gebhart/patrepeval huggingface dataset:
On spatial smoothing for direction-of-arrival estimation of coherent signals (1985)

We present an analysis of a "spatial smoothing" preprocessing scheme, recently suggested by Evans et al., to circumvent problems encountered in direction-of-arrival estimation of fully correlated signals. Simulation results that illustrate the performance of this scheme in conjunction with the eigenstructure technique are described.
A nucleus-basal body connector in Chlamydomonas reinhardtii that may function in basal body localization or segregation. (1985)

We have isolated a nucleus-basal body complex from Chlamydomonas reinhardtii. The complex is strongly immunoreactive to an antibody generated against a major protein constituent of isolated Tetraselmis striata flagellar roots (Salisbury, J. L., A. Baron, B. Surek, and M. Melkonian, J. Cell Biol., 99:962-970). Electrophoretic and immunoelectrophoretic analysis indicates that, like the Tetraselmis protein, the Chlamydomonas antigen consists of two acidic isoforms of approximately 20 kD. Indirect immunofluorescent staining of nucleus-basal body complexes reveals two major fibers in the connector region, one between each basal body and the nucleus. The nucleus is also strongly immunoreactive, with staining radiating around much of the nucleus from a region of greatest concentration at the connector pole. Calcium treatment causes shortening of the connector fibers and also movement of nuclear DNA towards the connector pole. Electron microscopic observation of negatively stained nucleus-basal body complexes reveals a cluster of approximately 6-nm filaments, suspected to represent the connector, between the basal bodies and nuclei. A mutant with a variable number of flagella, vfl-2-220, is defective with respect to the nucleus-basal body association. This observation encourages us to speculate that the nucleus-basal body union is important for accurate basal body localization within the cell and/or for accurate segregation of parental and daughter basal bodies at cell division. A physical association between nuclei and basal bodies or centrioles has been observed in a variety of algal, protozoan, and metazoan cells, although the nature of the association, in terms of both structure and function, has been obscure. We believe it likely that fibrous connectors homologous to those described here for Chlamydomonas are general features of centriole-bearing eucaryotic cells.
Heterogeneous expression of Wnt/β‐catenin target genes within colorectal cancer (2007)

Invasion of common colorectal adenocarcinomas is coupled with a transient loss of epithelial differentiation of tumor cells. Previously, we have shown that dedifferentiated tumor cells at the invasive front (IF) accumulate the transcriptional activator beta-catenin in the nucleus, in contrast to cells of the tumor center. To characterize the cells of these two morphogenic tumor areas, gene expression profiling was performed. Our study demonstrates that intratumorous heterogeneity in colorectal cancer correlates with differential expression of 510 genes between the central tumor region (TC) and the IF. Many genes differentially expressed at the IF are involved in cellular invasion processes like cell motility, cell adhesion and extracellular matrix interaction. This in vivo analysis shows overexpression of known Wnt/beta-catenin target genes either in the entire tumor tissue (compared to normal mucosa) or specifically at the IF. Thus, even though all tumor cells overexpress beta-catenin, the existence of at least 2 groups of Wnt/beta-catenin target genes selectively activated in different tumor regions is suggested. The concomitant high expression of inflammation- and tissue repair-related genes at the IF supports the hypothesis that an inflammation-activated microenvironment may trigger selective Wnt/beta-catenin target gene expression and contribute to the malignant progression of colorectal cancer.
A Novel Mechanism for TNF-α Regulation by p38 MAPK: Involvement of NF-κB with Implications for Therapy in Rheumatoid Arthritis (2004)

