gebhart/patrepeval huggingface dataset:
Minimum Requirements for Efficient Transduction of Dividing and Nondividing Cells by Feline Immunodeficiency Virus Vectors (1999)

The development of gene delivery vectors based on feline immunodeficiency virus (FIV) is an attractive alternative to vectors based on primate sources for the delivery of genes into humans. To investigate the requirements for efficient transduction of dividing and nondividing cells by vector particles based on FIV, a series of packaging and vector constructs was generated for which viral gene expression was minimized and from which unnecessary cis-acting sequences were deleted. Pseudotyped vector particles produced in 293T cells were used to transduce various target cells, including contact-inhibited human skin fibroblasts and growth-arrested HT1080 cells. FIV vectors in which the U3 promoter was replaced with the cytomegalovirus promoter gave rise to over 50-fold-higher titers than FIV vectors containing the complete FIV 5' long terminal repeat (LTR). Comparison of the transduction efficiencies of vectors containing different portions of the FIV Gag coding region indicates that at least a functional part of the FIV packaging signal (Psi) is located within an area which includes the 5' LTR and the first 350 bp of gag. Transduction efficiencies of vectors prepared without FIV vif and orf2 accessory gene expression did not differ substantially from those of vectors prepared with accessory gene expression in either dividing or nondividing cells. The requirement for FIV rev-RRE was, however, demonstrated by the inefficient production of vector particles in the absence of rev expression. Together, these results demonstrate the efficient transduction of nondividing cells in vitro by a multiply attenuated FIV vector and contribute to an understanding of the minimum requirements for efficient vector production and infectivity. In addition, we describe the ability of an FIV vector to deliver genes in vivo into hamster muscle tissue.
Purinergic Signalling—An Overview (2006)

A brief account of the early history of extracellular signalling by ATP will be followed by a summary of the current subclassification of receptors for purines and pyrimidines. On the basis of cloning, transduction mechanisms and pharmacology, the P1 (adenosine) receptor family has 4 subtypes, while the P2 (ATP, ADP and UTP) receptor family has been divided into P2X ionotropic receptors (7 subtypes) and P2Y metabotropic G protein-coupled receptors (8 subtypes). The distribution of purinoceptors in both neuronal and non-neuronal cells and the physiology and pathophysiology of purinergic signalling will be reviewed. Examples of fast purinergic signalling include cotransmission and neuromodulation, exocrine and endocrine secretion, platelet aggregation, vascular endothelial cell-mediated vasodilatation and nociceptive mechanosensory transduction. Examples of slow (trophic) purinergic signalling include cell proliferation, differentiation and apoptosis in embryological development, neural regeneration, bone resorption, cell turnover of epithelial cells in skin and visceral organs, inflammation, wound healing and cancer. Finally the purinoceptor subtypes expressed on astrocytes, oligodendrocytes, Schwann cells, microglia, Müller cells and enteric glial cells will be summarized as well as evidence for non-lytic release of ATP from glial cells.
Characterization of the membrane-bound and a soluble form of human IL-4 receptor α produced by alternative splicing (1999)

IL-4 plays a major role in IgE production. Its signal is conferred to effector cells through binding to the alpha chain of the membrane-bound human IL-4 receptor (huIL-4Ralpha). Here we present the genomic structure and organization of huIL-4Ralpha. The promotor region shows binding sites for several transcription factors involved in inflammatory processes. HuIL-4Ralpha has been shown to be organized differently to that of mouse IL-4Ralpha. A soluble form of huIL-4Ralpha is produced by alternative splicing of the huIL-4Ralpha gene (shuIL-4Ralpha/splice). Expression of the corresponding mRNA coding for the extracellular part of the receptor and an additional three amino acids is also shown. A second form of huIL-4Ralpha, i.e. shuIL-4Ralpha/prot, is produced by limited proteolysis of the receptor (shedding) and is already known. These results reveal a complex pattern for the regulation of the IL-4 pathway at the receptor level. The patterns of expression of all three receptor proteins as well as their individual meaning in the context of inflammation still have to be elucidated.
Persistence of Antibodies to Pneumococcal Capsular Polysaccharide Vaccine in the Elderly (1997)

