gebhart/patrepeval huggingface dataset:
Novel Peptide Conjugates for Tumor-Specific Chemotherapy (2001)

One of the major problems in cancer chemotherapy are the severe side effects that limit the dose of the anticancer drugs because of their unselectivity for tumor versus normal cells. In the present work, we show that coupling of anthracyclines to peptides is a promising approach to obtain selectivity. The peptide-drug conjugate was designed to bind to specific receptors expressed on the tumor cells with subsequent internalization of the ligand-receptor complex. Neuropeptide Y (NPY), a 36-amino acid peptide of the pancreatic polypeptide family, was chosen as model peptide because NPY receptors are overexpressed in a number of neuroblastoma tumors and the thereof derived cell lines. Daunorubicin and doxorubicin, two widely used antineoplastic agents in tumor therapy, were covalently linked to NPY via two spacers that differ in stability: an acid-sensitive hydrazone bond at the 13-keto position of daunorubicin and a stable amide bond at the 3'-amino position of daunorubicin and doxorubicin. Receptor binding of these three conjugates ([C(15)]-NPY-Dauno-HYD, [C(15)]-NPY-Dauno-MBS, and [C(15)]-NPY-Doxo-MBS) was determined at the human neuroblastoma cell line SK-N-MC, which selectively expresses the NPY Y(1) receptor subtype, and cytotoxic activity was evaluated using a XTT-based colorimetric cellular cytotoxicity assay. The different conjugates were able to bind to the receptor with affinities ranging from 25 to 51 nM, but only the compound containing the acid-sensitive bond ([C(15)]-NPY-Dauno-HYD) showed cytotoxic activity comparable to the free daunorubicin. This cytotoxicity is Y(1) receptor-mediated as shown in blocking studies with BIBP 3226, because tumor cells that do not express NPY receptors were sensitive to free daunorubicin, but not to the peptide-drug conjugate. The intracellular distribution was investigated by confocal laser scanning microscopy. We found evidence that the active conjugate [C(15)]-NPY-Dauno-HYD releases daunorubicin, which is localized close to the nucleus, whereas the inactive conjugate [C(15)]-NPY-Dauno-MBS is distributed distantly from the nucleus and does not seem to release the drug within the cell.
Expression of Acid Invertase Gene Controls Sugar Composition in Tomato (Lycopersicon) Fruit (1993)

A wild tomato species, Lycopersicon chmielewskii, accumulates high levels of soluble sugar in mature fruit and, unlike the domesticated tomato species, Lycopersicon esculentum, accumulates sucrose rather than glucose and fructose. Genetic and biochemical analyses of progeny resulting from a cross of L. chmielewskii with L. esculentum have previously indicated that the trait of sucrose accumulation is controlled by a single recessive gene and is associated with low levels of acid invertase protein in the developing fruit. Analysis of progeny from the BC2F3 generation from the L. esculentum x L. chmielewskii cross revealed that sucrose-accumulating fruit accumulate sugar in two phases corresponding to fruit expansion and fruit maturation and that the majority of the sucrose was stored in the latter phase after the fruit had reached maximum size. The only significant enzymic difference between the sucrose-accumulating and hexose-accumulating fruit was the lack of acid invertase activity in sucrose-accumulating fruit. Sucrose phosphate synthase activity did not increase in the sucrose-accumulating fruit during late development when the rate of sucrose accumulation increased. The lack of acid invertase activity in sucrose-accumulating fruit was correlated with inheritance of the L. chmielewskii acid invertase gene and the absence of acid invertase mRNA in developing fruit. This suggests that the L.chmielewskii invertase gene is transcriptionally silent in fruit and that this is the basis for sucrose accumulation in progeny derived from the interspecific cross of L. esculentum and L. chmielewskii.
LEC/chTNT-3 Fusion Protein for the Immunotherapy of Experimental Solid Tumors (2003)

