gebhart/patrepeval huggingface dataset:
Islet-1 Cells Are Cardiac Progenitors Present During the Entire Lifespan: From the Embryonic Stage to Adulthood (2010)

The aim of this study was to longitudinally characterize the distribution of cells actively expressing the progenitor transcription factor islet-1 (Isl1+) during the embryonic life, the postnatal period, and adulthood. In this study, we have used direct immunohistochemical staining toward the protein Isl1 in a longitudinal rat model. Cells actively expressing Isl1 were traced in embryos from gestational day (GD) 11 until adulthood. In early cardiac development (GD 11), the Isl1+ progenitors were located in a greater abundance in the paracardiac regions, areas suggested to be the second heart field. To a lesser extent, Isl1+ cells were present within the bulbotruncal region and the truncus arteriosus. During the following days until GD 15, the Isl1+ cells were mainly observed at the proximal outflow tract (OFT) and at the inflow area of the right atrium. No Isl1+ cells were detected in the left ventricle. Compared with GD 11, more Isl1+ cells seemed to co-express cardiomyocyte markers and a minority of the Isl1+ cells was undifferentiated. Unexpectedly, only few undifferentiated Isl1+ cells were Ki67+ while a lot of TnT+ cardiomyocytes were proliferating in the ventricles. After birth, immature Isl1+ cells were still present in the OFT where they resided until adulthood. Our data suggest that during embryogenesis, Isl1+ cells migrate from extracardiac regions into the proximal part of the heart, proliferating and giving rise to cardioblasts. Unexpectedly, only a minority of the Isl1+ cells while a majority of ventricular cardiomyocytes were proliferating. The Isl1+ cell pool persists into adulthood, which might open up new strategies to repair damaged myocardium.
Display of a PorA peptide from Neisseria meningitidis on the bacteriophage T4 capsid surface (1997)

The exterior of bacteriophage T4 capsid is coated with two outer capsid proteins, Hoc (highly antigenic outer capsid protein; molecular mass, 40 kDa) and Soc (small outer capsid protein; molecular mass, 9 kDa), at symmetrical positions on the icosahedron (160 copies of Hoc and 960 copies of Soc per capsid particle). Both these proteins are nonessential for phage infectivity and viability and assemble onto the capsid surface after completion of capsid assembly. We developed a phage display system which allowed in-frame fusions of foreign DNA at a unique cloning site in the 5' end of hoc or soc. A DNA fragment corresponding to the 36-amino-acid PorA peptide from Neisseria meningitidis was cloned into the display vectors to generate fusions at the N terminus of Hoc or Soc. The PorA-Hoc and PorA-Soc fusion proteins retained the ability to bind to the capsid surface, and the bound peptide was displayed in an accessible form as shown by its reactivity with specific monoclonal antibodies in an enzyme-linked immunosorbent assay. By employing T4 genetic strategies, we show that more than one subtype-specific PorA peptide can be displayed on the capsid surface and that the peptide can also be displayed on a DNA-free empty capsid. Both the PorA-Hoc and PorA-Soc recombinant phages are highly immunogenic in mice and elicit strong antipeptide antibody titers even with a weak adjuvant such as Alhydrogel or no adjuvant at all. The data suggest that the phage T4 hoc-soc system is an attractive system for display of peptides on an icosahedral capsid surface and may emerge as a powerful system for construction of the next generation multicomponent vaccines.
Human CD4+ T-cell response to hepatitis delta virus: identification of multiple epitopes and characterization of T-helper cytokine profiles (1997)