Persistence of antibodies to 23-valent pneumococcal vaccine was assessed among 62 subjects aged 65-88 years. IgG antibodies were measured by standardized EIA to serotypes 4, 6B, 9V, 14, 19F, and 23F before and 1 month, 1 year, and 3 years after vaccination. After satisfactory antibody responses (fold increases from 2.6 to 5.3), 3-year geometric mean concentrations (GMCs) had waned to close (for types 4, 9V, and 23F) or similar (for types 6B and 19F) to their prevaccination values. Type 14 was exceptional: 1-month GMC was 7.7-fold and 3-year GMC was 3.0-fold in comparison to the prevaccination GMC. Antibody concentrations decreased at an equal rate irrespective of serotype and age or sex of the vaccinee. The major factor predicting the persistence of antibodies above the prevaccination level was the magnitude of the original antibody response. Present results suggest that pneumococcal revaccination of the elderly may be needed as early as 3-4 years after the initial vaccination.
Assemblies of conjugated polymers: Intermolecular and intramolecular effects on the photophysical properties of conjugated polymers (2002)

Abstract Conjugated polymers are emerging materials for electronic applications due to the tunability of their properties through variation of their chemical structure. Their applications, which currently include light-emitting diodes (LEDs), field effect transistors (FETs), plastic lasers, batteries, and sensors, are expanding to many new areas. The two critical parameters that determine the function of conjugated polymer-based devices are chemical structure and nanostructure of a conjugated polymer in the solid state. While the physical properties of isolated polymers are primarily controlled by their chemical structure, these properties are drastically altered in the solid state due to electronic coupling between polymer chains as determined by their interpolymer packing and conformation. However, the development of effective and precise methods for controlling the nanostructure of polymers in the solid state has been limited because polymers often fail to assemble into organized structures due to their amorphous character and large molecular weight. In this review, recent developments of organizing methods of conjugated polymers and the conformation and interpolymer interaction effects on the photophysical properties of conjugated polymers are summarized.
MgcRacGAP Is Involved in Cytokinesis through Associating with Mitotic Spindle and Midbody (2001)

We have recently cloned a cDNA for a full-length form of MgcRacGAP. Here we show using anti-MgcRacGAP antibodies that, unlike other known GAPs for Rho family, MgcRacGAP localized to the nucleus in interphase, accumulated to the mitotic spindle in metaphase, and was condensed in the midbody during cytokinesis. Overexpression of an N-terminal deletion mutant resulted in the production of multinucleated cells in HeLa cells. This mutant lost the ability to localize in the mitotic spindle and midbody. MgcRacGAP was also found to bind alpha-, beta-, and gamma-tubulins through its N-terminal myosin-like domain. These results indicate that MgcRacGAP dynamically moves during cell cycle progression probably through binding to tubulins and plays critical roles in cytokinesis. Furthermore, using a GAP-inactive mutant, we have shown that the GAP activity of MgcRacGAP is required for cytokinesis, suggesting that inactivation of the Rho family of GTPases may be required for normal progression of cytokinesis.
Heterotypic passive protection induced by synthetic peptides corresponding to VP7 and VP4 of bovine rotavirus (1991)

We have evaluated the potential of two peptides derived from highly conserved regions of rotavirus outer capsid proteins (VP7 and VP4) to act as a rotavirus vaccine. The capacity of peptides coupled to rotavirus VP6 spherical particles to provide passive protection in a murine model was compared with the protection induced by peptide-keyhole limpet hemocyanin (KLH) conjugates. Female mice were immunized a total of three times before and during pregnancy. Suckling mouse pups were challenged at 7 days of age with either homologous or heterologous rotavirus serotypes. The efficacy of vaccination was determined by analyzing the clinical symptoms and measuring xylose adsorption in the intestine. In this model the VP4 peptide-VP6 conjugate provided protection equal to that obtained using bovine rotavirus (BRV) as the immunogen. The VP7 peptide-VP6 conjugate provided slightly less protection than the VP4 peptide-VP6 conjugate. A mixture of the VP4 peptide-VP6 and VP7 peptide-VP6 conjugates provided better heterologous protection than immunization with BRV. In contrast, KLH-conjugated peptides provided only partial protection. The significance of a synthetic-peptide-based rotavirus vaccine in the prevention of rotavirus infections is discussed.
4-Anilino-6,7-dialkoxyquinoline-3-carbonitrile Inhibitors of Epidermal Growth Factor Receptor Kinase and Their Bioisosteric Relationship to the 4-Anilino-6,7-dialkoxyquinazoline Inhibitors (2000)

