazoline (pEC50, 5.00 +/- 0.23) increased glucose uptake in a concentration-dependent manner, as did insulin (pEC50, 7.16 +/- 0.21). The alpha2-adrenoceptor agonist clonidine was without any stimulatory effect on glucose uptake. The stimulatory effect of cirazoline was inhibited by the alpha1-adrenoceptor antagonist prazosin, but not by the beta-adrenoceptor antagonist propranolol. RT-PCR showed that the alpha1A-adrenoceptor was the sole alpha1-adrenoceptor subtype expressed in L6 cells. Cirazoline- or insulin-mediated glucose uptake was inhibited by the phosphatidylinositol-3 kinase inhibitor LY294002, suggesting a possible interaction between the alpha1-adrenoceptor and insulin pathways. Cirazoline or insulin stimulated phosphatidylinositol-3 kinase activity, but alpha1-adrenoceptor activation did not phosphorylate Akt. Both cirazoline- and insulin-mediated glucose uptake were inhibited by protein kinase C (PKC), phospholipase C, and p38 kinase inhibitors, but not by Erk1/2 inhibitors (despite both treatments being able to phosphorylate Erk1/2). Insulin and cirazoline were able to activate and phosphorylate p38 kinase. The phorbol ester 12-O-tetradecanoylphorbol-13-acetate and the calcium ionophore A23187 produced significant increases in glucose uptake, indicating roles for PKC and calcium in glucose uptake. Down-regulation of conventional PKC isoforms inhibited glucose uptake mediated by 12-O-tetradecanoylphorbol-13-acetate, but not by insulin or cirazoline. This study demonstrates that alpha1-adrenoceptors mediate increases in glucose uptake in L6 muscle cells. This effect appears to be related to activation of phospholipase C, phosphatidylinositol-3 kinase, p38 kinase, and PKC.
On-line sensor validation of single sensors using artificial neural networks (2005)

We examine how the signal from a single sensor from a dynamic process might be analyzed to ascertain whether the sensor signal is valid or not. It is quite possible for the signal to indicate a change has occurred in the process when the sensor itself is what has changed. Two possible approaches to sensor validation discussed here are (1) use of second and higher order statistics rather than the mean of a signal, and (2) modeling the sensor signal via artificial neural networks.
The intrinsically disordered C-terminal region of Arabidopsis thaliana TCP8 transcription factor acts both as a transactivation and self-assembly domain (2013)

TCPs are plant specific transcription factors with non-canonical basic helix-loop-helix domains. While Arabidopsis thaliana has 24 TCPs involved in cell proliferation and differentiation, their mode of action has not been fully elucidated. Using bioinformatic tools, we demonstrate that TCP transcription factors belong to the intrinsically disordered proteins (IDP) family and that disorder is higher in class I TCPs than in class II TCPs. In particular, using bioinformatic and biochemical approaches, we have characterized TCP8, a class I TCP. TCP8 exhibits three intrinsically disordered regions (IDR) made of more than 50 consecutive residues, in which phosphorylable Ser residues are mainly clustered. Phosphorylation of Ser-211 that belongs to the central IDR was confirmed by mass spectrometry. Yeast two-hybrid assays also showed that the C-terminal IDR corresponds to a transactivation domain. Moreover, biochemical experiments demonstrated that TCP8 tends to oligomerize in dimers, trimers and higher-order multimers. Bimolecular fluorescence complementation (BiFC) experiments carried out on a truncated form of TCP8 lacking the C-terminal IDR indicated that it is effectively required for the pronounced self-assembly of TCP8. These data were reinforced by the prediction of a coiled coil domain in this IDR. The C-terminal IDR acts thus as an oligomerization domain and also a transactivation domain. Moreover, many Molecular Recognition Features (MoRFs) were predicted, indicating that TCP8 could interact with several partners to fulfill a fine regulation of transcription in response to various stimuli.
Apoptosis and APC in colorectal tumorigenesis. (1996)

Tumors result from disruptions in the homeostatic mechanisms that regulate cell birth and cell death. In colon cancer, one of the earliest manifestation of this imbalance is the formation of polyps, caused by somatic and inherited mutations of the adenomatous polyposis coli (APC) tumor suppressor gene in both humans and mice. While the importance of APC in tumorigenesis is well documented, how it functions to prevent tumors remains a mystery. Using a novel inducible expression system, we show that expression of APC in human colorectal cancer cells containing endogenous inactive APC alleles results in a substantial diminution of cell growth. Further evaluation demonstrated that this was due to the induction of cell death through apoptosis. These results suggest that apoptosis plays a role not only in advanced tumors but also at the very earliest stages of neoplasia.