The T-cell-mediated immune response plays a crucial role in defense against hepatotropic viruses as well as in the pathogenesis of viral chronic hepatitides. However, very little is known about the role of specific T cells during hepatitis delta virus (HDV) infection in humans. In this study, the T-cell response to HDV in chronic hepatitis B virus (HBV) carriers with HDV superinfection was investigated at different levels. Analysis of peripheral blood mononuclear cell (PBMC) proliferation in response to a recombinant form of large hepatitis delta antigen (HDAg) revealed that 8 of 30 patients studied (27%) specifically responded to HDAg. By employing synthetic peptides spanning the entire HDAg sequence, we found that T-cell recognition was directed against different antigenic determinants, with patient-to-patient variation in the pattern of response to peptides. Interestingly, all responders had signs of inactive HDV-induced disease, while none of the patients with active disease and none of the control subjects showed any significant proliferation. More accurate information about the specific T-cell response was obtained at the clonal level. A panel of HDAg-specific CD4+ T-cell clones from three HDV-infected individuals and fine-specificity analysis revealed that the clones tested individually recognized four epitopes corresponding to amino acids (aa) 26 to 41, 50 to 65, 66 to 81, or 106 to 121 of HDAg sequence. The study of human leukocyte antigen (HLA) restriction revealed that peptides 50 to 65 and 106 to 121 were presented to specific T cells in association with multiple class II molecules. In addition, peptide 26 to 41 was efficiently generated after processing of HDAg through the endogenous processing pathway. Cytokine secretion analysis showed that all the CD4+ T-cell clones assayed were able to produce high levels of gamma interferon (IFN-gamma), belonging either to T helper-1 (Th1) or Th0 subsets and that some of them were cytotoxic in a specific assay. This study provides the first evidence that detection of a specific T-cell response to HDAg in the peripheral blood of individuals with hepatitis delta is related to the decrease of HDV-induced disease activity. The HDAg epitopes identified here and particularly those recognized by CD4+ T cells in association with multiple major histocompatibility complex class II molecules may be potentially exploited for the preparation of a vaccine for prophylaxis and therapy of HDV infection.
Human Transaldolase and Cross-Reactive Viral Epitopes Identified by Autoantibodies of Multiple Sclerosis Patients (1999)

Multiple sclerosis is mediated by an autoimmune process causing selective destruction of oligodendrocytes. Transaldolase, which is expressed in the brain selectively in oligodendrocytes, is a target of high affinity autoantibodies in serum and cerebrospinal fluid of multiple sclerosis patients. A three-dimensional model of human transaldolase was developed based on the crystal structure of the enzyme from Escherichia coli. To identify immunodominant epitopes, 33 peptides overlapping human transaldolase by 5 amino acids were synthesized. Ab 12484, raised against enzymatically active human transaldolase, recognized antigenic determinants corresponding to linear epitopes (residues 27-31 and 265-290) and alpha helices (residues 75-98 and 302-329). Four immunodominant peptides harboring charged amino acid residues with topographically exposed side chains were identified by sera from 13 multiple sclerosis patients with predetermined autoreactivity to transaldolase. Autoantibodies binding to the most prominent human transaldolase epitope, between residues 271 and 285, showed cross-reactivity with Epstein-Barr and herpes simplex virus type 1 capsid-derived peptides. Molecular mimicry between immunodominant autoepitopes and viral Ags may be a decisive factor in directing autoimmunity to transaldolase in multiple sclerosis patients.
Solid-Phase Synthesis of β-Sultams (1997)

Solid-phase synthesis of beta-sultams amenable for construction of sulfonyl beta-lactam analogue combinatorial libraries is reported. Imine intermediates generated from polymer-immobilized amino acids and aldehydes are reacted with (chlorosulfonyl)acetates in the presence of pyridine to afford the solid-phase-tethered beta-sultam products. The latter can be released from support by acidic cleavage (TFA) or photocleavage, depending on the nature of the linker employed (acid-labile or photolabile linkers). Immobilized 4-(9-fluorenyl)methoxycarbonyl beta-sultams are further functionalized on supports to afford, upon cleavage, the respective carboxy and amido thiazetidine derivatives. The method can be employed in production of beta-sultam libraries for identification of new antibacterial agents.
Temporal trends in safety and complication rates of catheter ablation for atrial fibrillation (2018)

The safety profile of AF ablation has improved significantly in less than a decade.
Role of a bulged A residue in a specific RNA-protein interaction (1987)

