gebhart/patrepeval huggingface dataset:
A fluorescent indicator for measuring cytosolic free magnesium (1989)

The previously developed chelator O-aminophenol-N,N,O-triacetic acid (APTRA) (L. A. Levy, E. Murphy, B. Raju, and R. E. London. Biochemistry 27: 4041-4048, 1988) has been modified to yield a fluorescent analogue which can be utilized as an intracellular probe for ionized Mg2+. The fluorescent analogue, FURAPTRA, with a magnesium dissociation constant of 1.5 mM, is structurally analogous to the calcium chelator fura-2 and exhibits a similar excitation shift on magnesium complexation. Hence, data on the intracellular Mg2+ concentration can be obtained using an analogous ratio method. The acetoxymethyl form of the chelator is readily loaded into cells and has been used to determine a cytosolic free Mg2+ concentration of 0.59 mM for isolated rat hepatocytes. As a consequence of the relatively high levels of cytosolic Mg2+, the problem of ion buffering is much less severe than for the analogous calcium indicators.
Roflumilast, a phosphodiesterase 4 inhibitor, alleviates bleomycin‐induced lung injury (2009)

Roflumilast prevented the development of bleomycin-induced lung injury, and alleviated the lung fibrotic and vascular remodeling response to bleomycin in a therapeutic protocol, the latter being resistant to glucocorticoids.
Information Model: From Abstraction to Application (2005)

Today’s telecommunication structures, already widespread, are based on heterogeneous systems. In fact, in most networks, there are products and services from multiple vendors, and these products incorporate multiple technologies. So how can we manage networks which coexist, cooperate and internetwork in heterogeneous environment? As a matter of fact, we can say that management of network needs to have information on the whole behavior of all network elements. Thus, an information model must be provided, describing the way in which information is structured. We know that this information model is a critical component of a network management framework. Which are the main contributions of network management standards in this area? OSI management standards have adopted the object oriented paradigm for definition of management information [1]. Also, a semi-formal notation for the description of the syntactical elements of managed object classes, GDMO [2], has been defined. In addition, managed object sets (libraries) [3], are provided for developing its own specific information model. However, there is no provision of structuration of the information. On the contrary, CCITT [4] provides a generic network model without distinguishing between network and network element viewpoints [5] and without enhancing the service aspect. However, Network, Network Element and Service views are primordial for integrated management. The Internet community defines the MIB II (Management Information Base) [6]. The information is only attribute oriented. This is mainly for reasons of simplicity and quick provision of an operational network management framework. A main drawback is the lack of powerful modeling concepts. Each standard provides some elements of solution. However they still do not propose an integrated information model. In order to provide a complete answer that meets all requirements, it is necessary to reply to the following questions: Which are the main objectives of a satisfactory management information model? Which are the necessary conceptual tools? The answers lead us to propose an object oriented information model supporting both network and service aspects, which may be applied to any network element according to a particular visibility. To pass from this abstract model to its instantiation for a particular network configuration, we focus on the FDDI subnetwork management. Throughout this application, we enhance its efficiency for monitoring, controlling, analyzing and eventually managing the studied configuration. In addition, we provide the basic rules that guide us during the instantiation of the abstract model for any specific network.
Natural Protection Against HIV-1 Infection Provided by HIV-2 (1995)

Significant differences have been observed in the rates of transmission and disease development in human immunodeficiency virus (HIV) types 1 and 2. Because many HIV-2-infected people remain asymptomatic for prolonged periods, the hypothesis that HIV-2 might protect against subsequent infection by HIV-1 was considered. During a 9-year period in Dakar, Senegal, the seroincidence of both HIV types was measured in a cohort of commercial sex workers. Despite a higher incidence of other sexually transmitted diseases (STDs), HIV-2-infected women had a lower incidence of HIV-1 than did HIV-seronegative women, with a relative risk of 0.32 (P = 0.008). An understanding of the cross-protective mechanisms involved may be directly relevant to HIV-1 vaccine development.
Comparison of ribotyping and pulsed-field gel electrophoresis for subspecies differentiation of strains of Enterococcus faecalis (1993)

