gebhart/patrepeval huggingface dataset:
Targeting Slit–Roundabout signaling inhibits tumor angiogenesis in chemical‐induced squamous cell carcinogenesis (2008)

Slit is a secreted protein known to function through the Roundabout (Robo) receptor as a repellent for axon guidance and neuronal migration, and as an inhibitor in leukocyte chemotaxis. We have previously shown that Slit2 is also secreted by a variety of human cancer cells whereby it acts as a chemoattractant to vascular endothelial cells for tumor angiogenesis. We used a blocking antibody to investigate the role of Slit-Robo signaling in tumor angiogenesis during oral carcinogenesis. In this report we undertook a multistage model of 7,12-dimethyl-1,2-benzanthracene-induced squamous cell carcinoma in the hamster buccal pouch. R5, a monoclonal antibody against the first immunoglobulin domain of Robo1, was used to study whether R5 blocks the Slit-Robo interaction and furthermore inhibits tumor angiogenesis and growth in our model. In addition, the expression of Slit2, von Willebrand factor, and vascular endothelial growth factor were examined using human tissue of oral cheek mucosa with oral squamous cell carcinoma. Our data showed that Slit2 was expressed minimally in normal and hyperplastic mucosa, moderately in dysplastic mucosa, and highly in neoplastic mucosa obtained from hamster buccal pouch. We also found that increased Slit2 expression was associated with higher tumor angiogenesis, as reflected by increased vascular endothelial growth factor expression and microvessel density. A similar Slit2 expression profile was found in human tissue. Importantly, interruption of the Slit2-Robo interaction using R5 inhibited tumor angiogenesis and growth in our in vivo model, which indicates that Slit2-mediated tumor angiogenesis is a critical process underlying the carcinogenesis of chemical-induced squamous cell carcinoma. Therefore, targeting Slit-Robo signaling may offer a novel antiangiogenesis approach for oral cancer therapy.
Post‐Condensation Modifications of the Passerini and Ugi Reactions (2005)

This chapter contains sections titled: Convertible Isocyanides I-MCR Post-condensation Reactions in Synthesis of Open-chain Products Passerini-3CR + O-Deacylation Passerini-3CR + N-Deprotection + O → N Acyl Migration Ugi-4CR + Oxidation Ugi-4CR + Hydrolysis Ugi-4CR in Peptide Synthesis I-MCR Post-condensation Reactions in the Synthesis of Heterocycles Three-, Four-, and Five-membered Rings and their Benzo-fused Derivatives Oxiranes and β-Lactams by Passerini-3CR + O- or N-alkylation β-Lactams and Succinimides by Ugi-4CR + C-Alkylation Furans, Pyrroles, and Indoles by Passerini-3CR or Ugi-4CR and Knoevenagel Condensation Butenolides by Passerini-3CR and the Horner–Emmons–Wadsworth Reaction Pyrroles and γ-Lactams by Ugi-4CR and Hydrolysis Indazolinones by Ugi-4CR with N-deprotection and Aromatic Nucleophilic Substitution Oxazole Derivatives and Imidazoles by Passerini-3CR or Ugi-4CR and Davidson Cyclization 2-Imidazolines, Imidazolidin-2-ones and Benzimidazoles by Ugi-4CR with N-Deprotection and Cyclization Spiroimidazolones and Spirothioimidohydantoins by Ugi-4CR and Further Transformations Six-membered Rings and Their Benzo-fused Systems Pyridine Derivatives by Ugi-4CR and Aldol-type Condensation Pyridazine Derivatives by Ugi-4CR and Knoevenagel Condensation Phthalazine Derivatives by Ugi-4CR with N-Deprotection and Cyclization Piperazines and Pyrazin-2-ones by Ugi-4CR and Cyclization Ketopiperazines, 2,5-Diketopiperazines and Quinoxalines by Ugi-4CR with N-Deprotection and Intramolecular Amide Bond Formation 2,5-Diketopiperazines and Morpholines from Bifunctional Ugi-4CR Reagents Seven-membered Rings and Their Benzo-fused Systems Azepines by Ugi-4CR and Ring-closing Metathesis 1,4-Benzodiazepine-5-ones by Ugi-4CR with N-Deprotection and Aromatic Nucleophilic Substitution 1,4-Benzodiazepine-2,5-diones by Ugi-4CR with Convertible Isocyanides and UDC Bicyclic Systems Carbapenems and Carbacephems by Ugi-4CR and Dieckmann Condensation Bycyclic Systems by Ugi-4CR and Cyclization Polycyclic and Macrocyclic Systems Polycyclic Orthoamides by Passerini-3CR Polycyclic Systems via I-MCR and Intramolecular Diels–Alder Cycloaddition Macrocycles by Passerini-3CR, Ugi-4CR and Ring-closing Metathesis Macrocycles by Ugi-4CR and Nucleophilic Aromatic Substitution
Altered Cro repressors from engineered mutagenesis of a synthetic cro gene. (1985)

