gebhart/patrepeval huggingface dataset:
Immunogenicity and Protective Efficacy of DNA Vaccines Expressing Rhesus Cytomegalovirus Glycoprotein B, Phosphoprotein 65-2, and Viral Interleukin-10 in Rhesus Macaques (2006)

Rhesus cytomegalovirus (RhCMV) infection of macaques exhibits strong similarities to human CMV (HCMV) persistence and pathogenesis. The immunogenicity of DNA vaccines encoding three RhCMV proteins (a truncated version of glycoprotein B lacking the transmembrane region and endodomain [gBDeltaTM], phosphoprotein 65-2 [pp65-2], and viral interleukin-10 [vIL-10]) was evaluated in rhesus macaques. Two groups of monkeys (four per group) were genetically immunized four times with a mixture of either pp65-2 and gBDeltaTM or pp65-2, vIL-10, and gBDeltaTM. The vaccinees developed anti-gB and anti-pp65-2 antibodies in addition to pp65-2 cellular responses after the second booster immunization, with rapid responses observed with subsequent DNA injections. Weak vIL-10 immune responses were detected in two of the four immunized animals. Neutralizing antibodies were detected in seven monkeys, although titers were weak compared to those observed in naturally infected animals. The immunized monkeys and naïve controls were challenged intravenously with 10(5) PFU of RhCMV. Anamnestic binding and neutralizing antibody responses were observed 1 week postchallenge in the vaccinees. DNA vaccination-induced immune responses significantly decreased peak viral loads in the immunized animals compared to those in the controls. No difference in peak viral loads was observed between the pp65-2/gBDeltaTM DNA- and pp65-2/vIL-10/gBDeltaTM-vaccinated groups. Antibody responses to nonvaccine antigens were lower postchallenge in both vaccine groups than in the controls, suggesting long-term control of RhCMV protein expression. These data demonstrated that DNA vaccines targeting the RhCMV homologues of HCMV gB and pp65 altered the course of acute and persistent RhCMV infection in a primate host.
Enzyme replacement therapy – a brief history (2006)

The concept of enzyme replacement therapy for lysosomal storage diseases was enunciated by de Duve in 1964. However, much cell biology had to be learned before lysosomal enzymes could be developed into pharmaceuticals. A model system, consisting of cultured skin fibroblasts from patients with mucopolysaccharidoses (MPS), showed that their defective glycosaminoglycan catabolism could be corrected by factors derived from cells of a different genotype. The corrective factors were identified as lysosomal enzymes with a special feature, or recognition signal, that would permit efficient uptake. As the recognition signal was absent from a number of lysosomal enzymes secreted by fibroblasts from patients with I-cell disease (a monogenic disorder), it was postulated to be a post-translational modification of the lysosomal enzymes. It was subsequently shown to be a carbohydrate and identified as mannose-6-phosphate (M6P), which was recognized by ubiquitous M6P receptors. A second model system was the clearance, in vivo, of lysosomal enzymes from plasma. The recognition signal for this system was identified as mannose, and clearance was shown to be mediated by the mannose receptor of the reticuloendothelial system. This second system was immediately put to use for the treatment of Gaucher disease type I, in which macrophages are the affected cells. Native, and later recombinant, glucocerebrosidase was modified to expose terminal mannose residues; it became the first successful pharmaceutical for a lysosomal storage disease. Recombinant lysosomal enzymes containing the M6P signal have been developed (or are in the advanced stages of development) into pharmaceuticals for the treatment of Fabry disease, MPS I, MPS II, MPS VI and Pompe disease.
Interaction of Creatine Kinase from Monkey Brain with Substrate: Analysis of Kinetics and Fluorescence Polarization (1983)

