gebhart/patrepeval huggingface dataset:
Structure and Mechanism of DNA Polymerase β (2006)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStructure and Mechanism of DNA Polymerase βWilliam A. Beard and Samuel H. WilsonView Author Information Laboratory of Structural Biology, National Institute of Environmental Health Sciences, National Institutes of Health, P.O. Box 12233, Research Triangle Park, North Carolina 27709-12233 Cite this: Chem. Rev. 2006, 106, 2, 361–382Publication Date (Web):January 14, 2006Publication History Received28 September 2005Published online14 January 2006Published inissue 1 February 2006https://pubs.acs.org/doi/10.1021/cr0404904https://doi.org/10.1021/cr0404904research-articleACS PublicationsCopyright © Not subject to U.S. Copyright. Published 2006 American Chemical SocietyRequest reuse permissionsArticle Views3221Altmetric-Citations234LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Chemical structure,Conformation,Genetics,Monomers,Peptides and proteins Get e-Alerts
The ferrous iron transporter <scp>FtrABCD</scp> is required for the virulence of <i><scp>B</scp>rucella abortus</i> 2308 in mice (2013)

Iron transport has been linked to the virulence of Brucella strains in both natural and experimental hosts. The genes designated BAB2_0837-0840 in the Brucella abortus 2308 genome sequence are predicted to encode a CupII-type ferrous iron transporter homologous to the FtrABCD transporter recently described in Bordetella. To study the role of the Brucella FtrABCD in iron transport, an isogenic ftrA mutant was constructed from B. abortus 2308. Compared with the parental strain, the B. abortus ftrA mutant displays a decreased capacity to use non-haem iron sources in vitro, a growth defect in a low iron medium that is enhanced at pH 6, and studies employing radiolabelled FeCl3 confirmed that FtrABCD transports ferrous iron. Transcription of the ftrA gene is induced in B. abortus 2308 in response to iron deprivation and exposure to acid pH, and similar to other Brucella iron acquisition genes that have been examined the iron-responsiveness of ftrA is dependent upon the iron response regulator Irr. The B. abortus ftrA mutant exhibits significant attenuation in both cultured murine macrophages and experimentally infected mice, supporting the proposition that ferrous iron is a critical iron source for these bacteria in the mammalian host.
Zidovudine treatment results in the selection of human immunodeficiency virus type 1 variants whose genotypes confer increasing levels of drug resistance (1994)

High level resistance to 3'-azido-3'-deoxythymidine (AZT, zidovudine or Retrovir) is conferred by the presence of four or five mutations (Met-41-->Leu; Asp-67-->Asn; Lys-70-->Arg; Thr-215-->Tyr or Phe; Lys-219-->Gln) in the human immunodeficiency virus (HIV) reverse transcriptase. The order of appearance of these five mutations in asymptomatic patients during therapy has been studied. This has enabled us to propose a model for the acquisition of zidovudine resistance mutations during the treatment of high-risk asymptomatic HIV-infected individuals. A consistent acquisition pattern of mutations at codons 41, 70 and 215 was observed in 17 individuals. Complex mixtures of HIV species containing different combinations of single and linked double resistance mutations were present early in zidovudine therapy in isolates from two patients studied in detail. From these mixtures the linked Leu-41/Tyr-215 genotype outgrew all others initially. The development of each new virus population is likely to be mediated primarily by the increase in the level of drug resistance rather than changes in the growth kinetics of the virus. This leads us to conclude that one major driving force in the outgrowth of different mutant viruses is the selective advantage conferred by higher levels of drug resistance.
A Brief History of Alzheimer's Disease Gene Discovery (2012)

