gebhart/patrepeval huggingface dataset:
In vivo time-serial multi-modality optical imaging in a mouse model of ovarian tumorigenesis (2013)

Identification of the early microscopic changes associated with ovarian cancer may lead to development of a diagnostic test for high-risk women. In this study we use optical coherence tomography (OCT) and multiphoton microscopy (MPM) (collecting both two photon excited fluorescence [TPEF] and second harmonic generation [SHG]) to image mouse ovaries in vivo at multiple time points. We demonstrate the feasibility of imaging mouse ovaries in vivo during a long-term survival study and identify microscopic changes associated with early tumor development. These changes include alterations in tissue microstructure, as seen by OCT, alterations in cellular fluorescence and morphology, as seen by TPEF, and remodeling of collagen structure, as seen by SHG. These results suggest that a combined OCT-MPM system may be useful for early detection of ovarian cancer.
A Low-Pass Prototype Network for Microwave Linear Phase Filters (1970)

A new approximation theory is presented for a low-pass prototype filter which simultaneously optimizes both the passband amplitude and phase response of the scattering transfer coefficient over the same finite band. This closed form solution is expressed in terms of single polynomial, which is readily generated through a simple recurrence formula, and has been termed the equidistant linear phase polynomial since its phase deviation from linearity vanishes at equidistant points along the real frequency axis. A synthesis procedure is presented for the realization of this transfer function using a resistively terminated, symmetrical, lossless, two-port network where extensive use is made of the immittance inverter concept. The even-mode admittance, which defines the network, possesses a simple closed form representation in terms of the equidistant linear phase polynomial and its derivative, and consequently, the entire theory is derived in an analytic form. Typical performance characteristics are graphically presented for networks of up to 14th degree, illustrating the superiority of this new approach over any other known form of approximation theory for selective linear phase filters.
Hydroxylated 2-(5'-salicyl)naphthalenes as protein-tyrosine kinase inhibitors (1993)

The salicyl group figures prominently in several potent protein-tyrosine kinase (PTK) inhibitors, including the fermentation product lavendustin A (3), the salicylsulfonyl nitrostyryl 30, and our recently reported salicyl-containing stilbene 7. Taking compound 7 and the isomeric 8 as lead structures, bicyclic nuclei 9-12 were prepared as conformationally constrained mimetics in which the hydroxyphenyl rings of 7 and 8 are held coplanar with the stilbene ethylene bridge. A similar approach with styryl-based PTK inhibitors of structure 1 previously yielded analogues 2 with enhanced potency. In the present case, however, the resulting salicyl-containing bicyclics exhibited extremely poor inhibitory potency when examined against autophosphorylation of immunoprecipitated p56lck PTK preparations. The implications of these results are discussed as they relate to the potential ways in which salicyl-containing stilbenes may be oriented relative to styryl-based inhibitors of type 1 and to an emerging class of potent aryl-substituted bicyclic inhibitors exemplified by compound 31.
Ultrahigh-Density Nanowire Arrays Grown in Self-Assembled Diblock Copolymer Templates (2000)

We show a simple, robust, chemical route to the fabrication of ultrahigh-density arrays of nanopores with high aspect ratios using the equilibrium self-assembled morphology of asymmetric diblock copolymers. The dimensions and lateral density of the array are determined by segmental interactions and the copolymer molecular weight. Through direct current electrodeposition, we fabricated vertical arrays of nanowires with densities in excess of 1.9 x 10(11) wires per square centimeter. We found markedly enhanced coercivities with ferromagnetic cobalt nanowires that point toward a route to ultrahigh-density storage media. The copolymer approach described is practical, parallel, compatible with current lithographic processes, and amenable to multilayered device fabrication.
Production of Antigen-Specific Human Monoclonal Antibodies: Comparison of Mice Carrying IgH/κ or IgH/κ/λ Transloci (2002)

