gebhart/patrepeval huggingface dataset:
Biochemical properties of oligo[(+)]-carbocyclic-thymidylates] and their complexes (1990)

We report here spectroscopic and biochemical data of a novel series of sugar-modified oligodeoxy-nucleotides, the carbocyclic oligothymidylates, c(dT)3-20. In c(dT)n a methylene group has been substituted for the oxygen atom of the deoxyribose ring of the natural thymidylate unit. c(dT)10-20 form helical structures, in contrast with oligothymidylates or poly(dT), based on absorbance versus temperature melting profiles. Secondary structure of c(dT)n, where n greater than 10 is assumed to be double helix. In addition to this, c(dT)n forms as a stable duplex with complementary poly(dA) as does parent (dT)n. On the other hand, c(dT)n-containing oligo/poly duplex is nearly inactive either as a template or as a primer in various DNA polymerase systems, and c(dT)n inhibits DNA replication as well. c(dT)n can efficiently be extended by terminal transferase and shows an increased nuclease stability compared to (dT)n. Base-pairing ability and nuclease stability of c(dT)n suggest that (+)-carbocyclic nucleoside-containing oligomers could be new potential antisense oligodeoxynucleotides.
In vivorole of B lymphocytes in somatic transgene immunization (1997)

Immunity generated by in vivo inoculation of plasmid DNA is a straightforward and potentially valuable new approach to immunization. Little is known about the type of cells involved, the various immunological aspects, and the destiny of the transgene. In this report, we describe a system in which immunity is the result of in vivo targeting of B lymphocytes. This was accomplished using plasmid DNA encoding an immunoglobulin heavy-chain gene under the control of immunoglobulin promoter and enhancer elements. We show persistence of the transgene in splenic B lymphocytes for at least 3 months, i.e., the average life span of long-lived B lymphocytes in the mouse. The transgene could not be detected in any other lymphoid or nonlymphoid organs over a period of 6 months. We also established that the transgene is integrated in the host DNA. These studies bring new understanding to the events underlying the in vivo use of plasmid DNA. Moreover, the characteristics of this new approach make somatic transgene immunization a model system to study the immunogenicity of endogenous antigens in adult animals.
String Comparator Metrics and Enhanced Decision Rules in the Fellegi-Sunter Model of Record Linkage. (1990)

To locate matches across pairs of lists without unique identifiers it is sometimes necessary to compare strings of letters. String comparators are used in production computer matching software during the Post Enumeration Survey for the 1990 U.S. census. A string comparator metric is described that partial]y accounts for: (1) typographical variation in strings such as first name or surname; (2) decision rules that use the string comparator; and (3) improvements in empirical matching results. The string comparator metric for comparing partially agreeing strings extends the Jaro string comparator. How general methods of accounting for partial agreement fit with the Fellegi-Sunter (I. P. Fellegi and A. B. Sunter, 1969) model of record linkage is described. A formal method of modeling how to adjust matching weights between pure agreement and pure disagreement is presented. The procedure is illustrated for files for which the truth of matches is known. It is demonstrated that the theoretical rules of Fellegi and Sunter are still valid when general weighting adjustments accounting for partial agreement are performed. Eight tables contain illustrative data. (SLD) Reproductions supplied by EDRS are the best that can be mPde from the original document. U.S. DEPARTMENT OF SOUCATION Office al Educational ssssrcli and Improvement EDUCATIONAL RESOURCES INFORMATION CENTER (ERIC) is document hes been reproduced ea received horn th penal O orEaruciroOn cognate% it 0 Minor changes Rove been made to improve reproduction quality Points of view or opinions stated in th4 <Metament do not neasseenly represent official OERI position or policy PERMISSION TO REPRODUCE THIS MATERIAL HAS BEEN GRANTED BY
Class 1/3 outer membrane protein vaccine against group B, type 15, subtype 16 meningococci. (1986)