The rich and colorful history of gene discovery in Alzheimer's disease (AD) over the past three decades is as complex and heterogeneous as the disease, itself. Twin and family studies indicate that genetic factors are estimated to play a role in at least 80% of AD cases. The inheritance of AD exhibits a dichotomous pattern. On one hand, rare mutations inAPP, PSEN1, and PSEN2 are fully penetrant for early-onset (<60 years) familial AD, which represents <5% of AD. On the other hand, common gene polymorphisms, such as the 4 and 2 variants of the APOE gene, influence susceptibility for common (>95%) late-onset AD. These four genes account for 30-50% of the inheritability of AD. Genome-wide association studies have recently led to the identification of additional highly confirmed AD candidate genes. Here, I review the past, present, and future of attempts to elucidate the complex and heterogeneous genetic underpinnings of AD along with some of the unique events that made these discoveries possible.
ChemInform Abstract: Substituent Effects on the Photochemistry of o‐Tolualdehydes. (1989)

Abstract The aldehydes (Va) and (VIa), prepared from the alkoxytoluenes (Ia) or (Ib), are acylated to yield the compounds (Vb) ‐ (Vd) and (VIb) ‐(VId).
The Potential of Polyphosphazenes for Delivery of Vaccine Antigens and Immunotherapeutic Agents (2010)

Polyphosphazene polyelectrolytes are synthetic, biodegradable polymers that have shown great potential in vaccine and drug delivery applications. Numerous investigations in laboratory animals have revealed that polyphosphazenes are also potent immunological adjuvants that can dramatically enhance the magnitude, quality and duration of immune responses to a variety of bacterial and viral vaccine antigens. Evidence is accumulating that these polymers have potent adjuvant activity in large animals as well. Interestingly, polyphosphazenes can be combined with novel immune modulatory agents resulting in even more potent immune activity and protection against experimental infection. While most reports are on the activity of polyphosphazenes in aqueous formulations, these polymers can also be easily made into microparticles, making them especially attractive for mucosal delivery. The mechanisms which mediate the adjuvant activity of polyphosphazenes are not fully understood, but there is evidence to suggest that activation of innate immunity may be involved. Further research and development of polyphosphazene adjuvants is warranted to fully explore their potential in the delivery of vaccines and immunotherapeutic agents.
Generalized mosaicing: polarization panorama (2005)

We present an approach to image the polarization state of object points in a wide field of view, while enhancing the radiometric dynamic range of maging systems by generalizing image mosaicing. The approach is biologically-inspired, as it emulates spatially varying polarization sensitivity of some animals. In our method, a spatially varying polarization and attenuation filter is rigidly attached to a camera. As the system moves, it senses each scene point multiple times, each time filtering it through a different filter polarizing angle, polarizance, and transmittance. Polarization is an additional dimension of the generalized mosaicing paradigm, which has recently yielded high dynamic range images and multispectral images in a wide field of view using other kinds of filters. The image acquisition is as easy as in traditional image mosaics. The computational algorithm can easily handle nonideal polarization filters (partial polarizers), variable exposures, and saturation in a single framework. The resulting mosaic represents the polarization state at each scene point. Using data acquired by this method, we demonstrate attenuation and enhancement of specular reflections and semireflection separation in an image mosaic.
Acyl depsipeptide (ADEP) resistance in Streptomyces (2011)

ADEP, a molecule of the acyl depsipeptide family, has an antibiotic activity with a unique mode of action. ADEP binding to the ubiquitous protease ClpP alters the structure of the enzyme. Access of protein to the ClpP proteolytic chamber is therefore facilitated and its cohort regulatory ATPases (ClpA, ClpC, ClpX) are not required. The consequent uncontrolled protein degradation in the cell appears to kill the ADEP-treated bacteria. ADEP is produced by Streptomyces hawaiiensis. Most sequenced genomes of Streptomyces have five clpP genes, organized as two distinct bicistronic operons, clpP1clpP2 and clpP3clpP4, and a single clpP5 gene. We investigated whether the different Clp proteases are all sensitive to ADEP. We report that ClpP1 is a target of ADEP whereas ClpP3 is largely insensitive. In wild-type Streptomyces lividans, clpP3clpP4 expression is constitutively repressed and the reason for the maintenance of this operon in Streptomyces has been elusive. ClpP activity is indispensable for survival of actinomycetes; we therefore tested whether the clpP3clpP4 operon, encoding an ADEP-insensitive Clp protease, contributes to a mechanism of ADEP resistance by target substitution. We report that in S. lividans, inactivation of ClpP1ClpP2 production or protease activity is indeed a mode of resistance to ADEP although it is neither the only nor the most frequent mode of resistance. The ABC transporter SclAB (orthologous to the Streptomyces coelicolor multidrug resistance pump SCO4959-SCO4960) is also able to confer ADEP resistance, and analysis of strains with sclAB deletions indicates that there are also other mechanisms of ADEP resistance.
3H-batrachotoxinin-A benzoate binding to voltage-sensitive sodium channels: inhibition by the channel blockers tetrodotoxin and saxitoxin (1986)