Here we compare human monoclonal antibody (MAb) production from mouse strains that carry disruptions of their endogenous mouse IgH/Igκ loci and harbor human IgM + Igκ (BABκ) or human IgM + Igκ + Igλ transloci (BABκ,λ). We found that whereas both strains proved effective for the isolation of antigen-specific IgM antibodies, many of the IgM MAbs elicited from BABκ comprise human μ chains that are associated with mouse λ chains. In contrast, BABκ,λ mice gave rise to fully functional, polymeric human IgM antibodies comprising both human IgH and human IgL chains. Therefore, the inclusion of a human Igλ translocus (in addition to the human IgH + Igκ transloci) not only diminishes problems of endogenous mouse Igλ expression but also provides a strain of mice that yields fully human MAbs to a wide range of antigens, as witnessed by the isolation of MAbs to human blood cells, tumor cell lines, and an immunoglobulin idiotype.
Molecular cloning and expression of the catalytic subunit of bovine pyruvate dehydrogenase phosphatase and sequence similarity with protein phosphatase 2C (1993)

After many unsuccessful attempts to detect cDNA encoding the catalytic subunit of bovine pyruvate dehydrogenase phosphatase (PDPc) in bovine cDNA libraries, an approach based on the polymerase chain reaction (PCR) was undertaken. Overlapping DNA fragments were generated by PCR from bovine genomic DNA and from cDNA synthesized from total RNA with synthetic oligonucleotide primers on the basis of experimentally determined amino acid sequences. The DNA fragments were subcloned and sequenced. The complete cDNA is 1900 base pairs in length and contains an open reading frame of 1614 nucleotides encoding a putative presequence of 71 amino acid residues and a mature protein of 467 residues with a calculated M(r) of 52,625. Hybridization analysis showed a single mRNA transcript of about 2.0 kilobases. Comparison of the deduced amino acid sequences of the mitochondrial PDPc and the rat cytosolic protein phosphatase 2C indicates that these protein serine/threonine phosphatases evolved from a common ancestor. The mature form of PDPc was coexpressed in Escherichia coli with the chaperonin proteins groEL and groES. The recombinant protein (rPDPc) was purified to near homogeneity. Its activity toward the bovine 32P-labeled pyruvate dehydrogenase complex was Mg(2+)-dependent and Ca(2+)-stimulated and comparable to that of native bovine PDP. An active, truncated form of rPDPc, with M(r) approximately 45,000, was produced in variable amounts during growth of cells and/or during the purification procedure.
An Interframe Coding Technique for Broadcast Television (1980)

A technique for coding the luminance component of a broadcast television signal that was designed to operate at a transmission rate of 10 Mbit/s is described. The algorithm employs conditional interpolation in which one picture element of a block is accurately coded (using differential pulse code modulation) and an attempt is made to interpolate the remaining elements in the block. Those elements that are not accurately interpolated, according to a visually oriented criterion, are indicated by a code, and correction information is additionally transmitted. The algorithm codes with high quality the wide range of picture material likely to be encountered in broadcast television, where high levels of detail, fast panning, and noisy signals are problems. With a transmission error rate of 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-6</sup> (prior to error correction), picture quality remains very high, while at a rate of 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-4</sup> a small but noticeable increase in noise level is noticed adjacent to moving edges and in detailed areas.
A Homolog of CcpA Mediates Catabolite Control in Listeria monocytogenes but Not Carbon Source Regulation of Virulence Genes (1998)

Readily utilizable sugars down-regulate virulence gene expression in Listeria monocytogenes, which has led to the proposal that this regulation may be an aspect of global catabolite regulation (CR). We recently demonstrated that the metabolic enzyme alpha-glucosidase is under CR in L. monocytogenes. Here, we report the cloning and characterization from L. monocytogenes of an apparent ortholog of ccpA, which encodes an important mediator of CR in several low-G+C-content gram-positive bacteria. L. monocytogenes ccpA (ccpALm) is predicted to encode a 335-amino-acid protein with nearly 65% identity to the gene product of Bacillus subtilis ccpA (ccpABs). Southern blot analysis with a probe derived from ccpALm revealed a single strongly hybridizing band and also a second band of much lower intensity, suggesting that there may be other closely related sequences in the L. monocytogenes chromosome, as is the case in B. subtilis. Disruption of ccpALm resulted in the inability of the mutant to grow on glucose-containing minimal medium or increase its growth rate in the presence of preferred sugars, and it completely eliminated CR of alpha-glucosidase activity in liquid medium. However, alpha-glucosidase activity was only partially relieved from CR on solid medium. These results suggest that ccpA is an important element of carbon source regulation in L. monocytogenes. Nevertheless, utilizable sugars still down-regulate the expression of hly, which encodes the virulence factor hemolysin, in a ccpALm mutant, indicating that CcpA is not involved in carbon source regulation of virulence genes.
Therapeutic Potential of Splice-Switching Oligonucleotides (2020)