Hybridization of EcoRI- and HindIII-digested chromosomal DNAs from 41 isolates of Enterococcus faecalis with probes for rRNA genes was performed (ribotyping). The ability of ribotyping to distinguish strains at the subspecies level was compared with results previously determined by pulsed-field gel electrophoresis (PFGE). With EcoRI, seven ribopatterns (usually differing by only one band) were found, while PFGE had previously shown 25 clearly different patterns plus six related variants. Digestion with HindIII generated a few additional patterns but still failed to differentiate some strains that had very different PFGE patterns. Ribotyping with BscI has also been reported to be inadequate for subspecies strain differentiation (L. M. Hall, B. Duke, M. Guiney, and R. Williams, J. Clin. Microbiol. 30:915-919, 1992). Although ribotyping with other restriction endonucleases may perform better in distinguishing different strains, at present PFGE appears to be superior for strain differentiation.
Determination of DNA binding specificities of mutated zinc finger domains (1991)

By substituting non conserved amino acids present in the postulated alpha-helical region of zinc finger domains, we demonstrated that Cys2/His2 type zinc finger domains could be targeted to new DNA binding sites. The putative alpha-helical region of the second SP1 zinc finger (RSDELQRH) was replaced by amino acids (KSSALISH) occurring in analogous zinc finger positions of human zinc finger protein Kox 29. The DNA binding specificity of the FPLC purified chimaeric protein (SP1-Kox 29) was determined by use of the target detection assay (TDA). Chimaeric protein SP1-Kox 29 was subjected to randomized oligonucleotides (GGG NNNN GGC) that were designed on the basis that each SP1 zinc finger interacts with 3-4 nucleotides concerning its cognate target site GGG GCGG GGC. By this analysis the DNA binding specificity of SP1-Kox 29 was shown to have switched from the cognate SP1 binding site to GGG GGTG GGC. Structure-function analysis of this type should facilitate the determination of DNA binding specificities for any individual zinc finger of interest.
One-Step Electrospinning of Cross-Linked Chitosan Fibers (2007)

Chitin is a nitrogen-rich polysaccharide that is abundant in crustaceans, mollusks, insects, and fungi and is the second most abundant organic material found in nature next to cellulose. Chitosan, the N-deacetylated derivative of chitin, is environmentally friendly, nontoxic, biodegradable, and antibacterial. Fibrous mats are typically used in industries for filter media, catalysis, and sensors. Decreasing fiber diameters within these mats causes many beneficial effects such as increased specific surface area to volume ratios. When the intrinsically beneficial effects of chitosan are combined with the enhanced properties of nanofibrous mats, applications arise in a wide range of fields, including medical, packaging, agricultural, and automotive. This is particularly important as innovative technologies that focus around bio-based materials are currently of high urgency, as they can decrease dependencies on fossil fuels. We have demonstrated that Schiff base cross-linked chitosan fibrous mats can be produced utilizing a one-step electrospinning process that is 25 times faster and, therefore, more economical than a previously reported two-step vapor-cross-linking method. These fibrous mats are insoluble in acidic, basic, and aqueous solutions for 72 h. Additionally, this improved production method results in a decreased average fiber diameter, which measures 128 +/- 40 nm. Chemical and structural analyses were conducted utilizing Fourier transform infrared spectroscopy, solubility studies, and scanning electron microscopy.
The Hydrolysis of Cyclic Orthoesters. Stereoelectronic Control in the Cleavage of Hemiorthoester Tetrahedral Intermediates (1975)

The synthesis of several cyclic dialkoxy orthoesters is reported. Acid hydrolysis of these orthoesters under kinetically controlled conditions gives the corresponding hydroxy esters only. Conformationally rigid cyclic mixed orthoesters give a hydroxy ester by exclusive loss of the axial alkoxy group. A cyclic orthoester can have nine different gauche conformations. It is shown that they are hydrolyzed through only one gauche conformer. These results bring further experimental evidence that there is a stereoelectronic control in the cleavage of tetrahedral intermediates in the hydrolysis of esters.
Autoactivation of the marRAB multiple antibiotic resistance operon by the MarA transcriptional activator in Escherichia coli (1996)

