gebhart/patrepeval huggingface dataset:
Synthesis of 2′‐Aminoalkyl‐Substituted Fluorinated Nucleobases and Their Influence on the Kinetic Properties of Hammerhead Ribozymes (2004)

Hammerhead ribozymes are ribonucleic acids that catalyse the hydrolytic cleavage of RNA. They interfere with gene expression in a highly specific manner and recognize the mRNA target through Watson-Crick base pairing. To overcome the problem of point mutations (Watson-Crick "mismatches") occurring in viral genomes, we developed 2'-aminoethyl-substituted fluorinated nucleosides, which are universal nucleobases. The highly efficient synthetic pathway, which features a direct phthaloylamination of a primary alcohol under Mitsunobu conditions, leads to modified phosphoroamidites. The 1'-deoxy-1'-(4,6-difluoro-1H-benzimidazol-1-yl)-2'-(beta-aminoethyl)-beta-D-ribofuranose nucleoside analogue does not differentiate between the four natural nucleosides and leads to a RNA duplex that is as stable as the unmodified parent duplex. Upon incorporation into a ribozyme, the analogue's catalytic activity is equal for all four possible substrates, and the cleavage rates for the modified ribozymes are significantly higher (up to a factor of 13) than for the natural Watson-Crick "mismatch" base pairs. In agreement with the thermodynamic data obtained by measurement of the T(m) values of the RNA 12-mers, the cleavage rates for the 2'-substituted fluorinated benzimidazole derivative 4 are slightly higher than for the corresponding fluorinated benzene derivative 3.
Copper-Catalyzed Aerobic Oxidative Intramolecular C–H Amination Leading to Imidazobenzimidazole Derivatives (2011)

A highly efficient copper-catalyzed aerobic oxidative intramolecular C-H amination has been developed using substituted 2-(1H-imidazol-1-yl)-N-alkylbenzenamines as the starting materials, and the corresponding imidazobenzimidazole derivatives were obtained in excellent yields. This is an economical and practical method for the construction of N-heterocycles.
Influence of randomly varying domain lengths and nonuniform effective index on second-harmonic generation in quasi-phase-matching waveguides (1991)

The degradation of second-harmonic generation in quasi-phase-matching waveguides, when random errors occur in the domain boundary position and when the effective index varies along the waveguide, is studied theoretically. Two models for random errors are used, one assuming independent shifts of the domain boundaries and one assuming independent domain lengths. Only the influence of random errors following the statistics in the second model might be of any significance in practical implementations. It is shown that in this case the normalized output power is a decreasing function of the product of the number of domains and a relative variance of the stochastic disturbances. If the difference in effective indices between the interacting modes varies along the waveguide, the same kind of ripple that has been observed in birefringence phase matching occurs.
Targeted treatment of prostate cancer (2007)

Over a half century ago, Charles Huggins demonstrated the response of prostate cancer to androgen deprivation therapy. Subsequently, many discoveries and evolving findings continued to support a research rationale focused on the androgen receptor (AR) as a key target for prostate cancer. More recently, preliminary trials have suggested that other targets could also be useful in the treatment of prostate cancer, and the proposed strategies for treatment have ranged from targeted toxins to immunotherapeutic agents. We provide an overview of some of these approaches, with an emphasis on those that employ prostate specific membrane antigen (PSMA) as a target.
Ex-vivo whole blood secretion of interferon (IFN)-γ and IFN-γ-inducible protein-10 measured by enzyme-linked immunosorbent assay are as sensitive as IFN-γ enzyme-linked immunospot for the detection of gluten-reactive T cells in human leucocyte antigen (HLA)-DQ2·5+-associated coeliac disease (2013)