Alternative splicing enables a single pre-messenger RNA transcript to yield multiple protein isoforms, making it a major contributor to the diversity of the proteome. While this process is essential for normal development, aberrations in alternative splicing are the cause of a multitude of human diseases. Methods for manipulating alternative splicing would thus be of therapeutic value. Chemically modified antisense oligonucleotides that alter alternative splicing by directing splice site selection have been developed to achieve this end. These splice-switching oligonucleotides (SSOs) have been applied to correct aberrant splicing, induce expression of a therapeutic splice variant, or induce expression of a novel therapeutic splice variant in a number of disease-relevant genes. Recently, in vivo efficacy of SSOs has been reported using animal disease models, as well as in results from the first clinical trial.
PREPARATION AND CHARACTERIZATION OF AN IMMUNOELECTRON MICROSCOPE TRACER CONSISTING OF A HEME-OCTAPEPTIDE COUPLED TO Fab (1974)

A heme-octapeptide (mol wt 1,550) has been obtained from cytochrome c by successive pepsin and trypsin hydrolysis and purified by gel filtration and countercurrent distribution. It possesses peroxidatic activity characterized by an apparent K(m) of 0.2 M, an apparent v(max) of 4 mmol/min per mg of peptide, and a pH optimum of 7.0. Using a novel two-step conjugation procedure, the heme-octapeptide was coupled to rabbit Fab antibody fragments by first derivatizing it with the N-hydroxysuccinimide ester of p-formylbenzoic acid and subsequently allowing it to form a Schiff base with the amino groups of Fab. Stable covalent linkages were then obtained by reduction of the Schiff bases with sodium borohydride. The conjugate consists of approximately 2 heme-octapeptides attached to each Fab molecule. The molecular weight is 45,000 daltons when coupled to sheep Fab and 50,000 daltons with a Stokes radius of 32 A, when conjugated to rabbit Fab. Its peroxidatic activity is characterized by an apparent K(m) of 0.4 M, an apparent v(max) of 0.4 mmol/min and per mg of attached heme-octapeptide and a pH optimum of 7.0. The conjugate has been used for the localization at the electron microscope level of secretory immunoglobulins in the mammary gland of lactating rabbits.
Variant-Sequence Transthyretin (Isoleucine 122) in Late-Onset Cardiac Amyloidosis in Black Americans (1997)

The assessment of elderly black patients with unexplained heart disease should include a consideration of transthyretin amyloidosis, particularly that related to the Ile 122 allele.
Secretion and expression of the Pasteurella haemolytica Leukotoxin (1990)

The Pasteurella haemolytica leukotoxin gene cluster (lktCABD) is homologous to the Escherichia coli hemolysin locus (hlyCABD). Since the cloned leukotoxin (LktA) is not secreted from E. coli cells, a heteroplasmid complementation system was developed that permits secretion of the leukotoxin from cells expressing the hemolysin transport proteins HlyB and HlyD. We observed that the secreted leukotoxin protein had weak hemolytic activity when activated by either the HlyC or LktC proteins and that LktC expressed in E. coli could confer weak hemolytic activity upon hemolysin. Thus, it appears that the accessory proteins of the leukotoxin and hemolysin gene clusters are functionally similar, although their expression in E. coli is not equivalent. Northern (RNA) blot analysis of the P. haemolytica leukotoxin gene cluster revealed a major 3.5-kilobase transcript that includes the lktC and lktA genes. The start site for this transcript mapped to a cytosine residue 30 nucleotides upstream from the putative start of lktC; a similar initiation site was observed in E. coli, although adjacent cytosine and adenine residues were also utilized. The 3.5-kilobase transcript terminated near the rho-independent terminator structure between lktA and lktB, but transcription may continue, via antitermination or de novo transcription initiation, into the downstream lktB and lktD genes. We propose that the lack of LktB and LktD function in E. coli is a result, at least in part, of poor lktBD transcription and suggest that a P. haemolytica-specific regulator is required for optimal expression of the leukotoxin genes.
The resurfacing of adult rabbit articular cartilage by multiple perforations through the subchondral bone. (1976)

