gebhart/patrepeval huggingface dataset:
Synthesis, Ligand Binding, and Quantitative Structure−Activity Relationship Study of 3β-(4‘-Substituted phenyl)-2β-heterocyclic Tropanes:  Evidence for an Electrostatic Interaction at the 2β-Position (1996)

A set of 3β-(4‘-substituted phenyl)-2β-heterocyclic tropanes was designed, synthesized, and characterized. We discovered that these compounds can function as bioisosteric replacements for the corresponding WIN 35,065-2 analogs which possess a 2β-carbomethoxy group. Several of the compounds showed high affinity and selectivity for the dopamine transporter (DAT) relative to the serotonin and norepinephrine transporters. From the structure−activity relationship study, the 3β-(4‘-chlorophenyl)-2β-(3‘-phenylisoxazol-5-yl)tropane (5d) emerged as the most potent and selective compound. The binding data for 2β-heterocyclic tropanes were found to show a high correlation with molecular electrostatic potential (MEP) minima near one of the heteroatoms in the 2β-substituents. In contrast, low correlations were found for other MEP minima near the 2β-substituent as well as for calculated log P or substituent volume. These quantitative structure−activity relationship studies are consistent with an electrostatic contribution to the binding potency of these WIN 35,065-2 analogs at the DAT.
Genetic Modification of Oncolytic Newcastle Disease Virus for Cancer Therapy (2016)

Avian paramyxovirus type 1, NDV, has been an attractive oncolytic agent for cancer virotherapy. However, this virus can cause epidemic disease in poultry, and concerns about the potential environmental and economic impact of an NDV outbreak have precluded its clinical development. Here we describe generation and characterization of a highly potent oncolytic NDV variant that is unlikely to cause Newcastle disease in its avian host, representing an essential step toward moving NDV forward as an oncolytic agent. Several attenuation mechanisms have been genetically engineered into the recombinant NDV that reduce chicken pathogenicity to a level that is acceptable worldwide without impacting viral production in cell culture. The selective tumor replication of this recombinant NDV, both in vitro and in vivo, along with efficient tumor cell killing makes it an attractive oncolytic virus candidate that may provide clinical benefit to patients.
Association Between Regional Adipose Tissue Distribution and Both Type 2 Diabetes and Impaired Glucose Tolerance in Elderly Men and Women (2003)

Elderly men and women with normal body weight may be at risk for metabolic abnormalities, including type 2 diabetes, if they possess an inordinate amount of muscle fat or visceral abdominal fat.
Breast Cancer Susceptibility Genes: BRCA1 and BRCA2 (1998)

Mutations in the BRCA1 and BRCA2 genes lead to an increased susceptibility to breast, ovarian, and other cancers. It is estimated that 3%-8% of all women with breast cancer will be found to carry a mutation in 1 of these genes. Families with multiple affected first-degree relatives and patients with early-onset disease have been found to harbor mutations at a higher frequency. The BRCA1 and BRCA2 genes code for large proteins that bear no resemblance to other known genes. In the cell, they appear to act as tumor suppressor genes and play a role in the maintenance of genome integrity, although the precise function of these genes has yet to be discovered. A large number of distinct mutations have been found in cancer families around the world. The majority of the defined pathologic mutations result in premature truncation of the protein (frameshift and nonsense mutations). These mutations may substantially increase the risk for breast and ovarian cancer, but a precise risk estimate for each different mutation cannot be determined. Depending on the familial context, the risk of breast cancer associated with carrying a mutation has been estimated to range from 50% to 85%. The role of these genes in sporadic cancer remains unknown. Patients and physicians considering BRCA1 and BRCA2 genetic testing are faced with a difficult decision. The diversity of mutations and lack of general population data prevent accurate risk prediction. This is further complicated by the paucity of data on effective prevention strategies for those identified at higher risk. Thus, the nature of clinical testing for BRCA1 and BRCA2 continues to present challenges that reinforce the necessity of personal choice within the context of thorough genetic counseling.
Image learning classifier system using genetic algorithms (2003)