T cell cytokine release assays are used to diagnose infectious diseases, but not autoimmune or allergic disease. Coeliac disease (CD) is a common T cell-mediated disease diagnosed by the presence of gluten-dependent intestinal inflammation and serology. Many patients cannot be diagnosed with CD because they reduce dietary gluten before medical workup. Oral gluten challenge in CD patients treated with gluten-free diet (GFD) mobilizes gluten-reactive T cells measurable by interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) or major histocompatibility complex (MHC) class II tetramers. Immunodominant peptides are quite consistent in the 90% of patients who possess HLA-DQ2·5. We aimed to develop whole blood assays to detect gluten-specific T cells. Blood was collected before and after gluten challenge from GFD donors confirmed to have CD (n = 27, all HLA-DQ2·5(+) ), GFD donors confirmed not to have CD (n = 6 HLA-DQ2·5(+) , 11 HLA-DQ2·5(-) ) and donors with CD not following GFD (n = 4, all HLA-DQ2·5(+) ). Plasma IFN-γ and IFN-γ inducible protein-10 (IP-10) were measured by enzyme-linked immunosorbent assay (ELISA) after whole blood incubation with peptides or gliadin, and correlated with IFN-γ ELISPOT. No T cell assay could distinguish between CD patients and controls prior to gluten challenge, but after gluten challenge the whole blood IFN-γ ELISA and the ELISPOT were both 85% sensitive and 100% specific for HLA-DQ2·5(+) CD patients; the whole blood IP-10 ELISA was 94% sensitive and 100% specific. We conclude that whole blood cytokine release assays are sensitive and specific for detection of gluten-reactive T cells in CD; further clinical studies addressing the utility of these tests in patients with an uncertain diagnosis of CD is warranted.
Thermal conductivity and ballistic-phonon transport in the cross-plane direction of superlattices (1998)

Significant reductions in both the in-plane and cross-plane thermal conductivities of superlattices, in comparison to the values calculated from the Fourier heat conduction theory using bulk material properties, have been observed experimentally in recent years. Understanding the mechanisms controlling the thermal conductivities of superlattice structures is of considerable current interest for microelectronic and thermoelectric applications. In this work, models of the thermal conductivity and phonon transport in the direction perpendicular to the film plane of superlattices are established based on solving the phonon Boltzmann transport equation (BTE). Different phonon interface scattering mechanisms are considered, including elastic vs inelastic, and diffuse vs specular scattering of phonons. Numerical solution of the BTE yields the effective temperature distribution, thermal conductivity, and thermal boundary resistance (TBR) of the superlattices. The modeling results show that the effective thermal conductivity of superlattices in the perpendicular direction is generally controlled by phonon transport within each layer and the TBR between different layers. The TBR is no longer an intrinsic property of the interface, but depends on the layer thickness as well as the phonon mean free path. In the thin layer limit, phonon transport within each layer is ballistic, and the TBR dominates the effective thermal conductivity of superlattices. Approximate analytical solutions of the BTE are obtained for this thin-film limit. The modeling results based on partially specular and partially diffuse interface scattering processes are in reasonable agreement with recent experimental data on GaAs/AlAs and Si/Ge superlattices. From the modeling, it is concluded that the cross-plane thermal conductivity of these superlattices is controlled by diffuse and inelastic scattering processes at interfaces. Results of this work suggest that it is possible to make superlattice structures with thermal conductivity totally different from those of their constituting materials.
Transition from localized surface plasmon resonance to extended surface plasmon-polariton as metallic nanoparticles merge to form a periodic hole array (2004)

We present results of experiments to determine the dispersion of the plasmon modes associated with periodic silver nanoparticle and nanohole arrays fabricated using an extension of the nanosphere lithography technique. Ordered monolayers of polystyrene nanospheres were used as a deposition mask through which silver was deposited by thermal evaporation, subsequent removal of the nanospheres thus leaving an array of metallic nanoparticles. By reactive-ion etching of the nanospheres in an oxygen plasma prior to silver deposition, arrays consisting of particles of increasing size were fabricated. The extremities of the particles eventually merge to create a continuous metallic network perforated by subwavelength holes, thus allowing a study of the particle-hole transition. Combining optical measurements of transmittance and reflectance with information gained using scanning electron microscopy, three separate regimes were observed. For low etch times the samples comprise mainly individual nanoparticles and the optical response is dominated by localized surface plasmon resonances that show no dispersion. As the etch time is increased almost all of the nanoparticles merge with adjacent particles, although many defects are present---notably where some particles fail to merge, a small gap being left between them. The presence of these defects prevents an abrupt structural transition from metallic nanoparticles to a continuous metallic film perforated by an array of nanoholes. The presence of such gaps also results in dispersion data that lack clearly defined features. A further increase in etch time leads to samples with no gaps: instead, a continuous metal film perforated by a nanohole array is produced. The optical response of these structures is dominated by extended surface plasmon-polariton modes.
Cell-Laden and Cell-Free Biopolymer Hydrogel for the Treatment of Osteochondral Defects in a Sheep Model (2008)

