gebhart/patrepeval huggingface dataset:
A STUDY OF EXCESS MORTALITY DURING INFLUENZA EPIDEMICS IN THE UNITED STATES, 1968–19761 (1981)

The effect of epidemics of influenza A on mortality in the United States was assessed by studying the monthly numbers of deaths during the years 1968-1976. Deaths from all causes at all ages and among persons aged 65 and over, and also deaths from acute respiratory diseases, and from cardiovascular causes were studied. Deaths from acute respiratory diseases were closely correlated with those from influenza and were taken to be an indication of the severity of influenza outbreaks. This indicator combined with a regression function expressing seasonal variation and secular trend was used to predict total mortality, cardiovascular mortality, and deaths among persons aged 65 and over. In each case the predictions proved to be reasonably close to the observed numbers of deaths. Excess mortality from all causes above that expected from seasonal variation occurred principally in three periods during the eight years of study: 1968-1969, 1972-1973, and 1975-1976, each of which coincided with an epidemic of influenza A of the H3N2 subtype. Similar excesses were seen among persons aged 65 and over and in cardiovascular deaths during the two earlier periods. It is concluded that excess mortality occurred during at least three of the major outbreaks of influenza during the period 1968-1976. This points to the need of studying the effectiveness of immunization in preventing the disease.
Refined 1.8-.ANG. structure reveals the mode of binding of .beta.-cyclodextrin to the maltodextrin binding protein (1993)

The maltodextrin binding protein from Escherichia coli serves as the initial receptor for both the active transport of and chemotaxis toward a range of linear maltose sugars. The X-ray structures of both the maltose-bound and sugar-free forms of the protein have been previously described [Spurlino, J. C., Lu, G.-Y., & Quiocho, F. A. (1991) J. Biol. Chem. 266, 5202-5219; Sharff, A. J., Rodseth, L. E., Spurlino, J. C., & Quocho, F. A. (1992) Biochemistry 31, 10657-10663]. The X-ray crystal structure of the maltodextrin binding protein complexed with cyclomaltoheptaose (beta-cyclodextrin) has been determined from a single crystal. The structure has been refined to a final R-value of 21% at 1.8-A resolution. Although not a physiological ligand for the maltodextrin binding protein, beta-cyclodextrin has been shown to bind with a Kd of the same order as those of the linear maltodextrin substrates. The observed structure shows that the complexed protein remains in the fully open conformation and is almost identical to the structure of the unliganded protein. The sugar sits in the open cleft with three glucosyl units bound to the C-domain at the base of the cleft, in a similar position to maltotriose, the most tightly bound ligand. The top of the ring is loosely bound to the upper edge of the cleft on the N-domain. The sugar makes a total of 94 productive interactions (of less than 4.0-A length) with the protein and with bound water molecules.(ABSTRACT TRUNCATED AT 250 WORDS)
STRUCTURE OF MEMBRANE HOLES IN OSMOTIC AND SAPONIN HEMOLYSIS (1973)

Serial section electron microscopy of hemolysing erythrocytes (fixed at 12 s after the onset of osmotic hemolysis) revealed long slits and holes in the membrane, extending to around 1 microm in length. Many but not all of the slits and holes (about 100-1000 A wide) were confluent with one another. Ferritin and colloidal gold (added after fixation) only permeated those cells containing membrane defects. No such large holes or slits were seen in saponin-treated erythrocytes, and the membrane was highly invaginated, giving the ghost a scalloped outline. Freeze-etch electron microscopy of saponin-treated membranes revealed 40-50 A-wide pits in the extracellular surface of the membrane. If these pits represent regions from which cholesterol was extracted, then cholesterol is uniformly distributed over the entire erythrocyte membrane.
Regulatory functions of adenosine. (1987)

Adenosine has emerged as an important regulator of many physiological processes. This review briefly describes the formation and inactivation of the nucleoside, its effects in different tissues and the mechanism by which these effects are executed.
Cyclic polyamides for recognition in the minor groove of DNA. (1995)