Transcriptional activation of the promoters of the mar/soxRS regulons by the sequence-related but independently inducible MarA and SoxS proteins renders Escherichia coli resistant to a broad spectrum of antibiotics and superoxide generators. Here, the effects of MarA and SoxS on transcription of the marRAB promoter itself were assayed in vitro by using a minimal transcription system and in vivo by assaying beta-galactosidase synthesized from marR::lacZ fusions. Purified MarA and MalE-SoxS proteins stimulated mar transcription about 6- and 15-fold, respectively, when the RNA polymerase/DNA ratio was 1. Purified MarA bound as a monomer to a 16-bp "marbox" located 69 to 54 nucleotides upstream of a putative RNA initiation site. Deletion of the marbox reduced MarA-mar binding 100-fold, abolished the stimulatory effects of MarA and SoxS on transcription in vitro, and reduced marR::lacZ synthesis about 4-fold in vivo. Deletion of upstream DNA adjoining the marbox reduced MarA binding efficiency 30-fold and transcriptional activation 2- to 3-fold, providing evidence for an accessory marbox. Although MarA and the mar operon repressor, MarR, bound to independent sites, they competed for promoter DNA in band shift experiments. Assays of marR::lacZ transcriptional fusions in marRAB deletion or soxRS deletion strains showed that the superoxide generator paraquat stimulates mar transcription via soxRS and that salicylate stimulates mar transcription both by antagonizing MarR and by a MarR-independent mechanism. Thus, transcription of the marRAB operon is autorepressed by MarR and autoactivated by MarA at a site that also can be activated by SoxS.
Detection of N-acylhomoserine lactones in lung tissues of mice infected with Pseudomonas aeruginosa (2000)

The pathogenesis of Pseudomonas aeruginosa is associated with expression of virulence factors, many of which are controlled by two N:-acylhomoserine lactone (AHL)-based quorum-sensing systems. Escherichia coli strains equipped with a luxR-based monitor system expressing green fluorescent protein (GFP) in the presence of exogenous AHL molecules were used to detect the production of AHLs from P. aeruginosa in vivo. Mice were challenged intratracheally with alginate beads containing P. aeruginosa and E. coli and killed on different days after the challenge. By means of confocal scanning laser microscopy, GFP-expressing E. coli bacteria could be detected in the lung tissues, indicating production and excretion of AHL molecules in vivo by the infecting P. aeruginosa. AHL signals were detected mainly in lung tissues exhibiting severe pathological changes. These findings support the view that expression of AHL molecules by P. aeruginosa during infection coincides with its pathogenesis.
Production and Evaluation of Dry Alginate-Chitosan Microcapsules as an Enteric Delivery Vehicle for Probiotic Bacteria (2011)

This study investigates the production of alginate microcapsules, which have been coated with the polysaccharide chitosan, and evaluates some of their properties with the intention of improving the gastrointestinal viability of a probiotic ( Bifidobacterium breve ) by encapsulation in this system. The microcapsules were dried by a variety of methods, and the most suitable was chosen. The work described in this Article is the first report detailing the effects of drying on the properties of these microcapsules and the viability of the bacteria within relative to wet microcapsules. The pH range over which chitosan and alginate form polyelectrolyte complexes was explored by spectrophotometry, and this extended into swelling studies on the microcapsules over a range of pHs associated with the gastrointestinal tract. It was shown that chitosan stabilizes the alginate microcapsules at pHs above 3, extending the stability of the capsules under these conditions. The effect of chitosan exposure time on the coating thickness was investigated for the first time by confocal laser scanning microscopy, and its penetration into the alginate matrix was shown to be particularly slow. Coating with chitosan was found to increase the survival of B. breve in simulated gastric fluid as well as prolong its release upon exposure to intestinal pH.
P3‐288: Inhibition of PPAR‐γ using GW, attenuates transcription factor Nrf‐2 expression in PC12 cells (2011)