A portion of the gene coding for the Cro repressor protein of bacteriophage lambda has been chemically synthesized, incorporating base pair changes that generate restriction endonuclease sites without altering the amino acid coding sequence. These restriction endonuclease sites were used to remove small segments of the synthetic cro gene and the segments were replaced with duplexes carrying desired mutations. Altered Cro proteins produced by mutants constructed in this manner were then assayed for binding to lambda operator OR3 in vivo. Mutations directed into the region of the cro gene encoding the alpha-3 helix produced altered Cro proteins with a range of affinities for operator DNA. These changes suggest which amino acids play an important role in Cro-OR3 complex formation.
A wireless implantable multichannel digital neural recording system for a micromachined sieve electrode (1998)

This paper reports the development of an implantable, fully integrated, multichannel peripheral neural recording system, which is powered and controlled using an RF telemetry link. The system allows recording of /spl plusmn/500 /spl mu/V neural signals from axons regenerated through a micromachined silicon sieve electrode. These signals are amplified using on-chip 100 Hz to 3.1 kHz bandlimited amplifiers, multiplexed, and digitized with a low-power (<2 mW), moderate speed (8 /spl mu/s/b) current-mode 8-b analog-to-digital converter (ADC). The digitized signal is transmitted to the outside world using a passive RF telemetry link. The circuit is implemented using a bipolar CMOS process. The signal processing CMOS circuitry dissipates only 10 mW of power from a 5-V supply while operating at 2 MHz and consumes 4/spl times/4 mm/sup 2/ of area. The overall circuit including the RF interface circuitry contains over 5000 transistors, dissipates 90 mW of power, and consumes 4/spl times/6 mm/sup 2/ of area.
[Radiation characteristics in a tropical seasonal rain forest canopy gap]. (2004)

Based on the observations in the radiation with different wavelengths in tropical seasonal rain forest canopy gap, interior of forest, and meteorological station in different seasons, the radiation characteristics of canopy gap were discussed. The results showed that the value of different wavelength radiation had the phenomenon of "suddenly emergent" at the center and north edge of canopy gap. Moreover, each radiation value reached the maximum rapidly, and then decreased quickly around the noon. The daily gross radiation of different wavelengths within the canopy gap was bigger than that in the interior of forest, but smaller than that at meteorological station. Compared to the north edge, the daily gross radiation in the center of the gap was bigger in dry-hot season, rain season and later rain season, but smaller in fog-cool season, which was influenced by dense fog, solar angle and azimuth. The total daily gross solar radiation at the center was the maximum when the solar angle was the biggest in rain season, higher in later rain season and dry-hot season, and was the minimum in fog-cool season. The ratios of infrared and visible light radiation to total solar radiation varied with the seasons at the center and north edge of the canopy gap, which fully indicated the environmental heterogeneity within the canopy gap. Compared with meteorological station and interior of forest, the ratios of infrared radiation to total solar radiation in the gap were bigger than those of meteorological station, but smaller than those of interior of forest, which were just contrary to the ratios of visible light to total solar radiation. In addition, the seasonal variation of the ratios of visible light to total solar radiation was higher than that of the ratios of infrared radiation to total solar radiation within the gap. Generally, canopy gap could increase infrared radiation and decrease visible light radiation in tropical seasonal rainforest.
Bioactive IL7-diphtheria fusion toxin secreted by mammalian cells (2005)