The authors examine aspects of machine learning by classifier systems that use genetic algorithms. In particular, adaptive image learning and classification are considered. Standard classifier systems are not well suited for seeking out multiple goals as is necessary in image learning and classification problems. To improve the performance of standard classifier systems for the image learning task, several modifications are suggested. The modifications result in a far better performance for classifier system on the ImageLearn domain.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
The structure and function of fungal laccases (1994)

Microbiology Society journals contain high-quality research papers and topical review articles. We are a not-for-profit publisher and we support and invest in the microbiology community, to the benefit of everyone. This supports our principal goal to develop, expand and strengthen the networks available to our members so that they can generate new knowledge about microbes and ensure that it is shared with other communities.
Amino acid sequence of the nucleotide binding region of chloroplast coupling factor 1 (1987)

The labeling of chloroplast coupling factor 1 by 3'-O-(4-benzoyl)benzoyl-ATP (BzATP) was studied. When the enzyme was incubated with approximately 10 microM BzATP and 6 mM MgCl2 at pH 7.9 for approximately 20 min and passed through two Sephadex G-50 centrifuge columns, three BzATP molecules were bound per coupling factor molecule. Photolysis of radioactive enzyme-bound BzATP followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography revealed that the BzATP bound primarily to the beta-polypeptide. If unbound BzATP was not removed by centrifuge columns prior to photolysis, significant labeling of the alpha-polypeptide also occurred. After photolysis, the BzATP-labeled enzyme was treated with trypsin, and two radioactive peptides were isolated by high-performance liquid chromatography on a C18 column. The two peptides were sequenced and found to correspond to amino acids 360-378 and 393-397 of the beta-polypeptide. For the sequence 360-378, two specific amino acids were found to be radioactive (Tyr-362 and Asp-369). This region of the polypeptide is highly conserved in several different species and probably corresponds to part of the nucleotide binding region of the catalytic site. In the case of amino acids 393-397, a very low level of radioactivity was found for all amino acids. The significance of this peptide for the binding of nucleotides to coupling factor 1 could not be established.
Protein quality control: triage by chaperones and proteases. (1997)

Proteases and chaperones together serve to maintain quahty control of cellular proteins. Both types of en­ zymes have as their substrates the variety of misfolded and partially folded proteins that arise from slow rates of folding or assembly, chemical or thermal stress, intrinsic structural instability, and biosynthetic errors. The pri­ mary function of classical chaperones, such as the Esch­ erichia coh DnaK/Hsp70 and its cochaperones, DnaJ and GrpE, and GroEL/Hsp60 and its cochaperone, GroES, is to modulate protein folding pathways, thereby prevent­ ing misfolding and aggregation, promoting refolding and proper assembly. Recent work has demonstrated that ATP-dependent proteases, as well as closely related pro­ teins, have intrinsic chaperone activity, suggesting that the initial steps in energy-dependent protein degradation may be similar to those of chaperone-dependent protein folding. The classical chaperones are also required for degradation of certain proteins in vivo, but we propose below that generally they affect proteolysis indirectly by maintaining proteins in soluble forms that would other­ wise aggregate and become inaccessible to proteases. In this review we present the evidence linking the activi­ ties of chaperones and proteases, and propose a general model for what can be thought of as a triage system for handling misfolded proteins in vivo, assuring swift re­ folding of proteins with functional potential and rapid degradation of irreversibly denatured or damaged pro­ teins.
Internet Protocol, Version 6 (IPv6) Specification (2017)

In IPv6,
Development of a validated high‐throughput LC‐ESI‐MS method for determination of sirolimus on dried blood spots (2010)

A high-throughput liquid chromatography-electrospray ionization mass spectrometric (LC-ESI-MS) method for screening of sirolimus on dried blood spots (DBS) was developed and validated. It involves solvent extraction of a punch of DBS followed by reversed-phase LC on a relatively new monolithic column consisting of a silica rod with bimodal pore structure and detection by ESI-MS. The run time was less than 3 min with a very low backpressure at a flow rate of 0.5 mL/min. The method can analyze more than 100 samples in an 8 h working day, including sample preparation. The assay was linear from 1 to 100 ng/mL. The mean recovery was 92.42%. The mean inter-day and intra-day precisions were 1.23 and 1.41%, respectively. The developed method is simple, rapid and useful for clinical applications.
Slow-Release 5-Amino-Salicylic Acid (Pentasa®) for the Treatment of Active Crohn’s Disease (1990)