Small molecules that specifically bind with high affinity to any designated DNA sequence in the human genome would be useful tools in molecular biology and potentially in human medicine. Simple rules have been developed to rationally alter the sequence specificity of minor groove-binding polyamides containing N-methylimidazole and N-methylpyrrole amino acids. Crescent-shaped polyamides bind as antiparallel dimers with each polyamide making specific contacts with each strand on the floor of the minor groove. Cyclic polyamides have now been synthesized that bind designated DNA sequences at subnanomolar concentrations.
Pre-1994 South Africa: The homelands (2001)

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Longitudinal tumor hypoxia imaging with [18F]FAZA-PET provides early prediction of nanoliposomal irinotecan (nal-IRI) treatment activity (2015)

These findings highlight the potential use of FAZA-PET as an early marker of treatment response following multi-dose chemotherapy.
The bovine papillomavirus type 1 E2 transactivator and repressor proteins use different nuclear localization signals (1996)

The E2 gene of bovine papillomavirus type 1 encodes at least three nuclear phosphoproteins that regulate viral transcription and DNA replication. All three proteins have a common C-terminal domain that has DNA-binding and dimerization activities. A basic region in this domain forms an alpha helix which makes direct contact with the DNA target. In this study, it is shown that in addition to its role in DNA binding, this basic region functions as a nuclear localization signal both in the E2 DNA-binding domain and in a heterologous protein. Deletion of this signal sequence resulted in increased accumulation of the E2 transactivator and repressor proteins in the cytoplasm, but nuclear localization was not eliminated. In the full-length transactivator protein, another signal, present in the N-terminal transactivation domain, is used for transport to the nucleus, and the C-terminal nuclear localization signal(s) are masked. The use of different nuclear localization signals could potentially allow differential regulation of the subcellular localization of the E2 transactivator and repressor proteins at some stage in the viral life cycle.
Stepwise Assembly of the Same Polyelectrolytes Using Host−Guest Interaction To Obtain Microcapsules with Multiresponsive Properties (2008)

Poly(allylamine hydrochloride) (PAH) derivatives, that is, PAH-g-β-cyclodextrin (PAH-g-β-CD) and PAH-g-ferrocene with the same positive charges on their chains, were synthesized and employed as building blocks to obtain multilayer microcapsules by using a host−guest interaction between the β-CD and ferrocene. Alternative assembly of PAH-g-β-CD and PAH-g-ferrocene was conducted on sacrificial carbonate microparticles in a layer-by-layer (LbL) manner, followed by core dissolution with disodium ethylene diamine tetraacetate dihydrate (EDTA) to obtain the microcapsules. Step-wise increase of the layer thickness on silicone water was evidenced by ellipsometry, confirming the LbL growth mechanism. The hollow structure and morphology of the host−guest multilayer microcapsules were characterized by electron and scanning force microscopy. Owing to the charge interaction and host−guest interaction, the as-prepared microcapsules showed multiresponsiveness to pH, ionic strength, and host/guest molecules. For example, the capsule swelling and shrinking was observed at low and high pH and/or ionic strength, respectively. Progressive swelling of the microcapsules in β-CD solution was found also as a result of gradual decrease of the cross-linking degree contributed by the host−guest interaction. The capsule swelling and shrinking mediated by the change of pH and ionic strength is reversible at least for three cycles investigated so far. Using this feature, controllable loading and release of fluorescent probes was demonstrated.
A Series of Nonpolar Thymidine Analogues of Increasing Size:  DNA Base Pairing and Stacking Properties (2005)

[reaction: see text] We describe the properties in DNA of a set of five nonpolar nucleoside mimics in which shape is similar but size is increased gradually. The compounds vary in the size of their exocyclic substituents, which range from hydrogen to iodine, and are designed to test the steric effects of nucleosides, nucleotides, and DNA in biological systems in a systematic way. We describe the conversion of toluene, 2,4-difluorotoluene, 2,4-dichlorotoluene, 2,4-dibromotoluene, and 2,4-diiodotoluene deoxyribosides into suitably protected phosphoramidite derivatives and their incorporation into synthetic DNAs. Studies of their behavior in the context of hexamer and dodecamer duplexes were carried out, with comparison to natural thymine. Thermal melting data with compounds in 5' dangling positions showed that all five compounds stack more strongly than thymine, and all the dihalo-substituted cases stack more strongly than the unsubstituted toluene case. Stacking correlated with surface area and hydrophobicity, both of which increase across the series. In base-pairing studies, all five compounds showed destabilized pairing opposite natural bases (relative to thymine-adenine pairing), as expected. Notably, pairing among the nonpolar base analogues was considerably more stable, and some of the pairs involving the largest analogues showed stability equal to that of a natural thymine-adenine pair. The results establish the base pairing properties of a potentially useful new series of biochemical probes for DNA-protein interactions and also identify a set of new, stable hydrophobic base pairs for designed genetic pairing systems.
Use of Tissue-Specific MicroRNA to Control Pathology of Wild-Type Adenovirus without Attenuation of Its Ability to Kill Cancer Cells (2009)