The repair of articular cartilage removed from the femora of adult rabbits at the knee was studied. When multiple perforations were made through the subchondral bone a cartilaginous material, staining heavily with safranin O, first filled the holes. This material resembled hyaline cartilage, and by twelve months there was complete resurfacing of the joint, although the material lost its hyaline appearance after eight months and at one year it resembled dense collagenous tissue.
Cloning and mapping of the manganese superoxide dismutase gene (sodA) of Escherichia coli K-12 (1983)

An Escherichia coli gene bank composed of large DNA fragments (about 40 kilobases) was constructed by using the small cosmid pHC79. From it, a clone was isolated for its ability to overproduce superoxide dismutase. The enzyme overproduced was manganese superoxide dismutase, as determined by electrophoresis and antibody precipitation. Maxicell analysis and two-dimensional O'Farrell polyacrylamide gel electrophoresis demonstrated that the structural gene, sodA, of manganese superoxide dismutase was cloned. Subcloning fragments from the original cosmid located the sodA gene within a 4.8-kilobase EcoRI-BamHI fragment. This fragment was inserted into a lambda phage which was deleted for the att region and consequently could only lysogenize by recombination between the cloned bacterial DNA insertion and the bacterial chromosome. Genetic mapping of the prophage in such lysogens indicated that the chromosomal sodA locus lies near 87 min on the E. coli map.
Ultralow-refractive-index optical thin films through nanoscale etching of ordered mesoporous silica films (2012)

A great deal of intensive research has been conducted to obtain high-quality transparent ultralow-refractive-index and ultralow-dielectric-constant thin films for microptics and microelectronics applications. Here, we report a simple procedure to prepare highly porous silica thin films with high optical quality and water resistance through nano-etching of mesoporous silica films followed by fluoroalkylsilane surface modification. The films possess an ultralow refractive index of 1.03 (800 nm) and an ultralow dielectric constant of 1.30 (100 kHz), to our knowledge the lowest values ever reported in thin film materials. The films are superhydrophobic (water contact angle=156 deg), thus exhibit high moisture stability.
Thalidomide's effectiveness in erythema nodosum leprosum is associated with a decrease in CD4+ cells in the peripheral blood (1992)

Thalidomide is well documented as being an effective drug in the treatment of erythema nodosum leprosum (ENL). The mechanism of action of thalidomide in ENL as well as the pathogenesis of ENL are yet to be fully determined. Lepromatous leprosy patients experiencing ENL have been reported to have an increase in the ratio of CD4+ to CD8+ cells in their blood and ENL skin lesions. Thalidomide has been shown to cause a decrease in the ratio of CD4+ to CD8+ lymphocytes in the blood of healthy males. This decrease was due to a significant reduction in the numbers of Cd4+ lymphocytes and an apparent increase in the numbers of CD8+ lymphocytes. In this study, thalidomide's effectiveness in halting chronic ENL and arresting a relapse into ENL was consistently associated with a decrease in the numbers of CD4+ lymphocytes in the blood of 2 male lepromatous leprosy patients.
PbS colloidal quantum dot photoconductive photodetectors: Transport, traps, and gain (2007)

We investigate experimentally the origins of gain in PbS colloidal quantum dot photodetectors. We employ measurements of photocurrent, its transient behavior, and dark current over a wide range of temperatures. We find the hole mobility to have an activation energy of 0.16eV, and we identify photosensitizing centers at ∼0.1, 0.2, and 0.3eV below the conduction band edge. These centers account for the 60, 300, and 2000ms fall times observed in the transient response of the photocurrent at room temperature. These centers enable us to account for the constancy of photoconductive gain across the wide temperature range of 250–340K.
Activity and intracellular localization of the human cytomegalovirus protein pp71 (2002)