A double-blind, placebo-controlled trial of a slow-release preparation of 5-amino-salicylic acid (Pentasa) has been performed in 40 patients with active Crohn's disease. Over a 6-week period, Pentasa (1.5 g daily) was no different to the dummy tablet in terms of clinical activity (Harvey-Bradshaw Index) or laboratory indicators of inflammation. No serious adverse reactions occurred.
Spatio-temporally controlled site-specific somatic mutagenesis in the mouse (1997)

The efficient introduction of somatic mutations in a given gene, at a given time, in a specific cell type will facilitate studies of gene function and the generation of animal models for human diseases. We have shown previously that conditional recombination-excision between two loxP sites can be achieved in mice by using the Cre recombinase fused to a mutated ligand binding domain of the human estrogen receptor (Cre-ERT), which binds tamoxifen but not estrogens. DNA excision was induced in a number of tissues after administration of tamoxifen to transgenic mice expressing Cre-ERT under the control of the cytomegalovirus promoter. However, the efficiency of excision varied between tissues, and the highest level ( approximately 40%) was obtained in the skin. To determine the efficiency of excision mediated by Cre-ERT in a given cell type, we have now crossed Cre-ERT-expressing mice with reporter mice in which expression of Escherichia coli beta-galactosidase can be induced through Cre-mediated recombination. The efficiency and kinetics of this recombination were analyzed at the cellular level in the epidermis of 6- to 8-week-old double transgenic mice. We show that site-specific excision occurred within a few days of tamoxifen treatment in essentially all epidermis cells expressing Cre-ERT. These results indicate that cell-specific expression of Cre-ERT in transgenic mice can be used for efficient tamoxifen-dependent, Cre-mediated recombination at loci containing loxP sites to generate site-specific somatic mutations in a spatio-temporally controlled manner.
Impact of front-end non-idealities on bit error rate performance of WLAN-OFDM transceivers (2002)

New OFDM-based WLAN standards target wireless communications in the 5 GHz band for consumer multimedia applications. Given the high data rates with required low bit error rates, and given the nature of the OFDM signal, a conservative analysis of the front-end requirements lead to severe, over dimensioned specifications. Such a design would never meet this market, by necessity low-cost and low-power. To extract more optimal front-end specifications, we assess the BER performance of the complete WLAN-OFDM link. As a result, we first show that the transmitted symbols' word-length can be restricted to 8-bit and the normalized crest factor digitally limited at baseband to 4. Then we show that the power amplifier can operate with only 5.4 dB back-off between the average input power and the input-referred P/sub ldB/. Finally, we quantify in terms of implementation loss the influence of the I/Q imbalance and of the frequency synthesizer phase noise.
Treatment of strabismus in adults with botulinum toxin A. (1985)

Eighty-five adults with horizontal concomitant strabismus were treated with an injection of a low dose of botulinum toxin A (BTXA) into the lateral or medial rectus muscle. The ocular deviation was reduced by an average of 60% independently of its size and whether or not surgery had previously been performed. The change was temporary, however, except in those cases with binocular functions, when fusion was re-established. Repeated low dose injections can maintain the improvement, but at higher doses, although larger reductions are produced, temporary local side effects--ptosis and vertical strabismus--are common. The technique is simple, well tolerated, and has no systemic side effects.
Morphological filter mean-absolute-error theorem (1992)

The general characterization of optimal morphological filters is based on the Matheron representation for morphological filters. As conceived in its most general form, optimal- morphological-filter design involves a search over potential bases of structuring elements that can be used to form the Matheron erosion expansion. The present paper provides expressions for the mean-absolute error of general binary morphological filters formed from erosion bases in terms of mean-absolute errors of single-erosion filters. The theorem has a recursive form and use of this form in the derivation of optimal-filter bases is demonstrated.
300-Hz subthalamic oscillations in Parkinson's disease (2003)