TNF-alpha is a key factor in a variety of inflammatory diseases. This study examines the role of p38 MAPK in the regulation of TNF-alpha in primary human cells relevant to inflammation, e.g., macrophages and rheumatoid synovial cells. Using a dominant negative variant (D168A) of p38 MAPK and a kinase inhibitor, SB203580, we confirm in primary human macrophages that p38 MAPK regulates TNF-alpha production using a posttranscriptional mechanism requiring the 3' untranslated region of the gene. However, in LPS-activated primary human macrophages we also detect a second previously unidentified mechanism, the p38 MAPK modulation of TNF-alpha transcription. This is mediated through p38 MAPK regulation of NF-kappaB. Interestingly this mechanism was not observed in rheumatoid synovial cells. Importantly however, the dominant negative mutant of p38 MAPK, but not SB203580 was effective at inhibiting spontaneous TNF-alpha production in these ex vivo rheumatoid synovial cell cultures. These data indicate there are potential major differences in the role of p38 MAPK in inflammatory signaling that have a bearing on the use of this kinase as a target for therapy. These results indicate despite disappointing results with p38 MAPK inhibitors in the clinic, this kinase is a valid target in rheumatoid disease.
Complete Oxidation of Glycerol in an Enzymatic Biofuel Cell (2008)

Abstract Glycerol has drawn increasing attention as a prospective fuel because it has many desirable qualities and is abundant due to the fact that it is a by‐product of biodiesel production. Qualities such as nontoxicity, extremely low vapour pressure, low flammability and high energy density make glycerol very appealing as an energy source. Previous research has shown that partial oxidation of glycerol can occur at enzymatic bioanodes of biofuel cells utilising PQQ‐dependent alcohol dehydrogenase (PQQ‐ADH) and PQQ‐dependent aldehyde dehydrogenase (PQQ‐AldDH). In this paper, we describe the use of glycerol for a fuel in an enzymatic biofuel cell that utilizes a three‐enzyme cascade on the anode that can accomplish the complete oxidation of glycerol. The bioanode that was developed contained PQQ‐ADH, PQQ‐AldDH and oxalate oxidase immobilised within a tetrabutylammonium‐modified Nafion membrane. Our previous research has shown that glycerol is an effective fuel with the PQQ‐ADH and PQQ‐AldDH but still was unable to be fully oxidised. With the addition of oxalate oxidase, these glycerol/air biofuel cells have yielded power densities of up to 1.32 mW cm –2 , and have the ability to operate at high fuel concentrations. The oxidation products were confirmed with 13 C NMR and comprised mainly 13 C‐labelled carbonate and glycerate.
Modulation of biomarkers in minimal breast carcinoma (1998)

Biologic phenotypes of MBC can be interpreted as reflecting a dimension of neoplastic progression capacity that is independent of tumor size. This study suggests that biologic markers can be integrated with traditional pathologic indicators for accurate staging of patients.
Higher atrophy rate of entorhinal cortex than hippocampus in AD (2004)

The finding in AD that the atrophy rate in the entorhinal cortex is higher than in the hippocampus is consistent with the view that AD pathology begins in the entorhinal cortex.
849. Transduction of Mouse Dendritic Cells Is Enhanced by Repetitive Infection with Self-Complementary Adeno-Associated Virus 6 Combined with Immunostimulatory Ligands (2005)

The potential of adeno-associated virus (AAV)-based vectors in human gene therapy is being explored for several diseases. Although sustained transgene expression and low vector-associated cellular immunity are attractive features of recombinant (r) AAV, the wider application rAAV vectors encapsidated in serotype 2 capsid, the most commonly applied rAVV, is hampered by poor transduction efficiency in many target tissues. These include ex vivo generated dendritic cells (DC), which have demonstrated promising immunotherapeutic activity. We report here that efficient transduction of mouse bone marrow-derived DC can be achieved with self-complementary (sc) rAAV encapsidated in serotype 6 capsid. Sequential exposure of DC precursor cultures to IL-4 and GM-CSF with sc rAAV6 encoding the human tumor antigen, carcinoembryonic antigen (CEA), for seven days followed by activation with CpG oligodeoxynucleotides (ODN) and anti-mouse CD40 antibody resulted in highly efficient transduction of DC. DC surface markers as determined by flow cytometry analysis of sc rAAV6-transduced DC were comparable to non-transduced DC. Efficiency of vector transduction and transgene expression were confirmed by immunostaining and real-time PCR. Microarray analysis of RNA from CpG-ODN and CD40 antibody stimulated sc AAV6-transduced DC revealed upregulation of transcription factors and cytokines involved in immune activation and down-regulation of inhibitory factors, suggesting a possible role of transcriptional activation in the observed effect. The adoptive transfer into syngeneic mice of the ex vivo transduced and activated DC resulted in the development of CEA-specific antibody. Immunized mice also developed antibody to AAV-6 capsid protein which did not cross-react with AAV-2 capsid protein. These studies demonstrate the potential utility of sc rAAV serotype 6-based vectors in transduction of DC for genetic vaccination approaches.
Alanyl-glutamine Counteracts the Depletion of Free Glutamine and the Postoperative Decline in Protein Synthesis in Skeletal Muscle (1990)