Replicating viruses have broad applications in biomedicine, notably in cancer virotherapy and in the design of attenuated vaccines; however, uncontrolled virus replication in vulnerable tissues can give pathology and often restricts the use of potent strains. Increased knowledge of tissue-selective microRNA expression now affords the possibility of engineering replicating viruses that are attenuated at the RNA level in sites of potential pathology, but retain wild-type replication activity at sites not expressing the relevant microRNA. To assess the usefulness of this approach for the DNA virus adenovirus, we have engineered a hepatocyte-safe wild-type adenovirus 5 (Ad5), which normally mediates significant toxicity and is potentially lethal in mice. To do this, we have included binding sites for hepatocyte-selective microRNA mir-122 within the 3' UTR of the E1A transcription cassette. Imaging versions of these viruses, produced by fusing E1A with luciferase, showed that inclusion of mir-122 binding sites caused up to 80-fold decreased hepatic expression of E1A following intravenous delivery to mice. Animals administered a ten-times lethal dose of wild-type Ad5 (5x10(10) viral particles/mouse) showed substantial hepatic genome replication and extensive liver pathology, while inclusion of 4 microRNA binding sites decreased replication 50-fold and virtually abrogated liver toxicity. This modified wild-type virus retained full activity within cancer cells and provided a potent, liver-safe oncolytic virus. In addition to providing many potent new viruses for cancer virotherapy, microRNA control of virus replication should provide a new strategy for designing safe attenuated vaccines applied across a broad range of viral diseases.
Sensor-less fusion of speed for permanent magnet synchronous motors (2005)

In the field of electric motor control, extensive efforts have been devoted to the development of position sensorless motor drives. In this paper, a novel fusion algorithm is proposed. The algorithm seamlessly fuses the information generated by a high and a low-speed sensorless technique. The resulting sensorless drive, based on novel fusion algorithm, permits position sensorless operation over the entire speed range. Simulation results show minimal error between the estimated and actual motor position. Furthermore, it is shown that the novel fusion algorithm resolves the position polarity problem, which characterizes low-speed sensorless techniques.
Self-duplexing CUG repeats selectively inhibit mutant huntingtin expression (2013)

Huntington's disease (HD) is a neurodegenerative genetic disorder caused by the expansion of the CAG repeat in the translated sequence of the HTT gene. This expansion generates a mutant huntingtin protein that contains an abnormally elongated polyglutamine tract, which, together with mutant transcript, causes cellular dysfunction. Currently, there is no curative treatment available to patients suffering from HD; however, the selective inhibition of the mutant allele expression is a promising therapeutic option. In this study, we developed a new class of CAG repeat-targeting silencing reagents that consist of self-duplexing CUG repeats. Self-duplex formation was induced through one or several U-base substitutions. A number of self-duplexing guide-strand-only short interfering RNAs have been tested through transfection into cells derived from HD patients, showing distinct activity profiles. The best reagents were highly discriminatory between the normal and mutant HTT alleles (allele selectivity) and the HTT transcript and other transcripts containing shorter CAG repeats (gene selectivity). We also demonstrated that the self-duplexing CUG repeat short interfering RNAs use the RNA interference pathway to elicit silencing, and repeat-targeting reagents showed similar activity and selectivity when expressed from short hairpin RNA vectors to achieve more durable silencing effects.
The homeobox gene GLABRA 2 is required for position-dependent cell differentiation in the root epidermis of Arabidopsis thaliana (1996)