A number of targeted cytotoxic agents have been developed that selectively kill malignant or otherwise pathological cells. These engineered proteins consist of a potent cytotoxic element connected to a ligand domain that binds to specific molecules on the surface of the target cell. Several of these agents have shown promise in clinical trials and one is currently administered to patients. A significant technical obstacle that has impeded the development of some of these toxins is the difficulty of preparing certain recombinant proteins in properly folded forms. These fusion proteins have generally been produced in bacteria requiring them to be denatured and renatured in vitro. For some proteins this is an efficient process whereas for others it is not. We describe here a system to produce fusion toxins rapidly and efficiently by engineering mammalian cells to secrete them as properly folded molecules which can be purified in native form from cell culture medium. We have used this system to produce highly active preparations of DAB(389)-IL7, a molecule consisting of the catalytic and transmembrane domains of diphtheria toxin fused to interleukin 7. This system is generalizable and can be used to produce and evaluate rapidly fusion toxins incorporating novel or uncharacterized ligands.
Silicon on replacement insulator (SRI) floating body cell (FBC) memory (2010)

A 15-nm node floating body cell (FBC) memory was demonstrated utilizing silicon on replacement insulator (SRI) technology on bulk substrate. Highly selective SiGe etch and nano-scale anchors enabled the fabrication of silicon on thin replacement oxide of 12 nm. The memory characteristics show a memory signal of 7 μA and disturb retention time of 20 ms for a 51-nm gate length and 77-nm width device. This is the best FBC memory performance reported on bulk substrate.
S152 (CD27). A modulating disulfide-linked T cell activation antigen. (1988)

A large subset of normal resting peripheral blood T cells express a protein at low density defined by the murine mAb S152. Reactive T cells are present in both the CD4+ and CD8+ subpopulations. This determinant, however, is not expressed on growth factor-independent T cell lines. After activation of mononuclear cells by either Con A or PHA, greater than 80% of the cells stained at a mean fluorescence intensity that was more than six times that seen on resting cells. When PWM- or mixed lymphocyte reaction-activated cultures were studied, 7 to 22% of S152+ cells stained at high intensity whereas most cells stained at the baseline low intensity. The increased fraction of S152+ cells staining at high intensity after activation paralleled both the increased percentage of anti-Tac+ and 5E9+ cells and cellular proliferation measured by thymidine incorporation. Modulation of the S152 Ag was induced when either Con A- or PHA-activated mononuclear cells were placed into secondary cultures containing S152 mAb. Expression of the S152 Ag began to decrease after 2 h and reached a minimum after 6 h. Resting T cells, however, did not appear to modulate when cultured with S152 mAb. Immunoprecipitation and gel electrophoresis analysis revealed the S152 molecule to have a mobility of 120 kDa before reduction. After reduction the molecule was shown to be composed of two 55-kDa molecules with an isoelectric point of 5 to 6 indicating that the S152 Ag is a disulfide-linked homodimer. These studies confirm that the S152 mAb reacts with the newly defined CD27 molecule. The presence of the S152 Ag on resting and activated cells, its parallel increase with the Tac and 5E9 Ag, and its ability to modulate on activated cells suggest that this molecule may play a functional role during T cell activation.
Chemical processing on microchips for analysis, synthesis, and bioassay (2003)

This review describes our recent research on miniaturization of chemical systems. We have developed a miniaturization methodology based on pressure-driven multiphase laminar flow and a highly sensitive detection tool, the thermal lens microscope. Some representative applications of the methodology in the fields of analysis, synthesis, and bioassay are described.
Biology of Attenuated Modified Vaccinia Virus Ankara Recombinant Vector in Mice: Virus Fate and Activation of B- and T-Cell Immune Responses in Comparison with the Western Reserve Strain and Advantages as a Vaccine (2000)

The modified vaccinia virus Ankara (MVA) strain is a candidate vector for vaccination against pathogens and tumors, due to safety concerns and the proven ability of recombinants based on this vector to trigger protection against pathogens in animals. In this study we addressed the fate of the MVA vector in BALB/c mice after intraperitoneal inoculation in comparison with that of the replication-competent Western Reserve (WR) strain by measuring levels of expression of the reporter luciferase gene, the capability to infect target tissues from the site of inoculation, and the length of time of virus persistence. We evaluated the extent of humoral and cellular immune responses induced against the virus antigens and a recombinant product (beta-galactosidase). We found that MVA infects the same target tissues as the WR strain; surprisingly, within 6 h postinoculation the levels of expression of antigens were higher in tissues from MVA-infected mice than in tissues from mice infected with wild-type virus but at later times postinoculation were 2 to 4 log units higher in tissues from WR-infected mice. In spite of this, antibodies and cellular immune responses to viral vector antigens were considerably lower in MVA-inoculated mice than in WR virus-inoculated mice. In contrast, the cellular immune response to a foreign antigen expressed from MVA was similar to and even higher than that triggered by the recombinant WR virus. MVA elicited a Th1 type of immune response, and the main proinflammatory cytokines induced were interleukin-6 and tumor necrosis factor alpha. Our findings have defined the biological characteristics of MVA infection in tissues and the immune parameters activated in the course of virus infection. These results are of significance with respect to optimal use of MVA as a vaccine.
Effect of amiodarone and dronedarone administration in rats on thyroid hormone-dependent gene expression in different cardiac components (2007)