Abstract: Titrimetric determination of the dissociation constants for the binding of substrates to creatine kinase from monkey brain reveals 13‐fold and 4‐fold synergism in the forward and reverse directions, respectively. This synergism is expressed as a decrease in the K D for a given substrate in the ternary complex compared with the binary complex and may be a reflection of substrate‐induced conformational change. Creatine kinase labeled with two molecules of 5′‐iodoacetamidofluorescein displays a blue shift and a decrease in fluorescence intensity upon binding of MgADP, indicative of movement of the dye into a more hydrophobic environment and quenching of the extrinsic fluorescense. Rotational relaxation times determined from analysis of fluorescence polarization of dansylated brain creatine kinase decrease from 212 ± 7 ns to 189 ± 6 ns upon MgADP binding. Dansylated creatine kinase in 0.5% sodium dodecyl sulfate has a rotational relaxation time of 135 ± 6 ns. The rotational relaxation time of dansylated muscle‐type isoenzyme is unaffected by MgADP and has the same value as the brain isoenzyme‐MgADP complex. Polarization values at 25°C for muscle and brain enzyme labeled with 3 ‐ (4 ‐ maleimidylphenyl) ‐ 7 ‐ diethylamino ‐ 4 ‐ methylcoumarin compared with limiting polarization and polarization of the free dye suggest that the dye rotation is severely restricted in the muscle form, but possesses freedom of rotation in the brain form. These results support the conclusion that compared with the muscle isoenzyme, the brain isoenzyme is more open at the active site and more flexible overall. Binding of MgADP by brain creatine kinase produces a protein more compact across one or both of its rotational axes, thus resembling the conformation of the muscle isoenzyme. It is probable that creatine kinase in the brain, unlike that from muscle, is subject to kinetic regulation accompanied by conformational modification. This suggests that the neurobiochemical role of the brain isoenzyme is distinct from the metabolic function of the muscle isoenzyme.
Dynamic trust management for internet of things applications (2012)

We propose a dynamic trust management protocol for Internet of Things (IoT) systems to deal with misbehaving nodes whose status or behavior may change dynamically. We consider an IoT system being deployed in a smart community where each node autonomously performs trust evaluation. We provide a formal treatment of the convergence, accuracy, and resilience properties of our dynamic trust management protocol and validate these desirable properties through simulation. We demonstrate the effectiveness of our dynamic trust management protocol with a trust-based service composition application in IoT environments. Our results indicate that trust-based service composition significantly outperforms non-trust-based service composition and approaches the maximum achievable performance based on ground truth status. Furthermore, our dynamic trust management protocol is capable of adaptively adjusting the best trust parameter setting in response to dynamically changing environments to maximize application performance.
Expression and regulation of Lhx6 and Lhx7, a novel subfamily of LIM homeodomain encoding genes, suggests a role in mammalian head development (1998)

LIM-homeobox containing (Lhx) genes encode trascriptional regulators which play critical roles in a variety of developmental processes. We have identified two genes belonging to a novel subfamily of mammalian Lhx genes, designated Lhx6 and Lhx7. Whole-mount in situ hybridisation showed that Lhx6 and Lhx7 were expressed during mouse embryogenesis in overlapping domains of the first branchial arch and the basal forebrain. More specifically, expression of Lhx6 and Lhx7 was detected prior to initiation of tooth formation in the presumptive oral and odontogenic mesenchyme of the maxillary and mandibular processes. During tooth formation, expression was restricted to the mesenchyme of individual teeth. Using explant cultures, we have shown that expression of Lhx6 and Lhx7 in mandibular mesenchyme was under the control of signals derived from the overlying epithelium; such signals were absent from the epithelium of the non-odontogenic second branchial arch. Furthermore, expression studies and bead implantation experiments in vitro have provided strong evidence that Fgf8 is primarily responsible for the restricted expression of Lhx6 and Lhx7 in the oral aspect of the maxillary and mandibular processes. In the telencephalon, expression of both genes was predominantly localised in the developing medial ganglionic eminences, flanking a Fgf8-positive midline region. We suggest that Fgf8 and Lhx6 and Lhx7 are key components of signalling cascades which determine morphogenesis and differentiation in the first branchial arch and the basal forebrain.
Transfer of experimental autoimmune thyroiditis with T cell clones. (1987)

