gebhart/patrepeval huggingface dataset:
The inhibition of human farnesyl pyrophosphate synthase by nitrogen-containing bisphosphonates. Elucidating the role of active site threonine 201 and tyrosine 204 residues using enzyme mutants (2015)

Farnesyl pyrophosphate synthase (FPPS) is the major molecular target of nitrogen-containing bisphosphonates (N-BPs), used clinically as bone resorption inhibitors. We investigated the role of threonine 201 (Thr201) and tyrosine 204 (Tyr204) residues in substrate binding, catalysis and inhibition by N-BPs, employing kinetic and crystallographic studies of mutated FPPS proteins. Mutants of Thr201 illustrated the importance of the methyl group in aiding the formation of the Isopentenyl pyrophosphate (IPP) binding site, while Tyr204 mutations revealed the unknown role of this residue in both catalysis and IPP binding. The interaction between Thr201 and the side chain nitrogen of N-BP was shown to be important for tight binding inhibition by zoledronate (ZOL) and risedronate (RIS), although RIS was also still capable of interacting with the main-chain carbonyl of Lys200. The interaction of RIS with the phenyl ring of Tyr204 proved essential for the maintenance of the isomerized enzyme-inhibitor complex. Studies with conformationally restricted analogues of RIS reaffirmed the importance of Thr201 in the formation of hydrogen bonds with N-BPs. In conclusion we have identified new features of FPPS inhibition by N-BPs and revealed unknown roles of the active site residues in catalysis and substrate binding.
Effects of Zidovudine Use During Pregnancy on Resistance and Vertical Transmission of Human Immunodeficiency Virus Type 1 (1995)

The resistance of human immunodeficiency virus type 1 (HIV-1) to zidovudine and the vertical transmission of the virus were assessed among all 62 HIV-1-infected pregnant women identified prior to delivery at one institution. HIV-1 was transmitted to infants from 11 (26%) of 42 women who did not receive oral zidovudine but from only 1 of 20 women given such treatment (P = .04). Isolates of HIV-1 from 16 of the 20 zidovudine-treated women were available. Twelve of 16 isolates were wild-type for pol codons 41, 67, 70, 215, and 219; two (one susceptible and one moderately resistant to zidovudine) had mutations at codon 70; and two (both highly resistant to zidovudine) had mutations at codons 41 and 215. The virus was vertically transmitted from a woman infected with one of the highly resistant strains, and the infant's isolate was highly resistant to zidovudine. These limited data suggest that maternal treatment with oral zidovudine reduces the rate of vertical transmission of HIV-1 but that vertical transmission of virus resistant to zidovudine can occur.
Investigation of Three-Group Classifiers to Fully Automate Detection and Classification of Breast Lesions in an Intelligent CAD Mammography Workstation (2007)

Abstract : Our goal is to develop a fully automated classification scheme for computer-aided diagnosis in mammography. Our proposed scheme would classify computer detections into three groups: malignant lesions, benign lesions, and false-positive computer detections. We proved that the area under the ROC curve (AUC) is not useful in classification tasks with three or more groups, and showed that the three decision boundary lines used by the three-group ideal observer are intricately related to one another. We analyzed several recently proposed three-group classification methods in terms of the ideal observer. We collected a database of 270 mammographic images with clustered microcalcification lesions. We have developed a novel performance metric that may generalize better than AUC to tasks with more than two groups. A three-group classifier could potentially allow radiologists to detect more malignant breast lesions without increasing their false-positive biopsy rates.
A yeast protein possesses the DNA-binding properties of the adenovirus major late transcription factor. (1989)

The adenovirus major late transcription factor (MLTF), or upstream stimulatory factor, is a human promoter-specific transcription factor which recognizes the near-palindromic sequence GGCCACGTGACC (R. W. Carthew, L. A. Chodosh, and P. A. Sharp, Cell 43:439-448, 1985; L. A. Chodosh, R. W. Carthew, and P. A. Sharp, Mol. Cell. Biol. 6:4723-4733, 1986; M. Sawadogo and R. G. Roeder, Cell 43:165-175, 1985). We describe here a protein found in the yeast Saccharomyces cerevisiae which possesses DNA-binding properties that are virtually identical to those of human MLTF. These two proteins recognize the same DNA-binding site, make the same purine nucleotide contacts, and are affected in the same manner by mutations in the MLTF-binding site.
Artificial accommodating intraocular lens powered by an ion polymer-metal composite actuator (2021)