The objective of the current study was to determine the suitability of cell-laden and cell-free alginate-gelatin biopolymer hydrogel for osteochondral restoration in a sheep model (n = 12). Four femoral defects per animal were filled with hydrogel (cHG) plus autologous chondrocytes (cHG + C) or periosteal cells (cHG + P) or gel only (cHG) or were left untreated (E). In situ solidification enabled instantaneous implant fixation. Sixteen weeks postoperatively, defect sites were processed for light microscopy and immunofluorescence. A modified Mankin and a semi-quantitative immunoreactivity score were used to evaluate histology and immunofluorescence, respectively. Defects after cHG + C were restored with smooth, hyaline-like neo-cartilage and trabecular subchondral bone. cHG + P and cHG treatments revealed slightly inferior regenerate morphology. Undifferentiated tissue was found in E. The histological score showed significant (p < 0.05) differences between all treatment groups. In conclusion, cHG induces satisfactory defect regeneration. Complete filling of the cavity in one step and subsequent rapid in situ solidification was feasible and facilitated graft fixation. Cell implantation might be beneficial, because cells seem to play a key role in histological outcome. Still, their contribution to the repair process remains unresolved because host cell influx takes place. The combination of alginate and gelatin, however, creates an environment capable of serving implanted and host cells for osteo-chondrogenic tissue regeneration.
Identification of a prostate‐specific membrane antigen‐derived peptide capable of eliciting both cellular and humoral immune responses in HLA‐A24+ prostate cancer patients (2003)

We tried to identify prostate-specific membrane antigen (PSMA)-derived peptides capable of eliciting both cellular and humoral immune responses in peripheral blood mononuclear cells (PBMCs) and plasma of HLA-A24(+) prostate cancer patients, respectively. For cellular response, peptide-specific and prostate cancer-reactive responses of in vitro-stimulated PBMCs were examined with regard to interferon (IFN)-gamma production and cytotoxicity against both a parental HLA-A24(-) prostate cancer cell line (PC-93) and an HLA-A24-expressing transfectant cell line (PC93-A24). For humoral response, patients' plasma was tested for reactivity to the peptides by means of an enzyme-linked immunosorbent assay (ELISA). Among 13 PSMA peptides, PSMA 624-632 peptide induced peptide-specific and tumor-reactive cytotoxic T lymphocytes (CTLs) most effectively. The PSMA 624-632 peptide-stimulated PBMCs from either healthy donors or prostate cancer patients produced a significant level of IFN-gamma in response to prostate cancer cells in an HLA-A24-restricted manner, and also showed a higher level of cytotoxicity against PC93-A24 than against PC93. Antibodies to the PSMA 624-632 peptide, but not to any others, were detected in prostate cancer patients. These results demonstrate that the PSMA 624-632 peptide could be an appropriate molecule for use in specific immunotherapy of HLA-A24(+) patients with prostate cancer.
Immunogold-silver staining: new method of immunostaining with enhanced sensitivity. (1983)

A new method for demonstrating antigens in paraffin sections of formol sublimate-fixed tissue is described that utilizes an "indirect" immunohistological technique employing immunoglobulin adsorbed to colloidal gold as the secondary antiserum. The gold particles introduced to antigenic sites are revealed by a silver precipitation reaction. This technique, the immunogold-silver staining method, is of much enhanced sensitivity (up to 200-fold) as compared with standard immunoperoxidase and immunogold staining methods. The results have been confirmed in a study of immunoglobulins in reactive human tonsil. The use of this new method for double immunolabeling is also described.
Radionuclide selection and model absorbed dose calculations for radiolabeled tumor associated antibodies (1984)