The role of the Arabidopsis homeobox gene, GLABRA 2 (GL2), in the development of the root epidermis has been investigated. The wild-type epidermis is composed of two cell types, root-hair cells and hairless cells, which are located at distinct positions within the root, implying that positional cues control cell-type differentiation. During the development of the root epidermis, the differentiating root-hair cells (trichoblasts) and the differentiating hairless cells (atrichoblasts) can be distinguished by their cytoplasmic density, vacuole formation, and extent of elongation. We have determined that mutations in the GL2 gene specifically alter the differentiation of the hairless epidermal cells, causing them to produce root hairs, which indicates that GL2 affects epidermal cell identity. Detailed analyses of these differentiating cells showed that, despite forming root hairs, they are similar to atrichoblasts of the wild type in their cytoplasmic characteristics, timing of vacuolation, and extent of cell elongation. The results of in situ nucleic acid hybridization and GUS reporter gene fusion studies show that the GL2 gene is preferentially expressed in the differentiating hairless cells of the wild type, during a period in which epidermal cell identity is believed to be established. These results indicate that the GL2 homeodomain protein normally regulates a subset of the processes that occur during the differentiation of hairless epidermal cells of the Arabidopsis root. Specifically, GL2 appears to act in a cell-position-dependent manner to suppress hair formation in differentiating hairless cells.
Lac Sulfur Assisted Synthesis of Symmetrical Thioureas (1997)

Abstract This work presents a short and attractive method to synthesise a variety of 1,3-disubstituted symmetrical thioureas in high yields.
DNA-binding abilities of bisguanylhydrazones of anthracene-9,10-dicarboxaldehyde. (1986)

DNA-binding strengths of three anthracene-9,10-dicarboxaldehyde hydrazones were examined by spectral shifts of the drug-DNA combinations, spectral titration by Scatchard plots, elevation of DNA melting temperature during complexation and comparison of spectral shifts in the presence of DNA's having variable base contents. Dissociation of the DNA-complexes was also observed. The results showed a strong degree of binding by the three compounds. They did not exhibit noticeable base-pair specificity, but both associated with and dissociated rapidly from DNA. Scatchard plots for DNA association indicated two types of binding; the stronger was most likely due to intercalation of the planar anthracene ring into the DNA double helix. No direct correlation can be drawn between the observed anti-cancer activities and DNA binding affinities of these compounds in vitro.
The tortoise and the hare: choosing between noncoding plastome and nuclear Adh sequences for phylogeny reconstruction in a recently diverged plant group (1998)

Phylogenetic resolution is often low within groups of recently diverged taxa due to a paucity of phylogenetically informative characters. We tested the relative utility of seven noncoding cpDNA regions and a pair of homoeologous nuclear genes for resolving recent divergences, using tetraploid cottons (Gossypium) as a model system. The five tetraploid species of Gossypium are a monophyletic assemblage derived from an allopolyploidization event that probably occurred within the last 0.5-2 million years. Previous analysis of cpDNA restriction site data provided only partial resolution within this clade despite a large number of enzymes employed. We sequenced three cpDNA introns (rpl16, rpoC1, ndhA) and four cpDNA spacers (accD-psaI, trnL-trnF, trnT-trnL, atpB-rbcL) for a total of over 7 kb of sequence per taxon, yet obtained only four informative nucleotide substitutions (0.05%) resulting in incomplete phylogenetic resolution. In addition, we sequenced a 1.65-kb region of a homoeologous pair of nuclear-encoded alcohol dehydrogenase (Adh) genes. In contrast with the cpDNA sequence data, the Adh homoeologues yielded 25 informative characters (0.76%) and provided a robust and completely resolved topology that is concordant with previous cladistic and phenetic analyses. The enhanced resolution obtained using the nuclear genes reflects an approximately three- to sixfold increase in nucleotide substitution rate relative to the plastome spacers and introns.
Mitochondrial Topoisomerase I is Critical for Mitochondrial Integrity and Cellular Energy Metabolism (2012)