Taken together, our results indicate that AM and Dron have similar effects on the expression of TR isoforms in the RA, which could partly contribute to their ability to decrease heart rate. On the other hand, the more profound effect of AM appears on TR- and T3-dependent gene expression in the left ventricle suggests foetal reprogramming.
Nuclear magnetic resonance and optical spectroscopic studies of copolymers of polypeptides. II. Random copoly(benzyl‐L‐glutamate: Benzyl‐L‐aspartate) and (benzyl‐D‐glutamate: benzyl‐L‐aspartate) (1972)

Abstract High‐resolution NMR is used to study two series of benzyl‐ L ‐ or D ‐glutamate: benzyl‐ L ‐aspartate random copolymers. The helix sense of the L ‐aspartate residues determined from the αC H and N H chemical shifts agrees with that obtained from ORD. The stability of the helical copolymers to TFA addition shows a minimum at the composition of helix‐sense inversion for the L ‐glutamate: L ‐aspartate copolymers but no minimum for the lefthanded D ‐glutamate: L ‐aspartate series. The helix‐coil transition of the glutamate and aspartate residues in each polymer is compared. For the D ‐glutamate: L ‐aspartate series no differences are found, indicating random copolymerization. In the L ‐glutamate: L ‐aspartate series significant differences between the transition midpoints are interpreted as resulting from irregular distribution of component residues along the chain.
Displacement dewatering to maintain bulk (1991)

Lors du pressage humide conventionnel du papier, l'elimination d'eau est liee a la densification de la feuille. La desolidarisation partielle de ces deux phenomenes permettrait un meilleur controle des proprietes. C'est l'objectif d'une etude de la deshydratation par deplacement, dans laquelle une phase pressurisee d'air ou vapeur est utilisee pour chasser l'eau liquide du papier qui subit simultanement une pression mecanique. Ce procede combine un pressage humide modere avec un entrainement vapeur-liquide, ce qui permet d'accroitre et maintenir le gradient de pression hydraulique assurant la deshydratation. On presente des resultats experimentaux obtenus sur pilote.
Successful Immunization with a Single Injection of Non-integrating Lentiviral Vector (2007)

We evaluated the ability of an integrase (IN)-defective self-inactivating lentiviral vector (sinLV) for the delivery of human immunodeficiency virus-1 (HIV-1) envelope sequences in mice to elicit specific immune responses. BALB/c mice were immunized with a single intramuscular injection of the IN-defective sinLV expressing the codon optimized HIV-1(JR-FL) gp120 sequence, and results were compared with those for the IN-competent counterpart. The IN-defective sinLV elicited specific and long-lasting immune responses, as evaluated up to 90 days from the immunization by enzyme-linked immunosorbent spot (ELISPOT) and intracellular staining (ICS) for interferon-gamma (IFN-gamma) assays in both splenocytes and bone marrow (BM) cells, chromium release assay in splenocytes, and antibody detection in sera, without integration of the vector into the host genome. These data provide evidence that a single administration of an IN-defective sinLV elicits a significant immune response in the absence of vector integration and may be a safe and useful strategy for vaccine development.
Heregulin Reverses the Oligomerization of HER3 (2000)