An absorbed dose calculation comparison has been computed for radiolabeled tumor associated antibodies distributed over a standard geometry and tumor location. Half-life data, maximum specific activities, and relative organ doses of nine radionuclides, Cu-67, Br-77, Br-82, Y-90, Tc-99m, In-111, I-131, Re-186, and At-211, have been compiled in which the radionuclides were assumed to be coupled with antibody. These nuclides were chosen on the basis of physical characteristics that warranted their inclusion as either imaging or therapy radiolabels. Radionuclide biodistribution data based on current available estimates for antibody uptake and clearance in humans has been adopted. Re-186 and Y-90 have been determined to be among the best therapy radiolabels since they possess sufficiently long half lives necessary for tumor localization, little or no gamma radiation, intermediate beta energy, stable daughter products, and have a reasonable chance to form a stable chelate with an antibody system.
Surface Biopassivation of Replicated Poly(dimethylsiloxane) Microfluidic Channels and Application to Heterogeneous Immunoreaction with On-Chip Fluorescence Detection (2001)

Poly(dimethylsiloxane) (PDMS) appeared recently as a material of choice for rapid and accurate replication of polymer-based microfluidic networks. However, due to its hydrophobicity, the surface strongly interacts with apolar analytes or species containing apolar domains, resulting in significant uncontrolled adsorption on channel walls. This contribution describes the application and characterization of a PDMS surface treatment that considerably decreases adsorption of low and high molecular mass substances to channel walls while maintaining a modest cathodic electroosmotic flow. Channels are modified with a three-layer biotin-neutravidin sandwich coating, made of biotinylated IgG, neutravidin, and biotinylated dextran. By replacing biotinylated dextran with any biotinylated reagent, the modified surface can be readily patterned with biochemical probes, such as antibodies. Combination of probe immobilization chemistry with low nonspecific binding enables affinity binding assays within channel networks. The example of an electrokinetic driven, heterogeneous immunoreaction for human IgG is described.
Heparin induces apoptosis in human peripheral blood neutrophils (1996)

Programmed cell death, by apoptosis, has been shown to play an important role in the regulation of haemopoiesis. Using trypan blue exclusion for distinguishing intact membranes, flow cytometry for detection of sub G1 peak and in situ terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL), this study shows that heparin induces apoptosis in vitro in human peripheral blood neutrophils. The known anti-proliferative effect of heparin in several in vitro cell systems has therefore to be interpreted in the light of apoptosis. In addition, apoptosis may help explain the anti-inflammatory effects resulting from the interaction between vessel wall heparan sulphate and chemoattracted peripheral blood neutrophils.
A single amino acid substitution in v-erbB confers a thermolabile phenotype to ts167 avian erythroblastosis virus-transformed erythroid cells. (1986)

A library of recombinant bacteriophage was prepared from ts167 avian erythroblastosis virus-transformed erythroid precursor cells (HD6), and integrated proviruses from three distinct genomic loci were isolated. A subclone of one of these proviruses (pAEV1) was shown to confer temperature-sensitive release from transformation of erythroid precursor cells in vitro. The predicted amino acid sequence of the v-erbB polypeptide from the mutant had a single amino acid change when compared with the wild-type parental virus. When the wild-type amino acid was introduced into the temperature-sensitive avian erythroblastosis virus provirus in pAEV1, all erythroid clones produced in vitro were phenotypically wild type. The mutation is a change from a histidine to an aspartic acid in the temperature-sensitive v-erbB polypeptide. It is located in the center of the tyrosine-specific protein kinase domain and corresponds to amino acid position 826 of the human epidermal growth factor receptor sequence.
Nanoscale tissue engineering: spatial control over cell-materials interactions (2011)