Together, our data implicate Top1mt for mitochondrial integrity and energy metabolism. The compensation mechanism described here contributes to the survival of Top1mt-/- cells and mice despite alterations of mitochondrial functions and metabolism. Therefore, this study supports a novel model for cellular adaptation to mitochondrial damage.
A recombinase from Drosophila melanogaster embryos. (1988)

We have partially purified a DNA strand-exchange activity (recombinase) from nuclear extracts of Drosophila melanogaster embryos. The protein fraction forms a joint molecule between a circular single-strand DNA and a homologous linear duplex DNA that is resolved from the substrates by agarose gel electrophoresis. A strand-exchange activity can be obtained from nuclear extracts from embryos as old as 24 hr. The activity is similar to that partially purified from human cells [Hsieh, P., Meyn, S.M. & Camerini-Otero, R.D. (1986) Cell 44, 885-894]. It is homology-dependent, requires Mg2+, appears to be directional in that it prefers to displace the 3' end of the noncomplementary strand, and does not require exogenous ATP. Forty nanograms of protein in the partially purified DNA strand-exchange fraction from D. melanogaster embryos can completely convert 50 ng of substrate single-strand DNA into joint molecules in 10 min. In the electron microscope, joint molecules are seen to consist of a circular single-strand DNA molecule attached to only one end of a linear duplex DNA molecule; a displaced strand is also seen. The region of heteroduplex formation can be as long as 600 base pairs. The demonstration of a strand-exchange activity from wild-type D. melanogaster embryos invites analysis of recombination-defective mutants to explore the role of DNA strand exchange in homologous recombination.
Structural analogs of human insulin-like growth factor I with reduced affinity for serum binding proteins and the type 2 insulin-like growth factor receptor. (1988)

Four structural analogs of human insulin-like growth factor I (hIGF-I) have been prepared by site-directed mutagenesis of a synthetic IGF-I gene and subsequent expression and purification of the mutant protein from the conditioned media of transformed yeast. [Phe-1,Val1,Asn2, Gln3,His4,Ser8, His9,Glu12,Tyr15,Leu16]IGF-I (B-chain mutant), in which the first 16 amino acids of hIGF-I were replaced with the first 17 amino acids of the B-chain of insulin, has greater than 1,000-, 100-, and 2-fold reduced potency for human serum binding proteins, the rat liver type 2 IGF receptor, and the human placental type 1 IGF receptor, respectively. The B-chain mutant also has 4-fold increased affinity for the human placental insulin receptor. [Gln3,Ala4]IGF-I has 4-fold reduced affinity for human serum binding proteins, but is equipotent to hIGF-I at the types 1 and 2 IGF and insulin receptors. [Tyr15,Leu16]IGF-I has 4-fold reduced affinity for human serum binding proteins and 10-fold increased affinity for the insulin receptor. This peptide is also equipotent to hIGF-I at the types 1 and 2 IGF receptors. The peptide in which these four-point mutations are combined, [Gln3,Ala4,Tyr15,Leu16]IGF-I, has 600-fold reduced affinity for the serum binding proteins. This peptide has 10-fold increased potency for the insulin receptor, but is equipotent to hIGF-I at the types 1 and 2 IGF receptors. All four of these mutants stimulate DNA synthesis in the rat vascular smooth muscle cell line A10 with potencies reflecting their potency at the type 1 IGF receptor. These studies identify some of the domains of hIGF-I which are responsible for maintaining high affinity binding with the serum binding protein and the type 2 IGF receptor. In addition, these peptides will be useful in defining the role of the type 2 IGF receptor and serum binding proteins in the physiological actions of hIGF-I.
Analysis and simulation of a fair queueing algorithm (1989)

We discuss gateway queueing algorithms and their role in controlling congestion in datagram networks. A fair queueing algorithm, based on an earlier suggestion by Nagle, is proposed. Analysis and simulations are used to compare this algorithm to other congestion control schemes. We find that fair queueing provides several important advantages over the usual first-come-first-serve queueing algorithm: fair allocation of bandwidth, lower delay for sources using less than their full share of bandwidth, and protection from ill-behaved sources.
A West Nile Virus DNA Vaccine Induces Neutralizing Antibody in Healthy Adults during a Phase 1 Clinical Trial (2007)

ClinicalTrials.gov identifier: NCT00106769 .