Neisseria meningitidis capsular polysaccharides and outer membrane proteins have been incorporated in vaccines and the potential of these vaccines has been evaluated in man. Polysaccharides are the most attractive candidates for a vaccine against group A and C meningococci whereas outer membrane proteins may have a potential for a vaccine against group B meningococci. This paper describes the characteristics of the five classes of outer membrane proteins of group B meningococci and the protective (bactericidal) activity of monoclonal antibodies against class 1 and 2 or 3 outer membrane proteins. Monoclonal antibodies against class 1 outer membrane proteins were bactericidal irrespective of the growth conditions of the bacterium. On the other hand, these conditions influenced the bactericidal activity of monoclonal antibodies against class 2 or 3 outer membrane proteins. These data indicate that class 1 outer membrane protein is an attractive component of a vaccine. The Blake and Gotschlich procedure for the isolation of gonococcal outer membrane protein II (1) was adapted for the isolation of a combination of class 1 and 3 outer membrane proteins from group B, type 15 meningococci. The combination of both outer membrane proteins was adsorbed to ALPO4 in the presence of the detergent Zwittergent 3-14. The vaccine was injected into mice. The antibodies were strongly bactericidal and Western blot analysis indicated that both outer membrane proteins induced antibodies. The vaccine may have a potential to combat an epidemic caused by group B, type 15 meningococci. Such an epidemic was observed in some N.W. - European countries.
Sequence- and Structure-Specific RNA Processing by a CRISPR Endonuclease (2010)

Many bacteria and archaea contain clustered regularly interspaced short palindromic repeats (CRISPRs) that confer resistance to invasive genetic elements. Central to this immune system is the production of CRISPR-derived RNAs (crRNAs) after transcription of the CRISPR locus. Here, we identify the endoribonuclease (Csy4) responsible for CRISPR transcript (pre-crRNA) processing in Pseudomonas aeruginosa. A 1.8 angstrom crystal structure of Csy4 bound to its cognate RNA reveals that Csy4 makes sequence-specific interactions in the major groove of the crRNA repeat stem-loop. Together with electrostatic contacts to the phosphate backbone, these enable Csy4 to bind selectively and cleave pre-crRNAs using phylogenetically conserved serine and histidine residues in the active site. The RNA recognition mechanism identified here explains sequence- and structure-specific processing by a large family of CRISPR-specific endoribonucleases.
Enhancement of Oral Bioavailability and Solid Dispersion: A Review (2011)

Improving oral bioavailability of drugs those given as solid dosage forms remains a challenge for the formulation scientists due to solubility problems. Most of the newly invented chemical entities are poorly water soluble. As a result formulating them as oral solid dosage forms is a hurdle to the specialists. Many techniques have been exercised to improve oral bioavailability of drugs. Among several methods, solid dispersion has attracted attention of the researchers for previous 50 years. Different formulation strategies have been taken to prepare solid dispersions. It is evident that solid dispersions improve solubility of drug particles thus enhancing dissolution characteristics of drugs they increase the oral bioavailability. This review paper will focus on different aspects of solid dispersion preparation; their advantages, major challenges and preparation methods.
Influence of transmembrane domains on the fusogenic abilities of human and murine leukemia retrovirus envelopes (1995)

The envelopes of two highly divergent oncoviruses, human T-cell leukemia virus type 1 (HTLV-1) and Friend murine leukemia virus (F-MuLV), have distinct patterns of cellular receptor recognition, fusion, and syncytium formation. To analyze the influence of the transmembrane envelope subunit (TM) on fusogenic properties, we substituted either the entire TM or distinct domains from F-MuLV for the corresponding domains in the HTLV-1 envelope. Parental, chimeric, and truncated envelopes cloned into a eukaryotic expression vector were monitored for fusogenic potential in human, rat, and murine indicator cell lines by using a quantitative assay. This highly sensitive assay allowed us to assess the fusogenic properties and syncytium-forming abilities of the HTLV-1 envelope in murine NIH 3T3 cells. All chimeric envelopes containing extracellular sequences of the F-MuLV TM were blocked in their maturation process. Although deletions of the HTLV-1 cytoplasmic domain, alone and in combination with the membrane-spanning domain, did not prevent envelope cell surface expression, they impaired and suppressed fusogenic properties, respectively. In contrast, envelopes carrying substitutions of membrane-spanning and cytoplasmic domains were highly fusogenic. Our results indicate that these two domains in F-MuLV and HTLV-1 constitute structural entities with similar fusogenic properties. However, in the absence of a cytoplasmic domain, the F-MuLV membrane-spanning domain appeared to confer weaker fusogenic properties than the HTLV-1 membrane-spanning domain.
Artificial Photosynthesis for Sustainable Fuel and Chemical Production (2015)