The translational operator of the R17 replicase gene contains a bulged A residue that is essential for the specific binding to R17 coat protein. A large number of operator variants have been synthesized to more precisely examine the role of the bulged A residue on this specific protein-RNA interaction. By use of RNA ligase and transcription of synthetic DNA templates by T7 RNA polymerase, 14 different nucleotides were introduced to the bulged A position of three different coat protein binding fragments. The affinity between coat protein and each fragment was determined by a nitrocellulose filter binding assay. The data indicate that while functional groups on N1, C2, C6, N7, and 2'OH of the bulged A can be substituted without greatly changing protein binding, bulky substituents cannot be tolerated at these positions. Data from additional fragments that have base-pair changes adjacent to the bulged A suggest that the propensity of the bulged A to intercalate into the helix can affect protein binding.
Efficient in vivo editing of OTC-deficient patient-derived primary human hepatocytes (2019)

The ability to efficiently and safely correct disease-causing mutations remains the holy grail of gene therapy. Herein, we demonstrate, for the first time, efficient <i>in vivo</i> correction of a patient-specific disease-causing mutation in the <i>OTC</i> gene in primary human hepatocytes, using therapeutically relevant vector doses. We also highlight the challenges that need to be overcome for this technology to be translated into clinical practice.
Novel integration technique for silicon/III-V hybrid laser (2014)

Integrated semiconductor lasers on silicon are one of the most crucial devices to enable low-cost silicon photonic integrated circuits for high-bandwidth optic communications and interconnects. While optical amplifiers and lasers are typically realized in III-V waveguide structures, it is beneficial to have an integration approach which allows flexible and efficient coupling of light between III-V gain media and silicon waveguides. In this paper, we propose and demonstrate a novel fabrication technique and associated transition structure to realize integrated lasers without the constraints of other critical processing parameters such as the starting silicon layer thicknesses. This technique employs epitaxial growth of silicon in a pre-defined trench with taper structures. We fabricate and demonstrate a long-cavity hybrid laser with a narrow linewidth of 130 kHz and an output power of 1.5 mW using the proposed technique.
Uncertainty and Sensitivity Analyses of a Dynamic Economic Evaluation Model for Vaccination Programs (2008)

vary in their degree of analytical difficulty and in the nature of the information that they provide, and analysts should communicate results with a note that not all methods yield the same insights. The authors explore several sensitivity analysis methods to test whether the choice of method affects the insights and importance rankings of inputs from the analysis. They use a dynamic cost-effectiveness model of a hypothetical infectious disease as the basis to perform 1-way and multi-way sensitivity analyses, design of experiments, and Morris' method. They also compute partial derivatives as well as a number of probabilistic sensitivity measures, including correlations, regression coefficients, and the correlation ratio, to demonstrate the existing methods and to compare them. The authors find that the magnitudes and rankings of sensitivity measures depend on the selected method(s) and make recommendations regarding the choice of method depending on the complexity of the model, number of uncertain inputs, and desired types of insights from the sensitivity analysis.
A positive relationship between protein synthetic rate and intracellular glutamine concentration in perfused rat skeletal muscle (1987)

During muscle-protein wasting associated with injury and disease the distribution ratio of free glutamine between muscle and blood falls. In pursuing possible consequences of this, we investigated the relationship between the rate of muscle protein synthesis and intramuscular glutamine concentration, manipulated acutely in the isolated perfused rat hindquarter. Increasing perfusate glutamine from 0.67 to 5.0 mM caused a 200% increase in intracellular glutamine and a 66% increase in protein synthesis in the absence of insulin; in the presence of insulin a 30% increase in intramuscular glutamine was accompanied by an 80% increase in protein synthesis. Analysis of variance of the results confirmed the existence of positive relationships between intramuscular glutamine and protein synthesis in the presence or absence of insulin. Control of the size of the intramuscular free pool of glutamine may be important in determining the muscle protein mass.
A real-time electrical impedance tomograph (1995)