The current method of controlling the focus of an accommodating intraocular lens is based on ciliary muscle contraction and cannot be used in older patients with presbyopia. We aimed to develop a dynamically accommodating intraocular lens powered by a membrane-shaped ion polymer metal composite actuator that is thin enough to be inserted in the eye. This study addresses two key problems identified in our previous accommodating intraocular lens prototype: the lack of repeatability due to the use of swine lenses instead of artificial lenses and the occurrence of a sixth order aberration. Thus, we present a new accommodating intraocular lens design and a method to transfer energy to actuators. To accommodate lens deformation and depth of focus, we used a membrane-shaped ion polymer metal composite actuator, thin enough to be inserted in the eye, and used an artificial silicone lens. To prevent the sixth order aberration, we included a ring between the ion polymer metal composite actuator and the lens. Different voltage patterns were applied to the IPMC actuator and changes in focus were observed. We were able to obtain repeatability and prevent the sixth order aberration. The dioptric power changed to ±0.23 D when ±1.5 V was used; however, at >1.5 V, a large accommodating range occurred, in addition to astigmatic vision. Thus, we have developed a novel prototype that is completely artificial, allowing reproducible and repeatable results. Visual accommodative demands were successfully met; however, although astigmatic vision was lessened, it was not completely eradicated.
Evaluation of Nematicidal Activity ofStreptomyces yatensisKRA-28 againstMeloidogyne incognita (2020)

The root-knot nematode (<i>Meloidogyne incognita</i>) is an important pathogen in crop cultivation, however, few methods are available to control this parasitic roundworm. In this study, the nematicidal effects of approximately 30 <i>Streptomyces</i> strains isolated from soil samples of Mt. Naejang (Korea) were tested against <i>Meloidogyne incognita</i>, and the culture broth of the strains KRA- 24 and KRA-28 exhibited approximately 75% and 85% insecticidal activity, respectively, in in vitro assays. In in vivo pot experiments, these strains reduced the number of nematodes in the soil and the number of egg masses in the roots of red peppers. The two strains also survived in the presence of insecticidal agents (0.1 to 3.0%) such as fosthiazate, ethoprophos and terbufos when they were used in parallel. The mixture of KRA-24 or KRA-28 culture broth and fosthiazate exhibited nematicidal effects that were similar to those observed when KRA-24 or KRA-28 were used alone. Our results clearly suggest that the Streptomyces strains KRA-24 and KRA-28 should be promoted as a biocontrol agent against <i>Meloidogyne incognita</i>.
Utilization of magnesium chelates in the synthesis of 3-nitro- and 3-(methoxycarbonyl)-substituted 2-arylchromones (1984)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTUtilization of magnesium chelates in the synthesis of 3-nitro- and 3-(methoxycarbonyl)-substituted 2-arylchromonesMark Cushman and Aziz AbbaspourCite this: J. Org. Chem. 1984, 49, 7, 1280–1282Publication Date (Print):April 1, 1984Publication History Published online1 May 2002Published inissue 1 April 1984https://pubs.acs.org/doi/10.1021/jo00181a030https://doi.org/10.1021/jo00181a030research-articleACS PublicationsRequest reuse permissionsArticle Views91Altmetric-Citations3LEARN 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 Get e-Alerts
Isotropic and Anisotropic Composition Fluctuations Close to the Order-to-Disorder Transitionin an Asymmetric Diblock Copolymer Melt Subjected to Reciprocating Shear Fields (1996)

An asymmetric poly(ethylene-propylene)-poly(ethylethylene) (PEP-PEE) diblock copolymer was examined near the order-to-disorder transition temperature, TODT, by small-angle neutron scattering as a function of shear rate, $\dot{\gamma}$. Heating in the absence of shear disorders the material from a hexagonal structure at TODT=155±1 ○C. Application of a reciprocating simple shear field markedly influences the phase behavior near the ODT. Application of shear while heating increases TODT consistent with the theoretical prediction, $T_{\rm ODT}\sim\dot{\gamma}^{2} $. During fast cooling studies we observe an additional characteristic temperature, TS, at which the material spontaneously orders, which we interpret as a stability (i.e., spinodal) limit. this result also agrees with the theoretical prediction, $\tau_{\rm S}\sim\dot{\gamma}^{-1/3}$. Upon cessation of shear at temperatures close to but above the quiescent TODT a transient phase is observed before the system macroscopically disorders. The transient structure has a symmetry compatible with spheres arranged on a body centered cubic (BBC) space lattice, or undulating cylinders of the minority component (PEE). Anisotropic (i.e. lattice pinned) fluctuations can also be observed close to, but below, TODT upon heating the hexagonal structure under shear free conditions.
Receptive Field Properties of the Macaque Second Somatosensory Cortex: Representation of Orientation on Different Finger Pads (2006)