Cells interact with the surrounding environment by making tens to hundreds of thousands of nanoscale interactions with extracellular signals and features. The goal of nanoscale tissue engineering is to harness these interactions through nanoscale biomaterials engineering in order to study and direct cellular behavior. Here, we review two- and three-dimensional (2- and 3D) nanoscale tissue engineering technologies, and provide a holistic overview of the field. Techniques that can control the average spacing and clustering of cell adhesion ligands are well established and have been highly successful in describing cell adhesion and migration in 2D. Extension of these engineering tools to 3D biomaterials has created many new hydrogel and nanofiber scaffold technologies that are being used to design in vitro experiments with more physiologically relevant conditions. Researchers are beginning to study complex cell functions in 3D. However, there is a need for biomaterials systems that provide fine control over the nanoscale presentation of bioactive ligands in 3D. Additionally, there is a need for 2- and 3D techniques that can control the nanoscale presentation of multiple bioactive ligands and that can control the temporal changes in the cellular microenvironment.
The Regulation and Regulatory Activities of Alternative Splicing of the SMN Gene (2004)

Alternative splicing is an essential process that produces protein diversity in humans. It is also the cause of many complex diseases. Spinal muscular atrophy (SMA), the second most common autosomal recessive disorder, is caused by the absence of or mutations in the Survival Motor Neuron 1 (SMN1) gene, which encodes an essential protein. A nearly identical copy of the gene, SMN2, fails to compensate for the loss of SMN1 because exon 7 is alternatively spliced, producing a truncated protein, which is unstable. SMN1 and SMN2 differ by a critical C-to-T substitution at position 6 of exon 7 in SMN2 (C6U transition in mRNA). This substitution alone is enough to cause an exon 7 exclusion in SMN2. Various cis- and trans-acting factors have been shown to neutralize the inhibitory effects of C6U transition. Published reports propose models in which either abrogation of an enhancer element associated with SF2/ASF or gain of a silencer element associated with hnRNP A1 is the major cause of exon 7 exclusion in SMN2. Most recent model suggests the presence of an EXtended INhibitory ContexT (Exinct) that is formed as a consequence of C6U transition in exon 7 of SMN2. In Exinct model, several factors may affect exon 7 splicing through cooperative interactions. Such regulation may be common to many alternatively spliced exons in humans. Recent advances in our understanding of SMN gene splicing reveals multiple challenges that are specific to in vivo regulation, which we now know is intimately connected with other biological pathways.
NCAM polypeptides in heart development: association with Z discs of forms that contain the muscle-specific domain. (1995)

Previous studies of neural cell adhesion molecule (NCAM) cDNAs have revealed an alternatively spliced set of small exons (12A, 12B, 12C, and 12D) that encode a region in the extracellular portion of the molecule known as the muscle-specific domain (MSD). The entire MSD region can be expressed in skeletal muscle, heart, and skin; only exons 12A and 12D have been found in brain. These studies did not reveal which NCAM polypeptides contain the MSD region or the immunohistochemical distribution of these NCAM molecules. To address these questions, we prepared antibodies against the oligopeptides encoded by exons 12A and 12B and by exons 12C and 12D, and we used these antibodies to study the forms of NCAM containing the MSD region expressed during embryonic chicken heart development. These antibodies recognize certain forms of NCAM found in the heart, but they do not recognize brain NCAM. In the heart, each of the splice variants of NCAM (large cytoplasmic domain, small cytoplasmic domain, and small surface domain) that differ in their mode of attachment to the plasma membrane or in the size of their cytoplasmic domain is expressed in a form that contains and in a form that lacks the MSD region. No microheterogeneity is observed in the size of NCAM molecules containing the MSD region, even at the level of cyanogen bromide fragments, suggesting that exons 12A-D are expressed as a single unit. Depending on the site and the stage of development, the percent of NCAM molecules containing the MSD region can vary from nearly 0 to 100%. In general, this percentage increases during development. In immunohistochemical studies of hearts from stage 18 embryos, forms of NCAM containing the MSD region colocalized with Z discs. No other adhesion molecules were found in this distribution at this early stage of development. Studies on isolated cells in vitro demonstrate that the colocalization with Z discs of NCAM molecules containing the MSD region does not depend on cell-cell contact, and they raise the possibility that this form of NCAM is involved in cell-extracellular matrix interactions. The association of NCAM molecules containing the MSD region with Z discs suggests that this form of NCAM is involved in early myofibrillogenesis.