The apparent incongruity between the increasing consumption of fuels and chemicals and the finite amount of resources has led us to seek means to maintain the sustainability of our society. Artificial photosynthesis, which utilizes sunlight to create high-value chemicals from abundant resources, is considered as the most promising and viable method. This Minireview describes the progress and challenges in the field of artificial photosynthesis in terms of its key components: developments in photoelectrochemical water splitting and recent progress in electrochemical CO2 reduction. Advances in catalysis, concerning the use of renewable hydrogen as a feedstock for major chemical production, are outlined to shed light on the ultimate role of artificial photosynthesis in achieving sustainable chemistry.
Effect of size and roughness on light transmission in a Si/SiO2 waveguide: Experiments and model (2000)

In this letter, we experimentally evaluate the effect of miniaturization and surface roughness on transmission losses within a Si/SiO2 waveguide system, and explain the results using a theoretical model. Micrometer/nanometer-sized waveguides are imperative for its potential use in dense integrated optics and optical interconnection for silicon integrated circuits. A theoretical model was employed to predict the relationship between the transmission losses of the dielectric silicon waveguide and its width. This model accurately predicts that loss increases as waveguide width decreases. Furthermore, we show that a major source of loss comes from sidewall roughness. We have constructed a complete contour map showing the interdependence of sidewall roughness and transmission loss, to assist users in their design of an optimal waveguide fabrication process that minimizes loss. Additionally, users can find an effective path to reduce the scattering loss from sidewall roughness. Using this map, we confirm that nanometer-size silicon waveguides with 0.1 dB/cm transmission loss are possible with the currently available technology.
Three Chloro(trifluoromethyl)pyridines as Model Substrates for Regioexhaustive Functionalization (2004)

Abstract As a further test of the concept of regioexhaustive functionalization, 2‐chloro‐6‐(trifluoromethyl)pyridine, 2‐chloro‐5‐(trifluoromethyl)pyridine and 3‐chloro‐4‐(trifluoromethyl)pyridine were each converted into the three possible carboxylic acids 2, 4, 6, 8 , 10, 12 , 16, 17 and 20 . This was achieved by employing several, but not all of the organometallic “toolbox methods”: transformation of a more basic organometallic species into a less basic isomer by transmetalation‐equilibration, site discriminating deprotonation with lithium N , N ‐diisopropylamide or lithium 2,2,6,6‐tetramethylpiperidide, regio‐divergent iodine migration and steric screening of acidic positions by a bulky trialkylsilyl group. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2004)
A new confocal scanning beam laser MACROscope using a telecentric, f‐theta laser scan lens (1995)

SUMMARY A new confocal scanning beam system (MACROscope) that images very large‐area specimens is described. The MACROscope uses a telecentric, f‐theta laser scan lens as an objective lens to image specimens as large as 7·5 cm × 7·5 cm in 5 s. The lateral resolution of the MACROscope is 5 μm and the axial resolution is 200 μm. When combined with a confocal microscope, a new hybrid imaging system is produced that uses the advantages of small‐area, high‐speed, high‐resolution microscopy (0·2 μm lateral and 0·4 μm axial resolution) with the large‐area, high‐speed, good‐resolution imaging of the MACROscope. The advantages of the microscope/MACROscope are illustrated in applications which include reflected‐light confocal images of biological specimens, DNA sequencing gels, latent fingerprints and photoluminescence imaging of porous silicon.
Splicing abnormalities in congenital myasthenic syndromes. (2005)