Cyclooxygenase (COX) catalyzes the formation of prostaglandins from arachidonic acid. 15-Deoxy-delta (12,14)-prostaglandinJ2 (15d-PGJ2), a terminal dehydration product of prostaglandin D2, is an endogenous ligand of peroxisome proliferator-activated receptor- gamma (PPAR-γ). It is reported that, 15d-PGJ2 has neuroprotective effects induction of Nrf-2 activation as well as PPAR-γ expression. NS-398, a COX-2 inhibitor, has also been reported to exert neuroprotection in some contexts. In this study, we sought to determine whether co-administration of COX-2 inhibitor and PPAR-γ ligand will produce higher neuroprotection, and the involved mechanisms in PC12 cells. Using PC12 adrenal pheochromocytoma cells, the levels of NF-κB, Nrf2, ?-glutamylcysteine synthetase (?-GCS), hemeoxygenase (HO-1) and PPAR-γ were determined in the experimental groups using Western blot. Cell viability was determined by the conventional MTT (3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide) reduction assay. : Pretreatment of PC12 cells with NS-398 (COX-2 inhibitor), followed by exposure to LPS resulted in about 58% higher cell viability relative to the LPS-treated cells. The group that received NS-398, 15d-PGJ2 and LPS, showed higher cell viability (%69), as well as significantly increased expression of PPAR-γ, Nrf-2 and HO-1 and γ-GCS, which are considered as downstream products of activated Nrf-2 pathway. In the group that received NS-398, 15d-PGJ2, GW-9662 (PPAR-γinhibitor) and LPS, both cell viability and the expression of Nrf-2 and PPAR-γ decreased compared to the pervious group. Results indicated that protective effects of co-administration of NS-398 and 15d-PGJ2 in the context of this study are PPAR-γ-dependent. It is suggested that combination therapy with NS-398 and 15d-PGJ2 will result in a stronger neuroprotective outcome, compared to using them alone.
Fine Tuning of the Specificity of an Anti-progesterone Antibody by First and Second Sphere Residue Engineering (2005)

The specificity of anti-progesterone P15G12C12G11 antibody was improved by combination of in vitro scanning saturation mutagenesis and error-prone PCR. The most evolved mutant is able to discriminate against 5beta- or 5alpha-dihydroprogesterone, 23 and 15 times better than the starting antibody, while maintaining the affinity for progesterone that remains in the picomolar range. The high level of homology with anti-progesterone monoclonal antibody DB3 allowed the construction of three-dimensional models of P15G12C12G11 based on the structures of DB3 in complex with various steroids. These models together with binding data, derived from site-directed mutagenesis, were used to build a phage library in which five first sphere positions in complementarity-determining regions 2H and 3L were varied. Variants selected by an initial screening in competition against a large excess of 5beta- or 5alpha-dihydroprogesterone were characterized by a convergent amino acid signature different from that of the wild-type antibody and had lower cross-reactivity. Binding properties of this first set of mutants were further improved by the addition of second sphere mutations selected independently from an error-prone library. The three-dimensional models of the best variant show changes in the antigen binding site that explain well the increase in selectivity. The improvements are partly linked to a change in the canonical class of the light chain third hypervariable loop.
Force‐Directed Edge Bundling for Graph Visualization (2009)

Abstract Graphs depicted as node‐link diagrams are widely used to show relationships between entities. However, node‐link diagrams comprised of a large number of nodes and edges often suffer from visual clutter. The use of edge bundling remedies this and reveals high‐level edge patterns. Previous methods require the graph to contain a hierarchy for this, or they construct a control mesh to guide the edge bundling process, which often results in bundles that show considerable variation in curvature along the overall bundle direction. We present a new edge bundling method that uses a self‐organizing approach to bundling in which edges are modeled as flexible springs that can attract each other. In contrast to previous methods, no hierarchy is used and no control mesh. The resulting bundled graphs show significant clutter reduction and clearly visible high‐level edge patterns. Curvature variation is furthermore minimized, resulting in smooth bundles that are easy to follow. Finally, we present a rendering technique that can be used to emphasize the bundling.
An Ultra Low Power Wakeup Receiver for Wireless Sensor Nodes (2009)

An ultra-low power 2.4 GHz RF Wakeup Receiver is designed for wireless sensor networks nodes. The receiver demodulates On-Off Keying at 100 kbps. A 120 nm CMOS chip includes the analog front-end and consumes only 7.5 mu W from a single 1.5 V supply. The digital signal processing is implemented in an FPGA. The results of measures and simulations are evaluated for the use of this receiver in wireless sensor networks.
The effects of vasoactive agents, platelet agonists and anticoagulation on thrombelastography (2007)