The synthesis and SAR of a series of 4-anilino-6, 7-dialkoxyquinoline-3-carbonitrile inhibitors of epidermal growth factor receptor (EGF-R) kinase are described. Condensation of 3, 4-dialkoxyanilines with ethyl (ethoxymethylene)cyanoacetate followed by thermal cyclization gave, regiospecifically, 6,7-dialkoxy-4-oxo-1, 4-dihydroquinoline-3-carbonitriles. Chlorination (POCl(3)) followed by the reaction with substituted anilines furnished the 4-anilino-6, 7-dialkoxyquinoline-3-carbonitrile inhibitors of EGF-R kinase. An alternate synthesis of these compounds starts with a methyl 3, 4-dialkoxybenzoate. Nitration followed by reduction (Fe, NH(4)Cl, MeOH-H(2)O) gave a methyl 2-amino-4,5-dialkoxybenzoate. Amidine formation using DMF-acetal followed by cyclization using LiCH(2)CN furnished a 6,7-dialkoxy-4-oxo-1,4-dihydroquinoline-3-carbonitrile, which was transformed as before. Compounds containing acid, ester, amide, carbinol, and aldehyde groups at the 3-position of the quinoline ring were also prepared for comparison, as were several 1-anilino-6,7-dimethoxyisoquinoline-4-carbonitriles. The compounds were evaluated for their ability to inhibit the autophosphorylation of the catalytic domain of EGF-R. The SAR of these inhibitors with respect to the nature of the 6,7-alkoxy groups, the aniline substituents, and the substituent at the 3-position was studied. The compounds were further evaluated for their ability to inhibit the growth of cell lines that overexpress EGF-R or HER-2. It was found that 4-anilinoquinoline-3-carbonitriles are effective inhibitors of EGF-R kinase with activity comparable to the 4-anilinoquinazoline-based inhibitors. A new homology model of EGF-R kinase was constructed based on the X-ray structures of Hck and FGF receptor-1 kinase. The model suggests that with the quinazoline-based inhibitors, the N3 atom is hydrogen-bonded to a water molecule which, in turn, interacts with Thr 830. It is proposed that the quinoline-3-carbonitriles bind in a similar manner where the water molecule is displaced by the cyano group which interacts with the same Thr residue.
Simplified microwave measurement of uv photoplasmas (1980)

A simplified technique for electron density measurements in laser-type uv photoplasmas is described. This modified microwave transmission approach requires a minimum of test equipment and provides all data necessary for a full time analysis of the photoplasma from only a single photographically recorded pulsed measurement. Accuracy is comparable with that of conventional interferometers but speed and simplicity are much improved.
THE CAR AS A MOBILE-MEDIA PLATFORM (1998)

Vehicle and computer technologies are merging as the automotive industry scrambles to provide consumers with PC functionality in their vehicles. The article focuses on the Auto PC which will bring the benefits of interactive speech technology, connectivity, information on demand, and enhanced entertainment to the automobile.
Epidermal CCR6+ γδ T Cells Are Major Producers of IL-22 and IL-17 in a Murine Model of Psoriasiform Dermatitis (2011)

Cytokine components of Th17 pathway play vital roles in human psoriasis. Although much is known about TCR αβ T cells in psoriasis, the role of unconventional T cells, including γδ T cells, is unclear. In this study, using an IL-23 skin injection model of psoriasiform dermatitis in mice, we demonstrate that IL-22, IL-17A, and the IL-23R were highly enriched in a population of CCR6(+), TCR γδ-low expressing (GDL) T cells that accumulated in the epidermis after IL-23 injections. GDL cells were distinct from resident TCR γδ-high, Vγ3(+),CCR6(-) T cells in the epidermis that did not change appreciably in numbers following IL-23 injection. Large numbers of CCR6(+) cells were detected at or above the level of the epidermal basement membrane by confocal microscopy 5 d after repeated IL-23 injections at the same time GDL cells increased in numbers in the epidermis. TCR δ-deficient mice (lacking γδ T cells) exhibited decreased ear swelling and downregulated expression of IL-22 and IL-17A in the epidermis following IL-23 injection. Our data suggest that a subset of γδ T cells play a critical role in IL-23-mediated psoriasiform dermatitis.
Rate control for streaming video over wireless (2005)