We have investigated three T lymphocyte clones isolated from CBA/CaJ mice primed with mouse thyroid extract (MTE) in adjuvant. All three clones are L3T4+, Ig-, and Lyt2- and proliferate to MTE, mouse thyroglobulin (MTG) and rat thyroid extract. Clones A7 and B7 transfer thyroiditis to irradiated (475 rad) syngeneic mice, but not to normal recipients. The thyroid lesion induced by the B7 clone is characterized by the infiltration of both mononuclear and polymorphonuclear cells. The thyroiditis is transient in that lesions are apparent 7 and 14 days after transfer, but thyroids return to normal by day 21. Clone B7 showed helper activity for trinitrophenyl-keyhole limpet hemocyanin-primed B cells in vitro when stimulated with trinitrophenyl-MTG and also stimulated the production of anti-MTG antibody in recipient mice. Clone A7 induced thyroid lesions characterized by infiltration of the thyroid with mononuclear cells, with virtually no polymorphonuclear cell infiltration. This clone has shown no helper activity following stimulation with trinitrophenyl-MTG. The third clone (D2) proliferates to and shows helper activity to MTG, but fails to transfer thyroiditis to syngeneic, irradiated mice. On continuous culture, clone B7 lost its surface Thy. The loss of Thy appears unrelated to the ability to transfer thyroiditis since subclones of B7 with markedly different percentages of Thy+ cells transferred disease equally well.
Limits of Performance Gain of Aligned CNT Over Randomized Network: Theoretical Predictions and Experimental Validation (2007)

Nanobundle thin-film transistors (NB-TFTs) that are based on random networks of single-walled carbon nanotubes are often regarded as high performance alternative to amorphous-Si technology for various macroelectronic applications involving sensors and displays. Here, we use stick-percolation model to study the effect of collective (stick) alignment on the performance of NB-TFTs. For long-channel TFT, small degree of alignment improves the drain current due to the reduction of average path length; however, near-parallel alignment degrades the current rapidly, reflecting the decrease in the number of connecting paths bridging the source/drain. In this paper, we 1) use a recently developed alignment technique to fabricate NB-TFT devices with multiple densities D, alignment thetas, stick length L <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">S</sub> , and channel length L <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">C</sub> ; 2) interpret the experimental data with a stick- percolation model to develop a comprehensive theory of NB-TFT for arbitrary D,thetas, L <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">S</sub> , and L <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">C</sub> ; and 3) demonstrate theoretically and experimentally the feasibility of fivefold enhancement in current gain with optimized transistor structure.
Recent developments in aluminium contamination of products used in parenteral nutrition (2006)

The issues surrounding aluminium toxicity are real and must be addressed. In order to make meaningful changes in clinical practice, low aluminium parenteral nutrition additives are needed and studies must be conducted using currently available products. It remains a challenge to optimize nutritional intake from parenteral nutrition and at the same time reduce aluminium exposure.
The Power of Association Studies to Detect the Contribution of Candidate Genetic Loci to Variation in Complex Traits (1999)

The statistical power of five association study test statistics (two haplotype-based tests, two marker-based tests, and the Transmission Disequilibrium Test-Q5) to detect single nucleotide polymorphism (SNP)/phenotype associations in a linkage-disequilibrium-based candidate gene scan employing a number of SNPs is examined. Power is estimated as a function of realistic parameters expected to affect the likelihood of detecting a significant association: the number of SNPs examined, the scaled recombination size of the region examined, the proportion of variance in the trait attributable to a hidden causative polymorphism within the region, and the number of individuals or families examined. For the different combinations of parameter values, power is estimated from a large number of realizations of a simulated coalescent describing a single random mating population with mutation, random genetic drift, and recombination. This explicit population genetics model results in a distribution of DNA marker heterozygosities and linkage disequilibria that are likely to resemble those expected in actual population samples. The study concludes that (1) marker-based permutation tests are more powerful than simple haplotype-based tests, (2) there is sufficient power to detect the presence of causative polymorphisms of small effect if on the order of 500 individuals are sampled, (3) greater power is achieved by increasing the sample size than by increasing the number of polymorphisms, (4) association studies are generally more powerful than transmission disequilibrium-based tests, and (5) for the range of parameters considered association studies have a low repeatability unless sample sizes are on the order of 500 individuals. Estimates of 4Nc for a number of gene regions and human populations will be of use in determining the density of SNPs that are likely to be required for successful association studies.
Ensembles of engineered cardiac tissues for physiological and pharmacological study: Heart on a chip (2011)