The human chemokine liver-expression chemokine (LEC) was originally found in an expressed sequence tag library, and later the LEC gene was located to chromosome 17q in the ML chemokine gene cluster. LEC has been shown to chemoattract monocytes, lymphocytes, and polymorphonuclear leukocytes (PMNs) by its binding to CCR1 and CCR8 chemokine receptors. Because of its potency as a chemoattractant for immune cells, LEC was used to genetically engineer a fusion protein with chTNT-3, a monoclonal antibody previously shown to target tumors by binding to DNA exposed in necrotic zones. Because the N-terminus of chemokines is important for their activity, the C-terminus of LEC was genetically linked to the chTNT-3 heavy chain variable region and, along with the light chain gene, cotransfected into NSO murine myeloma cells using the glutamine synthetase gene amplification system. The expressed LEC/chTNT-3 fusion protein was purified by tandem protein-A affinity and ion-exchange chromatography and chemotaxis and binding assays confirmed the bioactivity of the purified fusion protein. Pharmacokinetic and biodistribution studies in vivo showed that LEC/chTNT-3 had a biologic half-life of 3 hours and had good uptake in tumor (2.4% injected dose/g), which remained stable at 12 and 24 hours postinjection. Immunotherapy studies performed in three solid tumor models of the BALB/c mouse showed between 37% and 55% tumor reduction at 19 days post-implantation. Immunohistochemical studies using tumor sections obtained at different time points after the administration of control chTNT-3 and LEC/chTNT-3 showed heavy infiltration of CD4+ and CD8+ T cells, PMNs, B cells, and CD11c+CD11b+ dendritic cells in the LEC/chTNT-3 treated groups. The results of these studies demonstrate that this novel fusion protein has potent antitumor activity that is associated with the infiltration of different subpopulations of immune cells. The targeting of LEC to necrotic areas of tumors where the release of tumor antigens is prevalent may be a new approach for the immunotherapy of solid tumors.
Acquisition of Lymphokine-Producing Phenotype by CD4+ T Cells (1994)

Naive CD4+ T cells when stimulated produce IL-2 as their major lymphokine. Upon priming, these cells develop into cells that produce either IFN gamma, TNF beta, and IL-2 or IL-4 and its congeners. The former cells are designated TH1-like, and the latter TH2-like. Here we review the regulation of the differentiation of naive CD4 cells into IFN gamma- or IL-4-producers. The dominant factors that determine such differentiation are lymphokines and other cytokines. IL-2 itself appears to be required for naive cells to develop into TH1- or TH2-like cells but is not deterministic of their differentiation fate. If IL-4 is also present during the priming period, the resultant CD4+ T cells produce IL-4 upon restimulation; the development of IFN gamma-producing cells is strikingly inhibited by IL-4. In the absence of IL-4, priming for IFN gamma-production occurs, but this is markedly enhanced by IL-12. The role of IFN gamma in enhancing priming for IFN gamma-production is not fully resolved. In some in vitro systems, it appears to act together with IL-12 to enhance such production. Anti-IFN gamma diminishes priming for IFN gamma production in vivo. Lymphokines also exert a "cross-regulatory" or inhibitory effect. As noted above, IL-4 strikingly diminishes priming for IFN gamma production, although this inhibitory effect is blunted in the presence of IL-12. IFN gamma similarly diminishes priming for IL-4 production; this effect is principally observed when low concentrations of IL-4 are used in the priming culture. Although other factors may play a role in the determination of lymphokine-producing phenotype, such as antigen dose, type of antigen-presenting cell, and expression of accessory molecules and hormones, these effects appear to be secondary to the dominant role of the lymphokines and cytokines.
Update on Clostridium difficile-induced colitis, part 2 (1994)