Rate control is an important issue in video streaming applications for both wired and wireless networks. A widely accepted rate control method in wired networks is TCP-friendly rate control (TFRC) (Floyd, 2000). It is equation-based rate control in which the TCP-friendly rate is determined as a function of packet loss rate, round-trip time, and packet size. TFRC assumes that packet loss in wired networks is primarily due to congestion, and as such is not applicable to wireless networks in which the main cause of packet loss is at the physical layer. In this article we review existing approaches to solve this problem. Then we propose multiple TFRC connections as an end-to-end rate control solution for wireless video streaming. We show that this approach not only avoids modifications to the network infrastructure or network protocol, but also results in full utilization of the wireless channel. NS-2 simulations, actual experiments over a 1/spl times/RTT CDMA wireless data network, and video streaming simulations using traces from the actual experiments are carried out to characterize the performance and show the efficiency of our proposed approach.
Insulin Regulates the Serum Levels of Low Molecular Weight Insulin-Like Growth Factor-Binding Protein* (1988)

The serum levels of 34K insulin-like growth factor (IGF)-binding protein were measured by RIA in 88 type 1 diabetic patients, 9 patients with type 2 diabetes, 7 patients with insulinoma, 19 normal subjects (all after an overnight fast), and 82 normal subjects after a breakfast meal. In addition, the effect of 2- to 3-h euglycemic steady state hyperinsulinemia on serum IGF-binding protein and IGF-1 levels was studied in some subjects in each of the fasted groups. Compared with normal subjects, the mean serum IGF-binding protein levels were 4-fold (P less than 0.001) higher in type I diabetic patients treated with conventional insulin injections, 2.5-fold (P less than 0.001) higher in those treated with continuous sc insulin infusion, and 2-fold (P less than 0.05) higher in patients with type 2 diabetes. In the patients with insulinoma, the mean IGF-binding protein level was 63% below normal (P less than 0.001), and it normalized after removal of the tumor. There was a slight negative correlation between the IGF-binding protein level and insulin dose in the diabetic patients (r = -0.22; P less than 0.05). In normal subjects, serum insulin concentrations were 2-fold higher (P less than 0.001) and the IGF-binding protein level was 29% lower after a meal (P less than 0.05) than in the fasting state. Serum IGF-I concentrations were virtually identical in the type 1 and 2 diabetic patients, insulinoma patients, and normal subjects. During steady state euglycemic hyperinsulinemia, the IGF-binding protein level fell by 40-70% in each group (P less than 0.001), whereas the IGF-I level declined (P less than 0.05) in the type 2 diabetic patients only. The decline of binding protein was closely related to the baseline level (r = 0.94; P less than 0.001). No correlation was found between serum IGF-I and binding protein levels in any group. In conclusion, 1) serum 34K IGF-binding protein levels are elevated in type 1 and 2 diabetic patients and decreased in patients with insulinoma; 2) the serum binding protein, but not IGF-I concentration is decreased by acute hyperinsulinemia; and 3) these data suggest that the serum insulin concentration plays a role in regulation of the serum 34K IGF-binding protein concentration.
Pulsed-Field Ablation in Ventricular Myocardium Using a Focal Catheter (2021)

[Figure: see text].
An adaptive rate algorithm for FH/BFSK signaling (1988)

The authors present a feedback rate control technique for FH/BFSK (frequency-hop/binary phase-shift keying) signaling over a jammed flat-flat fading channel. An algorithm is developed for tracking the channel fade level, dynamically adjusting the transmitted data rate, and mitigating the effects of partial-band noise jamming. Simulation studies indicate that improvements of about 2 dB can be obtained in the coded performance with the proposed adaptive rate system, when compared to a nonadaptive system operating over the same communication medium with identical power and bandwidth resources.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Physiological Basis for Novel Drug Therapies Used to Treat the Inflammatory Bowel Diseases I. Immunology and therapeutic potential of antiadhesion molecule therapy in inflammatory bowel disease (2005)