Despite several studies and models, much remains unclear about how the human basal ganglia operate. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for complicated Parkinson's disease, but how DBS acts also remains unknown. The clinical benefit of DBS at frequencies >100 Hz suggests the possible importance of neural rhythms operating at frequencies higher than the range normally considered for basal ganglia processing (<100 Hz). The electrodes implanted for DBS also offer the opportunity to record neural activity from the human basal ganglia. This study aimed to assess whether oscillations at frequencies >100 Hz operate in the human STN. While recording local field potentials from the STN of nine patients with Parkinson's disease through DBS electrodes, we found a dopamine- and movement-dependent 300-Hz rhythm. At rest, and in the absence of dopaminergic medication, in most cases (eight out of 11 nuclei) the 100-1000 Hz band showed no consistent rhythm. Levodopa administration elicited (or markedly increased) a 300-Hz rhythm at rest [(mean +/- SD) central frequency: 319 +/- 33 Hz; bandwidth: 72 +/- 21 Hz; power increase (after medication - before medication)/before medication: 1.30 +/- 1.25; n = 11, P = 0.00098]. The 300-Hz rhythm was also increased by apomorphine, but not by orphenadrine. The 300-Hz rhythm was modulated by voluntary movement. Before levodopa administration, movement-related power increase in the 300-Hz rhythm was variably present in different subjects, whereas after levodopa it became a robust phenomenon [before 0.014 +/- 0.014 arbitrary units (AU), after 0.178 +/- 0.339 AU; n = 8, P = 0.0078]. The dopamine-dependent 300-Hz rhythm probably reflects a bistable compound nuclear activity and supports high-resolution information processing in the basal ganglia circuit. An absent 300-Hz subthalamic rhythm could be a pathophysiological clue in Parkinson's disease. The 300-Hz rhythm also provides the rationale for an excitatory--and not only inhibitory--interpretation of DBS mechanism of action in humans.
Regulatory T cells and autoimmunity (2009)

Increasing insights into understanding the complex mechanisms of action of Tregs have already led to exciting therapeutic advances. This review provides an in-depth analysis of recent advances in the field of Tregs in autoimmunity. It highlights targets for future immunomodulatory therapy that may treat and potentially cure autoimmune disease, and it identifies areas for future research.
Telomere-proximal DNA in Saccharomyces cerevisiae is refractory to methyltransferase activity in vivo. (1992)

Genes located near telomeres in Saccharomyces cerevisiae undergo position-effect variegation; their transcription is subject to reversible but mitotically heritable repression. This position effect and the finding that telomeric DNA is late replicating suggest that yeast telomeres exist in a heterochromatin-like state. Mutations in genes that suppress the telomeric position effect suggest that a special chromatin structure exists near chromosomal termini. Thus transcriptional repression may be explained by the inability of DNA binding proteins to access the DNA near telomeres. To test this hypothesis, the Escherichia coli Dam DNA methyltransferase, which modifies the sequence GATC, was introduced into S. cerevisiae cells. DNA sequences near the telomere were highly refractive to Dam methylation but were modified when located at positions more internal on the chromosome. Telomeric sequences were accessible to methyltransferase activity in strains that contained a mutation that suppressed the telomeric position effect. These data support the model that sequence-specific DNA binding proteins are excluded from telomere-proximal sequences in vivo and show that expression of DNA methyltransferase activity may serve as a useful tool for mapping chromosomal structural domains in vivo.
The Influence of Dressing Conditions on the Surface Topography of Grinding Wheels (1993)

Performance of the grinding process is dependent on the topography of the grinding wheel surface which, in turn, results form the basic wheel specification and superimposed dressing conditions. If a satisfactory method can be found to specify the abrasive surface, a better means will be available for assessing its effect on the output of the grinding process, ie workpiece removal rate, surface finish, wheel wear, etc. Wheel profiles obtained by direct, limited penetration depth, stylus scanning is reported in which the effects of dressing conditions and type of dressing tool are studied using statistical functions.
Opsonic Defense to Staphylococcus epidermidis in the Premature Neonate (1985)