Clostridium difficile is a nosocomial pathogen able to survive unfavorable environments by sporulation; when conditions advantageous for rapid growth appear, the vegetative form is regenerated. Lack of conscientious hand washing and failure of health care providers to use disposable gloves facilitate transmission within institutions. Exposure to certain antimicrobials expedites C. difficile overgrowth within the colon by altering the composition of the normal gut microflora. Antineoplastic agents may also precipitate CDIC. The characteristics of the colonizing strain, the properties of the inciting drug, and individual host factors collectively seem to govern the expression of the disorder. Clinical presentations range from self-limiting diarrhea to severe diarrhea accompanied by abdominal pain, fever, and leukocytosis to potentially life-threatening PMC. A preponderance of data supports the interpretation that oral metronidazole and oral vancomycin are therapeutically equivalent for the treatment of all but the most severe cases of CDIC. Whether the two drugs are equivalent in severe CDIC is controversial and will probably remain so in the absence of a well-designed trial to expand on the findings of the study by Teasley et al. Because of the cost difference and therapeutic equivalence, oral metronidazole should be the preferred routine treatment for CDIC; oral vancomycin should be reserved for severe cases and cases that fail to respond to at least six days of oral metronidazole therapy. Another important argument, albeit a hypothetical one, for limiting institutional use of oral vancomycin is to minimize selective environmental pressure for the emergence and dissemination of vancomycin-resistant enterococci. An epidemic outbreak of CDIC caused by clindamycin-resistant C. difficile in an institution where clindamycin use was extremely high illustrates the possible consequences of such selective pressure. Oral metronidazole 250 mg four times daily will usually provide a satisfactory response, but clinicians may wish to consider increasing the total daily dose for some patients who have symptoms like fever and leukocytosis. For oral vancomycin, 125 mg four times daily is sufficient in virtually all circumstances. Ten days of therapy is usually adequate for either drug. CDIC in a patient unable to take medications orally presents a bit of a therapeutic dilemma. Two approaches that appear effective are rectal administration of vancomycin and intravenous administration of metronidazole, although intravenous metronidazole can fail to work, possibly because the colonic concentrations achieved are inadequate. Clinicians may wish to consider a total daily dose of intravenous metronidazole that is at the upper end of the adult dosage range, if this is feasible.(ABSTRACT TRUNCATED AT 400 WORDS)
A Drosophila Mechanosensory Transduction Channel (2000)

Mechanosensory transduction underlies a wide range of senses, including proprioception, touch, balance, and hearing. The pivotal element of these senses is a mechanically gated ion channel that transduces sound, pressure, or movement into changes in excitability of specialized sensory cells. Despite the prevalence of mechanosensory systems, little is known about the molecular nature of the transduction channels. To identify such a channel, we analyzed Drosophila melanogaster mechanoreceptive mutants for defects in mechanosensory physiology. Loss-of-function mutations in the no mechanoreceptor potential C (nompC) gene virtually abolished mechanosensory signaling. nompC encodes a new ion channel that is essential for mechanosensory transduction. As expected for a transduction channel, D. melanogaster NOMPC and a Caenorhabditis elegans homolog were selectively expressed in mechanosensory organs.
REDN: A Recursive Encoder-Decoder Network for Edge Detection (2020)

In this paper, we introduce REDN: A Recursive Encoder-Decoder Network with Skip-Connections for edge detection in natural images. The proposed network is a novel integration of a Recursive Neural Network with an Encoder-Decoder architecture. The recursive network enables iterative refinement of the edges using a single network model. Adding skip-connections between encoder and decoder helps the gradients reach all the layers of a network more easily and allows information related to finer details in the early stage of the encoder to be fully utilized in the decoder. Based on our extensive experiments on popular boundary detection datasets including BSDS500 [1], NYUD [2] and Pascal Context [3], REDN significantly advances the state-of-the-art on edge detection regarding standard evaluation metrics such as Optimal Dataset Scale (ODS) F-measure, Optimal Image Scale (OIS) F-measure, and Average Precision (AP).
Conformational Studies and Structure−Activity Analysis of Lissoclinamide 7 and Related Cyclopeptide Alkaloids (1998)