The human cytomegalovirus (HCMV) tegument phosphoprotein pp71 activates viral immediate early (IE) transcription and thus has a role in initiating lytic infection. Protein pp71 stimulates expression from a range of promoters in a sequence-independent manner, and in this respect behaves similarly to the herpes simplex virus type 1 (HSV-1) IE protein ICP0. The intracellular localization of pp71 was investigated after its expression from transfected plasmids or from HSV-1 mutants constructed to produce pp71 transiently. The protein colocalized with the cell promyelocytic leukaemia (PML) protein at nuclear domain 10 (ND10) structures but, unlike ICP0, pp71 did not induce disruption of ND10. The activity of pp71 in mouse sensory neurons in vivo was investigated after co-inoculation of animals with pairs of HSV-1 mutants, one expressing pp71 and the second containing the E. coli lacZ gene controlled by various promoters. In this system, pp71 stimulated beta-galactosidase expression from a range of viral IE promoters when mice were analysed at 4 days postinoculation. At later times, expression of pp71 resulted in a reduction in numbers of neurons containing beta-galactosidase, indicating cytotoxicity or promoter shutoff. The HSV-1 latency-active promoter was not responsive to pp71, demonstrating specificity in the activity of the protein. Pp71 was as active in mice lacking both copies of the PML gene (PML-/-) as in control animals, and in PML-/- fibroblasts pp71 stimulated gene expression as effectively as in other cell types. Therefore, neither the PML protein nor the normal ND10 structure is necessary for pp71 to stimulate gene expression.
Degradation of Carbon-Supported Pt Bimetallic Nanoparticles by Surface Segregation (2009)

Surface segregation of the non-noble component of a Pt bimetallic core-shell catalyst can occur even at room temperature under typical fuel cell cathode application conditions. While in an alkaline environment the nanoparticles remain stable, and the alteration in the surface composition can be tracked in situ; in an acidic electrolyte, any non-noble alloying material at the surface would immediately dissolve into the electrolyte. Therefore, such catalysts are expected to degrade steadily during operation in an acidic fuel cell until only Pt is left.
Identification of Cathepsin B as a Mediator of Neuronal Death Induced by Aβ-activated Microglial Cells Using a Functional Genomics Approach (2004)

Alzheimer's disease is a progressive neurodegenerative disease characterized by senile plaques, neurofibrillary tangles, dystrophic neurites, and reactive glial cells. Activated microglia are found to be intimately associated with senile plaques and may play a central role in mediating chronic inflammatory conditions in Alzheimer's disease. Activation of cultured murine microglial BV2 cells by freshly sonicated Abeta42 results in the secretion of neurotoxic factors that kill primary cultured neurons. To understand molecular pathways underlying Abeta-induced microglial activation, we analyzed the expression levels of transcripts isolated from Abeta42-activated BV2 cells using high density filter arrays. The analysis of these arrays identified 554 genes that are transcriptionally up-regulated by Abeta42 in a statistically significant manner. Quantitative reverse transcription-PCR was used to confirm the regulation of a subset of genes, including cysteine proteases cathepsin B and cathepsin L, tissue inhibitor of matrix metalloproteinase 2, cytochrome c oxidase, and allograft inflammatory factor 1. Small interfering RNA-mediated silencing of the cathepsin B gene in Abeta-activated BV2 cells diminished the microglial activation-mediated neurotoxicity. Moreover, CA-074, a specific cathepsin B inhibitor, also abolished the neurotoxic effects caused by Abeta42-activated BV2 cells. Our results suggest an essential role for secreted cathepsin B in neuronal death mediated by Abeta-activated inflammatory response.
Ethical issues in deep brain stimulation (2011)

Deep brain stimulation (DBS) is currently used to treat neurological disorders like Parkinson's disease, essential tremor, and dystonia, and is explored as an experimental treatment for psychiatric disorders like major depression and obsessive compulsive disorder. This mini review discusses ethical issues in DBS treatment and research, as they have been discussed in the medical and ethical literature. With regard to DBS treatment, the most important issues are balancing risks and benefits and ensuring respect for the autonomous wish of the patient. This implies special attention to patient selection, psycho-social impact of treatment, effects on personal identity, and treatment of children. Moreover, it implies a careful informed consent process in which unrealistic expectations of patients and their families are addressed and in which special attention is given to competence. In the context of research, the fundamental ethical challenge is to promote high-quality scientific research in the interest of future patients, while at the same time safeguarding the rights and interests of vulnerable research subjects. Several guidelines have been proposed to ensure this. One of the preconditions to further development of responsible and transparent research practices is the establishment of a comprehensive registry.