Traditionally, muscle physiology experiments require multiple tissue samples to obtain morphometric, electrophysiological, and contractility data. Furthermore, these experiments are commonly completed one at a time on cover slips of single cells, isotropic monolayers, or in isolated muscle strips. In all of these cases, variability of the samples hinders quantitative comparisons among experimental groups. Here, we report the design of a "heart on a chip" that exploits muscular thin film technology--biohybrid constructs of an engineered, anisotropic ventricular myocardium on an elastomeric thin film--to measure contractility, combined with a quantification of action potential propagation, and cytoskeletal architecture in multiple tissues in the same experiment. We report techniques for real-time data collection and analysis during pharmacological intervention. The chip is an efficient means of measuring structure-function relationships in constructs that replicate the hierarchical tissue architectures of laminar cardiac muscle.
NOTCH Signaling as a Novel Cancer Therapeutic Target (2006)

NOTCH-ligand interaction is a highly conserved mechanism that regulates specific cell fate decision during development. In addition to its functions in developmental and cell maturation processes, studies indicate that NOTCH activation plays a role in the onset and progression of many human malignancies. The prevailing new strategy for rationally targeted cancer treatment is aimed at the development of target-selective "smart" drugs on the basis of characterized mechanisms of action. The connection between NOTCH signaling and tumorigenesis suggests that NOTCH may be such a target candidate. Gamma-secretase is a large membrane-integral multisubunit protease complex, which is essential for NOTCH receptor activation. Inhibitors of this enzyme are being developed for Alzheimer's disease, due to its role in cleaving beta-amyloid precursor in the brain. Recently, Gamma-secretase inhibitors (GSIs), as well as various biopharmaceutical or genetic NOTCH signaling inhibitors have been suggested as potential novel cancer therapeutic strategies. This review summarizes the evidence linking NOTCH signaling to several types of cancer, as well as the possible therapeutic indications of NOTCH inhibitors and the challenges facing their clinical development.
Enhanced reverse transcriptase-polymerase chain reaction for prostate specific antigen as an indicator of true pathologic stage in patients with prostate cancer (1995)

The data from this follow-up study continue to support the utility of enhanced RT-PCR as an early staging modality for radical prostatectomy candidates.
A high-density genome scan detects evidence for a bipolar-disorder susceptibility locus on 13q32 and other potential loci on 1q32 and 18p11.2 (1999)

Bipolar disorder is a severe mental illness characterized by mood swings of elation and depression. Family, twin, and adoption studies suggest a complex genetic etiology that may involve multiple susceptibility genes and an environmental component. To identify chromosomal loci contributing to vulnerability, we have conducted a genome-wide scan on approximately 396 individuals from 22 multiplex pedigrees by using 607 microsatellite markers. Multipoint nonparametric analysis detected the strongest evidence for linkage at 13q32 with a maximal logarithm of odds (lod) score of 3.5 (P = 0. 000028) under a phenotype model that included bipolar I, bipolar II with major depression, schizoaffective disorder, and recurrent unipolar disorder. Suggestive linkage was found on 1q31-q32 (lod = 2. 67; P = 0.00022) and 18p11.2 (lod = 2.32; P = 0.00054). Recent reports have linked schizophrenia to 13q32 and 18p11.2. Our genome scan identified other interesting regions, 7q31 (lod = 2.08; P = 0. 00099) and 22q11-q13 (lod = 2.1; P = 0.00094), and also confirmed reported linkages on 4p16, 12q23-q24, and 21q22. By comprehensive screening of the entire genome, we detected unreported loci for bipolar disorder, found support for proposed linkages, and gained evidence for the overlap of susceptibility regions for bipolar disorder and schizophrenia.
Multiple Sclerosis — The Plaque and Its Pathogenesis (2006)