The sodium channel blockers tetrodotoxin (TTX) and saxitoxin (STX) and the channel activator batrachotoxin (BTX) produce their effects by binding to separate and distinct sites on the channel protein. The fact that TTX- and STX-modified sodium channels are blocked to sodium flux has precluded drawing any direct conclusions regarding the effect of TTX/STX on BTX binding based on electrophysiological or 22Na flux measurements. Nevertheless, these sites have been presumed to be non-interacting. In this study, 3H-batrachotoxinin-A benzoate (BTX-B), a tritiated congener of BTX, has been used to provide a direct assessment of these binding interactions. Equilibrium specific binding of 3H-BTX-B to sodium channels in vesicular preparations of mouse brain in the presence of scorpion toxin was measured using a filtration assay procedure. At 25 degrees C both TTX and STX inhibit 3H-BTX-B binding in a concentration-dependent and noncompetitive manner. This inhibition is markedly temperature-dependent, being negligible at 37 degrees C and maximal at 18 degrees C, the lowest temperature investigated. Scatchard analysis of BTX-B binding isotherms at 25 degrees C in the presence and absence of 1 microM TTX revealed that inhibition is due to a 3-fold decrease in the affinity of BTX-B binding with no change in the number of binding sites (Bmax). The concentration dependence for TTX inhibition of both specific 3H-STX and 3H-BTX-B binding is identical, suggesting that inhibition of 3H-BTX-B binding is due to a direct effect of TTX/STX binding at their specific sodium channel site. The channel blockers did not alter the binding of scorpion toxin under these assay conditions, nor did BTX-B affect the binding of 3H-STX.(ABSTRACT TRUNCATED AT 250 WORDS)
Sol–gel synthesis of monolithic materials with hierarchical porosity (2015)

The development of synthetic routes to hierarchically organized porous materials containing multiple, discrete sets of pores having disparate length scales is of high interest for a wide range of applications. One possible route towards the formation of multilevel porous architectures relies on the processing of condensable, network forming precursors (sol-gel processes) in the presence of molecular porogens, lyotropic mesophases, supramolecular architectures, emulsions, organic polymers, or ice. In this review the focus is on sol-gel processing of inorganic and organic precursors with concurrently occurring microscopic and/or macroscopic phase separation for the formation of self-supporting monoliths. The potential and the limitations of the solution-based approaches is presented with special emphasis to recent examples of hierarchically organized silica, metal oxides and phosphates as well as carbon monoliths.
Recognition of Hairpin-Containing Single-Stranded DNA by Oligonucleotides Containing Internal Acridine Derivatives (1999)