Electrical properties of tissues in the human body can be imaged using a technology known as Electrical Impedance Tomography. In this modality, sinusoidal electrical currents are applied to the body using electrodes attached to the skin, and voltages that are developed on the electrodes are measured. Using these data, a reconstruction algorithm computes the conductivity and permittivity distributions within the body. This paper describes the reconstruction algorithm, image display algorithm, and hardware of a real-time Electrical Impedance Tomograph known as the Real-Time Imaging System. The reconstruction algorithm, executed by a commercially available coprocessor board that resides in a 386-based personal computer, is a modification of the Newton's One Step Error Reconstructor (NOSER) that minimizes algorithm execution time by precomputing many quantities. The image display algorithm, also executed by the coprocessor board, maps the output of the reconstruction algorithm into an image which is displayed using a video graphics board. The architecture of the system and execution times of algorithms implemented by the system are discussed. Using the continuous data acquisition mode of the Real-Time Imaging System, data from the thorax of a normal human subject were collected. Admittivity changes in the chest, as a result of respiration and the cardiac cycle, are presented. Data that were collected from the leg of a normal subject are shown which demonstrate capabilities of the triggered data acquisition mode of the system, allowing data acquisition synchronization with an electrocardiogram.
Development of a Biolabeling System Using Ferromagnetic Nanowires (2018)

This paper presents the development of a biolabeling system using different ferromagnetic nanowire types. The proposed biolabeling system concept includes a cell separation procedure description using magnetic nanowires and how nanowires can be used and identified as biolabels. A study on single magnetic nanowire behavior is performed, and the algorithm used to characterize and identify each nanowire type separately and from a mix of multiple types is described. The algorithm is verified using measurement data from individual nanowire array samples and stacked combinations of cobalt, iron, and nickel. From the strong correlation between the measured transmission coefficient data of magnetic nanowire arrays and a mathematical model, the potential of interpreting multiple magnetic nanowire types inside cells is confirmed.
Pattern-based behavior synthesis for FPGA resource reduction (2008)

Pattern-based synthesis has drawn wide interest from researchers who tried to utilize the regularity in applications for design optimizations. In this paper we present a general pattern-based behavior synthesis framework which can efficiently extract similar structures in programs. Our approach is very scalable in benefit of advanced pruning techniques that include locality sensitive hashing and characteristic vectors. The similarity of structures is captured by a mismatch-tolerant metric: graph edit distance. The edit distance between two graphs is the minimum number of vertex/edge insertion, deletion, substitution operations to transform one graph into the other. Graph edit distance can naturally handle various program variations such as bit-width variations, structure variations and port variations. In addition, we apply our pattern-based synthesis system to FPGA resource optimization with the observation that multiplexors are particularly expensive on FPGA platforms. Considering knowledge of discovered patterns, the resource binding step can intelligently generate the data-path to reduce interconnect costs. Experiments show our approach can, on average, reduce the total area by about 20% with 7% latency overhead on the Xilinx Virtex-4 FPGAs, compared to the traditional behavior synthesis flow
Low Molecular-weight G-actin Binding Proteins Involved in the Regulation of Actin Assembly during Myofibrillogenesis. (1997)