The macrocyclic arrays of heterocycles and amides present in Lissoclinum peptides can serve as templates for selective metal ion binding and as lead structures for the design of conformationally preorganized peptides and peptidomimetics. The currently available secondary structure information for this class of marine alkaloids, however, is limited to 18- and 24-membered ring isomers. This work provides the first information on the solid state and solution conformation of the 21-membered class of Lissoclinum cyclopeptide alkaloids. The folding of lissoclinamide 7, both in the solid and in the solution state, is dominated by a combination of a type II β-turn formed at the prolyloxazoline moiety and a β-loop segment stabilized by intramolecular five-membered hydrogen bonds at the thiazoline−d-phenylalanine−thiazoline moiety. The resulting rigid backbone geometry controls the preferred stereochemistry at the stereogenic α-carbons, and the natural compound represents the thermodynamically most favorable stereoisomer. In addition to these structural studies, we have compared the relative cytotoxicity of lissoclinamide 7 with analogues with selective oxazoline and thiazoline heterocycle replacements. On the basis of in vitro cell toxicity assays, we can conclude that the substitution of thiazolines in the natural product with oxazoline rings leads to a general decrease in cellular toxicity. However, changes in the stereochemistry of the parent macrocycle also influence cytotoxicity.
Engineering 'hot spots' for surface-enhanced Raman scattering (2003)

Strong Raman signals have been observed in various molecules attached to rough metal film surfaces or nano silver/gold particles. This phenomenon is denoted as surface enhanced Raman scattering (SERS). Recent experiments have shown that the effective cross sections of Raman scattering can reach the same level that of fluorescence of good laser dyes, making SERS a promising single-molecular detection tool. The commonly used substrates for SERS consist of colloidal Ag/Au particle aggregates, where SERS active sites, called "hot spots", are only found by chance and not controllable. The poor repeatability and controllability of these SERS substrates have prevented SERS from viable industrial applications, therefore it is imperative to design and fabricate optimized "hot spots" with desired plasmon resonance frequency in a controllable fashion. In this paper, we present a new class of composite nano particles, which is consisted of stacked alternative metal/dielectric layers, called nanoburger. We study optical properties of these nanoburger particles by using discrete dipole approximation method. The numerical results show that nanoburger particles possess many advantages over single layered particles, including high brightness or scattering intensity, high local field enhancements, and more freedom of tuning plasmon resonance wavelength. Another important merit of the nanoburger particles is that they can be fabricated with traditional micro/nano lithography techniques, and thus are integrable with techniques such as lab-in-a-chip.
El desafío de crear experiencias (1997)

Wnt/β-catenin activation serves as an important mediator for fibrosis development resulting from NASH using a mouse model where NASH is mimicked by PTEN loss.
REPAIR OF OXIDATIVE DAMAGE TO DNA: Enzymology and Biology (1994)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
Serum Platelet-Activating Factor Acetylhydrolase Activity in Rats with Gastric Ulcers Induced by Water-Immersion Stress (1989)

Platelet-activating factor (PAF) acetylhydrolase is an enzyme which hydrolyzes PAF to yield inactive lysoPAF. This study focused on the influence of water-immersion stress on serum PAF acetylhydrolase activity. The enzyme activity was determined by measurement of [3H]acetate produced from 1-O-alkyl-2-[3H]acetyl-sn-glycero-3-phosphocholine upon precipitation of the complex of the radioactive substrate and albumin with trichloroacetic acid. The onset of water-immersion stress caused the development of gastric lesions associated with a significant increase in serum PAF acetylhydrolase activity. Serum PAF acetylhydrolase may leak into the blood from some tissues in rats with gastric injury induced by water-immersion stress and might control the action of PAF.
Three-Dimensional Image Registration of Phantom Vertebrae for Image-Guided Surgery: A Preliminary Study (2002)