We analyzed the propensity of the HER3 receptor and its extracellular domain (ECD) to undergo ligand-independent self-association. The HER3-ECD, purified from Drosophila S2 cells, binds the EGF-like domain of heregulin (hrg) with a K(d) of 1.9 nM as measured by surface plasmon resonance (SPR) studies. In a gel shift assay, the HER3-ECD self-associates into a uniform, slowly migrating species in a concentration-dependent manner, starting at concentrations of <10 nM. In contrast to the HER3-ECD, the ECD from the related HER2 receptor does not oligomerize under the same conditions. The direct interaction of HER3-ECDs was also demonstrated by pull-down assays and SPR measurements under physiological salt conditions. This self-association of the HER3-ECD was reversed by the addition of hrg but not by EGF. The apparent equilibrium dissociation constant for the HER3-ECD self-association is 15 nM, based on SPR measurements. In this analysis, hrg blocks HER3-ECD self-association, and the addition of hrg during the dissociation phase resulted in an accelerated off rate. This finding suggests that hrg can bind to and disrupt preexisting HER3-ECD oligomers. Full-length HER3 likewise exhibited self-association. Under conditions where co-immunoprecipitation and cross-linking of HER2 and HER3 were stimulated by hrg, HER3 self-association and cross-linking were disrupted by hrg. The implication is that the self-association of HER3-ECD favors the formation of catalytically inactive complexes of the HER3 receptor. Binding of hrg releases HER3 which may then form signaling-competent HER3-HER2 heterodimers.
Vehicles and ways for efficient nuclear transformation in plants (2010)

Transgenic science and technology are fundamental to the state-of-art plant molecular genetics and crop improvement. The new generation of technology endeavors to introduce genes 'stably' into 'site-specific' locations and in 'single copy' without the integration of extraneous vector 'backbone' sequences or 'selectable markers'. Numerous plant transformation technologies have developed with the aim of achieving these objectives. Here we discuss some of these technologies, which can push the development of 'better transgenic plants with desirable characters only'.
Influence of angiotensin converting enzyme inhibition on pump function and cardiac contractility in patients with chronic congestive heart failure. (1991)

Eleven patients with coronary artery disease and chronic heart failure were studied before and three months after the angiotensin converting enzyme inhibitor enalapril was added to their frusemide medication. The following were measured: left ventricular pressure and volume with transient occlusion of the inferior vena cava, radionuclide angiography, and hormone concentrations in plasma. As in other reported studies, the clinical condition of the patients improved and their exercise tolerance increased moderately. Addition of enalapril reduced end diastolic and systolic pressure, reduced ventricular volume, and concomitantly increased the ejection fraction. The end systolic pressure-volume relation shifted to the left as it did in a similar animal study. In the animal study unloading by a vasodilator did not induce a leftward shift, so it can be inferred that in the present study unloading combined with a decrease in the angiotensin concentration was instrumental in remodelling the heart. Though unloading was expected to have a beneficial effect on the oxygen supply/demand ratio of the heart, the patients still showed the same drop in the ejection fraction during exercise as they did before treatment with enalapril, and early diastolic filling did not improve. Normally, regression of cardiac dilatation is only found if pump function improves; the present study showed that unloading in combination with angiotensin converting enzyme inhibition reshapes the ventricle without improving intrinsic pump function.
Targeting RNA with Small-Molecule Drugs:  Therapeutic Promise and Chemical Challenges (2001)

Researchers' increasing awareness of the essential role played by RNA in many biological processes and in the progression of disease makes the discovery of new RNA targets an emerging field in drug discovery. Since most existing pharmacologically active compounds bind proteins, RNA provides nearly untapped opportunities for pharmacological development. The elucidation of the structure of the ribosome and other cellular and viral RNA motifs creates the opportunity for discovering new drug-like compounds that inhibit RNA function. However, further advances in understanding the chemistry and structure of RNA recognition are needed before these promises are fulfilled.
TLR4 antagonists for endotoxemia and beyond. (2005)

Toll-like receptor 4 (TLR4) controls the major responding signaling system that detects the presence of Gram-negative infectious pathogens, by responding to endotoxin from their outer membrane. Normally, TLR-bearing cells signal the immune system to mount a pro-inflammatory, antibacterial response and resolve infection. However, TLR4 can also respond to a variety of 'endogenous' ligands, such as fibronectin and heat shock proteins. Overstimulation or continued stimulation of TLR4 by any ligand can result in a systemic inflammatory response, progressing to hypotension, shock, organ failure and even death. This review discusses current, preclinical and clinical research regarding eritoran (E-5564), an analog of the non-toxic lipid A from Rhodobacter sphaeroides, as well as other antagonists of TLR4 in a variety of diseases.