Skeletal muscle protein and amino acid metabolism change after surgical trauma during a period characterized by skeletal muscle protein catabolism. Available total parenteral nutrition (TPN) not containing glutamine does not prevent these changes, while TPN enriched with glutamine has been shown to have beneficial effects on postoperative skeletal muscle protein metabolism. Glutamine, in the form of a dipeptide, alanyl-glutamine, was added to TPN. Patients undergoing elective cholecystectomy were given postoperative TPN. Two groups received isocaloric and isonitrogenous conventional TPN, one group with (n = 8) and the other without an addition of alanyl-glutamine (n = 8). Skeletal muscle protein metabolism was studied in muscle biopsy specimens from which the muscle free amino acid pattern and the concentration and size distribution of ribosomes, serving as a measure of protein synthesis, were determined. In the control group, muscle free glutamine decreased by 38.8% +/- 6.6% and the polyribosome concentration per mg of DNA decreased by 21% +/- 5.2% after operation. In the group given TPN supplemented with alanyl-glutamine, these two parameters of muscle protein and amino acid metabolism did not change significantly. Compared to the control group, whole-body nitrogen balance was improved after operation by the addition of alanyl-glutamine to TPN (p less than 0.01). Muscle free glutamine and muscle protein synthesis were preserved after operation and the whole-body nitrogen balance was improved by adding glutamine in the form of alanyl-glutamine to TPN. The dipeptide alanyl-glutamine seems to be a suitable means of providing glutamine in a stable form.
Expanding the Genetic Code of Yeast for Incorporation of Diverse Unnatural Amino Acids via a Pyrrolysyl-tRNA Synthetase/tRNA Pair (2010)

We report the discovery of a simple system through which variant pyrrolysyl-tRNA synthetase/tRNA(CUA Pyl) pairs created in Escherichia coli can be used to expand the genetic code of Saccharomyces cerevisiae. In the process we have solved the key challenges of producing a functional tRNA(CUA Pyl) in yeast and discovered a pyrrolysyl-tRNA synthetase/tRNA(CUA Pyl) pair that is orthogonal in yeast. Using our approach we have incorporated an alkyne-containing amino acid for click chemistry, an important post-translationally modified amino acid and one of its analogs, a photocaged amino acid and a photo-cross-linking amino acid into proteins in yeast. Extensions of our approach will allow the growing list of useful amino acids that have been incorporated in E. coli with variant pyrrolysyl-tRNA synthetase/tRNA(CUA Pyl) pairs to be site-specifically incorporated into proteins in yeast.
New Practical Synthesis of Indazoles via Condensation of o-Fluorobenzaldehydes and Their O-Methyloximes with Hydrazine (2006)

The reaction of o-fluorobenzaldehydes and their O-methyloximes with hydrazine has been developed as a new practical synthesis of indazoles. Utilization of the methyloxime derivatives of benzaldehydes (in the form of the major E-isomers) in this condensation effectively eliminated a competitive Wolf-Kishner reduction to fluorotoluenes, which was observed in the direct preparations of indazoles from aldehydes. Reaction of Z-isomers of methyloximes with hydrazine resulted in the formation of 3-aminoindazoles via a benzonitrile intermediate.
Human serum amyloid P component is an invariant constituent of amyloid deposits and has a uniquely homogeneous glycostructure. (1994)