We previously demonstrated that small G-actin binding proteins, cofilin, ADF and profilin, are involved in the actin dynamics during myofibrillogenesis (OBINATA, T. (1993). Int. Rev. Cytol., 143: 153-189.). To better understand how they are responsible for the regulation of actin assembly, the amounts of the actin-binding proteins were quantified by means of quantitative immunoblotting and compared with that of G-actin pool. The sum of the amounts of cofilin, ADF and profilin was insufficient at early developmental stages but sufficient at later stages to account for the pool of G-actin in muscle cells. We detected expression of thymosin beta 4 at a considerable level in young embryonic but not in adult skeletal muscles. We, therefore, conclude that the G-actin pool in young embryonic skeletal muscle is mainly due to cofilin, ADF, profilin and thymosin beta 4. Switching from a non-muscle-type (NM-) cofilin to a muscle-type (M-) cofilin was observed during muscle development of mammals. In order to clarify cofilin-dependent regulation of actin assembly in muscle cells, cofilin tagged with fluorescence dyes was introduced into C2 myoblasts by a micro injection method. The exogeneous cofilin, but not ADF, caused quick disassembly of actin filaments and accumulated in furrow region of dividing cells. The analogs of the unphosphorylated form (A3-cofilin) and the phosphorylated form (D3-cofilin) were prepared by converting Ser3, a regulatory phosphorylation site, to Ala or Asp. When A3-cofilin and D3-cofilin were injected into living cells, the former was concentrated at the membrane ruffles and cleavage furrow, while the latter showed only diffuse distribution in the cytoplasm. These results suggest that the subcellular distribution of cofilin as well as its interaction with actin in vivo is regulated by its phosphorylation and dephosphorylation.
The linear free-energy relation between partition coefficients and the binding, and conformational perturbation of macromolecules by small organic compounds (1968)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe linear free-energy relation between partition coefficients and the binding, and conformational perturbation of macromolecules by small organic compoundsFriederike. Helmer, Karl. Kiehs, and Corwin. HanschCite this: Biochemistry 1968, 7, 8, 2858–2863Publication Date (Print):August 1, 1968Publication History Published online1 May 2002Published inissue 1 August 1968https://pubs.acs.org/doi/10.1021/bi00848a023https://doi.org/10.1021/bi00848a023research-articleACS PublicationsRequest reuse permissionsArticle Views320Altmetric-Citations134LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Type 1 diabetes: pathogenesis and prevention (2006)

Type 1 diabetes results from the autoimmune destruction of insulin-producing beta cells in the pancreas. Genetic and, as yet undefined, environmental factors act together to precipitate the disease. The excess mortality associated with the complications of type 1 diabetes and the increasing incidence of childhood type 1 diabetes emphasize the importance of therapeutic strategies to prevent this chronic disorder. Why is it considered that type 1 diabetes might be preventable? Different strands of diabetes research are coming together to suggest therapeutic targets. Islet cell autoantibody assays make it possible to accurately identify people at risk of future disease. In most cases, a long prodrome provides a window of opportunity to reverse the autoimmune process. Although no current "cure" exists, recent genetic data and preliminary trial results suggest T cells as a target for preventive strategies. Another potentially attainable target is induction of tolerance to the beta-cell proteins such as insulin that are inappropriately recognized. Other strategies involve beta-cell replacement, but currently there are insufficient donor cells available. This may be overcome as the processes controlling the differentiation of pancreatic and nonpancreatic progenitors as well as replication of existing islet beta cells are unravelled.
Incorporating chemical modification constraints into a dynamic programming algorithm for prediction of RNA secondary structure (2004)

A dynamic programming algorithm for prediction of RNA secondary structure has been revised to accommodate folding constraints determined by chemical modification and to include free energy increments for coaxial stacking of helices when they are either adjacent or separated by a single mismatch. Furthermore, free energy parameters are revised to account for recent experimental results for terminal mismatches and hairpin, bulge, internal, and multibranch loops. To demonstrate the applicability of this method, in vivo modification was performed on 5S rRNA in both Escherichia coli and Candida albicans with 1-cyclohexyl-3-(2-morpholinoethyl) carbodiimide metho-p-toluene sulfonate, dimethyl sulfate, and kethoxal. The percentage of known base pairs in the predicted structure increased from 26.3% to 86.8% for the E. coli sequence by using modification constraints. For C. albicans, the accuracy remained 87.5% both with and without modification data. On average, for these sequences and a set of 14 sequences with known secondary structure and chemical modification data taken from the literature, accuracy improves from 67% to 76%. This enhancement primarily reflects improvement for three sequences that are predicted with <40% accuracy on the basis of energetics alone. For these sequences, inclusion of chemical modification constraints improves the average accuracy from 28% to 78%. For the 11 sequences with <6% pseudoknotted base pairs, structures predicted with constraints from chemical modification contain on average 84% of known canonical base pairs.