Orientation tuning has been studied extensively in the visual system, but little is known about it in the somatosensory system. Here we investigate tuning in the second somatosensory (SII) region using a motorized stimulator that presented a small oriented bar to the 12 finger pads of digits 2-5 (D2-D5) of the macaque monkey. A subset (23%; n = 218) of the 928 SII region neurons [the same 928 neurons studied by Fitzgerald et al. (2004, 2006)] exhibited tuning, and most of these were tuned on one or two finger pads. All eight 22.5 degrees separated orientations were represented as the preferred orientation of multiple neurons, although not necessarily in equal numbers. A measure of bandwidth indicated that tuning in the SII region is sharp and is similar to the tuning observed in visual cortical areas. In addition, two-dimensional Gaussians that were fit to the tuning curves had very high r2 values, indicating that most tuning curves are both unimodal and symmetrical with respect to their preferred orientation. Most tuned neurons had additional untuned pads, although the responsiveness of these pads tended to be less than the responsiveness of tuned pads. Neurons with multiple tuned pads tended to have similar preferred orientations on their tuned pads, which can be interpreted as evidence for integration of information across fingers or as a form of positional invariance. Finally, comparison of the tuning properties showed that there are small but significant differences between the posterior, central, and anterior fields of the SII region.
A Synthetic Approach to a Peptide α‐Thioester from an Unprotected Peptide through Cleavage and Activation of a Specific Peptide Bond by N‐Acetylguanidine (2011)

A different route to peptide α-thioesters through a new peptide-bond-cleavage method at a cysteine residue by S-thiocarbonylation and subsequent treatment with N-acetylguanidine is described (see scheme). The resultant peptidyl-N-acetylguanidine can be converted into the corresponding peptide α-thioester and is also usable as an alternative to a peptide α-thioester. This method allows efficient kinetically controlled ligation in the presence of thiols. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
DIFFERENCE SETS (1983)

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Death of PC12 cells and hippocampal neurons induced by adenoviral-mediated FAD human amyloid precursor protein gene expression (1999)

We used adenoviral-mediated gene transfer of human amyloid precursor proteins (h-APPs) to evaluate the role of various h-APPs in causing neuronal cell death. We were able to infect PC12 cells with very high efficiency because approximately 90% of the cells were cytochemically positive for beta-galactosidase activity when an adenoviral vector containing LacZ cDNA was used to infect cells. Cells infected with adenovirus containing h-APP cDNA showed high-level transcription and expression of h-APP as measured by reverse transcriptase-polymerase chain reaction and Western immunoblot analyses, respectively. Intracellular and extracellular levels of h-APP were elevated approximately 17-and 24-fold in cultures infected with recombinant adenovirus containing wild-type mutant and 13- and 17-fold with V642F mutant. No elevation in h-APP was seen in cultures infected with antisense h-APP or null adenovirus. H-APP levels were maximal 3 days after infection. Overexpression of V642F mutant h-APP in PC12 cells and hippocampal neurons resulted in about a twofold increase in death compared with overexpression of wild-type h-APP. These results demonstrate the usefulness of recombinant adenoviral mediated gene transfer in cell culture studies and suggest that overexpression of a familial Alzheimer's disease mutant APP may be toxic to neuronal cells.
Chickens with humanized immunoglobulin genes generate antibodies with high affinity and broad epitope coverage to conserved targets (2017)

Transgenic animal platforms for the discovery of human monoclonal antibodies have been developed in mice, rats, rabbits and cows. The immune response to human proteins is limited in these animals by their tolerance to mammalian-conserved epitopes. To expand the range of epitopes that are accessible, we have chosen an animal host that is less phylogenetically related to humans. Specifically, we generated transgenic chickens expressing antibodies from immunoglobulin heavy and light chain loci containing human variable regions and chicken constant regions. From these birds, paired human light and heavy chain variable regions are recovered and cloned as fully human recombinant antibodies. The human antibody-expressing chickens exhibit normal B cell development and raise immune responses to conserved human proteins that are not immunogenic in mice. Fully human monoclonal antibodies can be recovered with sub-nanomolar affinities. Binning data of antibodies to a human protein show epitope coverage similar to wild type chickens, which we previously showed is broader than that produced from rodent immunizations.
High-throughput formation and image-based analysis of basal-in mammary organoids in 384-well plates (2022)

This manuscript describes a new method for forming basal-in MCF10A organoids using commercial 384-well ultra-low attachment (ULA) microplates and the development of associated live-cell imaging and automated analysis protocols. The use of a commercial 384-well ULA platform makes this method more broadly accessible than previously reported hanging drop systems and enables in-incubator automated imaging. Therefore, time points can be captured on a more frequent basis to improve tracking of early organoid formation and growth. However, one major challenge of live-cell imaging in multi-well plates is the rapid accumulation of large numbers of images. In this paper, an automated MATLAB script to handle the increased image load is developed. This analysis protocol utilizes morphological image processing to identify cellular structures within each image and quantify their circularity and size. Using this script, time-lapse images of aggregating and non-aggregating culture conditions are analyzed to profile early changes in size and circularity. Moreover, this high-throughput platform is applied to widely screen concentration combinations of Matrigel and epidermal growth factor (EGF) or heparin-binding EGF-like growth factor (HB-EGF) for their impact on organoid formation. These results can serve as a practical resource, guiding future research with basal-in MCF10A organoids.
Aggregatibacter actinomycetemcomitans Leukotoxin (LtxA; Leukothera®): Mechanisms of Action and Therapeutic Applications (2019)