Human serum amyloid P component (SAP) is a normal plasma protein and the precursor of amyloid P component (AP), a universal constituent of the abnormal tissue deposits in amyloidosis, including Alzheimer disease. We show here that its single N-linked biantennary oligosaccharide does not display the microheterogeneity usually characteristic of glycoproteins. The protein and the glycan structures of AP were also invariant, their resistance to degradation suggesting a role in persistence of amyloid deposits. Asialo-SAP was rapidly cleared from the circulation in mice by a mechanism dependent on terminal galactose residues and was catabolized in hepatocytes. However blockade of this pathway did not affect the clearance of native SAP. Rapid hepatic uptake and catabolism of human asialo-SAP in man were also directly demonstrated. The protein and glycan homogeneity of SAP and the integrity of AP suggest that the complete glycoprotein structure is important for the normal and the pathophysiological functions of this molecule.
Immunotherapy of tumors with vaccines based on xenogeneic homologous molecules (2002)

This review summarizes and discusses a new vaccine strategy based on xenogeneic homologous molecules by the breaking of immune tolerance against the growth factors or their receptors associated with tumor growth in a cross-reaction between the xenogeneic homologs and self-molecules. The xenogeneic vaccine may circumvent the fact that few tumor-specific antigens have been identified in human solid tumors and that the host usually shows immune tolerance to self-molecules as antigens. It may be of importance for the further exploration of the applications of xenogeneic homologous genes identified in human and other animal genome sequence projects in cancer therapy.
Homologous recombination as the main mechanism for DNA integration and cause of rearrangements in the filamentous ascomycete Ashbya gossypii. (1995)

A slow and a fast growth phenotype were observed after transformation of the phytopathogenic fungus Ashbya gossypii using a plasmid carrying homologous DNA and as selectable marker the Tn903 aminoglycoside resistance gene expressed from a strong A. gossypii promoter. Transformations with circular plasmids yielded slowly and irregularly growing geneticin-resistant mycelia in which 1% of nuclei contained plasmid sequences. Occasionally, fast growing sectors appeared which were shown to be initiated by homologous integration of the transforming DNA. Transformants obtained with plasmids linearized within the homology region immediately exhibited fast radial growth. In all 28 transformants analyzed plasmid DNA was integrated homologously. Such apparent lack of nonhomologous recombination has so far not been observed in filamentous ascomycetes. In 14 transformants two to four tandemly integrated plasmid copies were found. They underwent several types of genetic changes, mainly in the older mycelium: excision of whole plasmid copies and rearrangements within the integrated DNA (inversions and deletions). These internal rearrangements involved 360-bp inverted repeats, remnants of IS-elements flanking the resistance gene, and 156-bp direct repeats, originating from the strong A. gossypii promoter. Improved vectors lacking sequence repetitions were constructed and used for stable one-step gene replacement in A. gossypii.
Adaptation of OSEck for an FPGA-Based Soft Processor Platform (2007)

Integrated systems become larger and more complicated every day while time to market is shortened. Due to this, there is a need for flexible hardware platforms that use programmable logic not only for custom hardware but also for realizing embedded processors. This thesis aims to select a suitable, FPGA targeted, soft processor core and adapt the real-time operating system OSEck to run on the selected target. A study of possibilities to integrate setup and configuration of OSEck into the processor’s IDE is also performed. Studies of OSEck and the two processor candidates MicroBlaze and Nios II have been performed. The processor study showed that MicroBlaze and Nios II have a very similar architecture and both are suitable to host OSEck. MicroBlaze was chosen as target processor mainly because of more available documentation regarding operating system integration. Performance and footprint was measured with OSEck on MicroBlaze. The performance figures indicate that MicroBlaze can not be expected to have the same processing power as hard processors but works well as a control processor. To achieve high application performance, custom hardware accelerators can be connected. Integration investigations and tests have been performed with the goal of making an interface that conforms to the normal MicroBlaze design flow. OSEck has been successfully adapted to run on MicroBlaze and integration in the development environment is possible although some steps have to be done manually. Alternative integration options are discussed.
Transcription Activator-Like Effector Nucleases (TALEN)-Mediated Targeted DNA Insertion in Potato Plants (2016)