Oligodeoxynucleotides with an internal intercalating agent have been targeted to single-stranded sequences containing hairpin structures. The oligonucleotide binds to nonadjacent single-stranded sequences on both sides of the hairpin structure in such a way as to form a three-way junction. The acridine derivative is inserted at a position that allows it to interact with the three-way junction. The melting temperature (Tm) of complexes formed between the hairpin-containing target and oligonucleotides containing one internal acridine derivative was higher than that obtained with the same target and an unmodified oligonucleotide (DeltaTm = +13 degrees C). The internal acridine provided the oligonucleotide with a higher affinity than covalent attachment to the 5' end. Oligonucleotides could also be designed to recognize a hairpin-containing single-stranded nucleic acid by formation of Watson-Crick hydrogen bonds with a single-stranded part and Hoogsteen hydrogen bonds with the stem of the hairpin. An internal acridine derivative was introduced at the junction between the two domains, the double helix domain with Watson-Crick base pairs and the triple helix domain involving Hoogsteen base triplets in the major groove of the hairpin stem. Oligonucleotides with an internal acridine or an acridine at their 5' end have similar binding affinities for the stem-loop-containing target. The bis-modified oligonucleotide containing two acridines, one at the 5' end and one at an internal site, did not exhibit a higher affinity than the oligonucleotides with only one intercalating agent. The design of oligonucleotides with an internal intercalating agent might be of interest to control gene expression through recognition of secondary structures in single-stranded targets.
EORTC Early Clinical Studies Group early phase II trial of S-1 in patients with advanced or metastatic colorectal cancer (2003)

Cancer of the colon and rectum is one of the most frequent malignancies both in the US and Europe. Standard palliative therapy is based on 5-fluorouracil/folinic acid combinations, with or without oxaliplatin or irinotecan, given intravenously. Oral medication has the advantage of greater patient convenience and acceptance and potential cost savings. S-1 is a new oral fluorinated pyrimidine derivative. In a nonrandomized phase II study, patients with advanced/metastatic colorectal cancer were treated with S-1 at 40 mg m-2 b.i.d. for 28 consecutive days, repeated every 5 weeks, but by amendment the dose was reduced to 35 mg m-2 during the study because of a higher than expected number of severe adverse drug reactions. In total 47 patients with colorectal cancer were included. In the 37 evaluable patients there were nine partial responses (24%), 17 stable diseases (46%) and 11 patients had progressive disease (30%). Diarrhoea occurred frequently and was often severe: in the 40 and 35 mg m-2 group, respectively, 38 and 35% of the patients experienced grade 3-4 diarrhoea. The other toxicities were limited and manageable. S-1 is active in advanced colorectal cancer, but in order to establish a safer dose the drug should be subject to further investigations.
Emergency signaling for a person with quadriplegia and extraordinary respiratory risk. (1982)

Individuals without extremity function and rectus abdominis control are at increased risk for respiratory obstruction, arrest and loss of ability to call for assistance. To assist distressed patients, a simple and reliable head controlled signaling mechanism was designed for electric wheelchair use. Components are available in most communities. By using the device patients increase the response rate to their calls for help, and improve their sense of confidence and safety. The simplicity of the idea may serve to encourage staff to be likewise creative in solving other problems.
Dangerous exercise: lessons learned from dysregulated inflammatory responses to physical activity (2007)

Exercise elicits an immunological "danger" type of stress and inflammatory response that, on occasion, becomes dysregulated and detrimental to health. Examples include anaphylaxis, exercise-induced asthma, overuse syndromes, and exacerbation of intercurrent illnesses. In dangerous exercise, the normal balance between pro- and anti-inflammatory responses is upset. A possible pathophysiological mechanism is characterized by the concept of exercise modulation of previously activated leukocytes. In this model, circulating leukocytes are rendered more responsive than normal to the immune stimulus of exercise. For example, in the case of exercise anaphylaxis, food-sensitized immune cells may be relatively innocuous until they are redistributed during exercise from gut-associated circulatory depots, like the spleen, into the central circulation. In the case of asthma, the prior activation of leukocytes may be the result of genetic or environmental factors. In the case of overuse syndromes, the normally short-lived neutrophil may, because of acidosis and hypoxia, inhibit apoptosis and play a role in prolongation of inflammation rather than healing. Dangerous exercise demonstrates that the stress/inflammatory response caused by physical activity is robust and sufficiently powerful, perhaps, to alter subsequent responses. These longer term effects may occur through as yet unexplored mechanisms of immune "tolerance" and/or by a training-associated reduction in the innate immune response to brief exercise. A better understanding of sometimes failed homeostatic physiological systems can lead to new insights with significant implication for clinical translation.
Improved watershed algorithm for dowels image segmentation (2008)