Modified TEG using heparin or argatroban might delineate the procoagulant effects of platelets by adding platelet specific agonist.
PepFect 14, a novel cell-penetrating peptide for oligonucleotide delivery in solution and as solid formulation (2011)

Numerous human genetic diseases are caused by mutations that give rise to aberrant alternative splicing. Recently, several of these debilitating disorders have been shown to be amenable for splice-correcting oligonucleotides (SCOs) that modify splicing patterns and restore the phenotype in experimental models. However, translational approaches are required to transform SCOs into usable drug products. In this study, we present a new cell-penetrating peptide, PepFect14 (PF14), which efficiently delivers SCOs to different cell models including HeLa pLuc705 and mdx mouse myotubes; a cell culture model of Duchenne's muscular dystrophy (DMD). Non-covalent PF14-SCO nanocomplexes induce splice-correction at rates higher than the commercially available lipid-based vector Lipofectamine 2000 (LF2000) and remain active in the presence of serum. Furthermore, we demonstrate the feasibility of incorporating this delivery system into solid formulations that could be suitable for several therapeutic applications. Solid dispersion technique is utilized and the formed solid formulations are as active as the freshly prepared nanocomplexes in solution even when stored at an elevated temperatures for several weeks. In contrast, LF2000 drastically loses activity after being subjected to same procedure. This shows that using PF14 is a very promising translational approach for the delivery of SCOs in different pharmaceutical forms.
Antibody response to immunization with ganglioside GD3 and GD3 congeners (lactones, amide and gangliosidol) in patients with malignant melanoma (1991)

GD3 is the ganglioside most abundantly expressed on the cell surface of human melanoma, and treatment with a murine MAb recognizing GD3 has induced major responses in a small proportion of patients with melanoma. We have therefore attempted to induce production of GD3 antibodies in melanoma patients by active immunization. We found, however, that vaccination with GD3-expressing melanoma cells or purified GD3 does not result in antibody production. We describe here attempts to overcome the poor immunogenicity of GD3 in patients with melanoma by chemical modification. GD3 lactones, GD3 amide and GD3 gangliosidol were synthesized, and the humoral immune response to these derivatives was analyzed. Immunization of melanoma patients with these GD3 derivatives resulted in production of IgM antibodies and, in the case of GD3 amide, also of IgG antibodies. The antibodies to the GD3 derivatives did not cross-react with GD3. This is in contrast to observations in the mouse, where GD3 lactone I induced antibodies that showed cross-reactivity with GD3. Thus, the human immune response was specifically directed toward the modified epitope, rather than to the native structure.
Trojan Microparticles for Drug Delivery (2012)

During the last decade, the US Food and Drug Administration (FDA) have regulated a wide range of products, (foods, cosmetics, drugs, devices, veterinary, and tobacco) which may utilize micro and nanotechnology or contain nanomaterials. Nanotechnology allows scientists to create, explore, and manipulate materials in nano-regime. Such materials have chemical, physical, and biological properties that are quite different from their bulk counterparts. For pharmaceutical applications and in order to improve their administration (oral, pulmonary and dermal), the nanocarriers can be spread into microparticles. These supramolecular associations can also modulate the kinetic releases of drugs entrapped in the nanoparticles. Different strategies to produce these hybrid particles and to optimize the release kinetics of encapsulated drugs are discussed in this review.
Tests for Linear Trends in Proportions and Frequencies (1955)

One frequently encounters data consisting of a series of proportions, occurring in groups which fall into some natural order. The question usually asked is then not so much whether the proportions differ significantly, but whether they show a significant trend, upwards or downwards, with the ordering of the groups, In the data shown in Table 1, for, instance, the usual test for a 2 X 3 contingency table yields a x2 equal to 7.89 on 2 degrees of freedom, corresponding to a probability of about 0.02. But this calculation takes no account of the fact that the carrier rate increases with the tonsil size, and it is reasonable to believe that a test specifically designed to detect a trend in the carrier rate as the tonsil size increases would show a much higher degree of significance.
Vertical Etching of Silicon at very High Aspect Ratios (1979)

This article reviews published data on the mechanical properties of additively manufactured metallic materials. The additive manufacturing techniques utilized to generate samples covered in this review include powder bed fusion (e.g., EBM, SLM, DMLS) and ...Read More