Adhesion molecules regulate the influx of leukocytes in normal and inflamed gut. They are also involved in local lymphocyte stimulation and antigen presentation within the intestinal mucosa. In intestinal inflammation, many adhesion molecules are upregulated, but alpha4-integrins most likely hold a key position in directing leukocytes into the inflamed bowel wall. Therapeutic compounds directed against trafficking of leukocytes have been designed and are being developed as a novel class of drugs in the treatment of Crohn's disease and ulcerative colitis. This review deals with the immunological aspects of leukocyte trafficking focused on gut homing of T cells. Second, the changes in adhesion molecules and T cell trafficking during intestinal inflammation are discussed. Finally, we review the clinical data that have been gathered with respect to the therapeutic potential and the safety of antiadhesion molecule treatment. Antegren, or natalizumab, a humanized anti-alpha4 integrin IgG4 antibody, has been most extensively evaluated and may be close to registration. A more specific humanized alpha4beta7-integrin MLN-02 has shown preliminary clinical efficacy in ulcerative colitis, and both antergren and MLN-02 appear to be very safe. Trials with the anti-ICAM-1 antisense oligonucleotide ISIS-2302 in steroid refractory Crohn's disease have provided conflicting efficacy data. In the near future, some of these novel biological agents may prove valuable therapeutic tools in the management of refractory inflammatory bowel disease, although it is too early to define the patient population that will benefit most from these agents.
Intrinsic potencies of novel thiol ester corticosteroids RS-85095 and RS-21314 as compared with clobetasol 17-propionate and fluocinonide (1989)

• The intrinsic potencies of two novel topical thiol ester corticosteroids, RS-85095 and RS-21314, were compared with the high potency corticosteroids clobetasol 17-propionate and fluocinonide, using human vasoconstriction assays. In these assays, four or five concentrations (0.03 to 3 mg/L) of the corticosteroids in 95% ethanol (alcohol,<i>USP</i>) were applied to predetermined sites on the forearm of volunteers and were occluded following evaporation of the alcohol. The responses were scored in terms of the presence or absence of vasoconstriction and the degree of vasoconstrictive intensity. No statistically significant difference was found in the intrinsic potencies of RS-85095, RS-21314, and clobetasol 17-propionate, and all three corticosteroids were significantly more potent than fluocinonide. (<i>Arch Dermatol.</i>1989;125:1662-1665)
Glycosynthases Enable a Highly Efficient Chemoenzymatic Synthesis of N-Glycoproteins Carrying Intact Natural N-Glycans (2009)

Homogeneous N-glycoproteins carrying defined natural N-glycans are essential for detailed structural and functional studies. The transglycosylation activity of the endo-beta-N-acetylglucosaminidases from Arthrobacter protophormiae (Endo-A) and Mucor hiemalis (Endo-M) holds great potential for glycoprotein synthesis, but the wild-type enzymes are not practical for making glycoproteins carrying native N-glycans because of their predominant activity for product hydrolysis. In this article, we report studies of two endoglycosidase-based glycosynthases, EndoM-N175A and EndoA-N171A, and their usefulness in constructing homogeneous N-glycoproteins carrying natural N-glycans. The oligosaccharide oxazoline corresponding to the biantennary complex-type N-glycan was synthesized and tested with the two glycosynthases. The EndoM-N175A mutant was able to efficiently transfer the complex-type glycan oxazoline to a GlcNAc peptide and GlcNAc-containing ribonuclease to form the corresponding homogeneous glycopeptide/glycoprotein. The EndoA-N171A mutant did not recognize the complex-type N-glycan oxazoline but could efficiently use the high-mannose-type glycan oxazoline for transglycosylation. These mutants possess the transglycosylation activity but lack the hydrolytic activity toward the product. Kinetic studies revealed that the dramatically enhanced synthetic efficiency of the EndoA-N171A mutant was due to the significantly reduced hydrolytic activity toward both the Man(9)GlcNAc oxazoline and the product as well as to its enhanced activity for transglycosylation. Thus, the two mutants described here represent the first endoglycosidase-based glycosynthases enabling a highly efficient synthesis of homogeneous natural N-glycoproteins.
The vector field histogram-fast obstacle avoidance for mobile robots (1991)

A real-time obstacle avoidance method for mobile robots which has been developed and implemented is described. This method, named the vector field histogram (VFH), permits the detection of unknown obstacles and avoids collisions while simultaneously steering the mobile robot toward the target. The VFH method uses a two-dimensional Cartesian histogram grid as a world model. This world model is updated continuously with range data sampled by onboard range sensors. The VFH method subsequently uses a two-stage data-reduction process to compute the desired control commands for the vehicle. Experimental results from a mobile robot traversing densely cluttered obstacle courses in smooth and continuous motion and at an average speed of 0.6-0.7 m/s are shown. A comparison of the VFN method to earlier methods is given.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>