A total of 173 mutations has been reported to date in eight genes in congenital myasthenic syndromes. Sixteen intronic and five exonic mutations in three genes affect pre-mRNA splicing. Eight of these are of particular interest, and are reviewed in this article. An A-to-G mutation at intron position +3 results in exon skipping only when there are mismatched nucleotides to U1 snRNA at positions +4 to +6. Similarly, a mutation at the last nucleotide of an exon causes exon skipping when a nucleotide at position +6 is not complementary to U1 snRNA. We observe the similar compensation mechanisms for mismatches to U1 snRNA at 179,917 native human splice donor sites. A 7-bp deletion in CHRNE exon 7 causes skipping of the preceding 101-bp exon 6. We found in general that the nonsense-mediated altered splicing of a remote exon (NASRE) is mediated by inherent weak splicing signals flanking the skipped exon and degradation of a normally spliced transcript by the nonsense-mediated mRNA decay (NMD). A 16-bp duplication spanning the CHRNE intron 10/exon 11 boundary generates two copies of 3' splice sites, and the downstream copy is exclusively silenced. Analysis of a series of artificial mutants conforms to the scanning model of recognition of the 3' splice site that predicts that the first 'ag' more than 13 nucleotides downstream of the branch point is selected for splicing. Splicing mutations may be more frequent than suspected, and one must always be aware of possible splicing abnormalities when analyzing human mutations.
Arterial heparin deposition: role of diffusion, convection, and extravascular space (1998)

Transvascular transport has been studied with atherogenic, tracer, and inert compounds such as low-density lipoprotein, horseradish peroxidase, and albumin, respectively. Few studies used vasoactive compounds, and virtually all studies examined entry from the lumen and not from the perivascular space. We compared several mechanisms that govern arterial heparin deposition after administration to the perivascular and endovascular aspects of the calf carotid artery in vitro and the rabbit iliac artery in vivo. In the absence of transmural hydrostatic pressure gradients, heparin deposition following endovascular administration was unaffected by deendothelialization and was indistinguishable from perivascular delivery. Deposition in the former was enhanced by the addition of a pressure gradient and to a greater extent in denuded arteries, indicating that convection influences transport but is dampened by the endothelium. Neither the endothelium nor the adventitia pose significant resistances to heparin. Deposition in vivo was greater following endovascular hydrogel release than perivascular application from similar devices to native or denuded arteries. The loss of drug to extra-arterial microvessels exceeded the loss of drug to the lumen flow. These findings are essential for describing vascular pharmacokinetics and for implementing local pharmacotherapies.
Surface structure and energetics of multiply twinned particles (1984)

Abstract Experimental results from thermally annealed particles of silver and gold in the size range 10–50 nm show the presence of re-entrant surfaces on the decahedral multiply twinned particles (MTPs). A theoretical model is developed to explain these results based on the Wulff construction modified to include twin-boundaries. In addition to reproducing the re-entrant surfaces, the theory suggests that the total surface energy of the decahedral form is sandwiched between those of a single crystal and an icosahedral MTP. Consequently the stability of the decahedral particles (in a certain size range) relative to single crystals can now be explained. A useful perturbation modification is also outlined which enables qualitative comparisons of the surface energies to be made, and shows that the twin boundaries in MTPs limit the possible surface facets. Explicit shapes and energies are presented for two extreme models of the faceting. Finally, a model is outlined to justify the difference between the structures reported here and the more common decahedra and Icosahedra—the standard forms are artefacts of the growth process; they are not the thermodynamically most stable structures.
Requirement of poly(ADP-ribose) polymerase in recovery from DNA damage in mice and in cells (1997)

Poly(ADP-ribose) polymerase [PARP; NAD+ ADP-ribosyltransferase; NAD+: poly(adenosine-diphosphate-D-ribosyl)-acceptor ADP-D-ribosyltransferase, EC 2.4.2.30] is a zinc-finger DNA-binding protein that detects specifically DNA strand breaks generated by genotoxic agents. To determine its biological function, we have inactivated both alleles by gene targeting in mice. Treatment of PARP-/- mice either by the alkylating agent N-methyl-N-nitrosourea (MNU) or by gamma-irradiation revealed an extreme sensitivity and a high genomic instability to both agents. Following whole body gamma-irradiation (8 Gy) mutant mice died rapidly from acute radiation toxicity to the small intestine. Mice-derived PARP-/- cells displayed a high sensitivity to MNU exposure: a G2/M arrest in mouse embryonic fibroblasts and a rapid apoptotic response and a p53 accumulation were observed in splenocytes. Altogether these results demonstrate that PARP is a survival factor playing an essential and positive role during DNA damage recovery.
The implementation of a state machine compiler (1987)

This paper describes VTIstate, VLSI Technology's state machine compiler. The compiler derives combinational logic and registers to make a state machine, and synthesizes the combinational logic with three optimization steps. The 1986 Design Automation conference synthesis benchmark set is used to compare the results with previously reported logic synthesis programs.
Recurrent inhibition in sacral parasympathetic pathways to the bladder (1968)