<i>Aggregatibacter actinomycetemcomitans</i> is an oral pathogen that produces the RTX toxin, leukotoxin (LtxA; Leukothera<sup>®</sup>). <i>A. actinomycetemcomitans</i> is strongly associated with the development of localized aggressive periodontitis. LtxA acts as a virulence factor for <i>A. actinomycetemcomitans</i> to subvert the host immune response by binding to the β<sub>2</sub> integrin lymphocyte function-associated antigen-1 (LFA-1; CD11a/CD18) on white blood cells (WBCs), causing cell death. In this paper, we reviewed the state of knowledge on LtxA interaction with WBCs and the subsequent mechanisms of induced cell death. Finally, we touched on the potential therapeutic applications of LtxA (trade name Leukothera<sup>®</sup>) toxin therapy for the treatment of hematological malignancies and immune-mediated diseases.
L1-CAM as a target for treatment of cancer with monoclonal antibodies. (2009)

L1 cell adhesion molecule (L1-CAM) is a neuronal adhesion molecule which is expressed in many tumor entities. L1-CAM was shown to be involved in proliferation, invasion and metastasis both in vitro and in vivo. L1-CAM is engaged in homophilic interactions and complexes with many other ligands in a context-dependent manner. Activation and modulation of the extracellular signal-related kinase pathway by L1-CAM has been documented. In normal tissues, L1-CAM expression is restricted to nerve bundles and kidney tubules; however, L1-CAM is expressed in many tumor entities and, with the exception of neuroblastoma, L1-CAM expression correlates with poor prognosis. L1-CAM occurs in two isoforms, full-length L1-CAM and a variant in which exons 2 and 27 have been deleted. Preclinical experiments with available monoclonal antibodies are summarized and L1-CAM is analysed as a target for treatment of cancer with monoclonal antibodies.
New endoscopic suturing device for closure of chronic gastrocutaneous fistula in an immunocompromised patient (2011)

A 46-year-old man with AIDS received a percutaneous endoscopic gastrostomy (PEG) tube in October 2009. His condition improved, and the PEG tube was removed in May 2010. Afterwards, the patient developed a persistent gastrocutaneous fistula at the site of the previous PEG. Multiple attempts to close the fistula with endoscopic clips, gastropexy, and an over-the-scope clip (Ovesco Endoscopy AG, Tbingen, Germany) failed. Upper endoscopy revealed a gastrocutaneous fistula 5 mm in diameter.
Study of stress in a shallow-trench-isolated Si structure using polarized confocal near-UV Raman microscopy of its cross section (2007)

Stress in shallow-trench-isolated structures with 250-nm-wide Si stripes was examined by 364nm excitation confocal Raman microscopy. Using objective lenses with the experimentally measured ∼150nm spatial resolution, we studied polarized Raman spectra from the section perpendicular to the stripes. Detection of two optical phonons enabled us to analyze orientation and intensity of local stress quantitatively. Uniaxial [001] compressive stress was found in the Si substrate under both the trench and the stripe, while the stress in the stripe was uniaxial [110] perpendicular to the stripe.
ChemInform Abstract: A New Chiral Auxiliary for Asymmetric Thermal Reactions: High Stereocontrol in Radical Addition, Allylation, and Annulation Reactions. (1992)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Fast methods for spatially correlated multilevel functional data (2010)

We propose a new methodological framework for the analysis of hierarchical functional data when the functions at the lowest level of the hierarchy are correlated. For small data sets, our methodology leads to a computational algorithm that is orders of magnitude more efficient than its closest competitor (seconds versus hours). For large data sets, our algorithm remains fast and has no current competitors. Thus, in contrast to published methods, we can now conduct routine simulations, leave-one-out analyses, and nonparametric bootstrap sampling. Our methods are inspired by and applied to data obtained from a state-of-the-art colon carcinogenesis scientific experiment. However, our models are general and will be relevant to many new data sets where the object of inference are functions or images that remain dependent even after conditioning on the subject on which they are measured. Supplementary materials are available at Biostatistics online.
The Computerate Specifying Paradigm (2000)

This document specifies a paradigm named Computerate Specifying,
designed to simultaneously document and formally specify communication
protocols. This paradigm can be applied to any document produced by
any Standard Developing Organization (SDO), but this document targets
specifically documents produced by the IETF.