The determinants of opsonic defense to Staphylococcus epidermidis were studied in 47 premature newborns. Opsonic activity for S. epidermidis in serum from premature newborns proved to be proportional to gestational age (r = .664, P less than .001). The level of IgG antibodies to staphylococcal peptidoglycan in neonatal sera was similarly proportional to gestational age (r = .604, P less than .001). However, all opsonic activity of premature neonatal serum proved to be heat labile, i.e., dependent on activation of complement. Thus, no heat-stable, IgG-dependent opsonic activity to S. epidermidis was detected in any of the preterm sera, despite the presence of IgG antibodies to peptidoglycan. Further studies with purified IgG isolated from paired sera from term neonates and their mothers revealed that at similar concentrations the opsonic activity to S. epidermidis of neonatal, transplacentally derived IgG was only 26% of the activity of maternal IgG, a finding that may explain the absence of heat-stable opsonic activity in preterm newborns.
Evolutionary pursuit and its application to face recognition (2000)

Introduces evolutionary pursuit (EP) as an adaptive representation method for image encoding and classification. In analogy to projection pursuit, EP seeks to learn an optimal basis for the dual purpose of data compression and pattern classification. It should increase the generalization ability of the learning machine as a result of seeking the trade-off between minimizing the empirical risk encountered during training and narrowing the confidence interval for reducing the guaranteed risk during testing. It therefore implements strategies characteristic of GA for searching the space of possible solutions to determine the optimal basis. It projects the original data into a lower dimensional whitened principal component analysis (PCA) space. Directed random rotations of the basis vectors in this space are searched by GA where evolution is driven by a fitness function defined by performance accuracy (empirical risk) and class separation (confidence interval). Accuracy indicates the extent to which learning has been successful, while separation gives an indication of expected fitness. The method has been tested on face recognition using a greedy search algorithm. To assess both accuracy and generalization capability, the data includes for each subject images acquired at different times or under different illumination conditions. EP has better recognition performance than PCA (eigenfaces) and better generalization abilities than the Fisher linear discriminant (Fisherfaces).
Structural and Spectral Response of Green Fluorescent Protein Variants to Changes in pH, (1999)

The green fluorescent protein (GFP) from the jellyfish Aequorea victoria has become a useful tool in molecular and cell biology. Recently, it has been found that the fluorescence spectra of most mutants of GFP respond rapidly and reversibly to pH variations, making them useful as probes of intracellular pH. To explore the structural basis for the titration behavior of the popular GFP S65T variant, we determined high-resolution crystal structures at pH 8.0 and 4.6. The structures revealed changes in the hydrogen bond pattern with the chromophore, suggesting that the pH sensitivity derives from protonation of the chromophore phenolate. Mutations were designed in yellow fluorescent protein (S65G/V68L/S72A/T203Y) to change the solvent accessibility (H148G) and to modify polar groups (H148Q, E222Q) near the chromophore. pH titrations of these variants indicate that the chromophore pKa can be modulated over a broad range from 6 to 8, allowing for pH determination from pH 5 to pH 9. Finally, mutagenesis was used to raise the pKa from 6.0 (S65T) to 7.8 (S65T/H148D). Unlike other variants, S65T/H148D exhibits two pH-dependent excitation peaks for green fluorescence with a clean isosbestic point. This raises the interesting possibility of using fluorescence at this isosbestic point as an internal reference. Practical real time in vivo applications in cell and developmental biology are proposed.
An introduction to InP-based generic integration technology (2014)

Photonic integrated circuits (PICs) are considered as the way to make photonic systems or subsystems cheap and ubiquitous. PICs still are several orders of magnitude more expensive than their microelectronic counterparts, which has restricted their application to a few niche markets. Recently, a novel approach in photonic integration is emerging which will reduce the R&amp;D and prototyping costs and the throughput time of PICs by more than an order of magnitude. It will bring the application of PICs that integrate complex and advanced photonic functionality on a single chip within reach for a large number of small and larger companies and initiate a breakthrough in the application of Photonic ICs. The paper explains the concept of generic photonic integration technology using the technology developed by the COBRA research institute of TU Eindhoven as an example, and it describes the current status and prospects of generic InP-based integration technology