Watershed algorithm is applied widely to image segmentation for its fast computing and high accuracy in locating the weak edges of adjacent regions. But classical watershed segmentation is sensitive to noise and can leads to serious over-segmentation. Aiming at the limitation of watershed segmentation, this paper presented an algorithm of watershed transformation based on opening-closing operation and distance transform. It improved the classical watershed segmentation algorithm based on distance transform, overcoming over-segmentation. The experiment result demonstrated that this method for segmentation inherits the advantage of watershed algorithm based on distance transform that it successfully segment out each dowel in the image bringing convenience to computer vision and auto-counting of dowels. It also overcame over-segmentation existed in traditional watershed segmentation preserving the original edges of each dowel in the image completely.
<i>Rhizoctonia</i> fungi enhance the growth of the endangered orchid <i>Cymbidium goeringii</i> (2010)

Orchids are among the most prized ornamental plants in many societies throughout the world. As a result, consumer demands have created a significant pressure on wild populations of many species, including Cymbidium goeringii Rchb. f., a rare terrestrial orchid endemic in China, Korea, and Japan. To help conserve natural populations of C. goeringii, we recently started investigating methods to cultivate these orchids. Here we fulfilled Koch’s postulates and demonstrated that fungal strains isolated from the roots of natural Cymbidium plants increased fresh mass, plant height, number of leaves, and root length of C. goeringii, and that the two fungal strains originally isolated from C. goeringii showed overall greater effects on growth than two other strains from other Cymbidium species. Internal transcribed spacer sequence analyses revealed that the four fungal strains likely represented at least two new taxonomic groups, both belonging to the family Ceratobasidiaceae of the Rhizoctonia fungi. Our study demonstrated that these fungal strains could potentially help the commercial cultivation of the increasingly rare and endangered orchid C. goeringii.
Peripheral reduction of β-amyloid is sufficient to reduce brain β-amyloid: Implications for Alzheimer's disease (2011)

Three loci that modify β-amyloid (Aβ) accumulation and deposition in the brains of a mouse model of Alzheimer's disease have been previously described. One encompasses the Psen2 gene encoding presenilin 2, a component of the γ-secretase activity responsible for generating Aβ by proteolysis. We show that the activity of mouse Psen2, as measured by levels of mRNA accumulation, unexpectedly is heritable in the liver but not the brain, suggesting liver as the origin of brain Aβ deposits. Administration of STI571, a cancer therapeutic that does not cross the blood-brain barrier, reduced accumulation of Aβ in both the blood and the brain, confirming brain Aβ's peripheral origin and suggesting that STI571 and related compounds might have therapeutic/prophylactic value in human Alzheimer's disease. The genes Cib1 and Zfhx1b reside within the other modifier loci and also exhibit heritable expression in the liver, suggesting that they too contribute to Aβ accumulation.
[Local therapy of androgenetic alopecia with 17 alpha-estradiol. A controlled, randomized double-blind study (author's transl)]. (1980)

In a controlled, randomized double-blind study, 51 patients with androgenetic alopecia and increased hair loss (telogen rate greater than 20%) were treated by local application of hair lotions with and without 17 alpha-estradiol (0.025%) for a period of at least 6 months. Before and after therapy trichograms were taken and evaluated under standardized conditions. In 63% of the treated patients a reduction of the amount of telogen hairs appeared, whereas in the control group the same reduction was found in only 37% of the cases. Similarly, in the treated group only 11% of the patients worsened, in contrast to 50% of the control group who showed an increased telogen rate (greater than 10%). The amount of growing anagen hairs and of seborrhea did not change significantly in both groups. Side effects were not seen. These findings indicate that hair lotions containing 17 alpha-estradiol may have a therapeutic value in reducing androgenetic hair loss, if applied topically for a long period of time, similar to 17 beta-estradiol. However, no regrowth of new hair was found.