Targeted DNA integration into known locations in the genome has potential advantages over the random insertional events typically achieved using conventional means of genetic modification. Specifically integrated transgenes are guaranteed to co-segregate, and expression level is more predictable, which makes downstream characterization and line selection more manageable. Because the site of DNA integration is known, the steps to deregulation of transgenic crops may be simplified. Here we describe a method that combines transcription activator-like effector nuclease (TALEN)-mediated induction of double strand breaks (DSBs) and non-autonomous marker selection to insert a transgene into a pre-selected, transcriptionally active region in the potato genome. In our experiment, TALEN was designed to create a DSB in the genome sequence following an endogenous constitutive promoter. A cytokinin vector was utilized for TALENs expression and prevention of stable integration of the nucleases. The donor vector contained a gene of interest cassette and a promoter-less plant-derived herbicide resistant gene positioned near the T-DNA left border which was used to select desired transgenic events. Our results indicated that TALEN induced T-DNA integration occurred with high frequency and resulting events have consistent expression of the gene of interest. Interestingly, it was found that, in most lines integration took place through one sided homology directed repair despite the minimal homologous sequence at the right border. An efficient transient assay for TALEN activity verification is also described.
Conjunctiva-Associated Lymphoid Tissue – Current Knowledge, Animal Models and Experimental Prospects (2009)

The conjunctiva contains organized lymphoid tissue that consists of intraepithelial lymphocytes, subepithelial lymphoid follicles and adjacent lymphatics and blood vessels. This conjunctiva-associated lymphoid tissue (CALT) is assumed to play a key role in the protection of the ocular surface by initiating and regulating immune responses. The article reviews the current knowledge of CALT in humans and compares its structure and functions with mucosa-associated lymphoid tissues at other mucosal sites. An update is given on CALT animal models and on functional studies on the transepithelial transport of microorganisms and antigenic substances by specialized epithelial cells. The use of two-photon microscopy is reviewed regarding its importance to the understanding of dynamic processes going on within CALT.
Antibody Engineering for Targeted Therapy of Cancer Recombinant Fv-Immunotoxins (2001)

Recombinant Fv-immunotoxins are a new class of biologic anticancer agents composed of a recombinant antibody fragment linked to a very potent bacterial toxin. These potent molecules are designed to specifically bind and kill cancer cells that express a specific target antigen on their cell surface. Recombinant Fv-immunotoxins are an excellent example for the concept of rational drug design. They combine the progress in understanding cancer biology, -the recent knowledge on the mechanisms of malignant transformation and the special properties of cancer cells, -with the enormous developments in recombinant DNA technology and antibody engineering. Recombinant Fv immunotoxins were developed for solid tumors and hematological malignancies and have been characterized intensively for their biological activity in vitro and in vivo in animal models. The excellent in vitro and in vivo activities of recombinant Fv-immunotoxins have lead to their pre-clinical development and to the initiation of clinical trial protocols. Recent trials have demonstrated potent clinical efficacy in patients with malignant diseases that are refractory to traditional modalities of cancer treatment. It is thus suggested that this strategy can be developed into a separate modality of cancer treatment with the basic rationale of specifically targeting cancer cells on the basis of their unique surface markers combined with potent effective biological toxic agents that directly kill the cancer cell. Efforts are now being made to improve the current molecules and to develop new agents with better clinical efficacy. In this review, we will describe the rationale in designing Fv-immunotoxins and will review current progress made in using these agents for cancer treatment.
Identification and Characterization of Nuclear and Nucleolar Localization Signals in the Adeno-Associated Virus Serotype 2 Assembly-Activating Protein (2015)

Adeno-associated virus (AAV) has become a popular and successful vector for in vivo gene therapy; however, its biology has yet to be fully understood. In this regard, the recent discovery of the assembly-activating protein (AAP), a nonstructural, nucleolar-localizing AAV protein essential for viral capsid assembly, has provided us a new opportunity to better understand the fundamental processes required for virion formation. Here, we identify clusters of basic amino acids in the carboxy terminus of AAP from AAV serotype 2 (AAV2) that act as nuclear and nucleolar localization signals. We also demonstrate their importance in maintaining AAP expression levels and efficient production of viral capsids. Insights into the functions of AAP can elucidate the requirements and process for AAV capsid assembly, which may lead to improved vector production for use in gene therapy. This study also contributes to the growing body of work on nuclear and nucleolar localization signals.