1. The effects produced by stimulation of the central end of transected ventral roots were observed on spontaneous and evoked vesical contractions and on the firing of sacral parasympathetic neurones.2. Recurrent inhibition of sacral parasympathetic neurones was demonstrated at frequencies of stimulation above 10/sec and at intensities above threshold for the parasympathetic axons.3. Recurrent inhibition was present in chloralose cats, as well as in decerebrate animals and was unaffected by chronic spinal transection.4. Interneurones were located which are presumed to be the autonomic equivalents of the somatic Renshaw cells. They were synaptically activated by antidromic stimulation of preganglionic fibres in sacral ventral roots.5. The inhibition of vesical contractions and the firing of the interneurones was reduced when the intravesical pressure was raised.6. The recurrent inhibition was unaffected by the intravenous injection of dihydro-beta-erythroidine.7. Strychnine reduced the recurrent inhibition in some experiments but the results were inconsistent. The effects of picrotoxin were inconclusive.8. The possible role of recurrent inhibition in micturition is discussed.
Metabolic Syndrome and Cognitive Impairment: Current Epidemiology and Possible Underlying Mechanisms (2010)

A possible role of vascular and lifestyle-related factors was recently proposed for age-related changes of cognitive function, predementia syndromes, and cognitive decline of degenerative (Alzheimer's disease, AD) or vascular origin (vascular dementia, VaD). At present, cumulative evidence suggests that vascular risk factors may be important in the development of mild cognitive impairment (MCI), dementia, and AD. Among vascular-related factors, metabolic syndrome (MetS) has been associated with the risk of cognitive decline, overall dementia, and VaD, but contrasting findings also existed on the possible role of MetS in AD. If MetS is associated with increased risk of developing cognitive impairment, regardless of mechanism, then early identification and treatment of these individuals at risk might offer new avenues for disease-course modification. Strategies towards early and effective risk factor management could be of value in reducing risk of metabolic and cognitive decline. Future research is needed to confirm the association between MetS and cognitive impairment and to determine the exact mechanism linking them. Such would provide important insights into the causes and interdependencies of predementia and dementia syndromes, and inspire novel strategies for treating and preventing these disorders. At present, vascular risk factor and MetS management could be employed to delay the onset of dementia syndromes or to prevent the progression of predementia syndromes. In the future, trials could be undertaken to determine whether modifications of these risk factors, including inflammation, could lower risk of developing cognitive decline.
Hygromycin B Phosphotransferase as a Selectable Marker for DNA Transfer Experiments with Higher Eucaryotic Cells (1984)

The DNA coding sequence for the hygromycin B phosphotransferase gene was placed under the control of the regulatory sequences of a cloned long terminal repeat of Moloney sarcoma virus. This construction allowed direct selection for hygromycin B resistance after transfection of eucaryotic cell lines not naturally resistant to this antibiotic, thus providing another dominant marker for DNA transfer in eucaryotic cells.
Hedgehog signaling activation induces stem cell proliferation and hormone release in the adult pituitary gland (2016)

Hedgehog (HH) signaling is known to be essential during the embryonal development of the pituitary gland but the knowledge about its role in the adult pituitary and in associated tumors is sparse. In this report we investigated the effect of excess Hh signaling activation in murine pituitary explants and analyzed the HH signaling status of human adenopituitary lobes and a large cohort of pituitary adenomas. Our data show that excess Hh signaling led to increased proliferation of Sox2(+) and Sox9(+) adult pituitary stem cells and to elevated expression levels of adrenocorticotropic hormone (Acth), growth hormone (Gh) and prolactin (Prl) in the adult gland. Inhibition of the pathway by cyclopamine reversed these effects indicating that active Hh signaling positively regulates proliferative processes of adult pituitary stem cells and hormone production in the anterior pituitary. Since hormone producing cells of the adenohypophysis as well as ACTH-, GH- and PRL-immunopositive adenomas express SHH and its target GLI1, we furthermore propose that excess HH signaling is involved in the development/maintenance of hormone-producing pituitary adenomas. These findings advance the understanding of physiological hormone regulation and may open new treatment options for pituitary tumors.