Objective: Applications of three-dimensional ultrasound (3D US) are emerging throughout the field of medicine. In this study, tracked, free-hand 3D phantom US images were mapped to computed tomograms (CT) as a development for image-guided surgery (IGS) of the spine. In the operating room, the registration of tracked 3D US images to other imaging modalities, such as CT, could allow the surgeon to identify more precisely the surgical target area prior to the incision. An independent quantitative measure of registration accuracy using a fiducial marker system was provided.Methods: Three-dimensional free-hand US images of a phantom spine were created by tracking the transducer with an optical sensing system. Two sets of images were acquired from three lumbar vertebrae using 4.5-and 7.5-MHz transducers. These images were then segmented for the extraction of the posterior vertebral surface. Next, a surface-based registration of US to the corresponding segmented CT images was performed. Registration errors were computed as the distance between a set of target points transformed using the experimental transformation and the same set of target points transformed using fiducial markers as a gold standard.Results: Results indicated that alignment of these image sets is feasible using only part of the vertebral surface. In particular, the regions of the spinous process and laminae were used for registration. Target registration errors (TREs) were found to be lowest using the highest resolution CT images. Using the CT scans with 2-mm slice thickness, the TRE was calculated to be 1.33 ± 0.30 mm for the 7.5-MHz US data set and 2.81 ± 0.10 mm for the 4.5-MHz US data set. Moreover, residual errors in these surface alignments were 0.69 ± 0.18 mm and 0.61 ± 0.20 mm for the 4.5-and 7.5-MHz sets, respectively.Conclusion: A rigid, surface-based registration of CT images to phantom spinal US images, acquired with a free-hand, tracked transducer, is achievable with a limited, easily obtainable portion of the vertebral surface.
The deprotection of Lys(Mtt) revisited (2000)

The selective deprotection of Lys(Mtt)-containing peptidyl resins was successfully monitored by RP-HPLC using very short linear gradients. RP-HPLC analyses of the acidic filtrates also revealed the partial cleavage of the Trt groups and of the peptide–resin bond. The absorbance of the Mtt carbocation at 470 nm is only twice that of the Trt cation. Thus, the UV monitoring at 470 nm seems to be inappropriate, especially at the end of the deprotection, when the Mtt and the Trt levels are comparable. Copyright © 2000 European Peptide Society and John Wiley & Sons, Ltd.
Physical and genetic characterization of symbiotic and auxotrophic mutants of Rhizobium meliloti induced by transposon Tn5 mutagenesis (1982)

We have physically and genetically characterized 20 symbiotic and 20 auxotrophic mutants of Rhizobium meliloti, the nitrogen-fixing symbiont of alfalfa (Medicago sativa), isolated by transposon Tn5 mutagenesis. A "suicide plasmid" mutagenesis procedure was used to generate TN-5-induced mutants, and both auxotrophic and symbiotic mutants were found at a frequency of 0.3% among strains containing random TN5 insertions. Two classes of symbiotic mutants were isolated: 4 of the 20 formed no nodules at all (Nod-), and 16 formed nodules which failed to fix nitrogen (Fix-). We used a combination of physical and genetic criteria to determine that in most cases the auxotrophic and symbiotic phenotypes could be correlated with the insertion of a single Tn5 elements. Once the Tn5 element was inserted into the R. meliloti genome, the frequency of its transposition to a new site was approximately 10-8 and the frequency of precise excision was less than 10-9. In approximately 25% of the mutant strains, phage Mu DNA sequences, which originated from the suicide plasmid used to generate the Tn5 transpositions, were also found in the R. meliloti genome contiguous with Tn5. These later strains exhibited anomalous conjugation properties, and therefore we could not correlate the symbiotic phenotype with a Tn5 insertion. In general, we found that both physical and genetic tests were required to fully characterize transposon-induced mutations.
Performance analysis of adaptive-optics systems using laser guide stars and sensors (1989)

Many current wave-front-reconstruction systems use localized phase-slope measurements to estimate wave fronts distorted by atmospheric turbulence. Analytical expressions giving the performance of this class of adaptive-optics system are derived. Performance measures include the mean-square residual phase error across the aperture, the optical transfer function, the point-spread function, and the Strehl ratio. Numerical examples show that the mean-square residual error and the Strehl ratio are sensitive to variations of the photon noise in the wave-front sensor and to variations in the sensor spacing and the actuator spacing. The Strehl ratio degrades rapidly as the diameters of the individual slope sensors are made larger than the Fried seeing-cell diameter r0 and when the sensor signal levels fall below 100 counts per slope measurement. On the other hand, the resolution of the optical system is relatively unaffected by moderate changes in the photon noise or the densities of sensors and actuators. The diameter of the individual slope sensors can be as much as 1.5 times r0 without significant degradation in angular resolution. These performance measures are particularly important in the design of adaptive telescopes used for imaging in astronomy. For adaptive telescopes using laser guide stars, these measures can be used to determine the key design parameters for the laser.