Substantial advances have elucidated some of the central mechanisms underlying the inflammation, demyelination, and neurodegeneration that occur in multiple sclerosis. Correspondingly, the clinical strategies available for the management of the disease have widened. This review focuses on the current knowledge of the pathogenesis of the inflammatory and neurodegenerative elements of the multiple sclerosis plaque.
The Large Subunit of the Mammalian Mitochondrial Ribosome (2001)

Identification of all the protein components of the large subunit (39 S) of the mammalian mitochondrial ribosome has been achieved by carrying out proteolytic digestions of whole 39 S subunits followed by analysis of the resultant peptides by liquid chromatography and mass spectrometry. Peptide sequence information was used to search the human EST data bases and complete coding sequences were assembled. The human mitochondrial 39 S subunit has 48 distinct proteins. Twenty eight of these are homologs of the Escherichia coli 50 S ribosomal proteins L1, L2, L3, L4, L7/L12, L9, L10, L11, L13, L14, L15, L16, L17, L18, L19, L20, L21, L22, L23, L24, L27, L28, L30, L32, L33, L34, L35, and L36. Almost all of these proteins have homologs in Drosophila melanogaster, Caenorhabditis elegans, and Saccharomyces cerevisiae mitochondrial ribosomes. No mitochondrial homologs to prokaryotic ribosomal proteins L5, L6, L25, L29, and L31 could be found either in the peptides obtained or by analysis of the available data bases. The remaining 20 proteins present in the 39 S subunits are specific to mitochondrial ribosomes. Proteins in this group have no apparent homologs in bacterial, chloroplast, archaebacterial, or cytosolic ribosomes. All but two of the proteins has a clear homolog in D. melanogaster while all can be found in the genome of C. elegans. Ten of the 20 mitochondrial specific 39 S proteins have homologs in S. cerevisiae. Homologs of 2 of these new classes of ribosomal proteins could be identified in the Arabidopsis thaliana genome.
Zinc Finger–Based Knockout Punches for Zebrafish Genes (2008)

The ability to manipulate the genome is critical to develop and test hypotheses based on genetics. Knockdown strategies focused on RNAi and/or morpholinos are excellent genetic tools, but they come with substantial technical limitations. A new gene targeting approach employing synthetic zinc finger nuclease (ZFN) technology is a powerful and complementary approach to directly modify genetic loci for many diverse applications, notably enhancing Danio rerio (the zebrafish) as an experimental organism for understanding human disease. This ZFN-based technology to generate targeted knockouts in this aquatic animal opens the door to an array of new biological models of human disease and genetic testing.
Dietary Fat and Age-Related Maculopathy (1995)

High intake of saturated fat and cholesterol is associated with increased risk for early age-related maculopathy in the Beaver Dam population. This supports the hypothesis that atherosclerosis or its risk factors are related to age-related maculopathy. Confirmation of this finding in other populations and in prospective studies is needed.
The coupling effects of hexapole and octopole fields in quadrupole ion traps: a theoretical study (2013)

A theoretical method, the harmonic balance method, was introduced to study the coupling effects of hexapole and octopole fields on ion motion in a quadrupole ion trap. Ion motion characteristics, such as ion motion center displacement, ion secular frequency shift, nonlinear resonance curve and buffer gas damping effects, have been studied with the presence of both hexapole and octopole fields. It is found that hexapole fields have bigger impacts on ion motion center displacement, while octopole fields dominate ion secular frequency shift. Furthermore, the nonlinear features originated from hexapole and octopole fields could enhance or cancel each other, which provide us more space in a practical ion trap design process. As an example, an ion trap with improved performance was designed using a specific combination of hexapole and octopole fields. In this ion trap, a hexapole field was used to achieve efficient ion directional ejection, while an octopole field was added to correct the chemical mass shift and resolution degradation introduced by the hexapole field.
HYPERACUTE REJECTION OF ORTHOTOPIC CARDIAC ALLOGRAFTS IN DOGS FOLLOWING SOLUBILIZED ANTIGEN PRETREATMENT (1973)

Caves, Philip K.; Dong, Eugene Jr.; Morris, Randall E.; Shumway, Norman E. Author Information